{"query": "How much impact do masks have on preventing the spread of the COVID-19?", "hits": [{"content": "Title: Who is wearing a mask? Gender-, age-, and location-related differences during the COVID-19 pandemic Content: Masks are an effective tool in combatting the spread of COVID-19 but wearing them remains controversial and has not been studied in the United States. To understand the demographics of mask wearers in the US, we observed shoppers (n = 5517) entering retail stores. 41.5% of the observed sample wore a mask. The odds of an individual wearing a mask increased significantly with age, and was also 1.5x greater for females than males. Additionally, the odds of observing a mask on an urban or suburban shopper were ~4x that for rural areas. Thus, gender, age, and location factor into whether American shoppers wear a mask or face covering. Regardless, all demographics wore masks at substantially lesser rates than required to stop the spread of COVID-19.", "qid": 44, "docid": "f4uh73j7", "rank": 1, "score": 0.914482593536377}, {"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": 2, "score": 0.9066604971885681}, {"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": 3, "score": 0.902779757976532}, {"content": "Title: Face mask use in the general population and optimal resource allocation during the COVID-19 pandemic Content: The ongoing novel coronavirus disease (COVID-19) pandemic has rapidly spread in early 2020, causing tens of thousands of deaths, over a million cases and widespread socioeconomic disruption. With no vaccine available and numerous national healthcare systems reaching or exceeding capacity, interventions to limit transmission are urgently needed. While there is broad agreement that travel restrictions and closure of non-essential businesses and schools are beneficial in limiting local and regional spread, recommendations around the use of face masks for the general population are less consistent internationally. In this study, we examined the role of face masks in mitigating the spread of COVID-19 in the general population, using epidemic models to estimate the total reduction of infections and deaths under various scenarios. In particular, we examined the optimal deployment of face masks when resources are limited, and explored a range of supply and demand dynamics. We found that face masks, even with a limited protective effect, can reduce infections and deaths, and can delay the peak time of the epidemic. We consistently found that a random distribution of masks in the population was a suboptimal strategy when resources were limited. Prioritizing coverage among the elderly was more beneficial, while allocating a proportion of available resources for diagnosed infected cases provided further mitigation under a range of scenarios. In summary, face mask use, particularly for a pathogen with relatively common asymptomatic carriage, can effectively provide some mitigation of transmission, while balancing provision between vulnerable healthy persons and symptomatic persons can optimize mitigation efforts when resources are limited.", "qid": 44, "docid": "qdamvwxl", "rank": 4, "score": 0.9006569981575012}, {"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": 5, "score": 0.900638222694397}, {"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": 6, "score": 0.8994390964508057}, {"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": 44, "docid": "iaiosjlu", "rank": 7, "score": 0.8978753685951233}, {"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": 44, "docid": "6tod4abn", "rank": 8, "score": 0.8978753685951233}, {"content": "Title: Efficacy of face mask in preventing respiratory virus transmission: a systematic review and meta-analysis Content: Background: Conflicting recommendations exist related to whether masks have a protective effect on the spread of respiratory viruses. Methods: The Preferred Reporting Items for Systematic Reviews and Meta-Analysis (PRISMA) statement was consulted to report this systematic review. Relevant articles were retrieved from PubMed, Web of Science, ScienceDirect, Cochrane Library, and Chinese National Knowledge Infrastructure (CNKI), VIP (Chinese) database. Results: A total of 21 studies met our inclusion criteria. Meta-analyses suggest that mask use provided a significant protective effect (OR = 0.35 and 95% CI = 0.24-0.51). Use of masks by healthcare workers (HCWs) and non-healthcare workers (Non-HCWs) can reduce the risk of respiratory virus infection by 80% (OR = 0.20, 95% CI = 0.11-0.37) and 47% (OR = 0.53, 95% CI = 0.36-0.79). The protective effect of wearing masks in Asia (OR = 0.31) appeared to be higher than that of Western countries (OR = 0.45). Masks had a protective effect against influenza viruses (OR = 0.55), SARS (OR = 0.26), and SARS-CoV-2 (OR = 0.04). In the subgroups based on different study designs, protective effects of wearing mask were significant in cluster randomized trials, case-control studies and retrospective studies. Conclusions: This study adds additional evidence of the enhanced protective value of masks, we stress that the use masks serve as an adjunctive method regarding the COVID-19 outbreak.", "qid": 44, "docid": "ropgq7tr", "rank": 9, "score": 0.8967347741127014}, {"content": "Title: Efficacy of face mask in preventing respiratory virus transmission: A systematic review and meta-analysis Content: BACKGROUND: Conflicting recommendations exist related to whether masks have a protective effect on the spread of respiratory viruses. METHODS: The Preferred Reporting Items for Systematic Reviews and Meta-Analysis (PRISMA) statement was consulted to report this systematic review. Relevant articles were retrieved from PubMed, Web of Science, ScienceDirect, Cochrane Library, and Chinese National Knowledge Infrastructure (CNKI), VIP (Chinese) database. RESULTS: A total of 21 studies met our inclusion criteria. Meta-analyses suggest that mask use provided a significant protective effect (OR = 0.35 and 95% CI = 0.24-0.51). Use of masks by healthcare workers (HCWs) and non-healthcare workers (Non-HCWs) can reduce the risk of respiratory virus infection by 80% (OR = 0.20, 95% CI = 0.11-0.37) and 47% (OR = 0.53, 95% CI = 0.36-0.79). The protective effect of wearing masks in Asia (OR = 0.31) appeared to be higher than that of Western countries (OR = 0.45). Masks had a protective effect against influenza viruses (OR = 0.55), SARS (OR = 0.26), and SARS-CoV-2 (OR = 0.04). In the subgroups based on different study designs, protective effects of wearing mask were significant in cluster randomized trials and observational studies. CONCLUSIONS: This study adds additional evidence of the enhanced protective value of masks, we stress that the use masks serve as an adjunctive method regarding the COVID-19 outbreak.", "qid": 44, "docid": "b4znk2wr", "rank": 10, "score": 0.8964124917984009}, {"content": "Title: Efficacy of face mask in preventing respiratory virus transmission: A systematic review and meta-analysis Content: BACKGROUND: Conflicting recommendations exist related to whether masks have a protective effect on the spread of respiratory viruses. METHODS: The Preferred Reporting Items for Systematic Reviews and Meta-Analysis (PRISMA) statement was consulted to report this systematic review. Relevant articles were retrieved from PubMed, Web of Science, ScienceDirect, Cochrane Library, and Chinese National Knowledge Infrastructure (CNKI), VIP (Chinese) database. RESULTS: A total of 21 studies met our inclusion criteria. Meta-analyses suggest that mask use provided a significant protective effect (OR = 0.35 and 95% CI = 0.24\u20130.51). Use of masks by healthcare workers (HCWs) and non-healthcare workers (Non-HCWs) can reduce the risk of respiratory virus infection by 80% (OR = 0.20, 95% CI = 0.11\u20130.37) and 47% (OR = 0.53, 95% CI = 0.36\u20130.79). The protective effect of wearing masks in Asia (OR = 0.31) appeared to be higher than that of Western countries (OR = 0.45). Masks had a protective effect against influenza viruses (OR = 0.55), SARS (OR = 0.26), and SARS-CoV-2 (OR = 0.04). In the subgroups based on different study designs, protective effects of wearing mask were significant in cluster randomized trials and observational studies. CONCLUSIONS: This study adds additional evidence of the enhanced protective value of masks, we stress that the use masks serve as an adjunctive method regarding the COVID-19 outbreak.", "qid": 44, "docid": "x9sfgtim", "rank": 11, "score": 0.8958376049995422}, {"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": 12, "score": 0.892888605594635}, {"content": "Title: Comprehensive review of mask utility and challenges during the COVID-19 pandemic Content: Masks are widely discussed during the course of the ongoing COVID-19 pandemic Most hospitals have implemented universal masking for their healthcare workers, and the Center for Disease Control currently advises even the general public to wear cloth masks when outdoors The pertinent need for masks arises from plausible dissemination of the SARS-CoV-2 through close contacts, as well as the possibility of virus transmission from asymptomatic, pre-symptomatic, and mildly symptomatic individuals Given current global shortages in personal protective equipment, the efficacy of various types of masks: N95 respirators, surgical masks, and cloth masks are researched To accommodate limited supplies, techniques for extended use, reuse, and sterilization of masks are strategized However, masks alone may not greatly slow down the COVID-19 pandemic unless they are coupled with adequate social distancing, diligent hand hygiene, and other proven preventive measures", "qid": 44, "docid": "7qj00qi9", "rank": 13, "score": 0.8913722038269043}, {"content": "Title: Face Masks Considerably Reduce Covid-19 Cases in Germany Content: We use the synthetic control method to analyze the effect of face masks on the spread of Covid-19 in Germany. Our identification approach exploits regional variation in the point in time when face masks became compulsory. Depending on the region we analyse, we find that face masks reduced the cumulative number of registered Covid-19 cases between 2.3% and 13% over a period of 10 days after they became compulsory. Assessing the credibility of the various estimates, we conclude that face masks reduce the daily growth rate of reported infections by around 40%.", "qid": 44, "docid": "yx9oa2ra", "rank": 14, "score": 0.8913692235946655}, {"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": 15, "score": 0.8913175463676453}, {"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": 16, "score": 0.8907772302627563}, {"content": "Title: Comprehensive review of mask utility and challenges during the COVID-19 pandemic. Content: Masks are widely discussed during the course of the ongoing COVID-19 pandemic. Most hospitals have implemented universal masking for their healthcare workers, and the Center for Disease Control currently advises even the general public to wear cloth masks when outdoors. The pertinent need for masks arises from plausible dissemination of the SARS-CoV-2 through close contacts, as well as the possibility of virus transmission from asymptomatic, pre-symptomatic, and mildly symptomatic individuals. Given current global shortages in personal protective equipment, the efficacy of various types of masks: N95 respirators, surgical masks, and cloth masks are researched. To accommodate limited supplies, techniques for extended use, reuse, and sterilization of masks are strategized. However, masks alone may not greatly slow down the COVID-19 pandemic unless they are coupled with adequate social distancing, diligent hand hygiene, and other proven preventive measures.", "qid": 44, "docid": "3ttcfhm3", "rank": 17, "score": 0.8907457590103149}, {"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": 18, "score": 0.884319543838501}, {"content": "Title: The scientific rationale for the use of simple masks or improvised facial coverings to trap exhaled aerosols and possibly reduce the breathborne spread of COVID-19 Content: The medical community agrees that breathborne infectious materials can be spread with exhaled aerosols and that asymptomatic people, i.e., those showing no symptoms, could be unknowingly infectious. With the current worldwide pandemic of the respiratory coronavirus disease 2019 (COVID-19), various health bodies and governments are recommending that the population wear some form of mask or improvised facial covers while out in public in an effort to reduce the spread of disease . The general concept is that more accessible masks or mask-like materials (scarves, bandanas, etc.) could serve to reduce the amount of infectious aerosol from infected people, and reduce the viral load in the environment. This editorial addresses the underlying scientific rationale that such inexpensive or improvised could indeed serve to reduce the emissions of infectious aerosol by the mechanism of surface adhesion and particle kinetics in addition to the filtration effect.", "qid": 44, "docid": "m17j5u0y", "rank": 19, "score": 0.8838847875595093}, {"content": "Title: Reply to Zhang et al.: Slowing the rate of spread of COVID-19 Content: Zhang et al. (2020) reported that mandating face coverings in public is necessary to decrease the rate of new COVID-19 infections. We present a counterexample that disproves this finding. We agree with Zhang et al. that masks can be an important element in reducing virus transmission and that widespread use may be essential for returning to full activity. However, their analysis neglects the potential importance of physical distancing for limiting COVID-19 transmission by misattributing its effect to mask requirements. A full suite of epidemiological tools is necessary in these challenging times.", "qid": 44, "docid": "8t8psk46", "rank": 20, "score": 0.8838135004043579}, {"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": 21, "score": 0.8828118443489075}, {"content": "Title: The effect of behavior of wearing masks on epidemic dynamics Content: Recently, COVID-19 has attracted a lot of attention of researchers from different fields. Wearing masks is a frequently adopted precautionary measure. In this paper, we investigate the effect of behavior of wearing masks on epidemic dynamics in the context of COVID-19. At each time, every susceptible individual chooses whether to wear a mask or not in the next time step, which depends on an evaluation of the potential costs and perceived risk of infection. When the cost of infection is high, the majority of the population choose to wear masks, where global awareness plays a significant role. However, if the mask source is limited, global awareness may give rise to a negative result. In this case, more mask source should be allocated to the individuals with high risk of infection.", "qid": 44, "docid": "2iokkog5", "rank": 22, "score": 0.8825209736824036}, {"content": "Title: Community Use Of Face Masks And COVID-19: Evidence From A Natural Experiment Of State Mandates In The US Content: State policies mandating public or community use of face masks or covers in mitigating novel coronavirus disease (COVID-19) spread are hotly contested. This study provides evidence from a natural experiment on effects of state government mandates in the US for face mask use in public issued by 15 states plus DC between April 8 and May 15. The research design is an event study examining changes in the daily county-level COVID-19 growth rates between March 31, 2020 and May 22, 2020. Mandating face mask use in public is associated with a decline in the daily COVID-19 growth rate by 0.9, 1.1, 1.4, 1.7, and 2.0 percentage-points in 1-5, 6-10, 11-15, 16-20, and 21+ days after signing, respectively. Estimates suggest as many as 230,000-450,000 COVID-19 cases possibly averted By May 22, 2020 by these mandates. The findings suggest that requiring face mask use in public might help in mitigating COVID-19 spread. [Editor's Note: This Fast Track Ahead Of Print article is the accepted version of the peer-reviewed manuscript. The final edited version will appear in an upcoming issue of Health Affairs.].", "qid": 44, "docid": "h2ahzau7", "rank": 23, "score": 0.8824694156646729}, {"content": "Title: Community Use Of Face Masks And COVID-19: Evidence From A Natural Experiment Of State Mandates In The US. Content: State policies mandating public or community use of face masks or covers in mitigating novel coronavirus disease (COVID-19) spread are hotly contested. This study provides evidence from a natural experiment on effects of state government mandates in the US for face mask use in public issued by 15 states plus DC between April 8 and May 15. The research design is an event study examining changes in the daily county-level COVID-19 growth rates between March 31, 2020 and May 22, 2020. Mandating face mask use in public is associated with a decline in the daily COVID-19 growth rate by 0.9, 1.1, 1.4, 1.7, and 2.0 percentage-points in 1-5, 6-10, 11-15, 16-20, and 21+ days after signing, respectively. Estimates suggest as many as 230,000-450,000 COVID-19 cases possibly averted By May 22, 2020 by these mandates. The findings suggest that requiring face mask use in public might help in mitigating COVID-19 spread. [Editor's Note: This Fast Track Ahead Of Print article is the accepted version of the peer-reviewed manuscript. The final edited version will appear in an upcoming issue of Health Affairs.].", "qid": 44, "docid": "9b6cepf4", "rank": 24, "score": 0.8824694156646729}, {"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": 44, "docid": "wni08lks", "rank": 25, "score": 0.8820432424545288}, {"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": 26, "score": 0.8819413185119629}, {"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": 44, "docid": "6wxjm7m0", "rank": 27, "score": 0.8809726238250732}, {"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": 44, "docid": "r1oqwdkz", "rank": 28, "score": 0.880301833152771}, {"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": 29, "score": 0.8781083226203918}, {"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": 30, "score": 0.8780966401100159}, {"content": "Title: Cloth Masks May Prevent Transmission of COVID-19: An Evidence-Based, Risk-Based Approach Content: As the COVID-19 pandemic progressed across the world, governments, international agencies, policymakers, and public health officials began recommending widespread use of nonmedical cloth masks to reduce the transmission of SARS-CoV-2. The authors of this article suggest that there is convincing evidence to support this recommendation.", "qid": 44, "docid": "8je46886", "rank": 31, "score": 0.8760291337966919}, {"content": "Title: How Efficient Can Non-Professional MasksSuppress COVID-19 Pandemic? Content: The coronavirus disease 2019 (COVID-19) pandemic is caused by the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), which can be transmitted via respiratory secretions. Since there are currently no specific therapeutics or vaccines available against the SARS-CoV-2, the commen nonpharmaceutical interventions (NPIs) are still the main measures to curb the COVID-19 epidemic. Face mask wearing is one important measure to suppress the pandemic. In order to know how efficient is face mask wearing in reducing the pandemic even with low efficiency non-professional face masks, we exploit physical abstraction to model the non-professional face masks made from cotton woven fabrics and characterize them by a parameter virus penetration rate (VPR){gamma}. Monte Carlo simulations exhibit that the effective reproduction number R of COVID-19 or similar pandemics can be approximately reduced by factor {gamma}4 with respect to the basic reproduction number R0,if the face masks with 70% <{gamma}< 90% are universally applied for the entire network. Furthermore, thought experiments and practical exploitation examples in country-level and city-level are enumerated and discussed to support our discovery in this study and indicate that the outbreak of a COVID-19 like pandemic can be even suppressed by the low efficiency non-professional face masks.", "qid": 44, "docid": "1yf1ae1d", "rank": 32, "score": 0.875392496585846}, {"content": "Title: Can wearing face masks in public affect transmission route and viral load in COVID-19? Content: The mandatory face mask wearing was implemented in the Czech Republic and Slovakia shortly after the COVID-19 outbreak in Central Europe. So far, the number of COVID-19-associated deaths per 100,000 individuals is far lower in these countries as compared with other neighbouring or close countries. The use of face masks in public may not protect the general public from contracting the virus, however, presumptively decreases the viral load and contributes to a favourable clinical outcome in COVID-19 disease. A certain time is required for antigen-specific T cells and B cells to fully develop. Obligatory face mask wearing in public favours the virus transmission through oral mucosa and/or conjunctival epithelium, which enables the adaptive immune responses to evolve. In the case of inhalation of high loads of SARS-CoV-2, the time for the development of fully protective adaptive immune responses seems to be insufficient. Then, a less specific and more damaging innate immune response prevails.", "qid": 44, "docid": "p93u753c", "rank": 33, "score": 0.8746280074119568}, {"content": "Title: Rational use of face mask in a tertiary care hospital setting during COVID-19 pandemic: An observational study Content: Masks play a role in the protection of health-care workers (HCWs) from acquiring respiratory infections, including coronavirus disease 2019 (COVID-19) in health-care settings. This observational study was conducted among 382 HCWs in a tertiary care setting over a period of 1 month. Descriptive analysis was done to assess the rational and recommended use of masks/respirators during COVID-19 pandemic using a structured observation checklist as a survey tool. A total of 374 HCWs were included, 64.9% of whom were using face masks rationally as mentioned per risk area categorization with a predominance of triple-layered mask during all 4 weeks. Overall, 64.1% used masks correctly. Clear guidelines and strategies can help to increase the compliance of HCWs with rational use of face masks.", "qid": 44, "docid": "57zwd3y6", "rank": 34, "score": 0.8742754459381104}, {"content": "Title: Rational use of face mask in a tertiary care hospital setting during COVID-19 pandemic: An observational study. Content: Masks play a role in the protection of health-care workers (HCWs) from acquiring respiratory infections, including coronavirus disease 2019 (COVID-19) in health-care settings. This observational study was conducted among 382 HCWs in a tertiary care setting over a period of 1 month. Descriptive analysis was done to assess the rational and recommended use of masks/respirators during COVID-19 pandemic using a structured observation checklist as a survey tool. A total of 374 HCWs were included, 64.9% of whom were using face masks rationally as mentioned per risk area categorization with a predominance of triple-layered mask during all 4 weeks. Overall, 64.1% used masks correctly. Clear guidelines and strategies can help to increase the compliance of HCWs with rational use of face masks.", "qid": 44, "docid": "t2e4bxsu", "rank": 35, "score": 0.8742754459381104}, {"content": "Title: Comparative efficacy of the front-line anti-HBV drugs in nucleos(t)ide analogue-naive chronic hepatitis B: A protocol for systematic review and network meta-analysis Content: BACKGROUND: During the COVID-19 period, there was a huge gap in the understanding of masks between east and west. At the same time, the mechanism of the mask and the effect after use, also appeared differences. The Objective of this Meta-analysis is to systematically evaluate the efficacy of masks for influenza in the community. METHODS: The Web of Science, PubMed, The Cochrane Library, EMBASE and Clinical Trials will be electronically searched to collect randomized controlled trials regarding the efficacy of masks for influenza in the community through Apr 2020. Two researchers independently screened and evaluated the obtained studies and extracted the outcome indexes. Revman 5.3 software will be used for the meta-analysis. RESULTS: The outbreak is continuing, and we need to be prepared for a long fight. If masks are effective, we need to promote their use as soon as possible. If masks are ineffective, strong evidence should be given. This is an urgent task and our team will finish it as soon as possible. CONCLUSION: Provide stronger evidence to solve the problem, should we wear masks or not right now.", "qid": 44, "docid": "29vynklv", "rank": 36, "score": 0.8738291263580322}, {"content": "Title: The efficacy of masks for influenza-like illness in the community: A protocol for systematic review and meta-analysis Content: BACKGROUND: During the COVID-19 period, there was a huge gap in the understanding of masks between east and west. At the same time, the mechanism of the mask and the effect after use, also appeared differences. The Objective of this Meta-analysis is to systematically evaluate the efficacy of masks for influenza in the community. METHODS: The Web of Science, PubMed, The Cochrane Library, EMBASE and Clinical Trials will be electronically searched to collect randomized controlled trials regarding the efficacy of masks for influenza in the community through Apr 2020. Two researchers independently screened and evaluated the obtained studies and extracted the outcome indexes. Revman 5.3 software will be used for the meta-analysis. RESULTS: The outbreak is continuing, and we need to be prepared for a long fight. If masks are effective, we need to promote their use as soon as possible. If masks are ineffective, strong evidence should be given. This is an urgent task and our team will finish it as soon as possible. CONCLUSION: Provide stronger evidence to solve the problem, should we wear masks or not right now.", "qid": 44, "docid": "p8lu5mc0", "rank": 37, "score": 0.8738291263580322}, {"content": "Title: The Effect of Mask Use on the Spread of Influenza During a Pandemic Content: Face masks have traditionally been used in general infection control, but their efficacy at the population level in preventing transmission of influenza viruses has not been studied in detail. Data from published clinical studies indicate that the infectivity of influenza A virus is probably very high, so that transmission of infection may involve low doses of virus. At low doses, the relation between dose and the probability of infection is approximately linear, so that the reduction in infection risk is proportional to the reduction in exposure due to particle retention of the mask. A population transmission model was set up to explore the impact of population\u2010wide mask use, allowing estimation of the effects of mask efficacy and coverage (fraction of the population wearing masks) on the basic reproduction number and the infection attack rate. We conclude that population\u2010wide use of face masks could make an important contribution in delaying an influenza pandemic. Mask use also reduces the reproduction number, possibly even to levels sufficient for containing an influenza outbreak.", "qid": 44, "docid": "mfb2or98", "rank": 38, "score": 0.8715716004371643}, {"content": "Title: Mask is the possible key for self\u2010isolation in COVID\u201019 pandemic Content: Ma's research shows N95 masks, medical masks, even homemade masks could block at least 90% of the virus in aerosols(1). This study puts the debate on whether the public wear masks back on the table. Recently Science interviewed Dr. Gao, director\u2010general of Chinese Center for Disease Control and Prevention (CDC). This article is protected by copyright. All rights reserved.", "qid": 44, "docid": "p5hljkkm", "rank": 39, "score": 0.871421217918396}, {"content": "Title: Visualizing the effectiveness of face masks in obstructing respiratory jets Content: The use of face masks in public settings has been widely recommended by public health officials during the current COVID-19 pandemic. The masks help mitigate the risk of cross-infection via respiratory droplets; however, there are no specific guidelines on mask materials and designs that are most effective in minimizing droplet dispersal. While there have been prior studies on the performance of medical-grade masks, there are insufficient data on cloth-based coverings, which are being used by a vast majority of the general public. We use qualitative visualizations of emulated coughs and sneezes to examine how material- and design-choices impact the extent to which droplet-laden respiratory jets are blocked. Loosely folded face masks and bandana-style coverings provide minimal stopping-capability for the smallest aerosolized respiratory droplets. Well-fitted homemade masks with multiple layers of quilting fabric, and off-the-shelf cone style masks, proved to be the most effective in reducing droplet dispersal. These masks were able to curtail the speed and range of the respiratory jets significantly, albeit with some leakage through the mask material and from small gaps along the edges. Importantly, uncovered emulated coughs were able to travel notably farther than the currently recommended 6-ft distancing guideline. We outline the procedure for setting up simple visualization experiments using easily available materials, which may help healthcare professionals, medical researchers, and manufacturers in assessing the effectiveness of face masks and other personal protective equipment qualitatively.", "qid": 44, "docid": "ohkki0ke", "rank": 40, "score": 0.8704453110694885}, {"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": 44, "docid": "kshjqsdj", "rank": 41, "score": 0.8700977563858032}, {"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": 44, "docid": "j0lpy07l", "rank": 42, "score": 0.8697975873947144}, {"content": "Title: Professional and Home-Made Face Masks Reduce Exposure to Respiratory Infections among the General Population Content: BACKGROUND: Governments are preparing for a potential influenza pandemic. Therefore they need data to assess the possible impact of interventions. Face-masks worn by the general population could be an accessible and affordable intervention, if effective when worn under routine circumstances. METHODOLOGY: We assessed transmission reduction potential provided by personal respirators, surgical masks and home-made masks when worn during a variety of activities by healthy volunteers and a simulated patient. PRINCIPAL FINDINGS: All types of masks reduced aerosol exposure, relatively stable over time, unaffected by duration of wear or type of activity, but with a high degree of individual variation. Personal respirators were more efficient than surgical masks, which were more efficient than home-made masks. Regardless of mask type, children were less well protected. Outward protection (mask wearing by a mechanical head) was less effective than inward protection (mask wearing by healthy volunteers). CONCLUSIONS/SIGNIFICANCE: Any type of general mask use is likely to decrease viral exposure and infection risk on a population level, in spite of imperfect fit and imperfect adherence, personal respirators providing most protection. Masks worn by patients may not offer as great a degree of protection against aerosol transmission.", "qid": 44, "docid": "umvrwgaw", "rank": 43, "score": 0.8694205284118652}, {"content": "Title: Mathematical Modeling of the Effectiveness of Facemasks in Reducing the Spread of Novel Influenza A (H1N1) Content: On June 11, 2009, the World Health Organization declared the outbreak of novel influenza A (H1N1) a pandemic. With limited supplies of antivirals and vaccines, countries and individuals are looking at other ways to reduce the spread of pandemic (H1N1) 2009, particularly options that are cost effective and relatively easy to implement. Recent experiences with the 2003 SARS and 2009 H1N1 epidemics have shown that people are willing to wear facemasks to protect themselves against infection; however, little research has been done to quantify the impact of using facemasks in reducing the spread of disease. We construct and analyze a mathematical model for a population in which some people wear facemasks during the pandemic and quantify impact of these masks on the spread of influenza. To estimate the parameter values used for the effectiveness of facemasks, we used available data from studies on N95 respirators and surgical facemasks. The results show that if N95 respirators are only 20% effective in reducing susceptibility and infectivity, only 10% of the population would have to wear them to reduce the number of influenza A (H1N1) cases by 20%. We can conclude from our model that, if worn properly, facemasks are an effective intervention strategy in reducing the spread of pandemic (H1N1) 2009.", "qid": 44, "docid": "36bfeoqv", "rank": 44, "score": 0.8692315816879272}, {"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": 44, "docid": "vjg2auh7", "rank": 45, "score": 0.8683009147644043}, {"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": 44, "docid": "gey0nidn", "rank": 46, "score": 0.8683009147644043}, {"content": "Title: Examining the protection efficacy of face shields against cough aerosol droplets using water sensitive papers Content: Simple plastic face shields have many advantages compared to regular medical masks. They are easily cleaned for reuse and comfortable to wear. In light of the spreading COVID-19 pandemic, the potential of face shields as a substitution for medical masks, as a recommendation to the general population, was tested. Testing the efficacy of the protective equipment utilized a cough simulator that was carefully tuned to replicate human cough in terms of droplet size distribution and outlet velocity. The tested protective equipment was worn on a manikin head simulating human breathing. An Aerodynamic Particle Sizer (APS) was used to analyze the concentration and size distribution of small particles that reach the manikin head respiration pathways. Additionally, Water sensitive papers were taped over and under the tested protective equipment, and were subsequently photographed and analyzed. For droplets larger than 3m by diameter, the efficiency of shields to block cough droplets was found to be comparable to that of regular medical masks, with enhanced protection on face parts the mask does not cover. Additionally, for finer particles, of the order 0.3 to few microns, a shield was found to perform even better, blocking about 10 times more fine particles than the medical mask. This implies that for the general population that is not intendedly exposed to confirmed infected individuals, recommending the use of face shields as an alternative to medical masks should be considered.", "qid": 44, "docid": "5b9jytph", "rank": 47, "score": 0.8682736158370972}, {"content": "Title: The role of community-wide wearing of face mask for control of coronavirus disease 2019 (COVID-19) epidemic due to SARS-CoV-2 Content: BACKGROUND: Face mask usage by the healthy population in the community to reduce risk of transmission of respiratory viruses remains controversial. We assessed the effect of community-wide mask usage to control coronavirus disease 2019 (COVID-19) in Hong Kong Special Administrative Region (HKSAR). METHODS: Patients presenting with respiratory symptoms at outpatient clinics or hospital wards were screened for COVID-19 per protocol. Epidemiological analysis was performed for confirmed cases, especially persons acquiring COVID-19 during mask-off and mask-on settings. The incidence of COVID-19 per million population in HKSAR with community-wide masking was compared to that of non-mask-wearing countries which are comparable with HKSAR in terms of population density, healthcare system, BCG vaccination and social distancing measures but not community-wide masking. Compliance of face mask usage in the HKSAR community was monitored. FINDINGS: Within first 100 days (31 December 2019 to 8 April 2020), 961 COVID-19 patients were diagnosed in HKSAR. The COVID-19 incidence in HKSAR (129.0 per million population) was significantly lower (p<0.001) than that of Spain (2983.2), Italy (2250.8), Germany (1241.5), France (1151.6), U.S. (1102.8), U.K. (831.5), Singapore (259.8), and South Korea (200.5). The compliance of face mask usage by HKSAR general public was 96.6% (range: 95.7% to 97.2%). We observed 11 COVID-19 clusters in recreational 'mask-off' settings compared to only 3 in workplace 'mask-on' settings (p\u00e2\u0080\u00af=\u00e2\u0080\u00af0.036 by Chi square test of goodness-of-fit). CONCLUSION: Community-wide mask wearing may contribute to the control of COVID-19 by reducing the amount of emission of infected saliva and respiratory droplets from individuals with subclinical or mild COVID-19.", "qid": 44, "docid": "wiel6zen", "rank": 48, "score": 0.8669804334640503}, {"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": 49, "score": 0.8655811548233032}, {"content": "Title: Facemasks and similar barriers to prevent respiratory illness such as COVID-19: A rapid systematic review Content: The current pandemic of COVID-19 has lead to conflicting opinions on whether wearing facemasks outside of health care facilities protects against the infection. To better understand the value of wearing facemasks we undertook a rapid systematic review of existing scientific evidence about development of respiratory illness, linked to use of facemasks in community settings. METHODS: We included all study designs. There were 31 eligible studies (including 12 RCTs). Narrative synthesis and random-effects meta-analysis of attack rates for primary and secondary prevention in 28 studies were performed. Results were reported by design, setting and type of face barrier in primary prevention, and by who wore the facemask (index patient or well contacts) in secondary prevention trials. The preferred outcome was influenza-like illness (ILI) but similar outcomes were pooled with ILI when ILI was unavailable. GRADE quality assessment was based on RCTs with support from observational studies. RESULTS: Where specific information was available, most studies reported about use of medical grade (surgical paper masks). In 3 RCTs, wearing a facemask may very slightly reduce the odds of developing ILI/respiratory symptoms, by around 6% (OR 0.94, 95% CI 0.75 to 1.19, I2 29%, low certainty evidence). Greater effectiveness was suggested by observational studies. When both house-mates and an infected household member wore facemasks the odds of further household members becoming ill may be modestly reduced by around 19% (OR 0.81, 95%CI 0.48 to 1.37, I 2 45%, 5 RCTs, low certainty evidence). The protective effect was very small if only the well person(OR 0.93, 95% CI 0.68 to 1.28, I2 11%, 2 RCTs, low uncertainty evidence) or the infected person wore the facemask (very low certainty evidence). DISCUSSION: Based on the RCTs we would conclude that wearing facemasks can be very slightly protective against primary infection from casual community contact, and modestly protective against household infections when both infected and uninfected members wear facemasks. However, the RCTs often suffered from poor compliance and controls using facemasks. Across observational studies the evidence in favour of wearing facemasks was stronger. We expect RCTs to under-estimate the protective effect and observational studies to exaggerate it. The evidence is not sufficiently strong to support widespread use of facemasks as a protective measure against COVID-19. However, there is enough evidence to support the use of facemasks for short periods of time by particularly vulnerable individuals when in transient higher risk situations. Further high quality trials are needed to assess when wearing a facemask in the community is most likely to be protective.", "qid": 44, "docid": "844229sb", "rank": 50, "score": 0.8649147152900696}, {"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": 51, "score": 0.864799976348877}, {"content": "Title: The use of facemasks may not lead to an increase in hand-face contact Content: Advocacy of the use of facemasks by the public as a measure against the spread of COVID-19 is controversial, with some healthcare professionals arguing that the use of a face mask may increase the rate at which people touch their faces, due to readjusting the mask. We assessed the facial touching behaviour of bus passengers in China before and after the outbreak of COVID-19 and found that wearing a face mask does not increase the number of hand-face contacts and is likely, therefore, to have a positive beneficial effect on suppressing the spread of COVID-19 within populations when used in conjunction with social distancing measures.", "qid": 44, "docid": "gaujhk7z", "rank": 52, "score": 0.8643411993980408}, {"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": 44, "docid": "9ye2okm5", "rank": 53, "score": 0.8640359044075012}, {"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": 54, "score": 0.8637614250183105}, {"content": "Title: Study of Air Curtain in Context of Individual Protection from Exposure to Coronavirus (SARS-CoV-2) Contained in Cough-Generated Fluid Particles Content: The ongoing respiratory COVID-19 pandemic has heavily impacted the social and private lives of the majority of the global population. This infection is primarily transmitted via virus-laden fluid particles (i.e., droplets and aerosols) that are formed in the respiratory tract of infected individuals and expelled from the mouth in the course of breathing, talking, coughing, and sneezing. To mitigate the risk of virus transmission, in many places of the world, the public has been asked or even obliged to use face covers. It is plausible that in the years ahead we will see the use of face masks, face shields and respirators become a normal practice in our life. However, wearing face covers is uncomfortable in some situations, like, for example, in summer heat, while staying on beaches or at hotel swimming pools, doing exercises in gyms, etc. Also, most types of face cover become contaminated with time and need to be periodically replaced or disinfected. These nuisances are caused by the fact that face covers are based on material barriers, which prevent inward and outward propagation of aerosol and droplets containing the pathogen. Applying well established gas-particle flow formalism, we study a non-material based protection barrier created by a flow of well directed down stream of air across the front of the open face. The~protection is driven by dragging virus-laden particles inside the width of the air flow and hence, as a consequence, displacing them away from their primary trajectories. The study, shows that such, potentially portable, air curtains can effectively provide both inward and outward protection and serve as an effective personal protective equipment (PPE) mitigating human to human transmission of virus infection like COVID-19.", "qid": 44, "docid": "4zrwxcwv", "rank": 55, "score": 0.8633226752281189}, {"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": 44, "docid": "oyxxji7r", "rank": 56, "score": 0.8630927801132202}, {"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": 57, "score": 0.8630857467651367}, {"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": 44, "docid": "fdkqs3rg", "rank": 58, "score": 0.8630238771438599}, {"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": 44, "docid": "cvulb9t6", "rank": 59, "score": 0.8630238771438599}, {"content": "Title: Physical interventions to interrupt or reduce the spread of respiratory viruses. Part 1 - Face masks, eye protection and person distancing: systematic review and meta-analysis Content: Abstract OBJECTIVE: To examine the effectiveness of eye protection, face masks, or person distancing on interrupting or reducing the spread of respiratory viruses. DESIGN: Update of a Cochrane review that included a meta-analysis of observational studies during the SARS outbreak of 2003. DATA SOURCES: Eligible trials from the previous review; search of Cochrane Central Register of Controlled Trials, PubMed, Embase and CINAHL from October 2010 up to 1 April 2020; and forward and backward citation analysis. DATA SELECTION: Randomised and cluster-randomised trials of people of any age, testing the use of eye protection, face masks, or person distancing against standard practice, or a similar physical barrier. Outcomes included any acute respiratory illness and its related consequences. DATA EXTRACTION AND ANALYSIS: Six authors independently assessed risk of bias using the Cochrane tool and extracted data. We used a generalised inverse variance method for pooling using a random-effects model and reported results with risk ratios and 95% Confidence Intervals (CI). RESULTS: We included 15 randomised trials investigating the effect of masks (14 trials) in healthcare workers and the general population and of quarantine (1 trial). We found no trials testing eye protection. Compared to no masks there was no reduction of influenza-like illness (ILI) cases (Risk Ratio 0.93, 95%CI 0.83 to 1.05) or influenza (Risk Ratio 0.84, 95%CI 0.61-1.17) for masks in the general population, nor in healthcare workers (Risk Ratio 0.37, 95%CI 0.05 to 2.50). There was no difference between surgical masks and N95 respirators: for ILI (Risk Ratio 0.83, 95%CI 0.63 to 1.08), for influenza (Risk Ratio 1.02, 95%CI 0.73 to 1.43). Harms were poorly reported and limited to discomfort with lower compliance. The only trial testing quarantining workers with household ILI contacts found a reduction in ILI cases, but increased risk of quarantined workers contracting influenza. All trials were conducted during seasonal ILI activity. CONCLUSIONS: Most included trials had poor design, reporting and sparse events. There was insufficient evidence to provide a recommendation on the use of facial barriers without other measures. We found insufficient evidence for a difference between surgical masks and N95 respirators and limited evidence to support effectiveness of quarantine. Based on observational evidence from the previous SARS epidemic included in the previous version of our Cochrane review we recommend the use of masks combined with other measures.", "qid": 44, "docid": "1vcc1khg", "rank": 60, "score": 0.8621958494186401}, {"content": "Title: The role of community-wide wearing of face mask for control of coronavirus disease 2019 (COVID-19) epidemic due to SARS-CoV-2 Content: Abstract Background Face mask usage by the healthy population in the community to reduce risk of transmission of respiratory viruses remains controversial. We assessed the effect of community-wide mask usage to control coronavirus disease 2019 (COVID-19) in Hong Kong Special Administrative Region (HKSAR). Methods Patients presenting with respiratory symptoms at outpatient clinics or hospital wards were screened for COVID-19 per protocol. Epidemiological analysis was performed for confirmed cases, especially persons acquiring COVID-19 during mask-off and mask-on settings. The incidence of COVID-19 per-million-population in HKSAR with community-wide masking was compared to that of non-mask-wearing countries which are comparable with HKSAR in terms of population density, healthcare system, BCG vaccination and social distancing measures but not community-wide masking. Compliance of face mask usage in the HKSAR community was monitored. Findings Within first 100 days (31 December 2019 to 8 April 2020), 961 COVID-19 patients were diagnosed in HKSAR. The COVID-19 incidence in HKSAR (129.0 per-million-population) was significantly lower (p<0.001) than that of Spain (2983.2), Italy (2250.8), Germany (1241.5), France (1151.6), U.S. (1102.8), U.K. (831.5), Singapore (259.8), and South Korea (200.5). The compliance of face mask usage by HKSAR general public was 96.6% (range: 95.7% to 97.2%). We observed 11 COVID-19 clusters in recreational \u2018mask-off\u2019 settings compared to only 3 in workplace \u2018mask-on\u2019 settings (p = 0.036 by Chi square test of goodness-of-fit). Conclusion Community-wide mask wearing may contribute to the control of COVID-19 by reducing virus shedding in saliva and respiratory droplets from individuals with subclinical or mild COVID-19.", "qid": 44, "docid": "9mn6trtn", "rank": 61, "score": 0.8621951937675476}, {"content": "Title: The N-95 mask: invaluable ally in the battle against the COVID-19 pandemic Content: The present COVID-19 pandemic, caused by the airborne SARS-CoV-2 virus, has highlighted the vital importance of appropriate personal protective equipment for all exposed health care workers The single most important part of this armor is the N-95 mask With the awareness that the virus is spread by both droplets and through the aerosolized route, the N-95 provides protection that a surgical mask cannot match This timely review looks at the special advantages that an N-95 offers over a surgical mask with specific reference to the COVID-19 epidemic It also emphasizes the crucial importance of ensuring quality masks with a proper fit Finally, with acute scarcities of N-95 masks being reported from hospitals globally, it reviews recent literature which attempts to prolong the life of these masks with extended use, reuse and decontamination of used masks", "qid": 44, "docid": "i1w2snyy", "rank": 62, "score": 0.8615598678588867}, {"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": 63, "score": 0.8615577220916748}, {"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": 64, "score": 0.8608970642089844}, {"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": 65, "score": 0.8605352640151978}, {"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": 66, "score": 0.8605352640151978}, {"content": "Title: Performance of fabrics for home-made masks against spread of respiratory infection through droplets: a quantitative mechanistic study Content: Respiratory infections may spread through droplets, airborne particles, and aerosols from infected individuals through coughing, sneezing, and speaking. In the case of Coronavirus Disease 2019 (COVID-19), droplet spread can occur from symptomatic as well as pre-symptomatic and asymptomatic persons. The U.S. Centers for Disease Control and Prevention (CDC) has therefore recently recommended home-made cloth face coverings for use by the general public in areas of significant community-based transmission. Because medical masks and N95 respirators are in short supply, these are to be reserved for healthcare workers. There is, however, little information on the effectiveness of home-made face coverings in reducing droplet dissemination. Here, we ascertained the performance of ten different fabrics, ranging from cotton to silk, in blocking high velocity droplets, using a 3-layered commercial medical mask as a benchmark material. We also assessed their breathability and ability to soak water. We reason that the materials should be as breathable as possible, without compromising blocking efficiency, to reduce air flow through the sides of the mask since such flow would defeat the purpose of the mask. We found that most home fabrics substantially block droplets, even as a single layer. With two layers, blocking performance can reach that of surgical mask without significantly compromising breathability. Furthermore, we observed that home fabrics are hydrophilic to varying degrees, and hence soak water. In contrast, medical masks are hydrophobic, and tend to repel water. Incoming droplets are thus soaked and 'held back' by home fabrics, which might offer an as of yet untapped and understudied advantage of home-made cloth masks. Overall, our study suggests that most double-layered cloth face coverings may help reduce droplet transmission of respiratory infections.", "qid": 44, "docid": "o71haprj", "rank": 67, "score": 0.8587371110916138}, {"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": 44, "docid": "8ko7mmu3", "rank": 68, "score": 0.8587331771850586}, {"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": 44, "docid": "in16u4pm", "rank": 69, "score": 0.8585575819015503}, {"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": 44, "docid": "zzumi9h5", "rank": 70, "score": 0.857992947101593}, {"content": "Title: Quantifying Respiratory Airborne Particle Dispersion Control Through Improvised Reusable Masks Content: Objective: To determine the effectiveness of non-medical grade washable masks or face coverings in controlling airborne dispersion from exhalation (both droplet and aerosol), and to aid in establishing public health strategies on the wearing of masks to reduce COVID-19 transmission. Design: This comparative effectiveness study using an exhalation simulator to conduct 94 experiment runs with combinations of 8 different fabrics, 5 mask designs, and airflows for both talking and coughing. Setting: Non-airtight fume hood and multiple laser scattering particle sensors. Participants: No human participants. Exposure: 10% NaCl nebulized solution delivered by an exhalation simulator through various masks and fabrics with exhalation airflows representative of \"coughing\" and \"talking or singing.\" Main Outcomes and Measures: The primary outcome was reduction in aerosol dispersion velocity, quantity of particles, and change in dispersion direction. Measurements used in this study included peak expiratory flow (PEF), aerosol velocity, concentration area under curve (AUC), and two novel metrics of expiratory flow dispersion factor (EDF) and filtration efficiency indicator (FEI). Results: Three-way multivariate analysis of variance establishes that factors of fabric, mask design, and exhalation breath level have a statistically significant effect on changing direction, reducing velocity or concentration (Fabric: P = < .001, Wilks' {Lambda} = .000; Mask design: P = < .001, Wilks' {Lambda} = .000; Breath level: P = < .001, Wilks' {Lambda} = .004). There were also statistically significant interaction effects between combinations of all primary factors. Conclusions and Relevance: The application of facial coverings or masks can significantly reduce the airborne dispersion of aerosolized particles from exhalation. The results show that wearing of non-medical grade washable masks or face coverings can help increase the effectiveness of non-pharmaceutical interventions (NPI) especially where infectious contaminants may exist in shared air spaces. However, the effectiveness varies greatly between the specific fabrics and mask designs used.", "qid": 44, "docid": "nt378esz", "rank": 71, "score": 0.8579442501068115}, {"content": "Title: Estimation of effects of contact tracing and mask adoption on COVID-19 transmission in San Francisco: a modeling study Content: The current COVID-19 pandemic has spurred concern about what interventions may be effective at reducing transmission. The city and county of San Francisco imposed a shelter-in-place order in March 2020, followed by use of a contact tracing program and a policy requiring use of cloth face masks. We used statistical estimation and simulation to estimate the effectiveness of these interventions in San Francisco. We estimated that self-isolation and other practices beginning at the time of San Francisco\u2019s shelter-in-place order reduced the effective reproduction number of COVID-19 by 35.4% (95% CI, \u221220.1%\u201381.4%). We estimated the effect of contact tracing on the effective reproduction number to be a reduction of approximately 44% times the fraction of cases that are detected, which may be modest if the detection rate is low. We estimated the impact of cloth mask adoption on reproduction number to be approximately 8.6%, and note that the benefit of mask adoption may be substantially greater for essential workers and other vulnerable populations, residents return to circulating outside the home more often. We estimated the effect of those interventions on incidence by simulating counterfactual scenarios in which contact tracing was not adopted, cloth masks were not adopted, and neither contact tracing nor cloth masks was adopted, and found increases in case counts that were modest, but relatively larger than the effects on reproduction numbers. These estimates and model results suggest that testing coverage and timing of testing and contact tracing may be important, and that modest effects on reproduction numbers can nonetheless cause substantial effects on case counts over time.", "qid": 44, "docid": "7hdx4ik4", "rank": 72, "score": 0.8577719926834106}, {"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": 44, "docid": "py38vnwc", "rank": 73, "score": 0.8568109273910522}, {"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": 44, "docid": "ckqdh4pg", "rank": 74, "score": 0.8553744554519653}, {"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": 44, "docid": "471z07ac", "rank": 75, "score": 0.8553744554519653}, {"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": 76, "score": 0.8553025722503662}, {"content": "Title: High Filtration Efficiency Face Masks made from Sterilization Wraps Content: COVID-19 pandemic has spawned the need for mass production of N-95 respirators. We used Sterilization Wraps to produce face masks which maintained 93% particle capture efficacy post sterilization. This ubiquitously available material could be explored for production of high quality face masks at a cost less than 30 US cents.", "qid": 44, "docid": "m6cxelu5", "rank": 77, "score": 0.8552129864692688}, {"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": 44, "docid": "tcijnphu", "rank": 78, "score": 0.8548331260681152}, {"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": 44, "docid": "xtraspw2", "rank": 79, "score": 0.8548331260681152}, {"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": 44, "docid": "30pl5tx3", "rank": 80, "score": 0.8545175790786743}, {"content": "Title: The history and value of face masks Content: In the human population, social contacts are a key for transmission of bacteria and viruses. The use of face masks seems to be critical to prevent the transmission of SARS-CoV-2 for the period, in which therapeutic interventions are lacking. In this review, we describe the history of masks from the middle age to modern times.", "qid": 44, "docid": "jyju71r1", "rank": 81, "score": 0.8542950749397278}, {"content": "Title: Potential utilities of mask-wearing and instant hand hygiene for fighting SARS-CoV-2 Content: The surge of patients in the pandemic of COVID-19 caused by the novel coronavirus SARS-CoV-2 may overwhelm the medical systems of many countries. Mask-wearing and handwashing can slow the spread of the virus, but currently, masks are in shortage in many countries, and timely handwashing is often impossible. In this study, the efficacy of three types of masks and instant hand wiping was evaluated using the avian influenza virus to mock the coronavirus. Virus quantification was performed using real-time reverse transcription-polymerase chain reaction. Previous studies on mask-wearing were reviewed. The results showed that instant hand wiping using a wet towel soaked in water containing 1.00% soap powder, 0.05% active chlorine, or 0.25% active chlorine from sodium hypochlorite removed 98.36%, 96.62%, and 99.98% of the virus from hands, respectively. N95 masks, medical masks, and homemade masks made of four-layer kitchen paper and one-layer cloth could block 99.98%, 97.14%, and 95.15% of the virus in aerosols. Medical mask-wearing which was supported by many studies was opposed by other studies possibly due to erroneous judgment. With these data, we propose the approach of mask-wearing plus instant hand hygiene (MIH) to slow the exponential spread of the virus. This MIH approach has been supported by the experiences of seven countries in fighting against COVID-19. Collectively, a simple approach to slow the exponential spread of SARS-CoV-2 was proposed with the support of experiments, literature review, and control experiences.", "qid": 44, "docid": "v0trjjni", "rank": 82, "score": 0.8541576266288757}, {"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\u2019s 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.", "qid": 44, "docid": "ahhrs3sy", "rank": 83, "score": 0.854150652885437}, {"content": "Title: Mask crisis during the COVID-19 outbreak Content: On December 31, 2019, the World Health Organization (WHO) reported a cluster of cases of pneumonia of unknown cause detected in Wuhan City, Hubei Province, China. As of February 29, 2020, the National Health Commission of China has reported 79,389 confirmed cases of SARS-CoV-2 infection in 34 provinces. The masks can be used to block respiratory transmission from human to human, and are an effective way to control influenza. It is, therefore, necessary to wear a mask when respiratory infectious diseases are prevalent. China has a population of 1.4 billion. Assuming that two-thirds of the people in China must wear a mask every day, the daily demand for masks will reach 900 million. The Chinese government has taken many measures to solve these problems. Additionally, more measures should be taken to properly dispose of mask garbage. Although the outbreak originated in China, person-to-person transmission of SARS-CoV-2 has been confirmed, which means that it can be spread to anywhere in the world if prevention measures fail. The issues regarding face mask shortages and garbage in China, therefore, deserve worldwide attention.", "qid": 44, "docid": "r95u121j", "rank": 84, "score": 0.8540512323379517}, {"content": "Title: Mask crisis during the COVID-19 outbreak. Content: On December 31, 2019, the World Health Organization (WHO) reported a cluster of cases of pneumonia of unknown cause detected in Wuhan City, Hubei Province, China. As of February 29, 2020, the National Health Commission of China has reported 79,389 confirmed cases of SARS-CoV-2 infection in 34 provinces. The masks can be used to block respiratory transmission from human to human, and are an effective way to control influenza. It is, therefore, necessary to wear a mask when respiratory infectious diseases are prevalent. China has a population of 1.4 billion. Assuming that two-thirds of the people in China must wear a mask every day, the daily demand for masks will reach 900 million. The Chinese government has taken many measures to solve these problems. Additionally, more measures should be taken to properly dispose of mask garbage. Although the outbreak originated in China, person-to-person transmission of SARS-CoV-2 has been confirmed, which means that it can be spread to anywhere in the world if prevention measures fail. The issues regarding face mask shortages and garbage in China, therefore, deserve worldwide attention.", "qid": 44, "docid": "61qrwza2", "rank": 85, "score": 0.8540512323379517}, {"content": "Title: Face masks for all and all for face masks in the COVID-19 pandemic: community level production to face the global shortage and shorten the epidemic Content: The current COVID-19 pandemic caused a global shortage of medical masks, leaving most exposed health personnel without appropriate protection.Since the beginning of the outbreak, the WHO has revised several times the recommendations on general use of facemasks. In various countries, the public was advised to wear facemasks, in order to ensure them to healthcare workers. Until recently, WHO recommended to limit the use of facemasks to symptomatic people and advised against off-standard solutions. Moreover, recommendations differ among and within countries, causing public confusion and individual initiative.There is wide consensus that universal appropriate use of masks may contribute both to contain the epidemic and to reduce the burden on national procurement, if a community production approach is followed. Especially in low-middle income countries, due to the scarce capacity of national industrial production or import, the use of masks produced at community level may become the only viable option.For the purpose ad hoc guidelines will be needed.Current knowledge and experience call for further and updated review of global and national guidelines in order to provide clear and consistent criteria to ensure the widest availability and appropriate use of facial protection, bearing in mind populations in socio-economic disadvantaged settings.", "qid": 44, "docid": "sd7ozaif", "rank": 86, "score": 0.8536809682846069}, {"content": "Title: Face masks for all and all for face masks in the COVID-19 pandemic: community level production to face the global shortage and shorten the epidemic. Content: The current COVID-19 pandemic caused a global shortage of medical masks, leaving most exposed health personnel without appropriate protection.Since the beginning of the outbreak, the WHO has revised several times the recommendations on general use of facemasks. In various countries, the public was advised to wear facemasks, in order to ensure them to healthcare workers. Until recently, WHO recommended to limit the use of facemasks to symptomatic people and advised against off-standard solutions. Moreover, recommendations differ among and within countries, causing public confusion and individual initiative.There is wide consensus that universal appropriate use of masks may contribute both to contain the epidemic and to reduce the burden on national procurement, if a community production approach is followed. Especially in low-middle income countries, due to the scarce capacity of national industrial production or import, the use of masks produced at community level may become the only viable option.For the purpose ad hoc guidelines will be needed.Current knowledge and experience call for further and updated review of global and national guidelines in order to provide clear and consistent criteria to ensure the widest availability and appropriate use of facial protection, bearing in mind populations in socio-economic disadvantaged settings.", "qid": 44, "docid": "krh7p1tg", "rank": 87, "score": 0.8536809682846069}, {"content": "Title: The use of facemasks may not lead to an increase in hand\u2013face contact Content: Advocacy of the use of facemasks by the public as a measure against the spread of COVID\u201019 is controversial, with some healthcare professionals arguing that the use of a face mask may increase the rate at which people touch their faces, due to readjusting the mask. We assessed the facial touching behaviour of bus passengers in China before and after the outbreak of COVID\u201019 and found that wearing a face mask does not increase the number of hand\u2010face contacts and is likely, therefore, to have a positive beneficial effect on suppressing the spread of COVID\u201019 within populations when used in conjunction with social distancing measures.", "qid": 44, "docid": "8g2v5cku", "rank": 88, "score": 0.8532322645187378}, {"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 controlling 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 [Formula: see text]), is less than unity. 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 the baseline levels of anti-COVID non-pharmaceutical interventions considered in the study) decrease dramatically by 80% and 64%, respectively, if the strict social-distancing measures implemented are maintained until the end of May or June, 2020. 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-distancing measures were implemented. The use of efficacious face-masks (such as surgical masks, with estimated efficacy [Formula: see text] 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": "41gd7rug", "rank": 89, "score": 0.8530892133712769}, {"content": "Title: Mathematical assessment of the impact of non-pharmaceutical interventions on curtailing the 2019 novel Coronavirus Content: A novel Coronavirus pandemic emerged in December of 2019, causing devastating public health impact across the world. In the absence of a safe and effective vaccine or antiviral, strategies for 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 these mitigation strategies. Simulations of the model, using data relevant to COVID-19 transmission in New York state and the entire US, show that the pandemic will peak in mid and late April, respectively. The worst-case scenario projections for cumulative mortality (based on the baseline levels of anti-COVID non-pharmaceutical interventions considered in the study) in New York State and the entire US decrease dramatically by 80% and 64%, respectively, if the strict social-distancing measures implemented are maintained until the end of May or June, 2020. This study shows that early termination of strict social-distancing could trigger a devastating second wave with burden similar to that projected before the onset of strict social-distance. The use of efficacious face-masks (efficacy greater than 70%) could lead to the elimination of the pandemic if at least 70% of the residents of New York state use such masks 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 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 other anti-COVID-19 intervention measures can lead to elimination of the pandemic. The mask coverage needed to eliminate COVID-19 decreases if mask-use is combined with strict social-distancing.", "qid": 44, "docid": "6gsg0u53", "rank": 90, "score": 0.8528702259063721}, {"content": "Title: Knowledge, Attitude, and Practices of Healthcare Workers Regarding the Use of Face Mask to Limit the Spread of the New Coronavirus Disease (COVID-19) Content: Introduction Many countries including Pakistan are currently using face masks in their pandemic control plans. Being highly prevalent, the correct use of these masks is particularly important, as an incorrect use and disposal may actually increase the rate of transmission. The purpose of this study was to investigate the knowledge, attitude, and practices of healthcare workers (HCWs) in wearing a surgical face mask to limit the spread of the new coronavirus disease 2019 (COVID-19). Materials and Methods This survey was conducted by interviewing HCWs using a questionnaire consisting of the basic demographic characteristics, and the knowledge, attitude, and practices regarding the use of surgical face mask to limit the new COVID-19 exposure. Each correct answer was scored 1 and each incorrect answer scored 0. The total number of questions was 16, and the final score was calculated and then labeled according to the percentage (out of 16) of correct responses as good (>80%), moderate (60-80%), and poor (<60%). Results A total of 392 participants with a mean age of 42.37 \u00b1 13.34 years (341 males and 51 females) were included in the study. The overall final results were good in 138 (35.2%), moderate in 178 (45.4%), and poor in 76 (19.3%). Around 43.6% of participants knew about the correct method of wearing the masks, 68.9% knew that there are three layers, 53% stated that the middle layer act as a filter media barrier, and 75.5% knew the recommended maximum duration of wearing it. The majority (88.2%) of participants knew that a cloth face mask is not much effective, around 79.8% knew that used face mask cannot be re-used, and 44.8% knew about the yellow-coded bag for disposal. Conclusions Knowledge, attitude, and practice of HCWs regarding the use of face masks were found to be inadequate. Studied HCWs had a positive attitude but moderate-to-poor level of knowledge and practice regarding the use of face mask. HCWs and general public awareness campaigns regarding the proper use of face mask by utilizing all social media available resources would be helpful during this pandemic.", "qid": 44, "docid": "0javg3m8", "rank": 91, "score": 0.8526933193206787}, {"content": "Title: Assessment of Fabric Masks as Alternatives to Standard Surgical Masks in Terms of Particle Filtration Efficiency Content: In response to the critical shortage of medical masks resulting from the COVID-19 pandemic, large portions of the population are mobilizing to produce cloth masks using locally-sourced fabrics, however the efficacy of these masks as a means of protecting the wearer from airborne particles carrying virus is not well known. Further, existing protocols are designed for testing the fit and performance N95 respirators and tight-fitting facemasks rather than the relatively more loose-fitting surgical mask style most cloth masks follow. In this study tools and methods typically used to assess tight-fitting facemasks were modified to assess the efficacy of community-produced fabric and commercially-produced surgical masks in terms of protecting the wearer from airborne particles that may be carrying virus. Two TSI PortaCount (model 8028) instruments were operated concurrently to collect particle counts (particles/cm^3) in size range 0.02 to >1 um from ambient air and air just inside the breathing zone of the mask (1 measurement per second, evaluation period of 1 minute per test). Percent particle removal was determined for ten home-made, fabric masks of different designs, with and without filter layers, as well as three commercially-produced surgical-type masks. N95 masks were used to validate the method, and a 3M model 1826 surgical mask was used as a baseline for comparison of other masks of this style. Home-made masks worn as designed always had lower particle removal rates than the 3M masks, achieving between 38% and 96% of this baseline. As has been previously observed by Cooper et al. (1983), adding a layer of nylon stocking over the masks minimized the flow of air around the edges of the masks and improved particle filtration efficiency for all masks, including all commercial products tested. Use of a nylon stocking overlayer brought the particle filtration efficiency for five of the ten fabric masks above the 3M surgical mask baseline. This rapid testing method (<2 hours per mask design) provides a holistic evaluation of mask particle removal efficacy (material, design, and fit), and use of this method for testing a wider range of mask materials and designs will provide the public and health care providers with information needed to optimize health protection given resources at hand.", "qid": 44, "docid": "mnjy6bq2", "rank": 92, "score": 0.8522065281867981}, {"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": 44, "docid": "h7ftu3ax", "rank": 93, "score": 0.8518667221069336}, {"content": "Title: [risk Assessment for Aerosol Infection by the New Corona Virus and Protection by Respirators] Content: INTRODUCTION: SARS-CoV-2 is dispersed from patients by talking, coughing and sneezing. The generated micro-droplets aerosols can travel up to 8 meters, stay suspended for long periods and preserve viral infectivity for a median of 2.7 hours. An unprotected person exposed to this cloud, might inhale a considerable amount of infectious viral doses, which will attach to the ACE 2 receptors on alveoli epithelium, resulting in infection. N95 respirators and surgical masks block 95% and 50-60% respectively of inhalable particles and protect the wearer from infection. Surgical masks and N95 without exhalation valve, protect both the wearer and the environment from carriers and sick people.", "qid": 44, "docid": "xlsqikjt", "rank": 94, "score": 0.8518605828285217}, {"content": "Title: [RISK ASSESSMENT FOR AEROSOL INFECTION BY THE NEW CORONA VIRUS AND PROTECTION BY RESPIRATORS]. Content: INTRODUCTION SARS-CoV-2 is dispersed from patients by talking, coughing and sneezing. The generated micro-droplets aerosols can travel up to 8 meters, stay suspended for long periods and preserve viral infectivity for a median of 2.7 hours. An unprotected person exposed to this cloud, might inhale a considerable amount of infectious viral doses, which will attach to the ACE 2 receptors on alveoli epithelium, resulting in infection. N95 respirators and surgical masks block 95% and 50-60% respectively of inhalable particles and protect the wearer from infection. Surgical masks and N95 without exhalation valve, protect both the wearer and the environment from carriers and sick people.", "qid": 44, "docid": "k47m3e92", "rank": 95, "score": 0.8515902161598206}, {"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": 44, "docid": "q0ey3wib", "rank": 96, "score": 0.851454496383667}, {"content": "Title: Importance of face masks for COVID-19 - a call for effective public education Content: Considerable debates about the general community use of face masks for protection against COVID-19 stemmed out from differing views taken by health authorities. Misconceptions and stigmatization towards the use of face masks may hinder the containment of the COVID-19 pandemic. We address this previous debate by analyzing the advice on the community use of masks across different credible health authorities: countries that promoted the use of masks acknowledged that masks are effective, but also explained the importance of their proper use along with other hygiene measures. In contrast, authorities that recommended against the community use of masks mainly cited shortage of supplies, the argument that the public do not have the adequate skills to wear them, or that wearing masks might reduce compliance with other important behaviors. We suggest promoting effective behavioral changes in personal protective measures by teaching microbiological knowledge instead of just listing out the \"dos-and-don'ts\".", "qid": 44, "docid": "wee1133a", "rank": 97, "score": 0.8508650064468384}, {"content": "Title: Novel role of plastic wrap in COVID-19. Content: The COVID-19 pandemic is spreading across the world rapidly and poses unprecedented challenges to healthcare systems around the world. It transmits primarily by the droplet route, though surface contact may play an important role as well.1 While people are aware of universal mask-wearing to reduce respiratory droplet transmission, contact transmission, particularly through the indirect contact transmission, is a hidden danger that is often overlooked. There are some sources of non-negligible routes for indirect contact in hospitals, such as the keyboard and elevator buttons often used daily by frontline health workers. However, it is difficult to disinfect these areas thoroughly due to their uneven surfaces. This constitutes a barrier to the precaution of contact transmission.", "qid": 44, "docid": "u04k1cfe", "rank": 98, "score": 0.8508095145225525}, {"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 controlling 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 \u00e2\u0084\u009bc), is less than unity. 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 the baseline levels of anti-COVID non-pharmaceutical interventions considered in the study) decrease dramatically by 80% and 64%, respectively, if the strict social-distancing measures implemented are maintained until the end of May or June, 2020. 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-distancing measures were implemented. The use of efficacious face-masks (such as surgical masks, with estimated efficacy &#8805; 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": "1yo8win8", "rank": 99, "score": 0.850684642791748}, {"content": "Title: Aerosol blocking assessment by different types of fabrics for homemade respiratory masks: spectroscopy and imaging study Content: During the COVID-19 pandemic, there is no agreement, until the current date, about the recommendations of homemade face mask use for the general population, and one of the reasons is a lack of information about their real protective rule on spreading aerosols and viruses. This is a comparative study regarding the relative efficiencies of commercial respiratory masks (medical masks) and homemade fabric masks, which may guide authorities across the globe, following the 'Advice on the use of masks in the context of COVID-19', by the World Health Organization. We described two optical methodologies for charactering respiratory masks. It happens that the aerosol scattering coefficient is linear as a function of its concentration inside the mask chamber. Quantitative optical properties of scattering for a large batch fabrication of masks were demonstrated, making the mask N95 suitable for use as a reference standard.", "qid": 44, "docid": "0lndg8s2", "rank": 100, "score": 0.850233793258667}]}
{"query": "How has the COVID-19 pandemic impacted mental health?", "hits": [{"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": 1, "score": 0.9184238910675049}, {"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": 2, "score": 0.9184238910675049}, {"content": "Title: Caring for patients with posttraumatic stress and substance use disorders during the COVID-19 pandemic Content: Although COVID-19 is a physical illness, it has had large impacts on mental health. For many individuals, social distancing has led to social isolation; individuals with posttraumatic stress disorder and substance use disorders are at a particular risk for negative outcomes due to the global pandemic. Here, we discuss the impacts we have noticed and procedures we have implemented to care for this population during the pandemic. (PsycInfo Database Record (c) 2020 APA, all rights reserved).", "qid": 45, "docid": "pfrnlvda", "rank": 3, "score": 0.917853832244873}, {"content": "Title: Caring for patients with posttraumatic stress and substance use disorders during the COVID-19 pandemic. Content: Although COVID-19 is a physical illness, it has had large impacts on mental health. For many individuals, social distancing has led to social isolation; individuals with posttraumatic stress disorder and substance use disorders are at a particular risk for negative outcomes due to the global pandemic. Here, we discuss the impacts we have noticed and procedures we have implemented to care for this population during the pandemic. (PsycInfo Database Record (c) 2020 APA, all rights reserved).", "qid": 45, "docid": "7uodxlrz", "rank": 4, "score": 0.917853832244873}, {"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": 5, "score": 0.9161767959594727}, {"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": 6, "score": 0.9131633043289185}, {"content": "Title: The impact of the COVID-19 pandemic on the mental health of healthcare professionals Content: INTRODUCTION: Healthcare professionals (HPs) have been confronted by unprecedented traumatic experiences during the novel coronavirus disease (COVID-19) pandemic, especially in countries that had not experienced similar epidemic outbreaks in recent years. AIM: To analyze the impact of the COVID-19 pandemic on the mental health of HPs. METHOD: We comprehensively reviewed the studies published in MEDLINE (PubMed), Web of Science and Google Scholar between December 2019 and May 2020. RESULTS: Most studies report a high prevalence of anxiety and depressive symptoms among HPs that can be associated with: (i) COVID-19 exposure; (ii) epidemiological issues; (iii) material resources; (iv) human resources; and (v) personal factors. The role of certain variables, before, during and after the pandemic, remains unexplored. Longitudinal studies will help elucidate which factors are associated with a higher risk of developing long-lasting negative effects. Qualitative studies may contribute to understanding the influence of individual and social narratives in HPs\u2019 distress. CONCLUSION: A deeper analysis on the individual, institutional, political and socio-cultural factors, meanings and values influencing HPs distress and resilience during the COVID-19 pandemic is needed.", "qid": 45, "docid": "5mq7h8ng", "rank": 7, "score": 0.9127033352851868}, {"content": "Title: The impact of the COVID-19 pandemic on the mental health of healthcare professionals Content: INTRODUCTION: Healthcare professionals (HPs) have been confronted by unprecedented traumatic experiences during the COVID-19 pandemic, especially in countries that had not experienced similar epidemic outbreaks in recent years. AIM: To analyze the impact of the COVID-19 pandemic on the mental health of HPs. METHOD: We comprehensively reviewed the studies published in MEDLINE (PubMed), Web of Science and Google Scholar between December 2019 and May 2020. RESULTS: Most studies report a high prevalence of anxiety and depressive symptoms among HPs that can be associated with: a) COVID-19 exposure; b) epidemiological issues; c) material resources; d) human resources; and e) personal factors. The role of certain variables, before, during and after the pandemic, remains unexplored. Longitudinal studies will help elucidate which factors are associated with a higher risk of developing long-lasting negative effects. Qualitative studies may contribute to understanding the influence of individual and social narratives in HPs' distress. CONCLUSION: A deeper analysis on the individual, institutional, political and socio-cultural factors, meanings and values influencing HPs distress and resilience during the COVID-19 pandemic is needed.", "qid": 45, "docid": "t9t2qlw4", "rank": 8, "score": 0.9125353097915649}, {"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": 9, "score": 0.909893810749054}, {"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": 10, "score": 0.9061641693115234}, {"content": "Title: [COVID-19 Concerns and Worries in Patients with Mental Illness]. Content: OBJECTIVE This study examines the impact of the COVID-19 pandemic and the lock-down on patients with mental illness. METHODS Patients in inpatient or outpatient psychiatric treatment received a questionnaire, examining psychological distress and psychiatric care during the COVID-19 pandemic. RESULTS More than half of the patients indicated that the state of emergency had a negative impact on their mental illness. Severely ill patients were more affected. CONCLUSION Patients with mental illness are a particularly vulnerable group in the current crisis. Psychiatric and psychotherapeutic care needs to be adapted accordingly; the specific burden and distress needs to be examined actively in patients from all diagnostic groups.", "qid": 45, "docid": "96wi5b3a", "rank": 11, "score": 0.904335081577301}, {"content": "Title: Depression and Anxiety in Hong Kong during COVID-19 Content: It has been three months since the first confirmed case of coronavirus disease 2019 (COVID-19) in Hong Kong, and people now have a more complete picture of the extent of the pandemic. Therefore, it is time to evaluate the impacts of COVID-19 on mental health. The current population-based study aimed to evaluate the depression and anxiety of people in Hong Kong during the COVID-19 pandemic. Respondents were randomly recruited and asked to complete a structured questionnaire, including the patient health questionnaire-9 (PHQ-9), the generalized anxiety disorder-7 (GAD-7), the global rating of change scale and items related to COVID-19. Of the 500 respondents included in the study, 19% had depression (PHQ-9 score &#8805; 10) and 14% had anxiety (GAD score &#8805; 10). In addition, 25.4% reported that their mental health had deteriorated since the pandemic. Multiple logistic regression analysis found that not experiencing the SARS outbreak in 2003, being worried about being infected by COVID-19, being bothered by having not enough surgical masks and being bothered by not being able to work from home were associated with a poorer mental health status. Psychological support, such as brief, home-based psychological interventions, should be provided to citizens during the pandemic.", "qid": 45, "docid": "bqeu51ch", "rank": 12, "score": 0.9041014909744263}, {"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": 13, "score": 0.9027664661407471}, {"content": "Title: Depression and Anxiety in Hong Kong during COVID-19 Content: It has been three months since the first confirmed case of coronavirus disease 2019 (COVID-19) in Hong Kong, and people now have a more complete picture of the extent of the pandemic. Therefore, it is time to evaluate the impacts of COVID-19 on mental health. The current population-based study aimed to evaluate the depression and anxiety of people in Hong Kong during the COVID-19 pandemic. Respondents were randomly recruited and asked to complete a structured questionnaire, including the patient health questionnaire-9 (PHQ-9), the generalized anxiety disorder-7 (GAD-7), the global rating of change scale and items related to COVID-19. Of the 500 respondents included in the study, 19% had depression (PHQ-9 score \u2265 10) and 14% had anxiety (GAD score \u2265 10). In addition, 25.4% reported that their mental health had deteriorated since the pandemic. Multiple logistic regression analysis found that not experiencing the SARS outbreak in 2003, being worried about being infected by COVID-19, being bothered by having not enough surgical masks and being bothered by not being able to work from home were associated with a poorer mental health status. Psychological support, such as brief, home-based psychological interventions, should be provided to citizens during the pandemic.", "qid": 45, "docid": "vdf441lf", "rank": 14, "score": 0.9019187688827515}, {"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": 15, "score": 0.9016183018684387}, {"content": "Title: COVID-19 pandemic and mental health consequences: systematic review of the current evidence Content: BACKGROUND: During the COVID-19 pandemic general medical complications have received the most attention, whereas only few studies address the potential direct effect on mental health of SARS-CoV-2 and the neurotropic potential. Furthermore, the indirect effects of the pandemic on general mental health are of increasing concern, particularly since the SARS-CoV-1 epidemic (2002-2003) was associated with psychiatric complications. METHODS: We systematically searched the database Pubmed including studies measuring psychiatric symptoms or morbidities associated with COVID-19 among infected patients and among none infected groups the latter divided in psychiatric patients, health care workers and non-health care workers. RESULTS: A total of 43 studies were included. Out of these, only two studies evaluated patients with confirmed COVID-19 infection, whereas 41 evaluated the indirect effect of the pandemic (2 on patients with preexisting psychiatric disorders, 20 on medical health care workers, and 19 on the general public). 18 of the studies were case-control studies/compared to norm, while 25 of the studies had no control groups. The two studies investigating COVID-19 patients found a high level of post-traumatic stress symptoms (PTSS) (96.2%) and significantly higher level of depressive symptoms (p=0.016). Patients with preexisting psychiatric disorders reported worsening of psychiatric symptoms. Studies investigating health care workers found increased depression/depressive symptoms, anxiety, psychological distress and poor sleep quality. Studies of the general public revealed lower psychological well-being and higher scores of anxiety and depression compared to before COVID-19, while no difference when comparing these symptoms in the initial phase of the outbreak to four weeks later. A variety of factors were associated with higher risk of psychiatric symptoms and/or low psychological well-being including female gender, poor-self-related health and relatives with COVID-19. CONCLUSION: Research evaluating the direct neuropsychiatric consequences and the indirect effects on mental health is highly needed to improve treatment, mental health care planning and for preventive measures during potential subsequent pandemics.", "qid": 45, "docid": "019rcbpg", "rank": 16, "score": 0.90057772397995}, {"content": "Title: COVID-19 pandemic and mental health consequences: Systematic review of the current evidence Content: BACKGROUND: During the COVID-19 pandemic general medical complications have received the most attention, whereas only few studies address the potential direct effect on mental health of SARS-CoV-2 and the neurotropic potential. Furthermore, the indirect effects of the pandemic on general mental health are of increasing concern, particularly since the SARS-CoV-1 epidemic (2002-2003) was associated with psychiatric complications. METHODS: We systematically searched the database Pubmed including studies measuring psychiatric symptoms or morbidities associated with COVID-19 among infected patients and among none infected groups the latter divided in psychiatric patients, health care workers and non-health care workers. RESULTS: A total of 43 studies were included. Out of these, only two studies evaluated patients with confirmed COVID-19 infection, whereas 41 evaluated the indirect effect of the pandemic (2 on patients with preexisting psychiatric disorders, 20 on medical health care workers, and 19 on the general public). 18 of the studies were case-control studies/compared to norm, while 25 of the studies had no control groups. The two studies investigating COVID-19 patients found a high level of post-traumatic stress symptoms (PTSS) (96.2%) and significantly higher level of depressive symptoms (p = 0.016). Patients with preexisting psychiatric disorders reported worsening of psychiatric symptoms. Studies investigating health care workers found increased depression/depressive symptoms, anxiety, psychological distress and poor sleep quality. Studies of the general public revealed lower psychological well-being and higher scores of anxiety and depression compared to before COVID-19, while no difference when comparing these symptoms in the initial phase of the outbreak to four weeks later. A variety of factors were associated with higher risk of psychiatric symptoms and/or low psychological well-being including female gender, poor-self-related health and relatives with COVID-19. CONCLUSION: Research evaluating the direct neuropsychiatric consequences and the indirect effects on mental health is highly needed to improve treatment, mental health care planning and for preventive measures during potential subsequent pandemics.", "qid": 45, "docid": "0jfwzfge", "rank": 17, "score": 0.90057772397995}, {"content": "Title: COVID-19 and mental health: A review of the existing literature Content: The COVID-19 pandemic is a major health crisis affecting several nations, with over 720,000 cases and 33,000 confirmed deaths reported to date. Such widespread outbreaks are associated with adverse mental health consequences. Keeping this in mind, existing literature on the COVID-19 outbreak pertinent to mental health was retrieved via a literature search of the PubMed database. Published articles were classified according to their overall themes and summarized. Preliminary evidence suggests that symptoms of anxiety and depression (16-28%) and self-reported stress (8%) are common psychological reactions to the COVID-19 pandemic, and may be associated with disturbed sleep. A number of individual and structural variables moderate this risk. In planning services for such populations, both the needs of the concerned people and the necessary preventive guidelines must be taken into account. The available literature has emerged from only a few of the affected countries, and may not reflect the experience of persons living in other parts of the world. In conclusion, subsyndromal mental health problems are a common response to the COVID-19 pandemic. There is a need for more representative research from other affected countries, particularly in vulnerable populations.", "qid": 45, "docid": "6gtgohci", "rank": 18, "score": 0.9002512693405151}, {"content": "Title: Heterogeneous mental health consequences of COVID-19: Costs and benefits Content: In this commentary, I argue that the mental health impact of COVID-19 will show substantial variation across individuals, contexts, and time. Further, one key contributor to this variation will be the proximal and long-term impact of COVID-19 on the social environment. In addition to the mental health costs of the pandemic, it is likely that a subset of people will experience improved social and mental health functioning. (PsycInfo Database Record (c) 2020 APA, all rights reserved).", "qid": 45, "docid": "ingq7m2m", "rank": 19, "score": 0.9001617431640625}, {"content": "Title: Heterogeneous mental health consequences of COVID-19: Costs and benefits. Content: In this commentary, I argue that the mental health impact of COVID-19 will show substantial variation across individuals, contexts, and time. Further, one key contributor to this variation will be the proximal and long-term impact of COVID-19 on the social environment. In addition to the mental health costs of the pandemic, it is likely that a subset of people will experience improved social and mental health functioning. (PsycInfo Database Record (c) 2020 APA, all rights reserved).", "qid": 45, "docid": "u02vjcjs", "rank": 20, "score": 0.9001617431640625}, {"content": "Title: Psychiatric Symptoms Related to the COVID-19 Pandemic Content: The COVID-19 pandemic and the consequential societal changes are likely to have major health consequences way beyond those caused by the virus infection. One of the medical fields that may experience significant consequences of the pandemic is that of psychiatry. Importantly, individuals who already live with mental disorders may be particularly vulnerable to the psychological stress associated with the pandemic. However, data on how the COVID-19 pandemic affects this group of people is largely absent from the literature. Here, we report data from a quality development project conducted at the psychiatric services of the Central Denmark Region (CDR), which has a catchment area of approximately 1.3 million people covered by five psychiatric hospitals providing inpatient and outpatient treatment of all types of mental disorders. Based on a manual screening of all clinical notes from the period from February 1st to March 23rd 2020 that contained at least one of the following words: corona, COVID, virus, epidemic, pandemic, and contaminate/contamination (including compound words), we found 1357 notes from 918 adult patients that described pandemic-related psychopathology (symptoms that appeared to be caused/deteriorated by the pandemic and/or its societal consequences). To our knowledge, this is the first investigation of COVID-19 pandemic-related psychopathology from a large psychiatric treatment setting. The results clearly suggest that this phenomenon exists among individuals with mental illness. However, as the data from this investigation stems from standard clinical practice where the patients were not systematically assessed for pandemic-related psychopathology, we cannot speak to its overall prevalence. Nevertheless, we believe that our findings underline the necessity of taking urgent action to mitigate the negative effects of the COVID-19 pandemic on patients with mental disorders. A low-cost intervention would be to simply discuss the ongoing pandemic and its societal consequences with patients seeking care in psychiatric settings - as this may lead to relief of pandemic-related symptoms via general comforting, and clarification of misunderstandings/false beliefs regarding the pandemic.", "qid": 45, "docid": "gy90nvir", "rank": 21, "score": 0.8995043039321899}, {"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": 22, "score": 0.8992817997932434}, {"content": "Title: Mental health and psychosocial well-being during the COVID-19 pandemic: the invisible elephant in the room Content: The novel SARS-CoV-2 coronavirus pandemic has emerged as a truly formidable threat to humankind\u2019s existence. In the wake of the massively volatile global situation created by COVID-19, it is vital to recognize that the trauma it causes can affect people in different ways, at the individual and collective levels, resulting in mental health challenges for many. Although mental health problems account for about one-third of the world\u2019s disability among adults, these issues tend to be under-addressed and overlooked in society and are closely associated with deadly disease outbreaks. In large scale outbreaks, the mental health problems experienced are not limited to infected persons but also extend to involve frontline health workers and community members alike. While it is crucial to limit the spread of infections during an outbreak, previous experience suggests that mental and behavioural health interventions should be fully included in public health response strategies.", "qid": 45, "docid": "ypgor52g", "rank": 23, "score": 0.8975430727005005}, {"content": "Title: COVID-19 and mental health: A review of the existing literature Content: Abstract The COVID-19 pandemic is a major health crisis affecting several nations, with over 720,000 cases and 33,000 confirmed deaths reported to date. Such widespread outbreaks are associated with adverse mental health consequences. Keeping this in mind, existing literature on the COVID-19 outbreak pertinent to mental health was retrieved via a literature search of the PubMed database. Published articles were classified according to their overall themes and summarized. Preliminary evidence suggests that symptoms of anxiety and depression (16\u201328%) and self-reported stress (8%) are common psychological reactions to the COVID-19 pandemic, and may be associated with disturbed sleep. A number of individual and structural variables moderate this risk. In planning services for such populations, both the needs of the concerned people and the necessary preventive guidelines must be taken into account. The available literature has emerged from only a few of the affected countries, and may not reflect the experience of persons living in other parts of the world. In conclusion, subsyndromal mental health problems are a common response to the COVID-19 pandemic. There is a need for more representative research from other affected countries, particularly in vulnerable populations.", "qid": 45, "docid": "o72unm3q", "rank": 24, "score": 0.8973680138587952}, {"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": 25, "score": 0.8958683013916016}, {"content": "Title: Impact of COVID-19 on mental health in a Low and Middle-Income Country Content: Mental disorders (MD) are commonly comorbid with cardiovascular, metabolic, and some infectious diseases. Since the current SARS-CoV-2 epidemic is affecting the most multimorbid individuals, we might expect that the epidemic will be particularly problematic for people with MD. Understanding the burden of an outbreak on mental health is fundamental to effective action towards containing the spread of the disease, as psychopathology might reduce endurance during the lockdown. This can potentially reduce adhesion to ongoing treatment resulting in avoidable recurrence of a disorder. Additionally, there is the stress caused by the eminent risk of infection or economic uncertainty, especially in low-middle income settings. This is an overview on the expected influence of the COVID-19 on mental health from a research group that has not long ago been involved in the Zika epidemic. It aims to discuss the effects of the pandemic on a Low and Middle-Income country (LMIC), Brazil.", "qid": 45, "docid": "6wioennp", "rank": 26, "score": 0.8957129716873169}, {"content": "Title: Impact of COVID-19 on mental health in a Low and Middle-Income Country. Content: Mental disorders (MD) are commonly comorbid with cardiovascular, metabolic, and some infectious diseases. Since the current SARS-CoV-2 epidemic is affecting the most multimorbid individuals, we might expect that the epidemic will be particularly problematic for people with MD. Understanding the burden of an outbreak on mental health is fundamental to effective action towards containing the spread of the disease, as psychopathology might reduce endurance during the lockdown. This can potentially reduce adhesion to ongoing treatment resulting in avoidable recurrence of a disorder. Additionally, there is the stress caused by the eminent risk of infection or economic uncertainty, especially in low-middle income settings. This is an overview on the expected influence of the COVID-19 on mental health from a research group that has not long ago been involved in the Zika epidemic. It aims to discuss the effects of the pandemic on a Low and Middle-Income country (LMIC), Brazil.", "qid": 45, "docid": "oaf3zj2z", "rank": 27, "score": 0.8957129716873169}, {"content": "Title: Risk Factors Associated with Mental Illness in Hospital Discharged Patients Infected with COVID-19 in Wuhan, China Content: The coronavirus disease 2019 (COVID-19) pandemic can have a profound impact on the mental health of patients who survived the illness. However, little is known about the prevalence rate of mental health disorders among hospital discharged COVID-19 patients and its associated factors. A cross-sectional survey of hospital discharged patients was conducted April 11-22, 2020 in Wuhan, China (where the pandemic began). 675 participants completed the survey, including 90 (13.3%) medical staff (physicians and nurses who had been ill). We used Fisher's exact test and multivariable logistic regression methods to explore the risk factors associated with mental health problems (anxiety, depression, and PTSD symptoms associated with COVID-19 hospitalization). Adverse mental health effects of COVID-19 are evident after discharge from the hospital, with sleep difficulties highlighted as a central issue. As we found that perceived discrimination was a central predictor of mental illness, preventing and addressing social stigma associated with COVID-19 may be crucial for improving mental health for recovered patients.", "qid": 45, "docid": "cot4e737", "rank": 28, "score": 0.8951081037521362}, {"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": 29, "score": 0.8950759172439575}, {"content": "Title: Coping with Mental Health Challenges During COVID-19 Content: The ongoing pandemic of COVID-19 is a global challenge which resulted in significant morbidity and mortality worldwide. It has also adversely affected the economy and social integrity. There is rising concern about the mental health challenges of the general population, COVID-19-infected patients, close contacts, elderly, children and health professionals. This chapter focusses on various mental health challenges during the COVID-19 pandemic.", "qid": 45, "docid": "50palac7", "rank": 30, "score": 0.8950724601745605}, {"content": "Title: Emotional impact of the COVID-19 pandemic on U.S. health care workers: A gathering storm Content: The COVID-19 pandemic is placing enormous stress on U.S. health care workers. Prior studies of infectious disease outbreaks and other catastrophic events have shown the damaging mental health impacts caused by these events. Implications for the policy and treatment of health care workers facing the COVID-19 crisis are discussed in this commentary. (PsycInfo Database Record (c) 2020 APA, all rights reserved).", "qid": 45, "docid": "u2wu0s10", "rank": 31, "score": 0.8935955762863159}, {"content": "Title: Emotional impact of the COVID-19 pandemic on U.S. health care workers: A gathering storm. Content: The COVID-19 pandemic is placing enormous stress on U.S. health care workers. Prior studies of infectious disease outbreaks and other catastrophic events have shown the damaging mental health impacts caused by these events. Implications for the policy and treatment of health care workers facing the COVID-19 crisis are discussed in this commentary. (PsycInfo Database Record (c) 2020 APA, all rights reserved).", "qid": 45, "docid": "m39egxs3", "rank": 32, "score": 0.8935955762863159}, {"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": 33, "score": 0.8925979137420654}, {"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": 34, "score": 0.8925979137420654}, {"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": 45, "docid": "c7weqc03", "rank": 35, "score": 0.8916817903518677}, {"content": "Title: The psychological impact of COVID-19 on the mental health in the general population Content: As a result of the emergence of coronavirus disease 2019 (COVID-19) outbreak caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection in the Chinese city of Wuhan, a situation of socio-economic crisis and profound psychological distress rapidly occurred worldwide. Various psychological problems and important consequences in terms of mental health including stress, anxiety, depression, frustration, uncertainty during COVID-19 outbreak emerged progressively. This work aimed to comprehensively review the current literature about the impact of COVID-19 infection on the mental health in the general population. The psychological impact of quarantine related to COVID-19 infection has been additionally documented together with the most relevant psychological reactions in the general population related to COVID-19 outbreak. The role of risk and protective factors against the potential to develop psychiatric disorders in vulnerable individuals has been addressed as well. The main implications of the present findings have been discussed.", "qid": 45, "docid": "by4js46v", "rank": 36, "score": 0.8914570212364197}, {"content": "Title: A longitudinal study on the mental health of general population during the COVID-19 epidemic in China Content: In addition to being a public physical health emergency, Coronavirus disease 2019 (COVID-19) affected global mental health, as evidenced by panic-buying worldwide as cases soared. Little is known about changes in levels of psychological impact, stress, anxiety and depression during this pandemic. This longitudinal study surveyed the general population twice - during the initial outbreak, and the epidemic's peak four weeks later, surveying demographics, symptoms, knowledge, concerns, and precautionary measures against COVID-19. There were 1738 respondents from 190 Chinese cities (1210 first-survey respondents, 861 s-survey respondents; 333 respondents participated in both). Psychological impact and mental health status were assessed by the Impact of Event Scale-Revised (IES-R) and the Depression, Anxiety and Stress Scale (DASS-21), respectively. IES-R measures PTSD symptoms in survivorship after an event. DASS -21 is based on tripartite model of psychopathology that comprise a general distress construct with distinct characteristics. This study found that there was a statistically significant longitudinal reduction in mean IES-R scores (from 32.98 to 30.76, p < 0.01) after 4 weeks. Nevertheless, the mean IES-R score of the first- and second-survey respondents were above the cut-off scores (>24) for PTSD symptoms, suggesting that the reduction in scores was not clinically significant. During the initial evaluation, moderate-to-severe stress, anxiety and depression were noted in 8.1%, 28.8% and 16.5%, respectively and there were no significant longitudinal changes in stress, anxiety and depression levels (p > 0.05). Protective factors included high level of confidence in doctors, perceived survival likelihood and low risk of contracting COVID-19, satisfaction with health information, personal precautionary measures. As countries around the world brace for an escalation in cases, Governments should focus on effective methods of disseminating unbiased COVID-19 knowledge, teaching correct containment methods, ensuring availability of essential services/commodities, and providing sufficient financial support.", "qid": 45, "docid": "7uw8k8cq", "rank": 37, "score": 0.8914540410041809}, {"content": "Title: The psychological impact of COVID-19 on the mental health in the general population Content: As a result of the emergence of coronavirus disease 2019 (COVID-19) outbreak caused by acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection in the Chinese city of Wuhan, a situation of socio-economic crisis and profound psychological distress rapidly occurred worldwide. Various psychological problems and important consequences in terms of mental health including stress, anxiety, depression, frustration, uncertainty during COVID-19 outbreak emerged progressively. This work aimed to comprehensively review the current literature about the impact of COVID-19 infection on the mental health in the general population. The psychological impact of quarantine related to COVID-19 infection has been additionally documented together with the most relevant psychological reactions in the general population related to COVID-19 outbreak. The role of risk and protective factors against the potential to develop psychiatric disorders in vulnerable individuals has been addressed as well. The main implications of the present findings have been discussed.", "qid": 45, "docid": "5uhen4qe", "rank": 38, "score": 0.8914480805397034}, {"content": "Title: A Longitudinal Study on the Mental Health of General Population during the COVID-19 Epidemic in China Content: Abstract In addition to being a public physical health emergency, Coronavirus disease 2019 (COVID-19) affected global mental health, as evidenced by panic-buying worldwide as cases soared. Little is known about changes in levels of psychological impact, stress, anxiety and depression during this pandemic. This longitudinal study surveyed the general population twice - during the initial outbreak, and the epidemic's peak four weeks later, surveying demographics, symptoms, knowledge, concerns, and precautionary measures against COVID-19. There were 1738 respondents from 190 Chinese cities (1210 first-survey respondents, 861 second-survey respondents; 333 respondents participated in both). Psychological impact and mental health status were assessed by the Impact of Event Scale-Revised (IES-R) and the Depression, Anxiety and Stress Scale (DASS-21), respectively. IES-R measures PTSD symptoms in survivorship after an event. DASS -21 is based on tripartite model of psychopathology that comprise a general distress construct with distinct characteristics. This study found that there was a statistically significant longitudinal reduction in mean IES-R scores (from 32.98 to 30.76, p<0.01) after 4 weeks. Nevertheless, the mean IES-R score of the first- and second-survey respondents were above the cut-off scores (>24) for PTSD symptoms, suggesting that the reduction in scores was not clinically significant. During the initial evaluation, moderate-to-severe stress, anxiety and depression were noted in 8.1%, 28.8% and 16.5%, respectively and there were no significant longitudinal changes in stress, anxiety and depression levels (p>0.05). Protective factors included high level of confidence in doctors, perceived survival likelihood and low risk of contracting COVID-19, satisfaction with health information, personal precautionary measures. As countries around the world brace for an escalation in cases, Governments should focus on effective methods of disseminating unbiased COVID-19 knowledge, teaching correct containment methods, ensuring availability of essential services/commodities, and providing sufficient financial support.", "qid": 45, "docid": "j6ihxzm2", "rank": 39, "score": 0.8905417919158936}, {"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": 40, "score": 0.888202428817749}, {"content": "Title: [Telepsychiatry in adults and adolescents: a useful tool against CoViD-19.] Content: CoViD-19 is a disease caused by the novel coronavirus (SARS-CoV-2), originated from China in December 2019. In March 2020, CoViD-19 was declared a pandemic, having spread all over the word. The psychological impact of CoViD-19 disease must be recognized alongside the physical symptoms for all those affected. Furhermore quarantine for coronavirus has serious psychological side effects, such as depression and anxiety that are more likely to occur and worsen. Furhermore quarantine reduces the availability of psychiatric and psychological interventions. The evidence base for telepsychiatry is growing in adults and adolescents. A growing body of literature suggests that use of telepsychiatry to provide mental health services has the potential to remove geographic barriers between patients and providers and improves quality care. It has increased the volume of patients that physicians can reach and diagnose, as well as allowing them to treat patients.", "qid": 45, "docid": "u2n65e3w", "rank": 41, "score": 0.8879784941673279}, {"content": "Title: Psychiatric advice during Covid-19 pandemic for patients with multiple sclerosis Content: The new pandemic coronavirus disease 2019 (COVID-19) that is caused by a new strain of coronavirus, named severe acute respiratory syndrome coronavirus 2 (SARSCoV-2), has become an issue for governments and health care providers such as specialists including psychiatrists worldwide (1). Treatment strategies and vaccination for this disease are yet to be explored. Therefore, at this time, the best-proposed health measure to break the chain of transmission is social distancing or, in some instances, quarantine. In a recent systematic review published in Lancet, Brooks et al. (2) evaluated the psychological impacts of quarantine during the 2003 SARS outbreak and the 2014 Ebola outbreak. Accordingly, most of the reviewed studies reported adverse psychological effects, including post-traumatic stress symptoms, confusion, and anger (2). Delays in psychological interventions in such situations can lead to psychological damage to individuals who are involved (3). However, people with a pre-existing mental health problem such as anxiety or depressive disorder would be more vulnerable to experience adverse psychological effects of quarantine and social distancing.", "qid": 45, "docid": "cy0w4kdy", "rank": 42, "score": 0.8875348567962646}, {"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": 43, "score": 0.8865793943405151}, {"content": "Title: Considering grief in mental health outcomes of COVID-19 Content: The novel coronavirus disease of 2019 (COVID-19) pandemic has created challenging circumstances for the physical and mental health of individuals across the United States. This commentary addresses the role of grief in mental health outcomes relating to the pandemic. (PsycInfo Database Record (c) 2020 APA, all rights reserved).", "qid": 45, "docid": "4cpuwrci", "rank": 44, "score": 0.8864290118217468}, {"content": "Title: Considering grief in mental health outcomes of COVID-19. Content: The novel coronavirus disease of 2019 (COVID-19) pandemic has created challenging circumstances for the physical and mental health of individuals across the United States. This commentary addresses the role of grief in mental health outcomes relating to the pandemic. (PsycInfo Database Record (c) 2020 APA, all rights reserved).", "qid": 45, "docid": "cj8g4jpv", "rank": 45, "score": 0.8864290118217468}, {"content": "Title: Mental health in the UK during the COVID-19 pandemic: early observations Content: Background: Previous pandemics have resulted in significant consequences for mental health. Here we report the mental health sequela of the COVID-19 pandemic on the UK population and examine modifiable and non-modifiable explanatory factors associated with mental health outcomes. We focus on the short-term consequences for mental health, as reported during the first four-six weeks of social distancing measures being introduced. Methods: A community cohort study was conducted with adults aged [\u2265]18 years recruited through a mainstream and social media campaign between 3/4/20-30/4/20. Consenting participants completed an online survey measuring depression, anxiety and stress and explanatory variables hypothesised to be related to these mental health outcomes. Outcomes: N=3097 eligible individuals participated. The cohort was predominantly female (85%); mean age forty-four years; 10% from minority ethnic groups; 50% described themselves as key-workers and 20% identified as having clinical risk factors putting them at increased risk of COVID-19. Mean scores for depression, stress and anxiety significantly exceeded population norms. Analysis of non-modifiable factors indicated that being younger and female were associated with all outcomes, with the final multivariable models accounting for 7-13% of variance. When adding modifiable factors, significant independent effects emerged for positive mood, perceived loneliness and worry about getting COVID-19 for all outcomes, with the final multivariable models accounting for 54-57% of variance. Interpretation: Increased psychological morbidity was evident in this UK cohort, with younger people and women at particular risk. Interventions targeting perceptions of: loneliness, risk of COVID-19, worry about COVID-19, and positive mood may be effective.", "qid": 45, "docid": "pgrhe3jj", "rank": 46, "score": 0.8864040970802307}, {"content": "Title: The effect of the COVID-19 lockdown on parents: A call to adopt urgent measures Content: The COVID-19 health crisis is strongly affecting the mental health of the general population. In particular, the pandemic may be producing psychological distress and collateral concerns for parents in lockdown, due to unstable financial circumstances, school closures, and suspended educational services for children. A call for measures to increase family-based interventions during the emergency is urgently needed to forestall psychopathological trajectories and prevent the exacerbation of vulnerable conditions. (PsycInfo Database Record (c) 2020 APA, all rights reserved).", "qid": 45, "docid": "jtxqybzu", "rank": 47, "score": 0.8862848281860352}, {"content": "Title: The effect of the COVID-19 lockdown on parents: A call to adopt urgent measures. Content: The COVID-19 health crisis is strongly affecting the mental health of the general population. In particular, the pandemic may be producing psychological distress and collateral concerns for parents in lockdown, due to unstable financial circumstances, school closures, and suspended educational services for children. A call for measures to increase family-based interventions during the emergency is urgently needed to forestall psychopathological trajectories and prevent the exacerbation of vulnerable conditions. (PsycInfo Database Record (c) 2020 APA, all rights reserved).", "qid": 45, "docid": "p9pggrq9", "rank": 48, "score": 0.8862848281860352}, {"content": "Title: Supporting health care workers during the COVID-19 pandemic: Mental health support initiatives and lessons learned from an academic medical center Content: The unprecedented COVID-19 pandemic has put a great strain on the physical and mental health of health care workers across the globe. This commentary provides an overview of mental health initiatives implemented at an academic medical center to support health care workers during this challenging time and highlights lessons learned. (PsycInfo Database Record (c) 2020 APA, all rights reserved).", "qid": 45, "docid": "uvhjb8t6", "rank": 49, "score": 0.8861438632011414}, {"content": "Title: Supporting health care workers during the COVID-19 pandemic: Mental health support initiatives and lessons learned from an academic medical center. Content: The unprecedented COVID-19 pandemic has put a great strain on the physical and mental health of health care workers across the globe. This commentary provides an overview of mental health initiatives implemented at an academic medical center to support health care workers during this challenging time and highlights lessons learned. (PsycInfo Database Record (c) 2020 APA, all rights reserved).", "qid": 45, "docid": "qc5eumi8", "rank": 50, "score": 0.8861438035964966}, {"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": 51, "score": 0.8859962224960327}, {"content": "Title: Covid-19, Mental Health and Psychological First Aid Content: Crises such as the global pandemic of Covid-19 (coronavirus) elicit a range of responses from individuals and societies adversely affecting physical and emotional well-being. This article provides an overview of factors elicited in response to Covid-19 and their impact on immunity, physical health, mental health and wellbeing. Certain groups, such as individuals with mental illness, are especially vulnerable, so it is important to maximise the supports available to this population and their families during the pandemic. More broadly, the World Health Organization recommends \"Psychological First Aid\" as a useful technique that can help many people in a time of crisis.", "qid": 45, "docid": "ljsoikhk", "rank": 52, "score": 0.8856252431869507}, {"content": "Title: Covid-19, Mental Health and Psychological First Aid. Content: Crises such as the global pandemic of Covid-19 (coronavirus) elicit a range of responses from individuals and societies adversely affecting physical and emotional well-being. This article provides an overview of factors elicited in response to Covid-19 and their impact on immunity, physical health, mental health and wellbeing. Certain groups, such as individuals with mental illness, are especially vulnerable, so it is important to maximise the supports available to this population and their families during the pandemic. More broadly, the World Health Organization recommends \"Psychological First Aid\" as a useful technique that can help many people in a time of crisis.", "qid": 45, "docid": "j7c7hk2h", "rank": 53, "score": 0.8856252431869507}, {"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": 54, "score": 0.8849624395370483}, {"content": "Title: Evaluating the Mental Health Impacts of the COVID-19 Pandemic in Urban South Africa: Perceived Risk of COVID-19 Infection and Childhood Trauma Predict Adult Depressive Symptoms Content: South Africa\u2019s national lockdown introduced serious threats to public mental health in a society where one in three individuals develop a psychiatric disorder during their life. We aimed to evaluate the mental health impacts of the COVID-19 pandemic using a mixed methods design. This longitudinal study drew from a preexisting sample of 957 adults living in Soweto, a major township near Johannesburg. Psychological assessments were administered across two waves: between August 2019-March 2020 and during the first six weeks of the lockdown (late March-early May 2020). Interviews on COVID-19 experiences were administered in the second wave. Multiple regression models examined relationships between perceived COVID-19 risk and depression. Full data on perceived COVID-19 risk, depression, and covariates were available in 221 adults. 14.5% of adults were at risk for depression. Higher perceived COVID-19 risk predicted greater depressive symptoms (p < 0.001) particularly among adults with histories of childhood trauma, though this effect was marginally significant (p = 0.062). Adults were two times more likely to experience significant depressive symptoms for every one unit increase in perceived COVID-19 risk (p = 0.016; 95% CI [1.14, 3.49]). Qualitative data identified potent experiences of anxiety, financial insecurity, fear of infection, and rumination. Higher perceived risk of COVID-19 infection is associated with greater depressive symptoms among adults with histories of childhood trauma during the first six weeks of quarantine. High rates of severe mental illness and low availability of mental healthcare amidst COVID-19 emphasize the need for immediate and accessible psychological resources in South Africa.", "qid": 45, "docid": "hug3pz1m", "rank": 55, "score": 0.8848569989204407}, {"content": "Title: Utilization of Teleconsultation: Mitigation in Handling Mental Disorders in the COVID-19 Era Content: The COVID-19 pandemic has caused many undesirable effects, including death. The COVID-19 outbreak occurred suddenly, and many countries were ill prepared to face it. Community behaviour has been altered due to the pandemic. Uncertainty surrounding the disease triggered panic buying; public panic caused additional worry about limited food supplies, and thus demand increased. World economies have also felt the impacts of the COVID-19 outbreak. Owing to the measures put in place to address the spread of COVID-19, many service providers and industries were closed, resulting in financial losses, and the risk of unemployment was elevated, which inevitably increased negative emotions in individuals. A psychosocial consequence of the COVID-19 pandemic is worldwide fear. Because psychological defence is a supporting factor for the recovery of COVID-19 patients, it is important to encourage prevention of mental stress. Psychotherapy is able to provide counselling services to the community through teleconsultation. Strengthening psychological defences can help countries fight against this disease.", "qid": 45, "docid": "7vowrme2", "rank": 56, "score": 0.8848493695259094}, {"content": "Title: Health behaviour changes during COVID-19 and the potential consequences: A mini-review Content: The COVID-19 pandemic has brought about profound changes to social behaviour. While calls to identify mental health effects that may stem from these changes should be heeded, there is also a need to examine potential changes with respect to health behaviours. Media reports have signalled dramatic shifts in sleep, substance use, physical activity and diet, which may have subsequent downstream mental health consequences. We briefly discuss the interplay between health behaviours and mental health, and the possible changes in these areas resulting from anti-pandemic measures. We also highlight a call for greater research efforts to address the short and long-term consequences of changes to health behaviours.", "qid": 45, "docid": "nypmshw5", "rank": 57, "score": 0.8847529292106628}, {"content": "Title: Health behaviour changes during COVID-19 and the potential consequences: A mini-review. Content: The COVID-19 pandemic has brought about profound changes to social behaviour. While calls to identify mental health effects that may stem from these changes should be heeded, there is also a need to examine potential changes with respect to health behaviours. Media reports have signalled dramatic shifts in sleep, substance use, physical activity and diet, which may have subsequent downstream mental health consequences. We briefly discuss the interplay between health behaviours and mental health, and the possible changes in these areas resulting from anti-pandemic measures. We also highlight a call for greater research efforts to address the short and long-term consequences of changes to health behaviours.", "qid": 45, "docid": "afcg1v1x", "rank": 58, "score": 0.8847529292106628}, {"content": "Title: Psycho-Neuroendocrine-Immune Interactions in COVID-19: Potential Impacts on Mental Health Content: Coronavirus disease 2019 (COVID-19) is caused by the Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2). The impacts of the disease may be beyond the respiratory system, also affecting mental health. Several factors may be involved in the association between COVID-19 and psychiatric outcomes, such as fear inherent in the pandemic, adverse effects of treatments, as well as financial stress, and social isolation. Herein we discuss the growing evidence suggesting that the relationship between SARS-CoV-2 and host may also trigger changes in brain and behavior. Based on the similarity of SARS-CoV-2 with other coronaviruses, it is conceivable that changes in endocrine and immune response in the periphery or in the central nervous system may be involved in the association between SARS-CoV-2 infection and impaired mental health. This is likely to be further enhanced, since millions of people worldwide are isolated in quarantine to minimize the transmission of SARS-CoV-2 and social isolation can also lead to neuroendocrine-immune changes. Accordingly, we highlight here the hypothesis that neuroendocrine-immune interactions may be involved in negative impacts of SARS-CoV-2 infection and social isolation on psychiatric issues.", "qid": 45, "docid": "7lrhf88p", "rank": 59, "score": 0.8844768404960632}, {"content": "Title: Fallout from the Covid-19 pandemic - should we prepare for a tsunami of post viral depression? Content: The current Covid-19 pandemic is not just a medical and social tragedy, but within the threat of the outbreak looms the potential for a significant and persistent negative mental health impact, based on previous experience with other pandemics such as SARS in 2003 and the earlier H1N1 outbreak of 1918. This piece will highlight the links between depression and viral illnesses and explore important overlaps with Myalgic Encephalomyelitis/Chronic Fatigue Syndrome, potentially implicating inflammatory mechanisms in those exposed to a range of viral agents. While containment of psychological distress currently focuses on social anxiety and quarantine measures, a second wave of psychological morbidity due to viral illness may be imminent.", "qid": 45, "docid": "drrrstgr", "rank": 60, "score": 0.8844179511070251}, {"content": "Title: Levels and predictors of anxiety, depression and health anxiety during COVID-19 pandemic in Turkish society: The importance of gender Content: BACKGROUND: The COVID-19 pandemic is having negative effects on societies' mental health. Both the pandemic and the measures taken to combat it can affect individuals' mental health. AIMS: The purpose of this study was to evaluate the levels of depression, anxiety and health anxiety in Turkish society during the COVID-19 pandemic, and to examine the factors affecting these. METHOD: The study was performed using an online questionnaire. Participants were asked to complete a sociodemographic data form, the Hospital Anxiety and Depression Scale (HADS) and the Health Anxiety Inventory (HAI). The effects on depression, anxiety and health anxiety levels of factors such as age, sex, marital status, living with an individual aged above 60, the presence of a new Coronavirus+ patient among friends or relatives, previous and current psychiatric illness and presence of accompanying chronic disease were then investigated. RESULTS: In terms of HADS cut-off points, 23.6% (n = 81) of the population scored above the depression cut-off point, and 45.1% (n = 155) scored above the cut-off point for anxiety. In regression analysis, female gender, living in urban areas and previous psychiatric illness history were found as risk factors for anxiety; living in urban areas was found as risk factor for depression; and female gender, accompanying chronic disease and previous psychiatric history were found as risk factors for health anxiety. CONCLUSION: The results of this cross-sectional study suggest that the groups most psychologically affected by the COVID-19 pandemic are women, individuals with previous psychiatric illness, individuals living in urban areas and those with an accompanying chronic disease. Priority might therefore be attached to these in future psychiatric planning.", "qid": 45, "docid": "6pv0c1iu", "rank": 61, "score": 0.8842530250549316}, {"content": "Title: Coronavirus disease (COVID-19) pandemic: Furnishing experiences from India Content: The current work seeks to address the issues and ramifications of the rapid spread of the coronavirus disease (COVID-19) in India. Ever since COVID-19 was declared a pandemic, leading to a nationwide lockdown, a majority of people in India have faced a myriad of hardships, with mental health crisis being the most prominent one. The evidence at hand points toward an array of mental health issues in people that include a sense of uncertainty, anxiety, depression, sleep disturbances, panic attacks, and loneliness. (PsycInfo Database Record (c) 2020 APA, all rights reserved).", "qid": 45, "docid": "8t83xcu8", "rank": 62, "score": 0.884082555770874}, {"content": "Title: Coronavirus disease (COVID-19) pandemic: Furnishing experiences from India. Content: The current work seeks to address the issues and ramifications of the rapid spread of the coronavirus disease (COVID-19) in India. Ever since COVID-19 was declared a pandemic, leading to a nationwide lockdown, a majority of people in India have faced a myriad of hardships, with mental health crisis being the most prominent one. The evidence at hand points toward an array of mental health issues in people that include a sense of uncertainty, anxiety, depression, sleep disturbances, panic attacks, and loneliness. (PsycInfo Database Record (c) 2020 APA, all rights reserved).", "qid": 45, "docid": "vgyp6z6h", "rank": 63, "score": 0.884082555770874}, {"content": "Title: Are we facing a crashing wave of neuropsychiatric sequelae of COVID-19? Neuropsychiatric symptoms and potential immunologic mechanisms Content: Abstract The coronavirus disease 19 (COVID-19) pandemic is a significant psychological stressor in addition to its tremendous impact on every facet of individuals\u2019 lives and organizations in virtually all social and economic sectors worldwide. Fear of illness and uncertainty about the future precipitate anxiety- and stress-related disorders, and several groups have rightfully called for the creation and dissemination of robust mental health screening and treatment programs for the general public and front-line healthcare workers. However, in addition to pandemic-associated psychological distress, the direct effects of the virus itself (several acute respiratory syndrome coronavirus; SARS-CoV-2), and the subsequent host immunologic response, on the human central nervous system (CNS) and related outcomes are unknown. We discuss currently available evidence of COVID-19 related neuropsychiatric sequelae while drawing parallels to past viral pandemic-related outcomes. Past pandemics have demonstrated that diverse types of neuropsychiatric symptoms, such as encephalopathy, mood changes, psychosis, neuromuscular dysfunction, or demyelinating processes, may accompany acute viral infection, or may follow infection by weeks, months, or longer in recovered patients. The potential mechanisms are also discussed, including viral and immunological underpinnings. Therefore, prospective neuropsychiatric monitoring of individuals exposed to SARS-CoV-2 at various points in the life course, as well as their neuroimmune status, are needed to fully understand the long-term impact of COVID-19, and to establish a framework for integrating psychoneuroimmunology into epidemiologic studies of pandemics.", "qid": 45, "docid": "stnva6pv", "rank": 64, "score": 0.8840652704238892}, {"content": "Title: Predictors of Mental Health during the early Covid-19 Pandemic in the US: role of economic concerns, health worries and social distancing Content: Objective: To assess mental health in the US adult population in the Covid-19 pandemic and explore the roles of economic concerns, health worries and social distancing in shaping mental health outcomes. Methods: We analyze online survey data from the \"Understanding America Study\" (UAS) that is representative of the US adult population and covers the period of March 10-31st 2020 (sample size: 6436). Results: About 29% (CI:27.4-.30.4%) of the US adult population reported some depression/anxiety symptoms over the study period, with symptoms deteriorating over the month of March. Worsening mental health was most strongly associated with concerns about the economic consequences of the pandemic, while concerns about the potential impact of the virus on respondents' own health and the practice of social distancing also predicted the presence of depression and anxiety symptoms, albeit less strongly. Conclusions: Our findings point towards a major mental health crisis unfolding simultaneously with the pandemic in the US. They also highlight the importance of economic countermeasures and social policy for mitigating the impact of Covid-19 on adult mental health in the US over and above an effective public health response.", "qid": 45, "docid": "omv50b7j", "rank": 65, "score": 0.8837853670120239}, {"content": "Title: Mental health of family, friends, and co-workers of COVID-19 patients in Japan Content: As the coronavirus disease 2019 (COVID-19) pandemic rages on, the mental health of both the infected and non-infected is a rising concern. We used administrative survey data (16402 responses in the last two weeks) using a chatbot on LINE, the most popular social networking service (SNS) in Japan, to show that people with COVID-19 patients in a close setting had higher psychological distress level than those without. We believe that the results indicate an urgent need to prioritize the establishment and implementation of mental health and psychosocial support tailored to family, close relatives, and friends of COVID-19 patients.", "qid": 45, "docid": "t9b3yr6w", "rank": 66, "score": 0.8836661577224731}, {"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": 67, "score": 0.8836003541946411}, {"content": "Title: Are we facing a crashing wave of neuropsychiatric sequelae of COVID-19? Neuropsychiatric symptoms and potential immunologic mechanisms Content: The coronavirus disease 19 (COVID-19) pandemic is a significant psychological stressor in addition to its tremendous impact on every facet of individuals' lives and organizations in virtually all social and economic sectors worldwide. Fear of illness and uncertainty about the future precipitate anxiety- and stress-related disorders, and several groups have rightfully called for the creation and dissemination of robust mental health screening and treatment programs for the general public and front-line healthcare workers. However, in addition to pandemic-associated psychological distress, the direct effects of the virus itself (several acute respiratory syndrome coronavirus; SARS-CoV-2), and the subsequent host immunologic response, on the human central nervous system (CNS) and related outcomes are unknown. We discuss currently available evidence of COVID-19 related neuropsychiatric sequelae while drawing parallels to past viral pandemic-related outcomes. Past pandemics have demonstrated that diverse types of neuropsychiatric symptoms, such as encephalopathy, mood changes, psychosis, neuromuscular dysfunction, or demyelinating processes, may accompany acute viral infection, or may follow infection by weeks, months, or longer in recovered patients. The potential mechanisms are also discussed, including viral and immunological underpinnings. Therefore, prospective neuropsychiatric monitoring of individuals exposed to SARS-CoV-2 at various points in the life course, as well as their neuroimmune status, are needed to fully understand the long-term impact of COVID-19, and to establish a framework for integrating psychoneuroimmunology into epidemiologic studies of pandemics.", "qid": 45, "docid": "8yjdeyog", "rank": 68, "score": 0.8833243250846863}, {"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": 69, "score": 0.8827008008956909}, {"content": "Title: COVID-19 and Severe Mental Illness: Impact on patients and its relation with their awareness about COVID-19 Content: COVID-19 outbreak has promoted many public health measures in the general population. However, its impact on a vulnerable population with severe mental illness (SMI) is less addressed. Aim of this study was to determine the impact of COVID -19 to patients with SMI and identify its relation with their COVID-19 knowledge. A cross-sectional telephonic survey among 132 patients with SMI who were clinically stable before the COVID-19 pandemic was conducted. A 23 item interview proforma comprising of self-reported knowledge related to COVID-19 by patients and their illness and treatment status from their caregivers. Eleven patients were completely not aware of the ongoing COVID-19 pandemic. Three fourth of patients were not worried about getting COVID-19 and lacks adequate knowledge to identify symptoms. Two-third of patients lacked adequate knowledge of precautionary measures against COVID-19. One out of five patients lacked knowledge of the mode of transmission and stopped their psychiatric treatment. Thirty percent showed features of relapse of symptoms during this lockdown period. In multivariate regression analysis, patients from lower socioeconomic status, low literacy levels, with inadequate social support showed less knowledge related to COVID-19. Mental health services which target this vulnerable population during early disaster reduce the burden to the community.", "qid": 45, "docid": "dv6o3pa4", "rank": 70, "score": 0.8825479745864868}, {"content": "Title: The Psychological and Mental Impact of Coronavirus Disease 2019 (COVID-19) on Medical Staff and General Public \u2013 A Systematic Review and Meta-analysis Content: The coronavirus disease 2019 (COVID-19) pandemic has caused enormous psychological impact worldwide. We conducted a systematic review and meta-analysis on the psychological and mental impact of COVID-19 among healthcare workers, the general population, and patients with higher COVID-19 risk published between 1 Nov 2019 to 25 May 2020. We conducted literature researching used Embase, PubMed, Google scholar and WHO COVID-19 databases. Among the initial search of 9207 studies, 62 studies with 162,639 participants from 17 countries were included in the review. The pooled prevalence of anxiety and depression was 33% (95% confidence interval: 28%-38%) and 28% (23%-32%), respectively. The prevalence of anxiety and depression was the highest among patients with pre-existing conditions and COVID-19 infection (56% [39%-73%] and 55% [48%-62%]), and it was similar between healthcare workers and the general public. Studies from China, Italy, Turkey, Spain and Iran reported higher-than-pooled prevalence among healthcare workers and the general public. Common risk factors included being women, being nurses, having lower socioeconomic status, having high risks of contracting COVID-19, and social isolation. Protective factors included having sufficient medical resources, up-to-date and accurate information, and taking precautionary measures. In conclusion, psychological interventions targeting high-risk populations with heavy psychological distress are in urgent need.", "qid": 45, "docid": "hl3tvivk", "rank": 71, "score": 0.8820297122001648}, {"content": "Title: The impact of the COVID19 pandemic and initial period of lockdown on the mental health and wellbeing of UK adults Content: Mental health and wellbeing impacts of COVID19 were assessed in a convenience sample of 600 UK adults using a cross-sectional design. Recruited over a two-week period during the initial phase of the government lockdown, participants completed an online survey that included COVID19-related questions, the Hospital Anxiety and Depression Scale, the WHO-5 and the OXCAP-MH. Self-isolating prior to lockdown, increased feelings of isolation since the lockdown, and having COVID19-related livelihood concerns, were associated with poorer mental health, wellbeing and quality of life. Perceiving increased kindness, community connectedness, and being an essential worker were associated with better mental health and wellbeing outcomes.", "qid": 45, "docid": "4twkfrfg", "rank": 72, "score": 0.8820144534111023}, {"content": "Title: The psychological and mental impact of coronavirus disease 2019 (COVID-19) on medical staff and general public - A systematic review and meta-analysis Content: The coronavirus disease 2019 (COVID-19) pandemic has caused enormous psychological impact worldwide. We conducted a systematic review and meta-analysis on the psychological and mental impact of COVID-19 among healthcare workers, the general population, and patients with higher COVID-19 risk published between 1 Nov 2019 to 25 May 2020. We conducted literature research using Embase, PubMed, Google scholar and WHO COVID-19 databases. Among the initial search of 9207 studies, 62 studies with 162,639 participants from 17 countries were included in the review. The pooled prevalence of anxiety and depression was 33% (95% confidence interval: 28%-38%) and 28% (23%-32%), respectively. The prevalence of anxiety and depression was the highest among patients with pre-existing conditions and COVID-19 infection (56% [39%-73%] and 55% [48%-62%]), and it was similar between healthcare workers and the general public. Studies from China, Italy, Turkey, Spain and Iran reported higher-than-pooled prevalence among healthcare workers and the general public. Common risk factors included being women, being nurses, having lower socioeconomic status, having high risks of contracting COVID-19, and social isolation. Protective factors included having sufficient medical resources, up-to-date and accurate information, and taking precautionary measures. In conclusion, psychological interventions targeting high-risk populations with heavy psychological distress are in urgent need.", "qid": 45, "docid": "3xzhi7gh", "rank": 73, "score": 0.8814939260482788}, {"content": "Title: Mental Health Effects of COVID-19 Pandemia: A Review of Clinical and Psychological Traits Content: OBJECTIVE: As the coronavirus (COVID-19) pandemic sweeps across the world, it is causing widespread concern, fear and stress, all of which are natural and normal reactions to the changing and uncertain situation that everyone finds themselves in. METHODS: In this general review, we examined the literature about the psychological effects of COVID-19 pandemia. In total 65 papers were reviewed using the Medline computer database. Only publications in English were selected. RESULTS: Children are likely to be experiencing worry, anxiety and fear and older people are also those with underlying health conditions, having been identified as more vulnerable to COVID-19, can be extremely frightening and very fear-inducing. China and several other countries took strict isolation measures. Medical staff and affiliated healthcare workers (staff) are under both physical and psychological pressure. CONCLUSION: The COVID-19 pandemic is exceptional. Its effect will likely be imprinted on each individual involved. Extensive stressors will emerge or become worsened. Many medical staff workers will be harmfully psychologically affected.", "qid": 45, "docid": "9jl89mry", "rank": 74, "score": 0.8812911510467529}, {"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": 75, "score": 0.8811678886413574}, {"content": "Title: Fear and agony of the pandemic leading to stress and mental illness: An emerging crisis in the novel coronavirus (COVID-19) outbreak Content: The outbreak of novel Coronavirus (COVID-19), later named as a pandemic affecting nearly 210 countries and territories has led to negative emotions of fear and agony in the general population and healthcare staff professionals. The healthcare regulators and the governments have imposed emergencies and lockdowns in their countries which has led to an adverse effect on the mental health of people ultimately leading to a rise in anxiety, depression, and associated mental illness. The fear and uncertainty increased by the COVID-19 crisis are putting extreme pressure on our finite resources. This report aims to synthesis the dilemma of mental illness as a result of pandemic and initiates suggestions to help the general public, healthcare professionals, and workers mitigate the negative emotions to improve the mental wellbeing in this detached period of isolation.", "qid": 45, "docid": "2sr3lgol", "rank": 76, "score": 0.8811346292495728}, {"content": "Title: Fear and agony of the pandemic leading to stress and mental illness: An emerging crisis in the novel coronavirus (COVID-19) outbreak. Content: The outbreak of novel Coronavirus (COVID-19), later named as a pandemic affecting nearly 210 countries and territories has led to negative emotions of fear and agony in the general population and healthcare staff professionals. The healthcare regulators and the governments have imposed emergencies and lockdowns in their countries which has led to an adverse effect on the mental health of people ultimately leading to a rise in anxiety, depression, and associated mental illness. The fear and uncertainty increased by the COVID-19 crisis are putting extreme pressure on our finite resources. This report aims to synthesis the dilemma of mental illness as a result of pandemic and initiates suggestions to help the general public, healthcare professionals, and workers mitigate the negative emotions to improve the mental wellbeing in this detached period of isolation.", "qid": 45, "docid": "20bgev65", "rank": 77, "score": 0.8811346292495728}, {"content": "Title: Mental Health Status of the General Population during the COVID-19 Pandemic: A Cross-sectional National Survey in Japan Content: The ongoing COVID-19 pandemic may have detrimental mental health consequences. However, as yet, there is limited understanding of its impact on the mental health of the general population. The aim of this study is to examine the mental health of the Japanese general population by conducting the first systematic survey during the pandemic (N=1,000), with a particular focus on identifying the most vulnerable groups. Results from logistic regression analyses showed that the mental health of young and middle-aged individuals was significantly worse than that of older individuals during the pandemic. There was also some indication that individuals who were not currently working were significantly more likely to report a high level of anxiety and depressive symptoms. Part-time and temporary contract-based workers were also more likely to suffer from anxiety disorder. Our results highlight that monitoring the mental health of younger and economically vulnerable individuals may be especially important. In addition, they also indicate that population mental health might not only be affected by the direct health consequences of COVID-19, but also by the economic ramifications of the pandemic.", "qid": 45, "docid": "wpxrzjzx", "rank": 78, "score": 0.8809900879859924}, {"content": "Title: Why all COVID-19 Hospitals should have Mental Health Professionals: The importance of mental health in a worldwide crisis! Content: Abstract COVID-19 pandemic has led to a worldwide crisis. At present, everyone is focusing on the prevention of COVID-19 infection, preparing and discussing issues related to physical health consequences. However, it is important to understand that the life-threatening negative physical health consequences are going to be faced by a few, but everyone is going to face the negative mental health consequences of the pandemic. At various places COVID-19 hospitals are being established, to address the physical health consequences of the pandemic. However, mental health professionals have not been very actively involved in the management of people going through this pandemic. This viewpoint discusses the mental health consequences of the pandemic for the health care workers, people who are undergoing quarantine, people who are admitted to the COVID-19 hospitals, and those who have recovered from the infection. The article also highlights the mental health needs of people at different levels and the kind of interventions, which may be carried out.", "qid": 45, "docid": "2q7fb55t", "rank": 79, "score": 0.8809834122657776}, {"content": "Title: Flattening the mental ill-health curve: the importance of primary prevention in managing the mental health impacts of COVID19 Content: The COVID19 pandemic is one the biggest challenges the global community has faced. The threat of the virus coupled with the impacts of the social and economic shut-down measures required to slow its spread, already appear to be impacting on people's mental health and wellbeing. Over the weeks, months and years ahead it is likely that many countries will experience a \u2018wave\u2019 of COVID19 related mental disorders as a result of an increase in risk factors linked to the pandemic such as social isolation; child-maltreatment; intimate partner violence; unemployment; housing and income stress; workplace trauma; and grief and loss. The \u2018two-pronged\u2019 approach used to deal with COVID19, provides an excellent blueprint for managing its mental health impacts as well. Nations must focus on preventing the occurrence of new cases of mental disorders as well as strengthening their mental healthcare response to support people who become mentally unwell. A focus on primary prevention is particularly important to \u2018flatten the curve\u2019 and avoid a surge in incidence of mental disorders stemming from the COVID19 pandemic. Many evidence-based interventions designed to prevent common disorders are already available and should be scaled-up. These interventions include parenting programs, social and emotional learning programs, self-care strategies, and workplace mental wellbeing programs, among others.", "qid": 45, "docid": "pl5hyzwp", "rank": 80, "score": 0.8808876872062683}, {"content": "Title: Psychological interventions during COVID-19: Challenges for low and middle income countries Content: At the start of 2020, the 2019 coronavirus disease (COVID-19), originating from China has spread to the world. There have been increasing numbers of confirmed cases and deaths around the globe. The COVID-19 pandemic has paved the way for considerable psychological and psychosocial morbidity among the general public and health care providers. An array of guidelines has been put forward by multiple agencies for combating mental health challenges. This paper addresses some of the mental health challenges faced by low and middle income countries (LMIC). It is worthwhile to note that these are challenges at the current stage of the pandemic and may change with the course of the pandemic itself.", "qid": 45, "docid": "obrmy0zf", "rank": 81, "score": 0.8808510303497314}, {"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": 82, "score": 0.8807889223098755}, {"content": "Title: Covid-19 and anxiety: A review of psychological impacts of infectious disease outbreaks Content: Context: The advent of coronavirus disease 2019 (COVID-19) has caused confusion, changed people\u2019s living conditions, including commuting restrictions, fear of disease transmission, and closure of schools and businesses, and brought about devastating psychological impacts, like anxiety. However, most studies only have focused on clinical data. Evidence Acquisition: In this short review, the psychological effects of COVID-19 and its association with anxiety were examined. Accordingly, the electronic databases, including PubMed, Medline, Elsevier, and Science Direct were reviewed for relevant studies that have conducted since 2007. Results: The current study was carried out to indicate that COVID-19 has negative psychological problems other than mortality. A review of the studies performed in other parts of the world showed that COVID-19 has caused several psychological impacts, including increased anxiety. Conclusions: By an increase in the prevalence rate of COVID-19 and its resulted restrictions, the level of anxiety increases, as well; therefore, raising public awareness of the disease and providing positive psychological programs in the media aimed at controlling stress can reduce anxiety in society.", "qid": 45, "docid": "m8a98j99", "rank": 83, "score": 0.880483090877533}, {"content": "Title: Levels and predictors of anxiety, depression and health anxiety during COVID-19 pandemic in Turkish society: The importance of gender. Content: BACKGROUND The COVID-19 pandemic is having negative effects on societies' mental health. Both the pandemic and the measures taken to combat it can affect individuals' mental health. AIMS The purpose of this study was to evaluate the levels of depression, anxiety and health anxiety in Turkish society during the COVID-19 pandemic, and to examine the factors affecting these. METHOD The study was performed using an online questionnaire. Participants were asked to complete a sociodemographic data form, the Hospital Anxiety and Depression Scale (HADS) and the Health Anxiety Inventory (HAI). The effects on depression, anxiety and health anxiety levels of factors such as age, sex, marital status, living with an individual aged above 60, the presence of a new Coronavirus+ patient among friends or relatives, previous and current psychiatric illness and presence of accompanying chronic disease were then investigated. RESULTS In terms of HADS cut-off points, 23.6% (n = 81) of the population scored above the depression cut-off point, and 45.1% (n = 155) scored above the cut-off point for anxiety. In regression analysis, female gender, living in urban areas and previous psychiatric illness history were found as risk factors for anxiety; living in urban areas was found as risk factor for depression; and female gender, accompanying chronic disease and previous psychiatric history were found as risk factors for health anxiety. CONCLUSION The results of this cross-sectional study suggest that the groups most psychologically affected by the COVID-19 pandemic are women, individuals with previous psychiatric illness, individuals living in urban areas and those with an accompanying chronic disease. Priority might therefore be attached to these in future psychiatric planning.", "qid": 45, "docid": "64zz84u7", "rank": 84, "score": 0.8804154992103577}, {"content": "Title: COVID-19 Exposes the Cracks in Our Already Fragile Mental Health System Content: The coronavirus pandemic has caused enormous concern among many people. Every morning, we are met with an increasing deluge of dire news about the most recent number of people to contract COVID-19 and to die from it, decreases in the stock market, and countries implementing broad travel restrictions and stay-at-home orders.1,2 The current state of affairs is having a negative effect on the mental well-being of our country's residents. It also highlights the policy gaps in our current system that inhibit the vital conditions for well-being and resiliency.3 Although the primary focus has rightfully been on stopping the spread of COVID-19, we should also quickly prepare to address the mental toll the pandemic is taking on individuals and communities across the country. (Am J Public Health. Published online ahead of print May 21, 2020: e1-e2. doi:10.2105/AJPH.2020.305699).", "qid": 45, "docid": "dc8j05vf", "rank": 85, "score": 0.8803715109825134}, {"content": "Title: COVID-19 Exposes the Cracks in Our Already Fragile Mental Health System. Content: The coronavirus pandemic has caused enormous concern among many people. Every morning, we are met with an increasing deluge of dire news about the most recent number of people to contract COVID-19 and to die from it, decreases in the stock market, and countries implementing broad travel restrictions and stay-at-home orders.1,2 The current state of affairs is having a negative effect on the mental well-being of our country's residents. It also highlights the policy gaps in our current system that inhibit the vital conditions for well-being and resiliency.3 Although the primary focus has rightfully been on stopping the spread of COVID-19, we should also quickly prepare to address the mental toll the pandemic is taking on individuals and communities across the country. (Am J Public Health. Published online ahead of print May 21, 2020: e1-e2. doi:10.2105/AJPH.2020.305699).", "qid": 45, "docid": "xolflz8g", "rank": 86, "score": 0.8803715109825134}, {"content": "Title: The COVID-19 pandemic and its impact on mental health Content: Similarities exist between our past experience of viral diseases and COVID-19 concerning the mental health issues of sufferers of an epidemic, frontline health workers and the social and psychological impact on society. There is significant evidence that a novel illness such as COVID-19 can cause widespread fear, panic, anxiety and xenophobia. Dr Chakraborty explores the latest literature and what it means for mental health.", "qid": 45, "docid": "xqmw84dz", "rank": 87, "score": 0.8801853656768799}, {"content": "Title: Why all COVID-19 hospitals should have mental health professionals: The importance of mental health in a worldwide crisis! Content: COVID-19 pandemic has led to a worldwide crisis. At present, everyone is focusing on the prevention of COVID-19 infection, preparing and discussing issues related to physical health consequences. However, it is important to understand that the life-threatening negative physical health consequences are going to be faced by a few, but everyone is going to face the negative mental health consequences of the pandemic. At various places COVID-19 hospitals are being established, to address the physical health consequences of the pandemic. However, mental health professionals have not been very actively involved in the management of people going through this pandemic. This viewpoint discusses the mental health consequences of the pandemic for the health care workers, people who are undergoing quarantine, people who are admitted to the COVID-19 hospitals, and those who have recovered from the infection. The article also highlights the mental health needs of people at different levels and the kind of interventions, which may be carried out.", "qid": 45, "docid": "74ovl7ls", "rank": 88, "score": 0.8800225257873535}, {"content": "Title: The psychology of coronavirus fear: Are healthcare professionals suffering from corona-phobia? Content: Background: Coronaviruses are a category of associated viruses that trigger diseases, including severe acute respiratory syndrome-related coronavirus (SARS-CoV) in 2003, human coronavirus NL63 (HCoV NL63) in 2004, human coronavirus HKU1 (HKU1) in 2005, Middle East respiratory syndrome-related coronavirus (MERS-CoV) in 2012, and severe acute respiratory syndrome-related coronavirus-2 (SARS-CoV-2) in December 2019. Objective: This study used a qualitative and quantitative approach to measure Covid-19 pandamic\u2019s impact on psychological well-being. At the moment, the world is fearing from this widespread pandemic, its outbreak and has no idea how it is leaving psychological effects on human well-being. Method: This study designed questionnaires to judge the psychological health of healthcare professionals those are directly treating quarantined patients within the hospital. We asked questions from 250-healthcare professionals (including doctors, nurses, and paramedical staff) who are treating quarantined patients at different hospitals of Lahore, Pakistan. Results: This study concludes that corona-phobia persist in healthcare professionals and cause various psychological symptoms on their mental health. Conclusion & Policy Implication: This study suggests the government need to provide medical facilities/equipment with those healthcare professionals who are frontline soldiers in treating quarantine patients.", "qid": 45, "docid": "cl64kf3p", "rank": 89, "score": 0.8795928955078125}, {"content": "Title: The Nature and Treatment of Pandemic-Related Psychological Distress Content: The COVID-19 crisis has created a \u201cmental health pandemic\u201d throughout the world. Scientific data are not available to fully understand the nature of the resulting mental health impact given the very recent onset of the pandemic, nevertheless, there is a need to act immediately to develop psychotherapeutic strategies that may alleviate pandemic-related distress. The psychological distress, in particular fear and sadness, is a function of the pandemic\u2019s negative impact upon people\u2019s ability to meet their most basic needs (e.g., physical safety, financial security, social connection, participation in meaningful activities). This paper presents evidence-based cognitive behavioral strategies that should prove useful in reducing the emotional suffering associated with the COVID crisis.", "qid": 45, "docid": "3q0ujnjq", "rank": 90, "score": 0.8795812129974365}, {"content": "Title: Mental Health Policy in the Era of COVID-19 Content: The response to the global COVID-19 pandemic has important ramifications for mental health systems and the patients they serve. This article describes significant changes in mental health policy prompted by the COVID-19 crisis across five major areas: legislation, regulation, financing, accountability, and workforce development. Special considerations for mental health policy are discussed, including social determinants of health, innovative technologies, and research and evaluation. These extraordinary advances provide an unprecedented opportunity to evaluate the effects of mental health policies that may be adopted in the post-COVID-19 era in the United States.", "qid": 45, "docid": "rw5a8tkj", "rank": 91, "score": 0.8794633150100708}, {"content": "Title: Mental Health Policy in the Era of COVID-19. Content: The response to the global COVID-19 pandemic has important ramifications for mental health systems and the patients they serve. This article describes significant changes in mental health policy prompted by the COVID-19 crisis across five major areas: legislation, regulation, financing, accountability, and workforce development. Special considerations for mental health policy are discussed, including social determinants of health, innovative technologies, and research and evaluation. These extraordinary advances provide an unprecedented opportunity to evaluate the effects of mental health policies that may be adopted in the post-COVID-19 era in the United States.", "qid": 45, "docid": "zg8l6std", "rank": 92, "score": 0.8794633150100708}, {"content": "Title: Psychological Interventions during COVID-19: Challenges for low and middle income countries Content: Abstract At the start of 2020, the 2019 coronavirus disease (COVID-19), originating from China has spread to the world. There have been increasing numbers of confirmed cases and deaths around the globe. The COVID-19 pandemic has paved the way for considerable psychological and psychosocial morbidity among the general public and health care providers. An array of guidelines has been put forward by multiple agencies for combating mental health challenges. This paper addresses some of the mental health challenges faced by low and middle income countries (LMIC). It is worthwhile to note that these are challenges at the current stage of the pandemic and may change with the course of the pandemic itself.", "qid": 45, "docid": "hn6oao66", "rank": 93, "score": 0.8793337941169739}, {"content": "Title: Coronavirus disease: challenges for psychiatry Content: Coronavirus disease (COVID-19) presents two urgent health problems: the illness caused by the virus itself and the anxiety, panic and psychological problems associated with the pandemic. Both problems present substantial challenges for our patients, their families, our multidisciplinary teams and our psychiatrist colleagues. We need good psychiatry, now more than ever.", "qid": 45, "docid": "542e5h1u", "rank": 94, "score": 0.8788722157478333}, {"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": 95, "score": 0.8783367872238159}, {"content": "Title: Mental Health Impact of COVID-19: A global study of risk and resilience factors Content: This study anonymously screened 13,332 individuals worldwide for psychological symptoms related to Corona virus disease 2019 (COVID-19) pandemic from March 29th to April 14th, 2020. A total of n=12,817 responses were considered valid with responses from 12 featured countries and five WHO regions. Female gender, pre-existing psychiatric condition, and prior exposure to trauma were identified as notable riskfactors, whereas optimism, ability to share concerns with family and friends like usual,positive prediction about COVID-19, and daily exercise predicted fewer psychologicalsymptoms. These results could aid in dynamic optimization of mental health services during and following the COVID-19 pandemic.", "qid": 45, "docid": "3qgknhmv", "rank": 96, "score": 0.8783278465270996}, {"content": "Title: Changing dynamics of psychoneuroimmunology during COVID-19 pandemic Content: The Coronavirus Disease-2019 (COVID-19) pandemic has led to a global health care crisis in recent times. Emerging research suggest an unanticipated impact of COVID-19 on mental and/or psychological health of both the general community and affected individuals. The fear of the COVID-19 epidemic and the consequent lockdown and economic crisis has led to globally increased psychological distress. The biological bases of immediate and new onset of psychiatric symptoms in individuals with COVID-19 are not yet known. COVID-19 infection may lead to activated immune-inflammatory pathways and cytokine storm. Activated immune-inflammatory pathways, especially chronic low-grade inflammation, are associated with major psychiatric disorders in at least a subset of individuals. We propose that both the (sub)chronic inflammatory response and cytokine storm might crucially be involved in the immediate manifestation of neuropsychiatric symptoms in individuals with COVID-19 infection as well as heightened expression of psychiatric symptoms in COVID-19 infected individuals with prior psychiatric conditions. These events might expand concepts in psychoneuroimmunology, with the importance of chronic-low grade inflammation augmented by the cytokine storm hypothesis. Additionally, this might augment and refine diagnosis and prognostic management as well as treatment.", "qid": 45, "docid": "yne0dus9", "rank": 97, "score": 0.8782756924629211}, {"content": "Title: Focus on Mental Health During the Coronavirus (COVID-19) Pandemic: Applying Learnings from the Past Outbreaks Content: The 2019 novel coronavirus (COVID-19) has gained global attention after it originated from China at the end of 2019, and later turned into pandemic as it affected about 118,000 in 114 countries by March 11, 2020. By March 13, 2020, it was declared a national emergency in the United States as the number of COVID-19 cases, and the death toll rose exponentially. To contain the spread of the disease, the world scientist community came together. However, the unpreparedness of the nations, even with the advanced medical sciences and resources, has failed to address the mental health aspect amongst the public, as all efforts are focused on understanding the epidemiology, clinical features, transmission patterns, and management of COVID-19 pneumonia. Our efforts in this review are to evaluate and study similar outbreaks from the past to understand its adverse impact on mental health, implement adequate steps to tackle and provide a background to physicians and healthcare workers at the time of such outbreaks to apply psychological first aid.", "qid": 45, "docid": "feqwdynl", "rank": 98, "score": 0.8781931400299072}, {"content": "Title: Do psychiatric patients experience more psychiatric symptoms during COVID-19 pandemic and lockdown? A case-control study with service and research implications for immunopsychiatry Content: This study aimed to assess and compare the immediate stress and psychological impact experienced by people with and without psychiatric illnesses during the peak of 2019 coronavirus disease (COVID-19) epidemic with strict lockdown measures. Seventy-six psychiatric patients and 109 healthy control subjects were recruited from Chongqing, China and completed a survey on demographic data, physical symptoms during the past 14 days and a range of psychiatric symptoms using the Impact of Event Scale-Revised (IES-R), Depression, Anxiety and Stress Scale (DASS-21) and Insomnia Severity Index (ISI). IES-R measures PTSD symptoms in survivorship after an event. DASS-21 is based on tripartite model of psychopathology that comprise a general distress construct with distinct characteristics. The mean IES-R, DASS-21 anxiety, depression and stress subscale and ISI scores were higher in psychiatric patients than healthy controls (p < 0.001). Serious worries about their physical health, anger and impulsivity and intense suicidal ideation were significantly higher in psychiatric patients than healthy controls (p < 0.05). More than one-third of psychiatric patients might fulfil the diagnostic criteria post-traumatic stress disorder (PTSD). More than one-quarter of psychiatric patients suffered from moderately severe to severe insomnia. Respondents who reported no change, poor or worse physical health status and had a psychiatric illness were significantly more likely to have higher mean IES-R, DASS depression, anxiety and stress subscale scores and ISI scores (p < 0.05). This study confirms the severity of negative psychological impact on psychiatric patients during the COVID-19 epidemic with strict lockdown measures. Understanding the psychological impact on psychiatric patients during the COVID-19 pandemic has the potential to provide insight into how to develop a new immunopsychiatry service. Further research is required to compare pro-inflammatory cytokines between psychiatric patients and healthy controls during the pandemic.", "qid": 45, "docid": "r946okl9", "rank": 99, "score": 0.8775674104690552}, {"content": "Title: The effect of the COVID-19 pandemic on healthcare workers' mental health. Content: The novel coronavirus (SARS-CoV-2) that emerged in late 2019 in Wuhan, China, commonly presents as a severe acute respiratory disease referred to as coronavirus disease-2019 (COVID-19). The rapid spread of the disease created challenges for healthcare systems and forced healthcare workers to grapple with clinical and nonclinical stressors, including shortages of personal protective equipment, mortality and morbidity associated with COVID-19, fear of bringing the virus home to family members, and the reality of losing colleagues to the disease. Evidence from previous outbreaks, along with early evidence from the COVID-19 pandemic, suggests that these events have significant short- and long-term effects on the mental health of healthcare workers. All healthcare stakeholders should create short- and long-term plans to support the mental health of workers during and after the COVID-19 pandemic.", "qid": 45, "docid": "436hvwtr", "rank": 100, "score": 0.8775137662887573}]}
{"query": "what evidence is there for dexamethasone as a treatment for COVID-19?", "hits": [{"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": 1, "score": 0.9075312614440918}, {"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": 2, "score": 0.9075312614440918}, {"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": 3, "score": 0.8941263556480408}, {"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": 46, "docid": "gc8770l9", "rank": 4, "score": 0.8914066553115845}, {"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": 5, "score": 0.887333869934082}, {"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": 0.8793537616729736}, {"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": 0.8745619654655457}, {"content": "Title: Use of Corticosteroids in Coronavirus Disease 2019 Pneumonia: A Systematic Review of the Literature Content: The aim was to investigate the effectiveness of glucocorticoid therapy in patients with COVID-19. A systematic search of the literature across nine databases was conducted from inception until 15th March 2020, following the PRISMA guidelines. Patients with a validated diagnosis of COVID-19 and using corticosteroids were included, considering all health outcomes. Four studies with 542 Chinese participants were included. Two studies reported negative findings regarding the use of corticosteroids in patients with COVID-19, i.e., corticosteroids had a detrimental impact on clinical outcomes. One study reported no significant association between the use of corticosteroids and clinical outcomes. However, one study, on 201 participants with different stages of pneumonia due to COVID-19, found that in more severe forms, the administration of methylprednisolone significantly reduced the risk of death by 62%. The literature to date does not fully support the routine use of corticosteroids in COVID-19, but some findings suggest that methylprednisolone could lower mortality rate in more severe forms of the condition.", "qid": 46, "docid": "ypeibwje", "rank": 8, "score": 0.8741477727890015}, {"content": "Title: Therapeutic Management of COVID-19 Patients: A systematic review Content: Background: SARS-CoV-2 is the cause of the COVID-19 that has been declared a global pandemic by the WHO in 2020. The COVID-19 treatment guidelines vary in each country, and yet there is no approved therapeutic for COVID-19. Aims of the study: this review aimed to report any evidence of therapeutics used for the management of COVID-19 patients in clinical practice since the emergence of the virus. Methods: A systematic review protocol was developed based on PRISMA Statement. Articles for review were selected from electronic databases (Embase, Medline and Google Scholar). Readily accessible peer-reviewed full articles in English published from December 1 st , 2019 to March 26 th , 2020 were included. The search terms included combinations of: COVID, SARS-COV-2, glucocorticoids, convalescent plasma, antiviral, antibacterial. There were no restrictions on the type of study design eligible for inclusion. Results: As of March 26, 2020, of the initial manuscripts identified (n=449) articles. Forty-one studies were included, of which clinical trials (n=3), (case reports n=7), case series (n=10), retrospective (n=11) and prospective (n=10) observational studies. Thirty-six studies were conducted in China (88%). The most common mentioned and reported medicine in this systematic review was corticosteroids (n=25), followed by Lopinavir (n=21) and oseltamivir (n=16). Conclusions: This is the first systematic review up to date related to the therapeutics used in COVID-19 patients. Only forty-one research articles on COVID-19 and therapeutics were found eligible to be included, most conducted in China, corticosteroid therapy was found to be the most used medicine in these studies.", "qid": 46, "docid": "w02mylsc", "rank": 9, "score": 0.8724361658096313}, {"content": "Title: COVID-19 and treatment with NSAIDs and corticosteroids: should we be limiting their use in the clinical setting? Content: Given the current SARS-CoV-2 (COVID-19) pandemic, the availability of reliable information for clinicians and patients is paramount. There have been a number of reports stating that non-steroidal anti-inflammatory drugs (NSAIDs) and corticosteroids may exacerbate symptoms in COVID-19 patients. Therefore, this review aimed to collate information available in published articles to identify any evidence behind these claims with the aim of advising clinicians on how best to treat patients. This review found no published evidence for or against the use of NSAIDs in COVID-19 patients. Meanwhile, there appeared to be some evidence that corticosteroids may be beneficial if utilised in the early acute phase of infection, however, conflicting evidence from the World Health Organisation surrounding corticosteroid use in certain viral infections means this evidence is not conclusive. Given the current availability of literature, caution should be exercised until further evidence emerges surrounding the use of NSAIDs and corticosteroids in COVID-19 patients.", "qid": 46, "docid": "0uengr9t", "rank": 10, "score": 0.8717029690742493}, {"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": 11, "score": 0.8707175850868225}, {"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": 12, "score": 0.8692491054534912}, {"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": 13, "score": 0.8687523007392883}, {"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": 14, "score": 0.8665512800216675}, {"content": "Title: Rheumatology Drugs and COVID-19 Content: Glucocorticoids have been used to treat SARS-CoV in 2003 but were associated with considerable side effects such as avascular bone necrosis [24] Glucocorticoids may also delay viral clearance and may lead to secondary infections in patients with MERS coronavirus infection [25] In fact, randomized controlled trials did not show benefit of glucocorticoids and may even aggravate lung injury in MERS and H1N1 pneumonia [26,27] With the availability of more targeted biological agents, glucocorticoids are currently out of favor for the treatment of severe COVID-19 The non-steroidal anti-inflammatory drugs (NSAIDs) are commonly used by rheumatologists for pain related to arthritis and myalgia Ibuprofen was commonly prescribed for early symptoms of COVID-19 in Italy and has been attributed to have caused the progression of infection because of its anti-inflammatory effects required for viral clearance [28] Although the deleterious effect of NSAIDs has yet to be confirmed, some European authorities have advised against their use in COVID-19 infection Several drugs commonly used by rheumatologists have been proposed to have potential efficacy in COVID-19 Rheumatologists may be consulted for the precautions and monitoring of these drugs should they be used in severe COVID-19 The optimal dosages of these agents in the treatment of COVID-19 have to be explored further On the other hand, a linkage between micro-organisms and the onset of autoimmune diseases has long been suggested [29] It is of intense interest to watch out for the incidence of rheumatic diseases in the next 12 to 24 months in our locality The COVID-19 Global Rheumatology Alliance has created a registry to capture rheumatology patients who have been infected with COVID-19 [30]", "qid": 46, "docid": "2ikathbz", "rank": 15, "score": 0.8647671937942505}, {"content": "Title: Therapeutic Management of COVID-19 Patients: A systematic review Content: Abstract Background SARS-CoV-2 is the causative agent of COVID-19; that has been declared a global pandemic by the WHO in 2020. The COVID-19 treatment guidelines vary in each country, and yet there is no approved therapeutic for COVID-19. Aims of the study this review aimed to report any evidence of therapeutics used for the management of COVID-19 patients in clinical practice since the emergence of the virus. Methods A systematic review protocol was developed based on PRISMA Statement. Articles for review were selected from electronic databases (Embase, Medline and Google Scholar). Readily accessible peer-reviewed, full articles in English published from December 1st , 2019 to March 26th , 2020 were included. The search terms included combinations of: COVID, SARS-COV-2, glucocorticoids, convalescent plasma, antiviral and antibacterial. There were no restrictions on the type of study design eligible for inclusion. Results As of March 26th, 2020, of the initial manuscripts identified (n=449); forty-one studies were included. These consisted of clinical trials (n=3), case reports (n=7), case series (n=10), retrospective (n=11) and prospective (n=10) observational studies. Thirty-six studies were conducted in China (88%). The most commonly reported medicine in this systematic review was corticosteroids (n=25), followed by Lopinavir (n=21) and Oseltamivir (n=16). Conclusions This is the first systematic review to date related to the therapeutics used in COVID-19 patients. Only 41 research articles on COVID-19 and therapeutics were found eligible to be included, most conducted in China. Corticosteroid therapy was found to be the most studied medicine in the literature.", "qid": 46, "docid": "uxl8liil", "rank": 16, "score": 0.8638152480125427}, {"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": 46, "docid": "yth9hh5q", "rank": 17, "score": 0.8619752526283264}, {"content": "Title: Operational protocol for donation of anti\u2010COVID\u201019 convalescent plasma in Italy Content: Coronavirus Disease 19 (COVID-19) represents a public health threat worldwide and Italy at the present time is considered the epicenter of this severe infection in the western world. Unfortunately, no standardized therapy does exist for COVID-19 and a number of investigational drugs for use in patients with life-threatening COVID-19 infections have been tried. One investigational treatment being explored for COVID-19 involves the use of convalescent plasma collected from recovered COVID-19 patients.", "qid": 46, "docid": "9yoqwrdi", "rank": 18, "score": 0.8616549968719482}, {"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": 46, "docid": "jxw6lr8d", "rank": 19, "score": 0.8611725568771362}, {"content": "Title: Drugs that aggravate the course of COVID-19 : really ?/ Traitements aggravant une infection par le COVID-19 : vraiment ? 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 La securite des AINS, corticoides et antihypertenseurs agissant sur le systeme renine-angiotensine lors dinfection a COVID-19 est mise en question Les AINS pourraient interferer avec le processus de defense face a une infection virale ;ils sont donc plutot a eviter Les corticoides systemiques nont pas montre de benefice lors dinfections virales, y compris a dautres coronavirus ;ils sont a eviter, sauf si prescrits pour une autre indication Le rapport benefice/risque est en revanche clairement en faveur de la poursuite des corticosteroides inhales chez les asthmatiques ou BPCO Les IEC et les sartans modulent lexpression de lenzyme de conversion de langiotensine 2 (ACE2), recepteur pulmonaire du SARS-CoV-2 Limpact clinique de ces traitements sur linfection a COVID-19 reste a preciser ;en attendant, ils sont a poursuivre", "qid": 46, "docid": "fsktig4m", "rank": 20, "score": 0.861130952835083}, {"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": 21, "score": 0.8605034351348877}, {"content": "Title: The use of corticosteroids for COVID-19 infection Content: The SARS-CoV-2 pandemic is continuing relentlessly in many parts of the world and has resulted in the outpouring of literature on various aspects of the infection, including studies and recommendations regarding the optimal treatment of infected patients. Not surprisingly, the use of corticosteroids in the management of such patients has featured prominently in many of these publications. There is considerable debate in the literature as to the likely benefits, as well as the potential detrimental effects of corticosteroid therapy in general viral respiratory infections and, in particular, COVID-19 infections. While the definitive answer may need to await the results of ongoing randomised, controlled trials recent studies suggest that corticosteroid use in COVID-19 cases with hypoxaemia may benefit from low-dose corticosteroid therapy.", "qid": 46, "docid": "y6fvjsjl", "rank": 22, "score": 0.8594965934753418}, {"content": "Title: Pros and cons of corticosteroid therapy for COVID-19 patients Content: In December 2019, an outbreak of severe pneumonia was reported in Wuhan, China. Later described as COVID-19 (coronavirus disease 2019), this infection caused by a virus from the Coronaviridae family (SARS-CoV-2) has spread globally. Effective therapies for this new disease are urgently needed. In this short communication, we will evaluate the use of corticosteroids as an adjunctive pharmacological therapy in the management of COVID-19 and describe its pros and cons in light of the latest available evidence.", "qid": 46, "docid": "mza0oz89", "rank": 23, "score": 0.8592054843902588}, {"content": "Title: Inhaled corticosteroids and COVID-19: a systematic review and clinical perspective Content: There is no evidence on benefits or harms of inhaled steroids in COVID-19. It is essential that epidemiological studies of COVID-19 include detailed information on comorbidities and prior medication to help answer this question. https://bit.ly/2XVwIsa", "qid": 46, "docid": "wh0ur249", "rank": 24, "score": 0.8587102293968201}, {"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": 46, "docid": "xpfhf0gc", "rank": 25, "score": 0.8569745421409607}, {"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": 26, "score": 0.8567657470703125}, {"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": 27, "score": 0.8564837574958801}, {"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": 28, "score": 0.8561263084411621}, {"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": 29, "score": 0.8561263084411621}, {"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": 30, "score": 0.8561147451400757}, {"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": 31, "score": 0.8561000823974609}, {"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": 32, "score": 0.8559823036193848}, {"content": "Title: Cardiovascular Disease Novel Coronavirus and the Search for Investigational Therapies Content: PURPOSE: The primary purpose of the current study was to investigate and summarize the registered trials that listed COVID-19 as the primary condition. METHODS: We performed a search on ClinicalTrials.gov using the independent search terms COVID-19, SARS, and SARS COV2, and then downloaded the data file on March 23, 2020. All trials were downloaded to a csv file and searched for appropriateness. RESULTS: Fifty-six of 124 (45.2%) registered trials were listed as recruiting. The majority (85, 68.5%) classified their study as interventional, 37 (29.8%) classified as observational and one (0.8%) each classified their study as either expanded access:individual patients | treatment IND/Protocol or expanded access:intermediate-size population | treatment IND/Protocol. There were 67 (54.0%) of the trials that listed drug as the type of study. Immunological and antiviral trials were the greatest, representing approximately 30% and 21%, respectively. When immunological and antiviral drugs were used alone or in combination, they represented 41.9% and 34.4%, respectively. Anti-malarial agents are represented in 7.5% of trials. Approximately 14% of trials involved Traditional Chinese Medicine. The aforementioned study agents used solely or in combination represented approximately 80% of therapeutic approaches to COVID19. CONCLUSION: There was a large and quick response on ClinicalTrials.gov to the COVID-19 outbreak. Many of the registered trials are currently recruiting new patients, while some will begin in the near future. Specific potential experimental therapies, including dosing and monitoring, might be found by reviewing content. Within clinicaltrials.gov, patients, family members, health care professionals and researchers can search and find ongoing and future trials for COVID-19.", "qid": 46, "docid": "4nci3fsi", "rank": 33, "score": 0.8540457487106323}, {"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": 46, "docid": "a1wfygyy", "rank": 34, "score": 0.853842556476593}, {"content": "Title: Efficacy and safety of corticosteroids in COVID-19 based on evidence for COVID-19, other coronavirus infections, influenza, community-acquired pneumonia and acute respiratory distress syndrome: a systematic review and meta-analysis Content: BACKGROUND: Very little direct evidence exists on use of corticosteroids in patients with coronavirus disease 2019 (COVID-19). Indirect evidence from related conditions must therefore inform inferences regarding benefits and harms. To support a guideline for managing COVID-19, we conducted systematic reviews examining the impact of corticosteroids in COVID-19 and related severe acute respiratory illnesses. METHODS: We searched standard international and Chinese biomedical literature databases and prepublication sources for randomized controlled trials (RCTs) and observational studies comparing corticosteroids versus no corticosteroids in patients with COVID-19, severe acute respiratory syndrome (SARS) or Middle East respiratory syndrome (MERS). For acute respiratory distress syndrome (ARDS), influenza and community-acquired pneumonia (CAP), we updated the most recent rigorous systematic review. We conducted random-effects meta-analyses to pool relative risks and then used baseline risk in patients with COVID-19 to generate absolute effects. RESULTS: In ARDS, according to 1 small cohort study in patients with COVID-19 and 7 RCTs in non-COVID-19 populations (risk ratio [RR] 0.72, 95% confidence interval [CI] 0.55 to 0.93, mean difference 17.3% fewer; low-quality evidence), corticosteroids may reduce mortality. In patients with severe COVID-19 but without ARDS, direct evidence from 2 observational studies provided very low-quality evidence of an increase in mortality with corticosteroids (hazard ratio [HR] 2.30, 95% CI 1.00 to 5.29, mean difference 11.9% more), as did observational data from influenza studies. Observational data from SARS and MERS studies provided very low-quality evidence of a small or no reduction in mortality. Randomized controlled trials in CAP suggest that corticosteroids may reduce mortality (RR 0.70, 95% CI 0.50 to 0.98, 3.1% lower; very low-quality evidence), and may increase hyperglycemia. INTERPRETATION: Corticosteroids may reduce mortality for patients with COVID-19 and ARDS. For patients with severe COVID-19 but without ARDS, evidence regarding benefit from different bodies of evidence is inconsistent and of very low quality.", "qid": 46, "docid": "r8rd5f2j", "rank": 35, "score": 0.8536808490753174}, {"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": 46, "docid": "8cvjsisw", "rank": 36, "score": 0.8532517552375793}, {"content": "Title: Cardiovascular disease due to novel coronavirus and the search for investigational therapies Content: OBJECTIVE: The primary purpose of the study was to investigate and to summarize the registered trials that listed COVID-19 as the primary condition. METHODS: We performed a search on ClinicalTrials.gov using the independent search terms COVID-19, SARS, and SARS-CoV-2 and then downloaded the data file on March 23, 2020. All trials were downloaded to a csv file and searched for appropriateness. RESULTS: Of 124 registered trials, 56 (45.2%) were listed as recruiting. The majority (85 [68.5%]) were classified as interventional, 37 (29.8%) as observational, and one (0.8%) each as either expanded access: individual patients|treatment investigational new drug/protocol or expanded access: intermediate-size population|treatment investigational new drug/protocol. There were 67 (54.0%) trials that listed drug as the type of study. Immunologic and antiviral trials were the most common, representing approximately 30% and 21%, respectively. When immunologic and antiviral drugs were used alone or in combination, they represented 41.9% and 34.4%, respectively. Antimalarial agents are represented in 7.5% of trials. Approximately 14% of trials involved traditional Chinese medicine. The study agents used solely or in combination represented approximately 80% of therapeutic approaches to COVID-19. CONCLUSIONS: There was a large and quick response on ClinicalTrials.gov to the COVID-19 outbreak. Many of the registered trials are currently recruiting new patients, whereas some will begin in the near future. Specific potential experimental therapies, including dosing and monitoring, might be found by reviewing content. Within ClinicalTrials.gov, patients, family members, health care professionals, and researchers can search and find ongoing and future trials for COVID-19.", "qid": 46, "docid": "y6mpjjr2", "rank": 37, "score": 0.8532329797744751}, {"content": "Title: Protective role of Bruton tyrosine kinase inhibitors in patients with chronic lymphocytic leukaemia and COVID\u201019 Content: Severe cases of coronavirus disease 2019 (COVID-19) are usually accompanied by an exuberant immune response comparable to cytokine release syndrome (CRS), with markedly elevated serum levels of proinflammatory cytokines which are thought to be a major drivers of morbidity and mortality for these patients (Huang, et al 2020). Several drugs with anti-inflammatory properties (tocilizumab, siltuximab, sarilumab, anakinra, among others) have been suggested as adjuncts to supportive care in the management of COVID-19, and several clinical trials are underway (NCT04315298, NCT04317092, NCT04306705).", "qid": 46, "docid": "2fyouaol", "rank": 38, "score": 0.8530223369598389}, {"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": 39, "score": 0.8526257276535034}, {"content": "Title: COVID-19: An Update about the Discovery Clinical Trial Content: Finding efficacious and safe treatments for COVID-19 emerges as a crucial need in order to control the spread of the pandemic. Whereas plasma therapy attracts much interest, the European project Discovery focuses on the potentialities of small molecules like remdesivir, the combination of lopinavir/ritonavir, hydroxychloroquine, and chloroquine. Results recently published on the clinical evaluation of those drugs are compiled in this brief report, although complete data are still impatiently awaited.", "qid": 46, "docid": "sqrbj5r4", "rank": 40, "score": 0.8525429964065552}, {"content": "Title: Sofosbuvir as Repurposed Antiviral Drug Against COVID-19: Why Were we Convinced to Evaluate the Drug in a Registered/Approved Clinical Trial? Content: COVID-19 is a devastating global pandemic around the world. While the majority of infected cases appear mild, in some cases individuals present respiratory complications with possible serious lung damage. There are no specific treatments for COVID-19 as yet, though a number are under evaluation, including experimental antivirals. Sofosbuvir, the clinically approved anti-hepatitis C virus (HCV) drug, is also capable of suppressing other families of positive-strand RNA viruses; Flaviviridae and Togaviridae. Coronaviruses are a family of positive-strand RNA viruses with conserved polymerase, so SARS-CoV-2 RdRp is very likely to be effectively inhibited by sofosbuvir. More importantly, sofosbuvir is safe and well tolerated at 400 mg daily in a 24 week therapeutic regimen. Sofosbuvir active metabolite, however, shows an extremely high intracellular stability So, it is hypothesized that SARS-CoV-2 infection could also be susceptible to sofosbuvir and we were convinced to design and run a clinical trial to evaluate the effect of sofosbuvir 400 mg (in combination with velpatasvir 100 mg, as add-on treatment, in addition to standard of care) on the COVID-19. However, we believe that this manuscript/correspondence should be made available to the international scientific community as soon as possible, with the help of this esteemed journal.", "qid": 46, "docid": "mhfncx8h", "rank": 41, "score": 0.852268636226654}, {"content": "Title: Sofosbuvir as Repurposed Antiviral Drug Against COVID-19: Why Were We Convinced to Evaluate the Drug in a Registered/Approved Clinical Trial? Content: COVID-19 is a devastating global pandemic around the world. While the majority of infected cases appear mild, in some cases individuals present respiratory complications with possible serious lung damage. There are no specific treatments for COVID-19 as yet, though a number are under evaluation, including experimental antivirals. Sofosbuvir, the clinically approved anti-hepatitis C virus (HCV) drug, is also capable of suppressing other families of positive-strand RNA viruses; Flaviviridae and Togaviridae. Coronaviruses are a family of positive-strand RNA viruses with conserved polymerase, so SARS-CoV-2 RdRp is very likely to be effectively inhibited by sofosbuvir. More importantly, sofosbuvir is safe and well tolerated at 400 mg daily in a 24 week therapeutic regimen. Sofosbuvir active metabolite, however, shows an extremely high intracellular stability So, it is hypothesized that SARS-CoV-2 infection could also be susceptible to sofosbuvir and we were convinced to design and run a clinical trial to evaluate the effect of sofosbuvir 400 mg (in combination with velpatasvir 100 mg, as add-on treatment, in addition to standard of care) on the COVID-19. However, we believe that this manuscript/correspondence should be made available to the international scientific community as soon as possible, with the help of this esteemed journal.", "qid": 46, "docid": "aq6fs1ds", "rank": 42, "score": 0.852268636226654}, {"content": "Title: Efficacy and safety of corticosteroids in COVID-19 based on evidence for COVID-19, other coronavirus infections, influenza, community-acquired pneumonia and acute respiratory distress syndrome: a systematic review and meta-analysis. Content: BACKGROUND Very little direct evidence exists on use of corticosteroids in patients with coronavirus disease 2019 (COVID-19). Indirect evidence from related conditions must therefore inform inferences regarding benefits and harms. To support a guideline for managing COVID-19, we conducted systematic reviews examining the impact of corticosteroids in COVID-19 and related severe acute respiratory illnesses. METHODS We searched standard international and Chinese biomedical literature databases and prepublication sources for randomized controlled trials (RCTs) and observational studies comparing corticosteroids versus no corticosteroids in patients with COVID-19, severe acute respiratory syndrome (SARS) or Middle East respiratory syndrome (MERS). For acute respiratory distress syndrome (ARDS), influenza and community-acquired pneumonia (CAP), we updated the most recent rigorous systematic review. We conducted random-effects meta-analyses to pool relative risks and then used baseline risk in patients with COVID-19 to generate absolute effects. RESULTS In ARDS, according to 1 small cohort study in patients with COVID-19 and 7 RCTs in non-COVID-19 populations (risk ratio [RR] 0.72, 95% confidence interval [CI] 0.55 to 0.93, mean difference 17.3% fewer; low-quality evidence), corticosteroids may reduce mortality. In patients with severe COVID-19 but without ARDS, direct evidence from 2 observational studies provided very low-quality evidence of an increase in mortality with corticosteroids (hazard ratio [HR] 2.30, 95% CI 1.00 to 5.29, mean difference 11.9% more), as did observational data from influenza studies. Observational data from SARS and MERS studies provided very low-quality evidence of a small or no reduction in mortality. Randomized controlled trials in CAP suggest that corticosteroids may reduce mortality (RR 0.70, 95% CI 0.50 to 0.98, 3.1% lower; very low-quality evidence), and may increase hyperglycemia. INTERPRETATION Corticosteroids may reduce mortality for patients with COVID-19 and ARDS. For patients with severe COVID-19 but without ARDS, evidence regarding benefit from different bodies of evidence is inconsistent and of very low quality.", "qid": 46, "docid": "ivm2d5rl", "rank": 43, "score": 0.8515725135803223}, {"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": 46, "docid": "a0drmmf7", "rank": 44, "score": 0.851312518119812}, {"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": 46, "docid": "4el6qq3n", "rank": 45, "score": 0.851312518119812}, {"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": 46, "docid": "9ryu9ady", "rank": 46, "score": 0.8511338233947754}, {"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": 46, "docid": "z91sksce", "rank": 47, "score": 0.8507006168365479}, {"content": "Title: Effectiveness and Safety of Glucocorticoids to Treat COVID-19: A Rapid Review and Meta-Analysis Content: Background: Glucocorticoids are widely used in the treatment of various pulmonary inflammatory diseases, but they are also often accompanied by significant adverse reactions. Published guidelines point out that low dose and short duration systemic glucocorticoid therapy may be considered for patients with rapidly progressing COVID-19 while the evidence is still limited. Methods: We comprehensively searched electronic databases and supplemented the screening by conducting a manual search. We included RCTs and cohort studies evaluating the effectiveness and safety of glucocorticoids in children and adults with COVID-19, SARS and MERS, and conducted meta-analyses of the main indicators that were identified in the studies. Results: Our search retrieved 23 studies, including one RCT and 22 cohort studies, with a total of 13,815 patients. In adults with COVID-19, the use of systemic glucocorticoid did not reduce mortality (RR=2.00, 95% CI: 0.69 to 5.75, I 2=90.9%) or the duration of lung inflammation (WMD=-1 days, 95% CI: -2.91 to 0.91), while a significant reduction was found in the duration of fever (WMD=-3.23 days, 95% CI: -3.56 to -2.90). In patients with SARS, glucocorticoids also did not reduce the mortality (RR=1.52, 95% CI: 0.89 to 2.60, I2=84.6%), duration of fever (WMD=0.82 days, 95% CI: -2.88 to 4.52, I2=97.9%) or duration of lung inflammation absorption (WMD=0.95 days, 95% CI: -7.57 to 9.48, I2=94.6%). The use of systemic glucocorticoid therapy prolonged the duration of hospital stay in all patients (COVID-19, SARS and MERS). Conclusions: Glucocorticoid therapy was found to reduce the duration of fever, but not mortality, duration of hospitalization or lung inflammation absorption. Long-term use of high-dose glucocorticoids increased the risk of adverse reactions such as coinfections, so routine use of systemic glucocorticoids for patients with COVID-19 cannot be recommend. Keywords: COVID-19; glucocorticoids; meta-analysis; rapid review", "qid": 46, "docid": "935r7w01", "rank": 48, "score": 0.8505746126174927}, {"content": "Title: Is the anti-filarial drug diethylcarbamazine useful to treat COVID-19 ? Content: SARS-CoV-2 virus has resulted in a devastating pandemic of COVID-19. Exploring compounds that could offer a breakthrough in treatment is the need of the hour. Re-positioning cheap, freely available and safe drugs is a priority. The paper proposes evidence for the potential use of diethylcarbamazine (DEC) in the treatment of COVID-19. DEC has inhibitory effects on arachidonic acid metabolism to prostaglandins, little known anti-viral effects on animal retroviruses and demonstrated anti-inflammatory actions in animal models of lung inflammation indicating the need to explore this hypothesis further. We believe this is the first time DEC is being proposed to treat COVID-19.", "qid": 46, "docid": "sdih33mv", "rank": 49, "score": 0.8505464196205139}, {"content": "Title: Three Novel Prevention, Diagnostic and Treatment Options for COVID-19 Urgently Necessitating Controlled Randomized Trials Content: PURPOSE: Asymptomatic or minimally symptomatic infection with COVID-19 can result in silent transmission to large numbers of individuals, resulting in expansion of the pandemic with a global increase in morbidity and mortality. New ways of screening the general population for COVID-19 are urgently needed along with novel effective prevention and treatment strategies. HYPOTHESIS: A hypothetical three-part prevention, diagnostic, and treatment approach based on an up-to-date scientific literature review for COVID- 19 is proposed. Regarding diagnosis, a validated screening questionnaire and digital app for COVID-19 could help identify individuals who are at risk of transmitting the disease, as well as those at highest risk for poor clinical outcomes. Global implementation and online tracking of vital signs and scored questionnaires that are statistically validated would help health authorities properly allocate essential health care resources to test and isolate those at highest risk for transmission and poor outcomes. Second, regarding prevention, no validated protocols except for physical distancing, hand washing, and isolation exist, and recently ivermectin and the antimalarial drugs chloroquine and hydroxychloroquine has been published to have anti-viral properties against COVID-19. A randomized trial of ivermectin or hydroxychloroquine alone, and/or nutraceuticals that have been published to support immune function including Vitamin C, zinc, and immunomodulatory supplements (3,6 Beta glucan) could be beneficial in preventing transmission or lessening symptomatology but requires statistical validation. Third, concerning treatment, COVID-19 induced inflammation and \u201ccytokine storm syndrome\u201d with hemophagocytic lymphohistiocytosis (HLH)/Macrophage Activation Syndrome (MAS) have resulted in extreme morbidity and mortality in those with certain comorbidities, secondary to \u201cacute respiratory distress syndrome\u201d (ARDS) and multiorgan dysfunction with disseminated intravascular coagulation (DIC). Deficiency in red blood cell, serum and alveolar glutathione has been published in the medical literature for ARDS, as well as viral and bacterial pneumonias, resulting from increased levels of free radical/oxidative stress. A randomized controlled trial of blocking NFKappa B and cytokine formation using glutathione precursors (N-acetyl-cysteine [NAC] and alpha lipoic acid) and PO/IV glutathione should be performed, along with an evaluation of Nrf2 activators (curcumin, sulforaphane glucosinolate) which have been scientifically proven to lower inflammation. Since high mortality rates from sepsis induced DIC due to COVID 19 infection has also been associated with thrombotic events and elevated levels of D-dimer, randomized controlled trials of using anticoagulant therapy with heparin is urgently required. This is especially important in patients on ventilators who have met certain sepsis induced coagulopathy (SIC) criteria. The use of acetazolamide with or without sildenafil also needs to be explored with or without heparin, since increased oxygen delivery to vital organs through prevention of thrombosis/pulmonary emboli along with carbonic anhydrase inhibition may help increase oxygenation and prevent adverse clinical outcomes. CONCLUSION AND IMPLICATIONS: a three-part prevention, diagnostic, and treatment plan is proposed for addressing the severe complications of COVID-19. Digital monitoring of symptoms to clinically diagnose early exposure and response to treatment; prevention with hydroxychloroquine and/or ivermetin as well as nutritional therapies that support a healthy immune response; treatment with anti-inflammatory therapies that block NFKappaB and activate Nrf2 pathways, as well as novel therapies that address COVID-19 pneumonia and ARDS with DIC including anticoagulation and/ or novel respiratory therapies with or without acetazolamide and sildenafil. These three broad-based interventions urgently need to be subjected to randomized, controlled trials.", "qid": 46, "docid": "39saijjp", "rank": 50, "score": 0.8497982025146484}, {"content": "Title: Corticosteroid therapy in ENT in the context of the COVID-19 pandemic Content: ABSTRACT This consensus statement about the indications and modalities of corticosteroid treatment in the context of the COVID-19 pandemic was jointly written by experts from the French Association of Otology and Oto-Neurology (AFON) and from the French Society of Otorhinolaryngology, Head and Neck Surgery (SFORL). There is currently not enough data in favour of danger or benefit from corticosteroids in COVID-19, so until this matter is resolved it is advisable to limit their indications to the most serious clinical pictures for which it is well established that this type of treatment has a positive impact on the progression of symptoms. In Grade V and VI Bell's palsy according to the House-Brackmann grading system, a week\u2019s course of oral corticosteroids is recommended. Corticosteroid therapy is also recommended in cases of sudden hearing loss of more than 60 dB, either in the form of intratympanic injections or a week\u2019s course of oral medication. In rhinology, there is no indication for systemic corticosteroid therapy in the current situation. However, patients are advised to continue with their local corticosteroid therapy in the form of a nasal spray or by inhalation. Treatments with corticosteroid nasal sprays can still be prescribed if there is no alternative.", "qid": 46, "docid": "wtnol2tl", "rank": 51, "score": 0.8497965931892395}, {"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": 46, "docid": "yoo3ic2c", "rank": 52, "score": 0.8497916460037231}, {"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": 46, "docid": "6cm1vp7h", "rank": 53, "score": 0.8497916460037231}, {"content": "Title: Treatment of SARS-CoV-2 with high dose oral zinc salts: A report on four patients Content: Coronavirus 2019 (COVID-19) is a pandemic with substantial mortality and no accepted therapy. We report here on four consecutive outpatients with clinical characteristics (CDC case definition) of and/or laboratory-confirmed COVID-19 who were treated with high dose zinc salt oral lozenges. All four patients experienced significant improvement in objective and symptomatic disease measures after one day of high dose therapy suggesting that zinc therapy was playing a role in clinical recovery. A mechanism for zinc's effects is proposed based on previously published studies on SARS- CoV-1, and randomized controlled trials assessing zinc shortening of common cold duration. The limited sample size and study design preclude a definitive statement about the effectiveness of zinc as a treatment for COVID-19 but suggest the variables to be addressed to confirm these initial findings in future trials.", "qid": 46, "docid": "rgt1h046", "rank": 54, "score": 0.8493056297302246}, {"content": "Title: Treatment of SARS-CoV-2 with high dose oral zinc salts: A report on four patients. Content: Coronavirus 2019 (COVID-19) is a pandemic with substantial mortality and no accepted therapy. We report here on four consecutive outpatients with clinical characteristics (CDC case definition) of and/or laboratory-confirmed COVID-19 who were treated with high dose zinc salt oral lozenges. All four patients experienced significant improvement in objective and symptomatic disease measures after one day of high dose therapy suggesting that zinc therapy was playing a role in clinical recovery. A mechanism for zinc's effects is proposed based on previously published studies on SARS- CoV-1, and randomized controlled trials assessing zinc shortening of common cold duration. The limited sample size and study design preclude a definitive statement about the effectiveness of zinc as a treatment for COVID-19 but suggest the variables to be addressed to confirm these initial findings in future trials.", "qid": 46, "docid": "w3jmi043", "rank": 55, "score": 0.8493056297302246}, {"content": "Title: Target Virus or Target Ourselves for COVID-19 Drugs Discovery?-Lessons learned from anti-influenzas virus therapies Content: The COVID-19 pandemic, after it was reported in December 2019, is a highly contagious and now spreading to over 190 countries, causing a severe public health burden. Currently, there is no vaccine or specific drug to treat COVID-19, which is caused by a novel coronavirus, SARS-2-CoV. For this emergency, the FDA has approved Remdesivir and Hydroxychloroquine for treatment of COVID-19 as Emergency Use Authorization. However, even after this pandemic, COVID-19 may still have a chance to come back. Therefore, we need to come out with new strategies for drug discovery for combating COVID-19 in the future.", "qid": 46, "docid": "dblg9wfk", "rank": 56, "score": 0.8492546677589417}, {"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": 46, "docid": "4ehhtkfn", "rank": 57, "score": 0.8489965200424194}, {"content": "Title: Emerging pharmacotherapies for COVID-19 Content: Novel Corona-virus Disease 2019 (nCOVID 19) is caused by a novel virulent corona virus and leads to potentially fatal virulent pneumonia and severe respiratory distress syndrome. It was initially declared as public health emergency if international concern by WHO followed by Pandemic on 12th March 2020. As of 10th April 2020, more than 1.5 million people are affected globally with around 95,000 deaths. Vaccines for this deadly virus are currently under development and many drugs used for other indications have been repurposed and investigated for prophylaxis and treatment of COVID 19. As per SOLIDARITY trial by WHO, some of the most promising candidates include chloroquine phosphate and hydroxychloroquine which are anti-malarial medications, Remdesivir, Lopinavir-Ritonavir combination with or without interferon which are anti-HIV drugs and convalescent plasma therapy. The current evidence of efficacy and ongoing research has been elaborated in the article. Besides, there has been evidence regarding inflammatory pathogenesis of this virus leading to cytokine storm in susceptible individuals. Thus, anti-proinflammatory cytokine drugs like Anakinra and Tocilizumab are undergoing multiple trials and some results are encouraging. Similarly, use of anti-inflammatory cytokines like IL-37 and IL-38 is hypothesised to be useful and is under research. The situation is still evolving and hence there is yet no definitive therapy but to conclude the use of repurposed medications can be a boon till a definitive therapy and vaccines are developed.", "qid": 46, "docid": "ydbp79wa", "rank": 58, "score": 0.8487585783004761}, {"content": "Title: Three novel prevention, diagnostic, and treatment options for COVID-19 urgently necessitating controlled randomized trials Content: PURPOSE: Asymptomatic or minimally symptomatic infection with COVID-19 can result in silent transmission to large numbers of individuals, resulting in expansion of the pandemic with a global increase in morbidity and mortality. New ways of screening the general population for COVID-19 are urgently needed along with novel effective prevention and treatment strategies. HYPOTHESIS: A hypothetical three-part prevention, diagnostic, and treatment approach based on an up-to-date scientific literature review for COVID-19 is proposed. Regarding diagnosis, a validated screening questionnaire and digital app for COVID-19 could help identify individuals who are at risk of transmitting the disease, as well as those at highest risk for poor clinical outcomes. Global implementation and online tracking of vital signs and scored questionnaires that are statistically validated would help health authorities properly allocate essential health care resources to test and isolate those at highest risk for transmission and poor outcomes. Second, regarding prevention, no validated protocols except for physical distancing, hand washing, and isolation exist, and recently ivermectin has been published to have anti-viral properties against COVID-19. A randomized trial of ivermectin, and/or nutraceuticals that have been published to support immune function including glutathione, vitamin C, zinc, and immunomodulatory supplements (3,6 Beta glucan) could be beneficial in preventing transmission or lessening symptomatology but requires statistical validation. Third, concerning treatment, COVID-19 induced inflammation and \"cytokine storm syndrome\" with hemophagocytic lymphohistiocytosis (HLH)/Macrophage Activation Syndrome (MAS) have resulted in extreme morbidity and mortality in those with certain comorbidities, secondary to \"acute respiratory distress syndrome\" (ARDS) and multiorgan dysfunction with disseminated intravascular coagulation (DIC). Deficiency in red blood cell, serum and alveolar glutathione has been published in the medical literature for ARDS, as well as viral and bacterial pneumonias, resulting from increased levels of free radical/oxidative stress. A randomized controlled trial of blocking NF-&#954;B and cytokine formation using glutathione precursors (N-acetyl-cysteine [NAC] and alpha lipoic acid) and PO/IV glutathione with associated anti-viral effects should be performed, along with an evaluation of Nrf2 activators (curcumin, sulforaphane glucosinolate) which have been scientifically proven to lower inflammation. Since high mortality rates from sepsis induced DIC due to COVID-19 infection has also been associated with thrombotic events and elevated levels of D-dimer, randomized controlled trials of using anticoagulant therapy with heparin is urgently required. This is especially important in patients on ventilators who have met certain sepsis induced coagulopathy (SIC) criteria. The use of acetazolamide with or without sildenafil also needs to be explored with or without heparin, since increased oxygen delivery to vital organs through prevention of thrombosis/pulmonary emboli along with carbonic anhydrase inhibition may help increase oxygenation and prevent adverse clinical outcomes. CONCLUSION AND IMPLICATIONS: A three-part prevention, diagnostic, and treatment plan is proposed for addressing the severe complications of COVID-19. Digital monitoring of symptoms to clinically diagnose early exposure and response to treatment; prevention with ivermectin as well as nutritional therapies that support a healthy immune response; treatment with anti-inflammatory therapies that block NF-&#954;B and activate Nrf2 pathways, as well as novel therapies that address COVID-19 pneumonia and ARDS with DIC including anticoagulation and/or novel respiratory therapies with or without acetazolamide and sildenafil. These three broad-based interventions urgently need to be subjected to randomized, controlled trials.", "qid": 46, "docid": "k1zlmd2k", "rank": 59, "score": 0.8486899137496948}, {"content": "Title: Is the anti-filarial drug diethylcarbamazine useful to treat COVID-19? Content: The SARS-CoV-2 virus has resulted in a devastating pandemic of COVID-19. Exploring compounds that could offer a breakthrough in treatment is the need of the hour. Re-positioning cheap, freely available and safe drugs is a priority. The paper proposes evidence for the potential use of diethylcarbamazine (DEC) in the treatment of COVID-19. DEC has inhibitory effects on arachidonic acid metabolism to prostaglandins, little known anti-viral effects on animal retroviruses and demonstrated anti-inflammatory actions in animal models of lung inflammation indicating the need to explore this hypothesis further. We believe this is the first time DEC is being proposed to treat COVID-19.", "qid": 46, "docid": "u3n60qjw", "rank": 60, "score": 0.8486807346343994}, {"content": "Title: Covid-19 and diabetes mellitus: unveiling the interaction of two pandemics Content: A novel RNA betacoronavirus causing coronavirus disease 2019 (Covid-19) has now been declared pandemic disease by WHO. Guo et al published the first report of biochemical features in patients with diabetes and the further risk that this disease can determine to the progression of Covid-19. Among different cytokines found significantly higher in patients with diabetes compared to those without, Interleukin-6 (IL-6), which is already increased in conditions of chronic inflammation, may play a more deleterious role in Covid-19 infection. Targeting the overexpression of Il-6 effects with a monoclonal antibody against IL-6 receptor or using Janus Kinase inhibitors may be particularly helpful for treatment of Covid-19 pneumonia in diabetes.", "qid": 46, "docid": "hjsy9rmc", "rank": 61, "score": 0.8482575416564941}, {"content": "Title: Nebulized Lidocaine in COVID-19, An Hypothesis. Content: Coronavirus Diseases-2019 (COVID-19) has caused a large global outbreak and has been declared as a pandemic by the World Health Organization (WHO). It has been proposed that COVID-19-related hyperinflammation and dysregulated immune response might play a critical role in developing a cytokine storm which usually progresses to a life-threatening acute lung injury or acute respiratory distress syndrome in infected individuals. Lidocaine, a local analgesic and anti-arrhythmic, is known for its anti-inflammatory actions and has been used to reduce cough and improve respiratory symptoms in severe asthmatic patients. It has a demonstrated safety profile. It is proposed that nebulized lidocaine might be beneficial in reducing cytokines, protecting patients' lungs and improving outcomes in COVID-19 patients when administered via inhalation as an adjunctive treatment for severe respiratory symptoms in patients fighting the novel Coronavirus. Additional investigation is warranted.", "qid": 46, "docid": "gkb6c24f", "rank": 62, "score": 0.8482226133346558}, {"content": "Title: Nebulized Lidocaine in COVID-19, An Hypothesis Content: Coronavirus Diseases-2019 (COVID-19) has caused a large global outbreak and has been declared as a pandemic by the World Health Organization (WHO). It has been proposed that COVID-19-related hyperinflammation and dysregulated immune response might play a critical role in developing a cytokine storm which usually progresses to a life-threatening acute lung injury or acute respiratory distress syndrome in infected individuals. Lidocaine, a local analgesic and anti-arrhythmic, is known for its anti-inflammatory actions and has been used to reduce cough and improve respiratory symptoms in severe asthmatic patients. It has a demonstrated safety profile. It is proposed that nebulized lidocaine might be beneficial in reducing cytokines, protecting patients' lungs and improving outcomes in COVID-19 patients when administered via inhalation as an adjunctive treatment for severe respiratory symptoms in patients fighting the novel Coronavirus. Additional investigation is warranted.", "qid": 46, "docid": "l7n23o45", "rank": 63, "score": 0.848222553730011}, {"content": "Title: Associations between COVID-19 infection, tobacco smoking and nicotine use, common respiratory conditions and inhaled corticosteroids: a prospective QResearch-Case Mix Programme data linkage study January-May 2020 Content: Introduction Epidemiological and laboratory research seems to suggest that smoking and perhaps nicotine alone could reduce the severity of COVID-19. Likewise, there is some evidence that inhaled corticosteroids could also reduce its severity, opening the possibility that nicotine and inhaled steroids could be used as treatments. Methods In this prospective cohort study, we will link English general practice records from the QResearch database to Public Health England's database of SARS-CoV-2 positive tests, Hospital Episode Statistics, admission to intensive care units, and death from COVID-19 to identify our outcomes: hospitalisation, ICU admission, and death due to COVID. Using Cox regression, we will perform sequential adjustment for potential confounders identified by separate directed acyclic graphs to: 1. Assess the association between smoking and COVID-19 disease severity, and how that changes on adjustment for smoking-related comorbidity. 2. More closely characterise the association between smoking and severe COVID-19 disease by assessing whether the association is modified by age (as a proxy of length of smoking), gender, ethnic group, and whether people have asthma or COPD. 3. Assess for evidence of a dose-response relation between smoking intensity and disease severity, which would help create a case for causality. 4. Examine the association between former smokers who are using NRT or are vaping and disease severity. 5. Examine whether pre-existing respiratory disease is associated with severe COVID-19 infection. 6. Assess whether the association between chronic obstructive pulmonary disease (COPD) and asthma and COVID-19 disease severity is modified by age, gender, ethnicity, and smoking status. 7. Assess whether the use of inhaled corticosteroids is associated with severity of COVID-19 disease. 8. To assess whether the association between use of inhaled corticosteroids and severity of COVID-19 disease is modified by the number of other airways medications used (as a proxy for severity of condition) and whether people have asthma or COPD. Conclusions This representative population sample will, to our knowledge, present the first comprehensive examination of the association between smoking, nicotine use without smoking, respiratory disease, and severity of COVID-19. We will undertake several sensitivity analyses to examine the potential for bias in these associations.", "qid": 46, "docid": "hlqqkn31", "rank": 64, "score": 0.8481576442718506}, {"content": "Title: Emerging pharmacotherapies for COVID-19 Content: Novel Corona-virus Disease 2019 (nCOVID 19) is caused by a novel virulent corona virus and leads to potentially fatal virulent pneumonia and severe respiratory distress syndrome. It was initially declared as public health emergency if international concern by WHO followed by Pandemic on 12(th) March 2020. As of 10(th) April 2020, more than 1.5 million people are affected globally with around 95000 deaths. Vaccines for this deadly virus are currently under development and many drugs used for other indications have been repurposed and investigated for prophylaxis and treatment of COVID 19. As per SOLIDARITY trial by WHO, some of the most promising candidates include chloroquine phosphate and hydroxychloroquine which are anti-malarial medications, Remdesivir, Lopinavir-Ritonavir combination with or without interferon which are anti-HIV drugs and convalescent plasma therapy. The current evidence of efficacy and ongoing research has been elaborated in the article. Besides, there has been evidence regarding inflammatory pathogenesis of this virus leading to cytokine storm in susceptible individuals. Thus, anti-proinflammatory cytokine drugs like Anakinra and Tocilizumab are undergoing multiple trials and some results are encouraging. Similarly, use of anti-inflammatory cytokines like IL-37 and IL-38 is hypothesised to be useful and is under research. The situation is still evolving and hence there is yet no definitive therapy but to conclude the use of repurposed medications can be a boon till a definitive therapy and vaccines are developed.", "qid": 46, "docid": "q6px4r3j", "rank": 65, "score": 0.8481088876724243}, {"content": "Title: Consensus statement. Corticosteroid therapy in ENT in the context of the COVID-19 pandemic Content: This consensus statement about the indications and modalities of corticosteroid treatment in the context of the COVID-19 pandemic was jointly written by experts from the French Association of Otology and Oto-Neurology (AFON) and from the French Society of Otorhinolaryngology, Head and Neck Surgery (SFORL). There is currently not enough data in favour of danger or benefit from corticosteroids in COVID-19, so until this matter is resolved it is advisable to limit their indications to the most serious clinical pictures for which it is well established that this type of treatment has a positive impact on the progression of symptoms. In Grade V and VI Bell's palsy according to the House-Brackmann grading system, a week's course of oral corticosteroids is recommended. Corticosteroid therapy is also recommended in cases of sudden hearing loss of more than 60dB, either in the form of intratympanic injections or a week's course of oral medication. In rhinology, there is no indication for systemic corticosteroid therapy in the current situation. However, patients are advised to continue with their local corticosteroid therapy in the form of a nasal spray or by inhalation. Treatments with corticosteroid nasal sprays can still be prescribed if there is no alternative. Finally, systemic or local corticosteroid therapy is not indicated for bacterial ENT infections.", "qid": 46, "docid": "ekvyyo5k", "rank": 66, "score": 0.8477725386619568}, {"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": 46, "docid": "0u4ar3b5", "rank": 67, "score": 0.8474924564361572}, {"content": "Title: Potential specific therapies in COVID-19 Content: COVID-19 has grown into a global pandemic that has strained healthcare throughout the world. There is a sense of urgency in finding a cure for this deadly virus. In this study, we reviewed the empiric options used in common practice for COVID-19, based on the literature available online, with an emphasis on human experiences with these treatments on severe acute respiratory syndrome-associated coronavirus (SARS-COV-1) and other viruses. Convalescent blood products are the most promising potential treatment for use in COVID-19. The use of chloroquine or hydroxychloroquine (HCQ), remdesivir, and tocilizumab are some of the other promising potential therapies; however, they are yet to be tested in randomized clinical trials (RCTs). The use of lopinavir-ritonavir did not prove beneficial in a large RCT. The use of corticosteroids should be avoided in COVID-19 pneumonia unless used for other indications, based on the suggestion of harm in patients with SARS-COV-1 and Middle Eastern Respiratory Syndrome (MERS) infection. The reviews of this paper are available via the supplemental material section.", "qid": 46, "docid": "agdec3vz", "rank": 68, "score": 0.8473861217498779}, {"content": "Title: Medical Management of COVID-19: Evidence and Experience Content: Coronavirus disease 2019 is caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), and this infectious disease is termed COVID-19 in short. On a global scale, as of June 1, 2020, the World Health Organization (WHO) published statistics of 6,057,853 infected patients and 371,166 deaths worldwide. Despite reported observational data about the experimental use of certain drugs, there is no conclusively proven curative therapy for COVID-19 as of now; however, remdesivir received emergency use authorization (EUA) by the Food and Drug Administration (FDA) recently for use in patients hospitalized with COVID-19. There are several ongoing clinical trials related to the pharmacological choices of therapy for COVID-19 patients; however, drug trials related to observational studies so far have yielded mixed results and therefore have created a sense of confusion among healthcare professionals (HCPs). In this review article, we seek to collate and provide a summary of treatment strategies for COVID-19 patients with a variable degree of illness and discuss pharmacologic and other therapies intended to be used either as experimental medicine/therapy or as part of supportive care in complicated cases of COVID-19.", "qid": 46, "docid": "svnz1ghh", "rank": 69, "score": 0.8472650647163391}, {"content": "Title: Drug repurposing clinical trials in the search for life-saving COVID-19 therapies;research targets and methodological and ethical issues Content: Introduction: So far, there is no vaccine, nor are there effective drugs to treat COVID-19, an emerging viral respiratory infection deadlier than influenza Objective: To take a snapshot picture of planned and ongoing clinical research addressing drugs potentially useful for treating SAR-CoV-2 infections Method: A search was conducted (20 April 2020) in an international registry of clinical studies (https://ClinicalTrials gov, US NIH) After excluding observational studies and other interventions that fell outside the scope of this study, 294 research protocols (out of 516 retrieved protocols) were selected for analysis Results: Of 294 included trials, 249 were Randomized Controlled Trials (RCT), 118 of which were double-, triple- or quadruple-blinded studies The interventions (drug therapies) were compared with \"standard-of-care\" (SOC) or with the placebo plus SOC, or yet with presumed \"active\" comparators RCT focused on the primary treatment of the disease (inhibitors of viral replication) or on the therapy for resolution of hyperinflammation in pneumonia/Acute Respiratory Distress Syndrome (ARDS) and thromboembolism associated with SARS-CoV-2 The trials found in the database involve existing antiviral compounds and drugs with multiple modes of antiviral action Antiparasitic drugs, which inhibited viral replication in cell-culture assays, are being tested as well Regarding the adjunctive immunomodulatory, anti-inflammatory and antithrombotic therapies, a number of drugs with distinct pharmacological targets are under investigation in trials enrolling patients with severe COVID-19 Conclusions: Although many clinical studies of drugs for COVID-19 are planned or in progress, only a minority of them are sufficiently large, randomized and placebo-controlled trials with masking and concealment of allocation Owing to methodological limitations, only a few clinical trials found in the registry are likely to yield robust evidence of effectiveness and safety of drugs repurposable for COVID-19", "qid": 46, "docid": "a4oibkt9", "rank": 70, "score": 0.8471941947937012}, {"content": "Title: Effects of methylprednisolone use on viral genomic nucleic acid negative conversion and CT imaging lesion absorption in COVID-19 patients under 50 years old Content: The use of corticosteroids has been controversial in viral pneumonia. In most cases, application of methylprednisolone in severe and critical viral pneumonia patients can quickly alleviate the symptoms of dyspnea and prevent disease progression. However, some scholars have confirmed that corticosteroids delayed the body's clearance of the virus. In our retrospective non-randomised study, 34 patients under 50 years old and diagnosed with coronavirus disease 2019 (COVID-19) were included, according to given methylprednisolone treatment (n = 18) or not (n = 16), they were separated into 2 groups. By comparing the clinical data we concluded that corticosteroids therapy can effectively release COVID-19 symptoms such as persistent fever and difficult breathing, improve oxygenation and prevent disease progression. However, it can prolong the negative conversion of nucleic acids. This article is protected by copyright. All rights reserved.", "qid": 46, "docid": "xq1lqjua", "rank": 71, "score": 0.8471769094467163}, {"content": "Title: Characteristics of registered clinical trials assessing treatments for COVID-19: a cross-sectional analysis Content: OBJECTIVES: The coronavirus disease 2019 (COVID-19) pandemic has prompted many initiatives to identify safe and efficacious treatments, yet little is known regarding where early efforts have focused. We aimed to characterise registered clinical trials assessing drugs or plasma treatments for COVID-19. DESIGN, SETTING AND PARTICIPANTS: Cross-sectional analysis of clinical trials for the treatment of COVID-19 that were registered in the USA or in countries contributing to the WHO's International Clinical Trials Registry Platform. Relevant trial entries of drugs or plasma were downloaded on 26 March 2020, deduplicated, verified with reviews of major medical journals and WHO websites and independently analysed by two reviewers. MAIN OUTCOMES: Trial intervention, sponsorship, critical design elements and specified outcomes RESULTS: Overall, 201 clinical trials were registered for testing the therapeutic benefits of 92 drugs or plasma, including 64 in monotherapy and 28 different combinations. Only eight (8.7%) products or combinations involved new molecular entities. The other test therapies had a wide range of prior medical uses, including as antivirals, antimalarials, immunosuppressants and oncology treatments. In 152 trials (75.7%), patients were randomised to treatment or comparator, including 55 trials with some form of blinding and 97 open-label studies. The 49 (24.4%) of trials without a randomised design included 29 single armed studies and 20 trials with some comparison group. Most trial designs featured multiple endpoints. Clinical endpoints were identified in 134 (66.7%) of trials and included COVID-19 symptoms, death, recovery, required intensive care and hospital discharge. Clinical scales were being used in 33 (16.4%) trials, most often measures of oxygenation and critical illness. Surrogate endpoints or biomarkers were studied in 88 (42.3%) of trials, primarily assays of viral load. Although the trials were initiated in more than 17 countries or regions, 100 (49.8%) were registered in China and 78 (37.8%) in the USA. Registered trials increased rapidly, with the number of registered trials doubling from 1 March to 26 March 2020. CONCLUSIONS: While accelerating morbidity and mortality from the COVID-19 pandemic has been paralleled by early and rapid clinical investigation, many trials lack features to optimise their scientific value. Global coordination and increased funding of high-quality research may help to maximise scientific progress in rapidly discovering safe and effective treatments.", "qid": 46, "docid": "k1eq4l3d", "rank": 72, "score": 0.8470752239227295}, {"content": "Title: COVID-19: An Update on the Epidemiological, Clinical, Preventive and Therapeutic Evidence and Guidelines of Integrative Chinese-Western Medicine for the Management of 2019 Novel Coronavirus Disease Content: As of 22 February 2020, more than 77662 cases of confirmed COVID-19 have been documented globally with over 2360 deaths. Common presentations of confirmed cases include fever, fatigue, dry cough, upper airway congestion, sputum production, shortness of breath, myalgia/arthralgia with lymphopenia, prolonged prothrombin time, elevated C-reactive protein, and elevated lactate dehydrogenase. The reported severe/critical case ratio is approximately 7-10% and median time to intensive care admission is 9.5-10.5 days with mortality of around 1-2% varied geographically. Similar to outbreaks of other newly identified virus, there is no proven regimen from conventional medicine and most reports managed the patients with lopinavir/ritonavir, ribavirin, beta-interferon, glucocorticoid and supportive treatment with remdesivir undergoing clinical trial. In China, Chinese medicine is proposed as a treatment option by national and provincial guidelines with substantial utilization. We reviewed the latest national and provincial clinical guidelines, retrospective cohort studies, and case series regarding the treatment of COVID-19 by add-on Chinese medicine. We have also reviewed the clinical evidence generated from SARS and H1N1 management with hypothesized mechanisms and latest in silico findings to identify candidate Chinese medicines for the consideration of possible trials and management. Given the paucity of strongly evidence-based regimens, the available data suggest that Chinese medicine could be considered as an adjunctive therapeutic option in the management of COVID-19.", "qid": 46, "docid": "hgsqd42a", "rank": 73, "score": 0.847007155418396}, {"content": "Title: COVID-19: An Update on the Epidemiological, Clinical, Preventive and Therapeutic Evidence and Guidelines of Integrative Chinese-Western Medicine for the Management of 2019 Novel Coronavirus Disease. Content: As of 22 February 2020, more than 77662 cases of confirmed COVID-19 have been documented globally with over 2360 deaths. Common presentations of confirmed cases include fever, fatigue, dry cough, upper airway congestion, sputum production, shortness of breath, myalgia/arthralgia with lymphopenia, prolonged prothrombin time, elevated C-reactive protein, and elevated lactate dehydrogenase. The reported severe/critical case ratio is approximately 7-10% and median time to intensive care admission is 9.5-10.5 days with mortality of around 1-2% varied geographically. Similar to outbreaks of other newly identified virus, there is no proven regimen from conventional medicine and most reports managed the patients with lopinavir/ritonavir, ribavirin, beta-interferon, glucocorticoid and supportive treatment with remdesivir undergoing clinical trial. In China, Chinese medicine is proposed as a treatment option by national and provincial guidelines with substantial utilization. We reviewed the latest national and provincial clinical guidelines, retrospective cohort studies, and case series regarding the treatment of COVID-19 by add-on Chinese medicine. We have also reviewed the clinical evidence generated from SARS and H1N1 management with hypothesized mechanisms and latest in silico findings to identify candidate Chinese medicines for the consideration of possible trials and management. Given the paucity of strongly evidence-based regimens, the available data suggest that Chinese medicine could be considered as an adjunctive therapeutic option in the management of COVID-19.", "qid": 46, "docid": "gizxnw4n", "rank": 74, "score": 0.847007155418396}, {"content": "Title: Associations between immune-suppressive and stimulating drugs and novel COVID-19\u2014a systematic review of current evidence Content: BACKGROUND: Cancer and transplant patients with COVID-19 have a higher risk of developing severe and even fatal respiratory diseases, especially as they may be treated with immune-suppressive or immune-stimulating drugs. This review focuses on the effects of these drugs on host immunity against COVID-19. METHODS: Using Ovid MEDLINE, we reviewed current evidence for immune-suppressing or -stimulating drugs: cytotoxic chemotherapy, low-dose steroids, tumour necrosis factor\u03b1 (TNF\u03b1) blockers, interlukin-6 (IL-6) blockade, Janus kinase (JAK) inhibitors, IL-1 blockade, mycophenolate, tacrolimus, anti-CD20 and CTLA4-Ig. RESULTS: 89 studies were included. Cytotoxic chemotherapy has been shown to be a specific inhibitor for severe acute respiratory syndrome coronavirus in in vitro studies, but no specific studies exist as of yet for COVID-19. No conclusive evidence for or against the use of non-steroidal anti-inflammatory drugs (NSAIDs) in the treatment of COVID-19 patients is available, nor is there evidence indicating that TNF\u03b1 blockade is harmful to patients in the context of COVID-19. COVID-19 has been observed to induce a pro-inflammatory cytokine generation and secretion of cytokines, such as IL-6, but there is no evidence of the beneficial impact of IL-6 inhibitors on the modulation of COVID-19. Although there are potential targets in the JAK-STAT pathway that can be manipulated in treatment for coronaviruses and it is evident that IL-1 is elevated in patients with a coronavirus, there is currently no evidence for a role of these drugs in treatment of COVID-19. CONCLUSION: The COVID-19 pandemic has led to challenging decision-making about treatment of critically unwell patients. Low-dose prednisolone and tacrolimus may have beneficial impacts on COVID-19. The mycophenolate mofetil picture is less clear, with conflicting data from pre-clinical studies. There is no definitive evidence that specific cytotoxic drugs, low-dose methotrexate for auto-immune disease, NSAIDs, JAK kinase inhibitors or anti-TNF\u03b1 agents are contraindicated. There is clear evidence that IL-6 peak levels are associated with severity of pulmonary complications.", "qid": 46, "docid": "za3qypgg", "rank": 75, "score": 0.846994936466217}, {"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": 46, "docid": "rn1t7612", "rank": 76, "score": 0.8469595909118652}, {"content": "Title: Is hydroxychloroquine beneficial for COVID-19 patients? Content: The outbreak of coronavirus disease 2019 (COVID-19) caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) was first reported in December 2019. As similar cases rapidly emerged around the world(1\u20133), the World Health Organization (WHO) declared a public health emergency of international concern on January 30, 2020 and pronounced the rapidly spreading coronavirus outbreak as a pandemic on March 11, 2020(4). The virus has reached almost all countries of the globe. As of June 3, 2020, the accumulated confirmed cases reached 6,479,405 with more than 383,013 deaths worldwide. The urgent and emergency care of COVID-19 patients calls for effective drugs, in addition to the beneficial effects of remdesivir(5), to control the disease and halt the pandemic.", "qid": 46, "docid": "hqkrer9m", "rank": 77, "score": 0.8466960191726685}, {"content": "Title: Baricitinib: A chance to treat COVID\u201019? Content: Currently, there are no approved therapies for the treatment of COVID-19. With most of the world on lockdown and the looming threat of millions of deaths, there is immense pressure to find a therapy for this disease. This article is protected by copyright. All rights reserved.", "qid": 46, "docid": "c5s447oc", "rank": 78, "score": 0.8466711044311523}, {"content": "Title: COVID-19: therapeutic approaches description and discussion Content: COVID-19 emerged in December 2019 in China, and since then, has disrupted global public health and changed economic paradigms. In dealing with the new Coronavirus, SARS-CoV-2, the world has not faced such extreme global fragility since the \"Spanish flu\" pandemic in 1918. Researchers globally are dedicating efforts to the search for an effective treatment for COVID-19. Drugs already used in a clinical setting for other pathologies have been tested as a new therapeutic approach against SARS-CoV-2, setting off a frenzy over the preliminary data of different studies. This work aims to compile and discuss the data published thus far. Despite the potential effects of some antivirals and antiparasitic against COVID-19, clinical studies must confirm real effectiveness. However, non-pharmacological approaches have proven to be the most efficient strategy to date.", "qid": 46, "docid": "vk5fdiv5", "rank": 79, "score": 0.8464384078979492}, {"content": "Title: COVID-19: therapeutic approaches description and discussion. Content: COVID-19 emerged in December 2019 in China, and since then, has disrupted global public health and changed economic paradigms. In dealing with the new Coronavirus, SARS-CoV-2, the world has not faced such extreme global fragility since the \"Spanish flu\" pandemic in 1918. Researchers globally are dedicating efforts to the search for an effective treatment for COVID-19. Drugs already used in a clinical setting for other pathologies have been tested as a new therapeutic approach against SARS-CoV-2, setting off a frenzy over the preliminary data of different studies. This work aims to compile and discuss the data published thus far. Despite the potential effects of some antivirals and antiparasitic against COVID-19, clinical studies must confirm real effectiveness. However, non-pharmacological approaches have proven to be the most efficient strategy to date.", "qid": 46, "docid": "u821twea", "rank": 80, "score": 0.8464384078979492}, {"content": "Title: Review on the global epidemiological situation and the efficacy of chloroquine and hydroxychloroquine for the treatment of COVID-19 Content: Covid-19 disease is caused by SARS-CoV-2, a virus belonging to the coronavirus family. Covid-19 is so new that there is currently no specific vaccine or treatment. Clinical trials are currently underway. In vitro tests are also being conducted to assess the efficacy of chloroquine and hydroxychloroquine for the treatment of this epidemic, which is considered a pandemic by the WHO. We note that the content of this review is dated. The information it contains is subject to change and modification as the epidemic progresses.", "qid": 46, "docid": "wbkn7yjh", "rank": 81, "score": 0.8463028073310852}, {"content": "Title: COVID-19 and heme oxygenase: novel insight into the disease and potential therapies Content: The COVID-19 pandemic needs therapies that are presently available and safe. We propose that subjects with metabolic syndrome, old age, and male gender have the greatest morbidity and mortality and have low stress proteins, in particular, low intracellular heme oxygenase (HO-1), making them particularly vulnerable to the disease. Additionally, COVID-19's heme reduction may contribute to even lower HO-1. Low-grade inflammation associated with these risk factors contributes to triggering a cytokine storm that spreads to multi-organ failure and near death. The high mortality of those treated with ventilator assistance may partially be explained by ventilator-induced inflammation. The cytoprotective and anti-inflammatory properties of HO-1 can limit the infection's damage. A paradox of COVID-19 hospital admissions data suggests that fewer cigarette-smokers are admitted compared with non-smokers in the general population. This unexpected observation may result from smoke induction of HO-1. Therapies with anti-viral properties that raise HO-1 include certain anesthetics (sevoflurane or isoflurane), hemin, estrogen, statins, curcumin, resveratrol, and melatonin. Controlled trials of these HO-1 inducers should be done in order to prevent or treat COVID-19 disease.", "qid": 46, "docid": "sabn9jwp", "rank": 82, "score": 0.8461506366729736}, {"content": "Title: COVID-19 and NSAIDS: A Narrative Review of Knowns and Unknowns Content: Concern about the appropriate role of nonsteroidal anti-inflammatory drugs (NSAIDs) in COVID-19 speculate that NSAIDs, in particular ibuprofen, may upregulate the entry point for the virus, the angiotensin-converting enzyme (ACE) 2 receptors and increase susceptibility to the virus or worsen symptoms in existing disease. Adverse outcomes with COVID-19 have been linked to cytokine storm but the most effective way to address exaggerated inflammatory response is complex and unclear. The Expert Working Group on the Commission of Human Medicines in the UK and other organizations have stated that there is insufficient evidence to establish a link between ibuprofen and susceptibility to or exacerbation of COVID-19. NSAID use must also be categorized by whether the drugs are relatively low-dose over-the-counter oral products taken occasionally versus higher-dose or parenteral NSAIDs. Even if evidence emerged arguing for or against NSAIDs in this setting, it is unclear if this evidence would apply to all NSAIDs at all doses in all dosing regimens. Paracetamol (acetaminophen) has been proposed as an alternative to NSAIDs but there are issues with liver toxicity at high doses. There are clearly COVID-19 cases where NSAIDs should not be used, but there is no strong evidence that NSAIDs must be avoided in all patients with COVID-19; clinicians must weigh these choices on an individual basis.", "qid": 46, "docid": "kxqj12z0", "rank": 83, "score": 0.8460456132888794}, {"content": "Title: COVID-19 and heme oxygenase: novel insight into the disease and potential therapies Content: The COVID-19 pandemic needs therapies that are presently available and safe. We propose that subjects with metabolic syndrome, old age, and male gender have the greatest morbidity and mortality and have low stress proteins, in particular, low intracellular heme oxygenase (HO-1), making them particularly vulnerable to the disease. Additionally, COVID-19\u2019s heme reduction may contribute to even lower HO-1. Low-grade inflammation associated with these risk factors contributes to triggering a cytokine storm that spreads to multi-organ failure and near death. The high mortality of those treated with ventilator assistance may partially be explained by ventilator-induced inflammation. The cytoprotective and anti-inflammatory properties of HO-1 can limit the infection\u2019s damage. A paradox of COVID-19 hospital admissions data suggests that fewer cigarette-smokers are admitted compared with non-smokers in the general population. This unexpected observation may result from smoke induction of HO-1. Therapies with anti-viral properties that raise HO-1 include certain anesthetics (sevoflurane or isoflurane), hemin, estrogen, statins, curcumin, resveratrol, and melatonin. Controlled trials of these HO-1 inducers should be done in order to prevent or treat COVID-19 disease.", "qid": 46, "docid": "ywu07bjk", "rank": 84, "score": 0.8458651304244995}, {"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": 46, "docid": "eu7m99a3", "rank": 85, "score": 0.845850944519043}, {"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": 46, "docid": "86h5ptxm", "rank": 86, "score": 0.8457423448562622}, {"content": "Title: Literature-based review of the drugs used for the treatment of COVID-19 Content: COVID-19 is primarily a respiratory disease caused by a newly discovered SARS-CoV-2 virus and identified in the city of Wuhan, China in December 2019. WHO has declared this disease as a pandemic, and warned other countries. Presently this has affected 216 countries, areas or territories worldwide, spreading of this disease is very fast in USA, Brazil, and Russia than in the country of its origin, China. Like other coronaviruses, this may develop respiratory tract infections in the patients range from mild to fatal illness like pneumonia and acute respiratory distress syndrome (ARDS). As of now, no effective drug, vaccine, or any procedure is available and experiments are underway. However, empirical therapy is being followed to manage and save the lives of the patients. There is a need for pharmacological alternatives to combat this deadly virus and its complications. Based on the previous experiences with similar coronavirus management and present preliminary data from uncontrolled studies, drugs like chloroquine, hydroxychloroquine, remdesivir, lopinavir/ritonavir, and favipiravir have been recommended by the researchers to manage COVID-19. This review had assessed the potential mechanisms, safety profile, availability and cost of these drugs. This review concludes that the drugs mentioned above are having different properties and act differently in combating the COVID-19 viruses. Instead of single drug, combination of antivirals with different mechanism of action may be more effective and at the same time their adverse events should not be underestimated.", "qid": 46, "docid": "sjtu4kn5", "rank": 87, "score": 0.8457248210906982}, {"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": 46, "docid": "rirzes0m", "rank": 88, "score": 0.8456090688705444}, {"content": "Title: [Farmakoter\u00e1pi\u00e1s lehetos\u00e9gek SARS-CoV-2-fertoz\u00e9s/COVID\u00ad19-betegs\u00e9g eset\u00e9n]/ Pharmacological options in treating SASR-CoV-2 infection/COVID-19 Content: There is currently no proven effective therapy for COVID-19. Here we discuss the drugs most investigated for the treatment of the disease. All the listed therapies are experimental at this stage. However, due to the severe healthcare effects of the pandemic and the potentially fatal outcome of COVID-19 patients treated in the intensive care units, their off-label use should none-the-less be considered. Orv Hetil. 2020; 161(17): 685\u00ad688.", "qid": 46, "docid": "ql3fvmrs", "rank": 89, "score": 0.8455491065979004}, {"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": 46, "docid": "s5lailkp", "rank": 90, "score": 0.8453946113586426}, {"content": "Title: Effects of Gene-Eden-VIR and Novirin on SARS-CoV: Implications for COVID-19 Content: The coronavirus (SARS-CoV-2), which causes COVID-19, is a betacoronavirus closely related to the human severe acute respiratory syndrome (SARS)-coronavirus (SARS-CoV). The recent COVID-19 outbreak created an urgent need for treatment. To expedite the development of such treatment, pharmaceutical companies and government agencies are currently testing several existing drugs for their effect on the virus. Gene-Eden-VIR and Novirin are natural, broad-spectrum, antiviral treatments proven to be safe and effective in several clinical studies. In this article, we present evidence indicating that the 5 Gene-Eden-VIR/Novirin ingredients have anti-betacoronavirus, and specifically, anti-SARS-CoV effects. We consider this evidence as a first indication of the anti-coronavirus effects of Gene-Eden-VIR/Novirin. Next, we are planning to conduct a clinical study with users of the treatments to test the effects of Gene-Eden-VIR/Novirin on individuals at risk and those infected with the virus.", "qid": 46, "docid": "82fzs0b3", "rank": 91, "score": 0.8453260660171509}, {"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": 46, "docid": "qsd49pvm", "rank": 92, "score": 0.8452255725860596}, {"content": "Title: Characteristics of registered clinical trials assessing treatments for COVID-19: a cross-sectional analysis Content: OBJECTIVES: The coronavirus disease 2019 (COVID-19) pandemic has prompted many initiatives to identify safe and efficacious treatments, yet little is known regarding where early efforts have focused. We aimed to characterise registered clinical trials assessing drugs or plasma treatments for COVID-19. DESIGN, SETTING AND PARTICIPANTS: Cross-sectional analysis of clinical trials for the treatment of COVID-19 that were registered in the USA or in countries contributing to the WHO\u2019s International Clinical Trials Registry Platform. Relevant trial entries of drugs or plasma were downloaded on 26 March 2020, deduplicated, verified with reviews of major medical journals and WHO websites and independently analysed by two reviewers. MAIN OUTCOME(S): Trial intervention, sponsorship, critical design elements and specified outcomes RESULTS: Overall, 201 clinical trials were registered for testing the therapeutic benefits of 92 drugs or plasma, including 64 in monotherapy and 28 different combinations. Only eight (8.7%) products or combinations involved new molecular entities. The other test therapies had a wide range of prior medical uses, including as antivirals, antimalarials, immunosuppressants and oncology treatments. In 152 trials (75.7%), patients were randomised to treatment or comparator, including 55 trials with some form of blinding and 97 open-label studies. The 49 (24.4%) of trials without a randomised design included 29 single armed studies and 20 trials with some comparison group. Most trial designs featured multiple endpoints. Clinical endpoints were identified in 134 (66.7%) of trials and included COVID-19 symptoms, death, recovery, required intensive care and hospital discharge. Clinical scales were being used in 33 (16.4%) trials, most often measures of oxygenation and critical illness. Surrogate endpoints or biomarkers were studied in 88 (42.3%) of trials, primarily assays of viral load. Although the trials were initiated in more than 17 countries or regions, 100 (49.8%) were registered in China and 78 (37.8%) in the USA. Registered trials increased rapidly, with the number of registered trials doubling from 1 March to 26 March 2020. CONCLUSIONS: While accelerating morbidity and mortality from the COVID-19 pandemic has been paralleled by early and rapid clinical investigation, many trials lack features to optimise their scientific value. Global coordination and increased funding of high-quality research may help to maximise scientific progress in rapidly discovering safe and effective treatments.", "qid": 46, "docid": "uqsjl4re", "rank": 93, "score": 0.8452239036560059}, {"content": "Title: Comparative Efficacy and Safety of Pharmacological Managements for Hospitalized COVID-19 Patients: Protocol for Systematic Review and Trade-Off Network Meta-Analysis. Content: Coronavirus-Disease 2019 (COVID-19) is the clinical disease caused by the SARS-CoV-2 virus, the infectious agent causing the ongoing pandemic that has impacted the lives of hundreds of millions of people in almost every nation worldwide. It is a potentially fatal disease to many vulnerable patients including the elderly and those with chronic illnesses; but because this virus is a novel one, there are no firmly established treatment protocols. Many treatment methods are being investigated worldwide, and scientific conclusions drawn from these endeavors are crucial for healthcare professionals in combating this disease. In this network meta-analysis, we focus specifically on the pharmacologic agents that have been investigated for the treatment of COVID-19 and aim to produce a comprehensive picture of the evidence from current data in order to produce relevant insights on the comparative efficacy and safety profiles of various pharmacologic agents against COVID-19.", "qid": 46, "docid": "30h09e1k", "rank": 94, "score": 0.8452059030532837}, {"content": "Title: Treatments Administered to the First 9152 Reported Cases of COVID-19: A Systematic Review Content: The emergence of SARS-CoV-2/2019 novel coronavirus (COVID-19) has created a global pandemic with no approved treatments or vaccines. Many treatments have already been administered to COVID-19 patients but have not been systematically evaluated. We performed a systematic literature review to identify all treatments reported to be administered to COVID-19 patients and to assess time to clinically meaningful response for treatments with sufficient data. We searched PubMed, BioRxiv, MedRxiv, and ChinaXiv for articles reporting treatments for COVID-19 patients published between 1 December 2019 and 27 March 2020. Data were analyzed descriptively. Of the 2706 articles identified, 155 studies met the inclusion criteria, comprising 9152 patients. The cohort was 45.4% female and 98.3% hospitalized, and mean (SD) age was 44.4 years (SD 21.0). The most frequently administered drug classes were antivirals, antibiotics, and corticosteroids, and of the 115 reported drugs, the most frequently administered was combination lopinavir/ritonavir, which was associated with a time to clinically meaningful response (complete symptom resolution or hospital discharge) of 11.7 (1.09) days. There were insufficient data to compare across treatments. Many treatments have been administered to the first 9152 reported cases of COVID-19. These data serve as the basis for an open-source registry of all reported treatments given to COVID-19 patients at www.CDCN.org/CORONA. Further work is needed to prioritize drugs for investigation in well-controlled clinical trials and treatment protocols. ELECTRONIC SUPPLEMENTARY MATERIAL: The online version of this article (10.1007/s40121-020-00303-8) contains supplementary material, which is available to authorized users.", "qid": 46, "docid": "v54xcglf", "rank": 95, "score": 0.8451828360557556}, {"content": "Title: Calcitriol, the active form of vitamin D, is a promising candidate for COVID-19 prophylaxis Content: COVID-19, the disease caused by SARS-CoV-2 (1), was declared a pandemic by the World Health Organization (WHO) in March 2020 (2). While awaiting a vaccine, several antivirals are being used to manage the disease with limited success (3, 4). To expand this arsenal, we screened 4 compound libraries: a United States Food and Drug Administration (FDA) approved drug library, an angiotensin converting enzyme-2 (ACE2) targeted compound library, a flavonoid compound library as well as a natural product library. Of the 121 compounds identified with activity against SARS-CoV-2, 7 were shortlisted for validation. We show for the first time that the active form of Vitamin D, calcitriol, exhibits significant potent activity against SARS-CoV-2. This finding paves the way for consideration of host-directed therapies for ring prophylaxis of contacts of SARS-CoV-2 patients.", "qid": 46, "docid": "sbon3aes", "rank": 96, "score": 0.8448789715766907}, {"content": "Title: Combating COVID-19 with integrated traditional Chinese and Western medicine in China Content: COVID-19, an acute respiratory infection caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), has spread throughout the world. China has achieved initial success in containing this highly infectious disease with integrated traditional Chinese and Western medicine. Current findings have shown that the Chinese protocol can reduce the incidence of severe or critical events, improve clinical recovery and help alleviate symptoms such as cough or fever. The inclusion of traditional Chinese medicine (TCM) in this protocol is based on its successful experience in fighting against pestilence. To date there are 133 ongoing registered clinical studies on TCM/integrated traditional Chinese and Western medicine. Although there are no high-quality clinical evidences, pharmacological studies have suggested that Chinese medicine is effective for COVID-19 probably through its host-directed regulation and certain antiviral effects.", "qid": 46, "docid": "kllpbcdd", "rank": 97, "score": 0.844706654548645}, {"content": "Title: Advice regarding COVID\u201019 and use of immunomodulators, in patients with severe dermatological diseases Content: Coronavirus disease 2019 (COVID-19) is the disease caused by the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), as named by the International Committee on Taxonomy of Viruses (ICTV). There is very limited evidence base to formulate specific advice for dermatology patients on immunomodulators with regards to COVID-19. The following is based on expert opinion, taking into account known risks of influenza (a negative sense single-stranded RNA virus) and other, positive-sense single-stranded, RNA virus infections (such as SARS, MERS, and the common cold). An Australia/New Zealand consensus document is in development.", "qid": 46, "docid": "nfjxp783", "rank": 98, "score": 0.8446959853172302}, {"content": "Title: Carvedilol as a potential addition to the Covid-19 therapeutic arsenal Content: No single therapeutic agent has been recognized so far as the ultimate treatment for COVID-19 and many treatment strategies rely on associating different medications with proven or hypothetical anti-viral effects Carvedilol is a third-generation beta-blocker displaying potential inhibitory properties on several key enzymatic processes and pathways involved in SARS-CoV-2 or other coronaviruses replication, in addition to the modulatory effect on several inflammatory messengers of COVID-19 These data could provide a reasonable hypothetical background for further investigating specific anti-SARS-CoV-2 effects and could pave the way for further clinical verification", "qid": 46, "docid": "lb0mnffc", "rank": 99, "score": 0.8446372747421265}, {"content": "Title: Combined IL-6 and JAK-STAT inhibition therapy in COVID-19 related sHLH, potential game changer Content: Coronavirus disease 2019 (COVID-19), caused by novel SARS-CoV-2, leads to significant mortality and morbidity with increasing evidence for inflammatory pathways being implicated in the lung damage it causes. (1,2) Severe COVID-19 patients present with increased inflammatory markers, akin to secondary haemophagocytic lymphohistiocytosis (sHLH), that have been shown to predict mortality. (3,4) There is emerging evidence for the use of an interleukin 6 (IL-6) inhibitor, tocilizumab (TCZ), for suppression of the inflammatory cytokine storm in this context. (5-7) Ruxolitinib (RXB), a JAK-STAT inhibitor, has also been shown to have proven efficacy in the treatment of sHLH. (8) Both agents appear to be promising in the fight against SARS-CoV-2 infection, (9,10) leading to an increasing number of trials being registered with their use. (11,12) Until this point, no single agent has shown a survival benefit against SARS-CoV-2 and it is possible that monotherapy may not suppress inflammation enough to overcome the COVID-19 related cytokine storm and hyper-inflammation.", "qid": 46, "docid": "3lwlt0ee", "rank": 100, "score": 0.8443624377250671}]}
{"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": 0.8677390813827515}, {"content": "Title: Coronavirus disease 2019 in children: Characteristics, antimicrobial treatment, and outcomes Content: BACKGROUND: At present, coronavirus disease 2019 (COVID-19) has spread in many countries. We conducted this study to help pediatricians understand the conditions of COVID-19 in children. METHODS: We retrospectively summarized the characteristics, treatment and outcomes of pediatric cases in Wuhan Children's Hospital which was the only designated hospital for children with COVID-19 in Hubei Province. A Cox proportional hazards regression analysis was used to evaluate factors associated with clinical outcomes. RESULTS: As of February 29, 75 children had been discharged, of which only one was has severe pneumonia and one was critical cases. Children younger than 2 years were more susceptible to COVID-19. All patients have received interferon-&#945; nebulization, and eight cases including the severe and critical cases were co-administrated ribavirin. Five patients with mild pneumonia were given arbidol. Twenty-three patients were given traditional Chinese medicine (TCM). The average length of stay (LOS) and the time of SARS-CoV-2 clearance were 10.57 and 6.39 days, respectively. None of the factors was associated with LOS or time of SARS-CoV-2 clearance. CONCLUSIONS: The severity of COVID-19 in pediatric cases were milder than adults. The efficacy of the antiviral therapy in children with COVID-19 remains to be evaluated.", "qid": 47, "docid": "t4tg0o8o", "rank": 2, "score": 0.8654477000236511}, {"content": "Title: The Epidemiology of SARS-CoV-2 in a Pediatric Healthcare Network in the United States Content: BACKGROUND: Understanding the prevalence and clinical presentation of COVID-19 in pediatric patients can help healthcare providers and systems prepare and respond to this emerging pandemic. METHODS: Retrospective case series of patients tested for SARS-CoV-2 across a pediatric healthcare network, including the clinical features and outcomes of those with positive test results. RESULTS: Of 7,256 unique children tested for SARS-CoV-2, 424 (5.8%) tested positive. Patients 18-21 years of age had the highest test positive rate (11.2%) while those 1-5 years of age had the lowest (3.9%). By race, 10.6% (226/2132) of Black children tested positive vs. 3.3% (117/3592) of White children. Of those with an indication for testing, 21.1% (371/1756) of patients with reported exposures or clinical symptoms tested positive vs. 3.8% (53/1410) of those undergoing pre-procedural or pre-admission testing. Of the 424 patients who tested positive for SARS-CoV-2, 182 (42.9%) had no comorbid medical conditions, 87 (20.5%) had asthma, 55 (13.0% had obesity, and 38 (9.0%) had mental health disorders. Overall, 52.1% had cough, 51.2% fever, and 14.6% shortness of breath. Seventy-seven (18.2%) SARS-CoV-2 positive patients were hospitalized, of which 24 (31.2%) required any respiratory support. SARS-CoV-2-targeted antiviral therapy was given to 9 patients, and immunomodulatory therapy to 18 patients. Twelve (2.8%) SARS-CoV-2 positive patients developed critical illness requiring mechanical ventilation and 2 patients required extracorporeal membrane oxygenation. Two patients died. CONCLUSIONS: In this large cohort of pediatric patients tested for SARS-CoV-2, the rate of infection was low, but varied by testing indication. The majority of cases were mild, few children had critical illness, and two patients died.", "qid": 47, "docid": "dqll7wmr", "rank": 3, "score": 0.8646862506866455}, {"content": "Title: Coronavirus Disease 2019 in Children \u2014 United States, February 12\u2013April 2, 2020 Content: As of April 2, 2020, the coronavirus disease 2019 (COVID-19) pandemic has resulted in >890,000 cases and >45,000 deaths worldwide, including 239,279 cases and 5,443 deaths in the United States (1,2). In the United States, 22% of the population is made up of infants, children, and adolescents aged <18 years (children) (3). Data from China suggest that pediatric COVID-19 cases might be less severe than cases in adults and that children might experience different symptoms than do adults (4,5); however, disease characteristics among pediatric patients in the United States have not been described. Data from 149,760 laboratory-confirmed COVID-19 cases in the United States occurring during February 12-April 2, 2020 were analyzed. Among 149,082 (99.6%) reported cases for which age was known, 2,572 (1.7%) were among children aged <18 years. Data were available for a small proportion of patients on many important variables, including symptoms (9.4%), underlying conditions (13%), and hospitalization status (33%). Among those with available information, 73% of pediatric patients had symptoms of fever, cough, or shortness of breath compared with 93% of adults aged 18-64 years during the same period; 5.7% of all pediatric patients, or 20% of those for whom hospitalization status was known, were hospitalized, lower than the percentages hospitalized among all adults aged 18-64 years (10%) or those with known hospitalization status (33%). Three deaths were reported among the pediatric cases included in this analysis. These data support previous findings that children with COVID-19 might not have reported fever or cough as often as do adults (4). Whereas most COVID-19 cases in children are not severe, serious COVID-19 illness resulting in hospitalization still occurs in this age group. Social distancing and everyday preventive behaviors remain important for all age groups as patients with less serious illness and those without symptoms likely play an important role in disease transmission (6,7).", "qid": 47, "docid": "7ru6tapp", "rank": 4, "score": 0.8644152283668518}, {"content": "Title: Clinical Characteristics of Children with COVID-19: A Rapid Review and Meta-Analysis Content: Abstract Background: Most guidelines on COVID-19 published so far include recommendations for patients regardless of age. Clinicians need a more accurate understanding of the clinical characteristics of children with COVID-19. Methods: We searched studies reporting clinical characteristics in children with COVID-19 published until March 31, 2020. We screened the literature, extracted the data and evaluated the risk of bias and quality of evidence of the included studies. We combined some of the outcomes (symptoms) in a single-arm meta-analysis using a random-effects model. Results: Our search retrieved 49 studies, including 25 case reports, 23 case series and one cohort study, with a total of 1667 patients. Our meta-analysis showed that most children with COVID-19 have mild symptoms. Eighty-three percent of the children were within family clusters of cases, and 19% had no symptoms. At least 7% with digestive symptoms. The main symptoms of children were fever (48%, 95% confidence interval [CI]: 39%, 56%) and cough (39%, 95% CI: 30%, 48%). The lymphocyte count was below normal level in only 15% [95% CI: 8%, 22%] of children which is different from adult patients. 66% [95% CI: 55%, 77%] of children had abnormal findings in CT imaging. Conclusions: Most children with COVID-19 have only mild symptoms, and many children are asymptomatic. Fever and cough are the most common symptoms in children. Vomiting and diarrhea were not common in children. The lymphocyte count is usually within the normal range in children.", "qid": 47, "docid": "jsjxdmi2", "rank": 5, "score": 0.8633922934532166}, {"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": 6, "score": 0.8599694967269897}, {"content": "Title: SARS-CoV-2 infection in infants under 1 year of age in Wuhan City, China Content: BACKGROUND: The clinical characteristics and outcome of COVID-19 in children are different from those in adults. We aimed to describe the characteristics of infants under 1 year of age (excluding newborns) with COVID-19. METHODS: We retrospectively retrieved data of 36 infants with SARS-CoV-2 infection in Wuhan Children\u2019s Hospital from January 26 to March 22, 2020. Clinical features, chest imaging findings, laboratory tests results, treatments and clinical outcomes were analyzed. RESULTS: The mean age of the infected infants was 6.43 months, with a range of 2\u201312 months. 61.11% of the patients were males and 38.89% females. 86.11% of the infants were infected due to family clustering. Cough (77.78%) and fever (47.22%) were the most common clinical manifestations. Chest CT scan revealed 61.11% bilateral pneumonia and 36.11% unilateral pneumonia. 47.22% of the infants developed complications. Increased leucocytes, neutrophils, lymphocytes, and thrombocytes were observed in 11.11, 8.33, 36.11 and 44.44% of infants, respectively. Decreased leucocytes, neutrophils, thrombocyte and hemoglobin were observed in 8.33, 19.44, 2.78 and 36.11% of infants, respectively. Increased C-reactive protein, procalcitonin, lactate dehydrogenase, alanine aminotransferase, creatine kinase and D-dimer were observed in 19.44, 67.74, 47.22, 19.44, 22.22 and 20.69% of infants, respectively. Only one infant had a high level of creatinine. Co-infections with other respiratory pathogens were observed in 62.86% of infants. CD3 (20.69%), CD4 (68.97%), CD19 (31.03%) and Th/Ts (44.83%) were elevated; CD8 (6.9%) and CD16+CD56 (48.28%) was reduced. IL-4 (7.69%), IL-6 (19.23%), IL-10 (50%), TNF-\u03b1 (11.54%) and IFN-\u03b3 (19.23%) were elevated. Up to March 22, 97.22% of infants recovered, while a critical ill infant died. When the infant\u2019s condition deteriorates rapidly, lymphocytopenia was discovered. Meanwhile, C-reactive protein, D-dimer, alanine aminotransferase, creatine kinase, creatinine, IL-6 and IL-10 increased significantly. CONCLUSIONS: In the cohort, we discovered that lymphocytosis, elevated CD4 and IL-10, and co-infections were common in infants with COVID-19, which were different from adults with COVID-19. Most infants with COVID-19 have mild clinical symptoms and good prognosis.", "qid": 47, "docid": "kqkbpkig", "rank": 7, "score": 0.8596335649490356}, {"content": "Title: Coronavirus Disease 2019 in Children: Characteristics, Antimicrobial Treatment, and Outcomes Content: Abstract Background At present, coronavirus disease 2019 (COVID-19) has spread in many countries. We conducted this study to help paediatricians To help pediatricians understand the conditions of COVID-19 in children, we conducted this study. Methods We retrospectively summarized the characteristics, treatment and outcomes of pediatric cases in Wuhan children's hospital which was the only designated hospital for children with COVID-19 in Hubei Province. A Cox proportional hazards regression analysis was used to evaluate factors associated with clinical outcomes. Results As of February 29, 75 children had been discharged, of which only one was has severe pneumonia and one was critical cases. Children younger than 2 years were more susceptible to COVID-19. All patients have received interferon-\u03b1 nebulization, and eight cases including the severe and critical cases were co-administrated ribavirin. Five patients with mild pneumonia were given arbidol. Twenty-three patients were given traditional Chinese medicine (TCM). The average length of stay (LOS) and the time of SARS-CoV-2 clearance were 10.57 and 6.39 days, respectively. None of the factors was associated with LOS or time of SARS-CoV-2 clearance. Conclusions The severity of COVID-19 in pediatric cases were milder than adults. The efficacy of the antiviral therapy in children with COVID-19 remains to be evaluated.", "qid": 47, "docid": "11es4w0u", "rank": 8, "score": 0.8591835498809814}, {"content": "Title: SARS-CoV-2 infection in infants under 1 year of age in Wuhan City, China Content: BACKGROUND: The clinical characteristics and outcome of COVID-19 in children are different from those in adults. We aimed to describe the characteristics of infants under 1 year of age (excluding newborns) with COVID-19. METHODS: We retrospectively retrieved data of 36 infants with SARS-CoV-2 infection in Wuhan Children's Hospital from January 26 to March 22, 2020. Clinical features, chest imaging findings, laboratory tests results, treatments and clinical outcomes were analyzed. RESULTS: The mean age of the infected infants was 6.43 months, with a range of 2-12 months. 61.11% of the patients were males and 38.89% females. 86.11% of the infants were infected due to family clustering. Cough (77.78%) and fever (47.22%) were the most common clinical manifestations. Chest CT scan revealed 61.11% bilateral pneumonia and 36.11% unilateral pneumonia. 47.22% of the infants developed complications. Increased leucocytes, neutrophils, lymphocytes, and thrombocytes were observed in 11.11, 8.33, 36.11 and 44.44% of infants, respectively. Decreased leucocytes, neutrophils, thrombocyte and hemoglobin were observed in 8.33, 19.44, 2.78 and 36.11% of infants, respectively. Increased C-reactive protein, procalcitonin, lactate dehydrogenase, alanine aminotransferase, creatine kinase and D-dimer were observed in 19.44, 67.74, 47.22, 19.44, 22.22 and 20.69% of infants, respectively. Only one infant had a high level of creatinine. Co-infections with other respiratory pathogens were observed in 62.86% of infants. CD3 (20.69%), CD4 (68.97%), CD19 (31.03%) and Th/Ts (44.83%) were elevated; CD8 (6.9%) and CD16+CD56 (48.28%) was reduced. IL-4 (7.69%), IL-6 (19.23%), IL-10 (50%), TNF-&#945; (11.54%) and IFN-\u00ce\u00b3 (19.23%) were elevated. Up to March 22, 97.22% of infants recovered, while a critical ill infant died. When the infant's condition deteriorates rapidly, lymphocytopenia was discovered. Meanwhile, C-reactive protein, D-dimer, alanine aminotransferase, creatine kinase, creatinine, IL-6 and IL-10 increased significantly. CONCLUSIONS: In the cohort, we discovered that lymphocytosis, elevated CD4 and IL-10, and co-infections were common in infants with COVID-19, which were different from adults with COVID-19. Most infants with COVID-19 have mild clinical symptoms and good prognosis.", "qid": 47, "docid": "eghxji0p", "rank": 9, "score": 0.8585109710693359}, {"content": "Title: Clinical characteristics of 182 pediatric COVID-19 patients with different severities and allergic status Content: BACKGROUND: The pandemic of coronavirus disease 2019 (COVID-19) caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection has made widespread impact recently. We aim to investigate the clinical characteristics of COVID-19 children with different severities and allergic status. METHODS: Data extracted from the electronical medical records, including demographics, clinical manifestations, comorbidities, laboratory and immunological results and radiological images of 182 hospitalized COVID-19 children were summarized and analyzed. RESULTS: The median age was 6 years old, ranging from 3 days to 15 years, and there were more boys (male-female ratio about 2:1) within the studied 182 patients. Most of the children were infected by family members. Fever (43.4%) and dry cough (44.5%) were common symptoms, and gastrointestinal manifestations accounted for 11.0%, including diarrhea, abdominal discomfort and vomiting. 71.4% had abnormal chest computed tomography (CT) scan images, and typical signs of pneumonia were ground-glass opacity and local patchy shadowing on admission. Laboratory results were mostly within normal ranges, and only a small ratio of lymphopenia (3.9%) and eosinopenia (29.5%) were observed. The majority (97.8%) of infected children were not severe, and 24 (13.2%) of them had asymptomatic infections. Compared to children without pneumonia(manifested as asymptomatic and acute upper respiratory infection), children with pneumonia were associated with higher percentages of the comorbidity history, symptoms of fever and cough, and increased levels of serum procalcitonin, alkaline phosphatase and serum interleukins (IL)-2, IL-4, IL-6, IL-10 and TNF-&#945;.There were no differences of treatments, duration of hospitalization, time from first positive to first negative nucleic acid testing and outcomes between children with mild pneumonia and without pneumonia. All the hospitalized COVID-19 children had recovered except one death due to intussusception and sepsis. In 43 allergic children with COVID-19, allergic rhinitis (83.7%) was the major disease, followed by drug allergy, atopic dermatitis, food allergy and asthma. Demographics and clinical features were not significantly different between allergic and non-allergic groups. Allergic patients showed less increase in acute phase reactants, procalcitonin, D-dimer and aspartate aminotransferase levels compared to all patients. Immunological profiles including circulating T, B and NK lymphocyte subsets, total immunoglobulin and complement levels and serum cytokines did not show any difference in allergic and pneumonia groups. Neither eosinophil counts nor serum total immunoglobulin E (IgE) levels showed a significant correlation with other immunological measures, such as other immunoglobulins, complements, lymphocyte subsets numbers and serum cytokine levels. CONCLUSION: Pediatric COVID-19 patients tended to have a mild clinical course. Patients with pneumonia had higher proportion of fever and cough and increased inflammatory biomarkers than those without pneumonia. There was no difference between allergic and non-allergic COVID-19 children in disease incidence, clinical features, laboratory and immunological findings. Allergy was not a risk factor for developing and severity of SARS-CoV-2 infection and hardly influenced the disease course of COVID-19 in children.", "qid": 47, "docid": "m63b9ekk", "rank": 10, "score": 0.8583092093467712}, {"content": "Title: Managing COVID-19 Iinfection in pediatric patients. Content: Children are less likely to be infected with SARS-CoV-2 than adults and often have a milder course of illness and a lower case fatality rate. Children account for an estimated 1% to 5% of those diagnosed with COVID-19.1 Even so, pre-school-aged children, infants, and children with underlying health conditions may still be at risk for severe disease and complications.2 Unique aspects of COVID-19 presentation and course in children and possible vertical transmission to newborns from COVID-19-positive mothers are discussed.", "qid": 47, "docid": "yxatsk8l", "rank": 11, "score": 0.8578068017959595}, {"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": 12, "score": 0.8577098846435547}, {"content": "Title: COVID-19 in 7780 pediatric patients: A systematic review Content: BACKGROUND: Studies summarizing the clinical picture of COVID-19 in children are lacking. This review characterizes clinical symptoms, laboratory, and imaging findings, as well as therapies provided to confirmed pediatric cases of COVID-19. METHODS: Adhering to PRISMA guidelines, we searched four medical databases (PubMed, LitCovid, Scopus, WHO COVID-19 database) between December 1, 2019 to May 14, 2020 using the keywords \u201cnovel coronavirus\u201d, \u201cCOVID-19\u201d or \u201cSARS-CoV-2\u201d. We included published or in press peer-reviewed cross-sectional, case series, and case reports providing clinical signs, imaging findings, and/or laboratory results of pediatric patients who were positive for COVID-19. Risk of bias was appraised through the quality assessment tool published by the National Institutes of Health. PROSPERO registration # CRD42020182261. FINDINGS: We identified 131 studies across 26 countries comprising 7780 pediatric patients. Although fever (59\u00b71%) and cough (55\u00b79%) were the most frequent symptoms 19\u00b73% of children were asymptomatic. Patchy lesions (21\u00b70%) and ground-glass opacities (32\u00b79%) depicted lung radiograph and computed tomography findings, respectively. Immunocompromised children or those with respiratory/cardiac disease comprised the largest subset of COVID-19 children with underlying medical conditions (152 of 233 individuals). Coinfections were observed in 5.6% of children and abnormal laboratory markers included serum D-dimer, procalcitonin, creatine kinase, and interleukin-6. Seven deaths were reported (0\u00b709%) and 11 children (0\u00b714%) met inclusion for multisystem inflammatory syndrome in children. INTERPRETATION: This review provides evidence that children diagnosed with COVID-19 have an overall excellent prognosis. Future longitudinal studies are needed to confirm our findings and better understand which patients are at increased risk for developing severe inflammation and multiorgan failure. FUNDING: Parker B. Francis and pilot grant from 2R25-HL126140. Funding agencies had no involvement in the study.", "qid": 47, "docid": "xv7vuypd", "rank": 13, "score": 0.8576037287712097}, {"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. ELECTRONIC SUPPLEMENTARY MATERIAL: The online version of this article (10.1007/s00431-020-03683-8) contains supplementary material, which is available to authorized users.", "qid": 47, "docid": "62ic8r0s", "rank": 14, "score": 0.857085108757019}, {"content": "Title: Psychopathological problems related to the COVID\u201019 pandemic and possible prevention with music therapy Content: COVID-19 is having a profound effect on societies worldwide and the impact that it is having on children cannot be underestimated. Although Brodin (1) stated that the disease tends to be mild in children, psychopathological considerations allow us to assume that the pandemic will have a high risk of long-term paediatric psychiatric sequelae and interdisciplinary preventative measures are needed.", "qid": 47, "docid": "0mxv8h06", "rank": 15, "score": 0.8568440079689026}, {"content": "Title: Clinical Characteristics of Children with COVID-19 Content: BACKGROUND: In December 2019, the infection caused by 2019 novel coronavirus (COVID-19) led to an outbreak in Wuhan, situated in the Hubei Province of China. Following this, there has been a rapid increase in the number of cases. On 12th March 2020, there were over 100,000 confirmed cases and almost 4,300 deaths worldwide. The clinical profile of children with COVID-19 is unknown due to the few number of cases reported. Currently, available data suggest they may have a milder form of illness. METHODS: A review of the literature published from June 2019 to March 2020 was undertaken to evaluate the clinical presentation, management and outcomes of COVID-19 in in children. Data sources included EMBASE, MEDLINE, Cochrane library, ISI Web of Knowledge and references within identified articles. RESULTS: We identified 303 potential studies, and 295 were excluded for reasons including duplicates, experimental studies and case reports. Eight studies were eligible for inclusion, including a total of 820 paediatric cases of COVID-19. Asymptomatic cases represented 14.3% (n = 117) of the total number of cases identified, and thus the remaining 85.7% (n = 703) experienced symptoms. Fever was the commonest symptom in 53.9% (n = 48) of cases, followed by cough in 39.3% (n = 35) of cases, and rhinorrhoea or pharyngeal congestion in 13.5% (n = 12) of cases. Diarrhoea and sore throats were less common symptoms, 7.9% (n = 7) and 9.0% (n = 8) respectively. Other symptoms, including fatigue, headache and dizziness were rare. CONCLUSION: Children are disproportionately affected by COVID-19 and are more likely to run a milder cause of illness following this infection compared to adults. This outbreak only started 3 months ago, therefore, further population wide studies are needed to validate these findings.", "qid": 47, "docid": "fg0lcl64", "rank": 16, "score": 0.8566220998764038}, {"content": "Title: Systematic review of COVID-19 in children shows milder cases and a better prognosis than adults Content: AIM: The coronavirus disease 2019 (COVID-19) pandemic has affected hundreds of thousands of people. Data on symptoms and prognosis in children are rare. METHODS: A systematic literature review was carried out to identify papers on COVID-19, which is caused by the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), using the MEDLINE and Embase databases between January 1 and March 18, 2020. RESULTS: The search identified 45 relevant scientific papers and letters. The review showed that children have so far accounted for 1%-5% of diagnosed COVID-19 cases, they often have milder disease than adults and deaths have been extremely rare. Diagnostic findings have been similar to adults, with fever and respiratory symptoms being prevalent, but fewer children seem to have developed severe pneumonia. Elevated inflammatory markers were less common in children, and lymphocytopenia seemed rare. Newborn infants have developed symptomatic COVID-19, but evidence of vertical intrauterine transmission was scarce. Suggested treatment included providing oxygen, inhalations, nutritional support and maintaining fluids and electrolyte balances. CONCLUSIONS: The coronavirus disease 2019 has occurred in children, but they seemed to have a milder disease course and better prognosis than adults. Deaths were extremely rare.", "qid": 47, "docid": "vij0hqsn", "rank": 17, "score": 0.856548011302948}, {"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": 18, "score": 0.8565038442611694}, {"content": "Title: Managing COVID-19 disease in pediatric patients Content: Children are less likely to be infected with SARS-CoV-2 than adults and often have a milder course of COVID-19 disease and a lower case fatality rate. Children account for an estimated 1% to 5% of those diagnosed with COVID-19. Even so, preschool-aged children, infants, and children with underlying health conditions may still be at risk for severe disease and complications. Unique aspects of COVID-19 presentation and disease course in children and possible vertical transmission to newborns from COVID-19-positive mothers are discussed.", "qid": 47, "docid": "4f8v0tou", "rank": 19, "score": 0.8556417226791382}, {"content": "Title: Epidemiology, Clinical Features, and Disease Severity in Patients With Coronavirus Disease 2019 (COVID-19) in a Children's Hospital in New York City, New York Content: Importance: Descriptions of the coronavirus disease 2019 (COVID-19) experience in pediatrics will help inform clinical practices and infection prevention and control for pediatric facilities. Objective: To describe the epidemiology, clinical, and laboratory features of patients with COVID-19 hospitalized at a children's hospital and to compare these parameters between patients hospitalized with and without severe disease. Design, Setting, and Participants: This retrospective review of electronic medical records from a tertiary care academically affiliated children's hospital in New York City, New York, included hospitalized children and adolescents (&#8804;21 years) who were tested based on suspicion for COVID-19 between March 1 to April 15, 2020, and had positive results for severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). Exposures: Detection of SARS-CoV-2 from a nasopharyngeal specimen using a reverse transcription-polymerase chain reaction assay. Main Outcomes and Measures: Severe disease as defined by the requirement for mechanical ventilation. Results: Among 50 patients, 27 (54%) were boys and 25 (50%) were Hispanic. The median days from onset of symptoms to admission was 2 days (interquartile range, 1-5 days). Most patients (40 [80%]) had fever or respiratory symptoms (32 [64%]), but 3 patients (6%) with only gastrointestinal tract presentations were identified. Obesity (11 [22%]) was the most prevalent comorbidity. Respiratory support was required for 16 patients (32%), including 9 patients (18%) who required mechanical ventilation. One patient (2%) died. None of 14 infants and 1 of 8 immunocompromised patients had severe disease. Obesity was significantly associated with mechanical ventilation in children 2 years or older (6 of 9 [67%] vs 5 of 25 [20%]; P = .03). Lymphopenia was commonly observed at admission (36 [72%]) but did not differ significantly between those with and without severe disease. Those with severe disease had significantly higher C-reactive protein (median, 8.978 mg/dL [to convert to milligrams per liter, multiply by 10] vs 0.64 mg/dL) and procalcitonin levels (median, 0.31 ng/mL vs 0.17 ng/mL) at admission (P < .001), as well as elevated peak interleukin 6, ferritin, and D-dimer levels during hospitalization. Hydroxychloroquine was administered to 15 patients (30%) but could not be completed for 3. Prolonged test positivity (maximum of 27 days) was observed in 4 patients (8%). Conclusions and Relevance: In this case series study of children and adolescents hospitalized with COVID-19, the disease had diverse manifestations. Infants and immunocompromised patients were not at increased risk of severe disease. Obesity was significantly associated with disease severity. Elevated inflammatory markers were seen in those with severe disease.", "qid": 47, "docid": "63c9dt8a", "rank": 20, "score": 0.8554420471191406}, {"content": "Title: Clinical characteristics of children with COVID-19: a rapid review and meta-analysis. Content: Background Most guidelines on COVID-19 published so far include recommendations for patients regardless of age. Clinicians need a more accurate understanding of the clinical characteristics of children with COVID-19. Methods We searched studies reporting clinical characteristics in children with COVID-19 published until March 31, 2020. We screened the literature, extracted the data and evaluated the risk of bias and quality of evidence of the included studies. We combined some of the outcomes (symptoms) in a single-arm meta-analysis using a random-effects model. Results Our search retrieved 49 studies, including 25 case reports, 23 case series and one cohort study, with a total of 1,667 patients. Our meta-analysis showed that most children with COVID-19 have mild symptoms. Eighty-three percent of the children were within family clusters of cases, and 19% had no symptoms. At least 7% with digestive symptoms. The main symptoms of children were fever [48%, 95% confidence interval (CI): 39%, 56%] and cough (39%, 95% CI: 30%, 48%). The lymphocyte count was below normal level in only 15% (95% CI: 8%, 22%) of children which is different from adult patients. 66% (95% CI: 55%, 77%) of children had abnormal findings in CT imaging. Conclusions Most children with COVID-19 have only mild symptoms, and many children are asymptomatic. Fever and cough are the most common symptoms in children. Vomiting and diarrhea were not common in children. The lymphocyte count is usually within the normal range in children.", "qid": 47, "docid": "n0r2imd4", "rank": 21, "score": 0.8545039892196655}, {"content": "Title: Clinical characteristics of 182 pediatric COVID\u201019 patients with different severities and allergic status Content: BACKGROUND: The pandemic of coronavirus disease 2019 (COVID\u201019) caused by severe acute respiratory syndrome coronavirus 2 (SARS\u2010CoV\u20102) infection has made widespread impact recently. We aim to investigate the clinical characteristics of COVID\u201019 children with different severities and allergic status. METHODS: Data extracted from the electronical medical records, including demographics, clinical manifestations, comorbidities, laboratory and immunological results and radiological images of 182 hospitalized COVID\u201019 children were summarized and analyzed. RESULTS: The median age was 6 years old, ranging from 3 days to 15 years, and there were more boys (male\u2010female ratio about 2:1) within the studied 182 patients. Most of the children were infected by family members. Fever (43.4%) and dry cough (44.5%) were common symptoms, and gastrointestinal manifestations accounted for 11.0%, including diarrhea, abdominal discomfort and vomiting. 71.4% had abnormal chest computed tomography (CT) scan images, and typical signs of pneumonia were ground\u2010glass opacity and local patchy shadowing on admission. Laboratory results were mostly within normal ranges, and only a small ratio of lymphopenia (3.9%) and eosinopenia (29.5%) were observed. The majority (97.8%) of infected children were not severe, and 24 (13.2%) of them had asymptomatic infections. Compared to children without pneumonia(manifested as asymptomatic and acute upper respiratory infection), children with pneumonia were associated with higher percentages of the comorbidity history, symptoms of fever and cough, and increased levels of serum procalcitonin, alkaline phosphatase and serum interleukins (IL)\u20102, IL\u20104, IL\u20106, IL\u201010 and TNF\u2010\u03b1.There were no differences of treatments, duration of hospitalization, time from first positive to first negative nucleic acid testing and outcomes between children with mild pneumonia and without pneumonia. All the hospitalized COVID\u201019 children had recovered except one death due to intussusception and sepsis. In 43 allergic children with COVID\u201019, allergic rhinitis (83.7%) was the major disease, followed by drug allergy, atopic dermatitis, food allergy and asthma. Demographics and clinical features were not significantly different between allergic and non\u2010allergic groups. Allergic patients showed less increase in acute phase reactants, procalcitonin, D\u2010dimer and aspartate aminotransferase levels compared to all patients. Immunological profiles including circulating T, B and NK lymphocyte subsets, total immunoglobulin and complement levels and serum cytokines did not show any difference in allergic and pneumonia groups. Neither eosinophil counts nor serum total immunoglobulin E (IgE) levels showed a significant correlation with other immunological measures, such as other immunoglobulins, complements, lymphocyte subsets numbers and serum cytokine levels. CONCLUSION: Pediatric COVID\u201019 patients tended to have a mild clinical course. Patients with pneumonia had higher proportion of fever and cough and increased inflammatory biomarkers than those without pneumonia. There was no difference between allergic and non\u2010allergic COVID\u201019 children in disease incidence, clinical features, laboratory and immunological findings. Allergy was not a risk factor for developing and severity of SARS\u2010CoV\u20102 infection and hardly influenced the disease course of COVID\u201019 in children.", "qid": 47, "docid": "gdzx3vlt", "rank": 22, "score": 0.8540652990341187}, {"content": "Title: Epidemiology, Clinical Features, and Disease Severity in Patients With Coronavirus Disease 2019 (COVID-19) in a Children's Hospital in New York City, New York. Content: Importance Descriptions of the coronavirus disease 2019 (COVID-19) experience in pediatrics will help inform clinical practices and infection prevention and control for pediatric facilities. Objective To describe the epidemiology, clinical, and laboratory features of patients with COVID-19 hospitalized at a children's hospital and to compare these parameters between patients hospitalized with and without severe disease. Design, Setting, and Participants This retrospective review of electronic medical records from a tertiary care academically affiliated children's hospital in New York City, New York, included hospitalized children and adolescents (\u226421 years) who were tested based on suspicion for COVID-19 between March 1 to April 15, 2020, and had positive results for severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). Exposures Detection of SARS-CoV-2 from a nasopharyngeal specimen using a reverse transcription-polymerase chain reaction assay. Main Outcomes and Measures Severe disease as defined by the requirement for mechanical ventilation. Results Among 50 patients, 27 (54%) were boys and 25 (50%) were Hispanic. The median days from onset of symptoms to admission was 2 days (interquartile range, 1-5 days). Most patients (40 [80%]) had fever or respiratory symptoms (32 [64%]), but 3 patients (6%) with only gastrointestinal tract presentations were identified. Obesity (11 [22%]) was the most prevalent comorbidity. Respiratory support was required for 16 patients (32%), including 9 patients (18%) who required mechanical ventilation. One patient (2%) died. None of 14 infants and 1 of 8 immunocompromised patients had severe disease. Obesity was significantly associated with mechanical ventilation in children 2 years or older (6 of 9 [67%] vs 5 of 25 [20%]; P = .03). Lymphopenia was commonly observed at admission (36 [72%]) but did not differ significantly between those with and without severe disease. Those with severe disease had significantly higher C-reactive protein (median, 8.978 mg/dL [to convert to milligrams per liter, multiply by 10] vs 0.64 mg/dL) and procalcitonin levels (median, 0.31 ng/mL vs 0.17 ng/mL) at admission (P < .001), as well as elevated peak interleukin 6, ferritin, and D-dimer levels during hospitalization. Hydroxychloroquine was administered to 15 patients (30%) but could not be completed for 3. Prolonged test positivity (maximum of 27 days) was observed in 4 patients (8%). Conclusions and Relevance In this case series study of children and adolescents hospitalized with COVID-19, the disease had diverse manifestations. Infants and immunocompromised patients were not at increased risk of severe disease. Obesity was significantly associated with disease severity. Elevated inflammatory markers were seen in those with severe disease.", "qid": 47, "docid": "51e8a6lz", "rank": 23, "score": 0.8533028960227966}, {"content": "Title: Spectrum of COVID-19 in Children Content: The prevalence of coronavirus disease 2019 (COVID-19) is lower in children compared to adults. Children contribute to 1-5% of all COVID-19 cases (1) . A recent study from China reported that 171(12.3%) of 1391 children with suspected disease had confirmed COVID-19 infection (2) . As of May 15, 2020, there are 33,241 children with COVID-19 in the United States (3) . The most common symptoms in children with confirmed and suspected COVID-19 include fever and cough followed by diarrhea, and abdominal pain.", "qid": 47, "docid": "el6cvwtk", "rank": 24, "score": 0.8529516458511353}, {"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": 25, "score": 0.8529420495033264}, {"content": "Title: Clinical Features and Outcome of SARS-CoV-2 Infection in Children: A Systematic Review and Meta-analysis Content: BACKGROUND AND OBJECTIVE: Knowledge about COVID-19 in children is limited due to the paucity of reported data. The pediatric age group comprises only less than 5% of total COVID-19 worldwide, therefore, large studies in this population are unlikely in the immediate future. Hence, we planned to synthesize the current data that will help in a better understanding of COVID-19 in children. METHODS: Four different electronic databases (MEDLINE, EMBASE, Web of Science, and CENTRAL) were searched for articles related to COVID-19 in the pediatric population. We included studies reporting disease characteristics and outcomes of COVID-19 in patients aged less than 19 years. We performed a random-effect meta-analysis to provide pooled estimates of various disease characteristics. RESULTS: 27 studies (4857 patients) fulfilling the eligibility criteria were included in this systematic review, from a total of 883 records. About half of the patients had each of fever and cough, 11% (6-17%) had fast breathing, and 6-13% had gastrointestinal manifestations. Most of the patients had mild to moderate disease, and only 4% had a severe or critical illness. Leukopenia was the commonest reported laboratory abnormality. CONCLUSION: Even among the symptomatic COVID-19 cases, severe manifestations are seen in very few children. Though fever and respiratory symptoms are most common, many children also have gastrointestinal manifestations.", "qid": 47, "docid": "z6trtz8s", "rank": 26, "score": 0.8522663116455078}, {"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": 27, "score": 0.8515559434890747}, {"content": "Title: Clinical characteristics of COVID-19 in children compared with adults in Shandong Province, China Content: AIMS AND BACKGROUND: The COVID-19 outbreak spread in China and is a threat to the world. We reported on the epidemiological, clinical, laboratory, and radiological characteristics of children cases to help health workers better understand and provide timely diagnosis and treatment. METHODS: Retrospectively, two research centers' case series of 67 consecutive hospitalized cases including 53 adult and 14 children cases with COVID-19 between 23 Jan 2020 and 15 Feb 2020 from Jinan and Rizhao were enrolled in this study. Epidemiological, clinical, laboratory, and radiological characteristics of children and adults were analyzed and compared. RESULTS: Most cases in children were mild (21.4%) and conventional cases (78.6%), with mild clinical signs and symptoms, and all cases were of family clusters. Fever (35.7%) and dry cough (21.4%) were described as clinical manifestations in children cases. Dry cough and phlegm were not the most common symptoms in children compared with adults (p = 0.03). In the early stages of the disease, lymphocyte counts did not significantly decline but neutrophils count did in children compared with adults (p = 0.02). There was a lower level of CRP (p = 0.00) in children compared with adults. There were 8 (57.1%) asymptomatic cases and 6 (42.9%) symptomatic cases among the 14 children cases. The age of asymptomatic patients was younger than that of symptomatic patients (p = 0.03). Even among asymptomatic patients, 5 (62.5%) cases had lung injuries including 3 (60%) cases with bilateral involvement, which was not different compared with that of symptomatic cases (p = 0.58, p = 0.74). CONCLUSIONS: The clinical symptoms of children are mild, there is substantial lung injury even among children, but that there is less clinical disease, perhaps because of a less pronounced inflammatory response, and that the occurrence of this pattern appears to inversely correlate with age.", "qid": 47, "docid": "fj06xnej", "rank": 28, "score": 0.8507711887359619}, {"content": "Title: Clinical Manifestations of Children with COVID-19: a Systematic Review Content: Context: The coronavirus disease 2019 (COVID-19) outbreak is an unprecedented global public health challenge, leading to thousands of deaths every day worldwide. Despite the epidemiological importance, clinical patterns of children with COVID-19 remain unclear. Objective: To describe the clinical, laboratorial and radiological characteristics of children with COVID-19. Data Sources: The Medline database was searched between December 1st 2019 and March 30th 2020. Study Selection: Inclusion criteria were: (1) studied patients younger than 18 years old; (2) presented original data from cases of COVID-19 confirmed by reverse-transcription polymerase chain reaction; and (3) contained descriptions of clinical manifestations, laboratory tests or radiological examinations. Data Extraction: Number of cases, gender, age, clinical manifestations, laboratory tests, radiological examinations and outcomes. Results: A total of 34 studies (1,118 cases) were included. From all the cases, 1,111 had their severity classified: 14.3% were asymptomatic, 36.4% were mild, 46.0% were moderate, 2.2% were severe and 1.2% were critical. The most prevalent symptom was fever (16.3%), followed by cough (14.4%), nasal symptoms (3.6%), diarrhea (2.7%) and nausea/vomiting (2.5%). One hundred forty-five (12.9%) children were diagnosed with pneumonia and 43 (3.8%) upper airway infections were reported. Reduced lymphocyte count were reported in 13.1% of cases. Abnormalities on computed tomography was reported in 62.7% of cases. The most prevalent abnormalities reported were ground glass opacities, patchy shadows and consolidations. Only one death was reported. Conclusions: Clinical manifestations of children with COVID-19 differ widely from adults cases. Fever and respiratory symptoms should not be considered a hallmark of COVID-19 in children.", "qid": 47, "docid": "r3cqvf0c", "rank": 29, "score": 0.8506608009338379}, {"content": "Title: Clinical characteristics of COVID-19 in children compared with adults in Shandong Province, China Content: AIMS AND BACKGROUND: The COVID-19 outbreak spread in China and is a threat to the world. We reported on the epidemiological, clinical, laboratory, and radiological characteristics of children cases to help health workers better understand and provide timely diagnosis and treatment. METHODS: Retrospectively, two research centers\u2019 case series of 67 consecutive hospitalized cases including 53 adult and 14 children cases with COVID-19 between 23 Jan 2020 and 15 Feb 2020 from Jinan and Rizhao were enrolled in this study. Epidemiological, clinical, laboratory, and radiological characteristics of children and adults were analyzed and compared. RESULTS: Most cases in children were mild (21.4%) and conventional cases (78.6%), with mild clinical signs and symptoms, and all cases were of family clusters. Fever (35.7%) and dry cough (21.4%) were described as clinical manifestations in children cases. Dry cough and phlegm were not the most common symptoms in children compared with adults (p = 0.03). In the early stages of the disease, lymphocyte counts did not significantly decline but neutrophils count did in children compared with adults (p = 0.02). There was a lower level of CRP (p = 0.00) in children compared with adults. There were 8 (57.1%) asymptomatic cases and 6 (42.9%) symptomatic cases among the 14 children cases. The age of asymptomatic patients was younger than that of symptomatic patients (p = 0.03). Even among asymptomatic patients, 5 (62.5%) cases had lung injuries including 3 (60%) cases with bilateral involvement, which was not different compared with that of symptomatic cases (p = 0.58, p = 0.74). CONCLUSIONS: The clinical symptoms of children are mild, there is substantial lung injury even among children, but that there is less clinical disease, perhaps because of a less pronounced inflammatory response, and that the occurrence of this pattern appears to inversely correlate with age.", "qid": 47, "docid": "o01s0upf", "rank": 30, "score": 0.8505369424819946}, {"content": "Title: Impact of the SARS-CoV-2 outbreak on pediatric liver transplant recipients residing in Lombardy, Northern Italy Content: The novel Severe Acute Respiratory Syndrome Coronavirus (SARS-CoV-2) disease (COVID-19) represents an unprecedented public health issue for the general population and for patients with underlying chronic conditions. Compared to adults, children seem to have a milder course of the disease, with very few requiring medical attention.", "qid": 47, "docid": "zddylfxq", "rank": 31, "score": 0.8497037291526794}, {"content": "Title: Clinical manifestations of children with COVID-19: A systematic review Content: BACKGROUND: The coronavirus disease 2019 (COVID-19) outbreak is an unprecedented global public health challenge, leading to thousands of deaths every day worldwide. Despite the epidemiological importance, clinical patterns of children with COVID-19 remain unclear. The aim of this study was to describe the clinical, laboratorial, and radiological characteristics of children with COVID-19. METHODS: The Medline database was searched between December 1st 2019 and April 6th 2020. No language restrictions were applied. Inclusion criteria were (a) studied patients younger than 18 years old; (b) presented original data from cases of COVID-19 confirmed by reverse-transcription polymerase chain reaction; and (c) contained descriptions of clinical manifestations, laboratory tests, or radiological examinations. RESULTS: A total of 38 studies (1124 cases) were included. From all the cases, 1117 had their severity classified: 14.2% were asymptomatic, 36.3% were mild, 46.0% were moderate, 2.1% were severe, and 1.2% were critical. The most prevalent symptom was fever (47.5%), followed by cough (41.5%), nasal symptoms (11.2%), diarrhea (8.1%), and nausea/vomiting (7.1%). One hundred forty-five (36.9%) children were diagnosed with pneumonia and 43 (10.9%) upper airway infections were reported. Reduced lymphocyte count was reported in 12.9% of cases. Abnormalities in computed tomography were reported in 63.0% of cases. The most prevalent abnormalities reported were ground-glass opacities, patchy shadows, and consolidations. Only one death was reported. CONCLUSIONS: Clinical manifestations of children with COVID-19 differ widely from adult cases. Fever and respiratory symptoms should not be considered a hallmark of COVID-19 in children.", "qid": 47, "docid": "e6br6v2d", "rank": 32, "score": 0.8492917418479919}, {"content": "Title: The clinical and immunological features of pediatric COVID-19 patients in China Content: Abstract In December 2019, the corona virus disease 2019 (COVID-19) caused by novel coronavirus (SARS-CoV-2) emerged in Wuhan, China and rapidly spread worldwide. Few information on clinical features and immunological profile of COVID-19 in paediatrics. The clinical features and treatment outcomes of twelve paediatric patients confirmed as COVID-19 were analyzed. The immunological features of children patients was investigated and compared with twenty adult patients. The median age was 14.5-years (range from 0.64 to 17), and six of the patients were male. The average incubation period was 8 days. Clinically, cough (9/12, 75%) and fever (7/12, 58.3%) were the most common symptoms. Four patients (33.3%) had diarrhea during the disease. As to the immune profile, children had higher amount of total T cell, CD8+ T cell and B cell but lower CRP levels than adults (P < 0.05). Ground-glass opacity (GGO) and local patchy shadowing were the typical radiological findings on chest CT scan. All patients received antiviral and symptomatic treatment and the symptom relieved in 3\u20134 days after admitted to hospital. The paediatric patients showed mild symptom but with longer incubation period. Children infected with SARS-CoV-2 had different immune profile with higher T cell amount and low inflammatory factors level, which might ascribed to the mild clinical symptom. We advise that nucleic acid test or examination of serum IgM/IgG antibodies against SARS-CoV-2 should be taken for children with exposure history regardless of clinical symptom.", "qid": 47, "docid": "6v763k4s", "rank": 33, "score": 0.8491110801696777}, {"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": 34, "score": 0.848576009273529}, {"content": "Title: The clinical and immunological features of pediatric COVID-19 patients in China Content: In December 2019, the corona virus disease 2019 (COVID-19) caused by novel coronavirus (SARS-CoV-2) emerged in Wuhan, China and rapidly spread worldwide. Few information on clinical features and immunological profile of COVID-19 in paediatrics. The clinical features and treatment outcomes of twelve paediatric patients confirmed as COVID-19 were analyzed. The immunological features of children patients was investigated and compared with twenty adult patients. The median age was 14.5-years (range from 0.64 to 17), and six of the patients were male. The average incubation period was 8 days. Clinically, cough (9/12, 75%) and fever (7/12, 58.3%) were the most common symptoms. Four patients (33.3%) had diarrhea during the disease. As to the immune profile, children had higher amount of total T cell, CD8+ T cell and B cell but lower CRP levels than adults (P < 0.05). Ground-glass opacity (GGO) and local patchy shadowing were the typical radiological findings on chest CT scan. All patients received antiviral and symptomatic treatment and the symptom relieved in 3-4 days after admitted to hospital. The paediatric patients showed mild symptom but with longer incubation period. Children infected with SARS-CoV-2 had different immune profile with higher T cell amount and low inflammatory factors level, which might ascribed to the mild clinical symptom. We advise that nucleic acid test or examination of serum IgM/IgG antibodies against SARS-CoV-2 should be taken for children with exposure history regardless of clinical symptom.", "qid": 47, "docid": "ablp64gz", "rank": 35, "score": 0.8484927415847778}, {"content": "Title: Haematological and Immunological Data of Chinese Children Infected with Coronavirus Disease 2019 Content: Haematological and immunological data of children with COVID-19 infection is lacking. Between 21(st) January and 20(th) March 2020, 244 children who were confirmed to have COVID-19 infection and admitted to the Wuhan Children's Hospital, China were retrospectively reviewed. 193 children were considered as symptomatic, which was defined as having either the presence of clinical symptoms or the presence of CT thorax abnormalities. Their haematological and immunological profiles, including complete blood counts, lymphocyte subsets (T, B and NK cell counts), immunoglobulin (Ig) profiles (IgG, IgA and IgM) and cytokine profiles were analysed and compared between the symptomatic and asymptomatic groups. The median values and the interquartile ranges were calculated. Comparison was made using the Mann\u2013Whitney U test. Children with symptomatic COVID-19 infection had significantly lower haemoglobin levels, but higher absolute lymphocyte and monocyte counts, IgG and IgA levels, as well as interleukin 6 (IL-6), IL-10, tumour necrosis factor alpha and interferon gamma levels. The obtained data will be utilized for further studies in comparing children and adults with COVID-19 infections in other parts of the world and with different severity.", "qid": 47, "docid": "2o3agh35", "rank": 36, "score": 0.8484292030334473}, {"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": 47, "docid": "h93g5hvf", "rank": 37, "score": 0.8481950759887695}, {"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": 47, "docid": "8du0s33p", "rank": 38, "score": 0.8479669094085693}, {"content": "Title: Clinical Features and Outcome of SARS-CoV-2 Infection in Children: A Systematic Review and Meta-analysis. Content: BACKGROUND AND OBJECTIVE Knowledge about COVID-19 in children is limited due to the paucity of reported data. The pediatric age group comprises only less than 5% of total COVID-19 worldwide, therefore, large studies in this population are unlikely in the immediate future. Hence, we planned to synthesize the current data that will help in a better understanding of COVID-19 in children. METHODS Four different electronic databases (MEDLINE, EMBASE, Web of Science, and CENTRAL) were searched for articles related to COVID-19 in the pediatric population. We included studies reporting disease characteristics and outcomes of COVID-19 in patients aged less than 19 years. We performed a random-effect meta-analysis to provide pooled estimates of various disease characteristics. RESULTS 27 studies (4857 patients) fulfilling the eligibility criteria were included in this systematic review, from a total of 883 records. About half of the patients had each of fever and cough, 11% (6-17%) had fast breathing, and 6-13% had gastrointestinal manifestations. Most of the patients had mild to moderate disease, and only 4% had a severe or critical illness. Leukopenia was the commonest reported laboratory abnormality. CONCLUSION Even among the symptomatic COVID-19 cases, severe manifestations are seen in very few children. Though fever and respiratory symptoms are most common, many children also have gastrointestinal manifestations.", "qid": 47, "docid": "6zqp53tk", "rank": 39, "score": 0.8479357957839966}, {"content": "Title: Spectrum of COVID\u201019 in Children Content: The prevalence of coronavirus disease 2019 (COVID\u201019) is lower in children compared to adults. Children contribute to 1\u20105% of all COVID\u201019 cases (1) . A recent study from China reported that 171(12.3%) of 1391 children with suspected disease had confirmed COVID\u201019 infection (2) . As of May 15, 2020, there are 33,241 children with COVID\u201019 in the United States (3) . The most common symptoms in children with confirmed and suspected COVID\u201019 include fever and cough followed by diarrhea, and abdominal pain.", "qid": 47, "docid": "3dcctl1c", "rank": 40, "score": 0.8476517796516418}, {"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": 41, "score": 0.8474457859992981}, {"content": "Title: Childhood COVID-19: a multicentre retrospective study Content: OBJECTIVES: To investigate the clinical and epidemiological characteristics of paediatric patients with coronavirus disease-19 (COVID-19). METHODS: Paediatric patients diagnosed with COVID-19 between January 15 and March 15, 2020, from seven hospitals in Zhejiang Province, China, were collected retrospectively and analysed. RESULTS: Thirty-two children with COVID-19, ranging in age from 3 months to 18 years, were enrolled. Family aggregation occurred in 87.5% of infant and preschool-aged children (7/8), and also school-aged children (14/16), but in only 12.5% (1/8) of adolescents (p < 0.05, p < 0.001). Most of these patients had mild symptoms: mainly fever (20/32) followed by cough (10/32) and fatigue (4/32). The average durations of viral RNA in respiratory samples and gastrointestinal samples were 15.8 d and 28.9 d, respectively. Detox duration in faeces decreased with age: 39.8 d, 27.5 d and 20.4 d in infants and preschool children, school children, and adolescents respectively (p0-6, -18 <0.01, p0-6, -14 <0.05). Pneumonia was found in 14 children, but there was no statistical significance in the incidence of pneumonia between different age groups. Thirty patients were treated with antiviral drugs, and all patients were stable and gradually improved after admission. CONCLUSIONS: Most children with COVID-19 had a mild process and a good prognosis. More attention should be paid to investigation of household contact history in the diagnosis of COVID-19 in young children. Viral RNA lasts longer in the gastrointestinal system than in the respiratory tract, especially in younger children.", "qid": 47, "docid": "v6kh517q", "rank": 42, "score": 0.8472694754600525}, {"content": "Title: Clinical Characteristics of Children with Coronavirus Disease 2019 in Hubei, China Content: Since December 2019, COVID-19 has occurred unexpectedly and emerged as a health problem worldwide. Despite the rapidly increasing number of cases in subsequent weeks, the clinical characteristics of pediatric cases are rarely described. A cross-sectional multicenter study was carried out in 10 hospitals across Hubei province. A total of 25 confirmed pediatric cases of COVID-19 were collected. The demographic data, epidemiological history, underlying diseases, clinical manifestations, laboratory and radiological data, treatments, and outcomes were analyzed. Of 25 hospitalized patients with COVID-19, the boy to girl ratio was 1.27:1. The median age was 3 years. COVID-19 cases in children aged <3 years, 3.6 years, and &#8805;6-years patients were 10 (40%), 6 (24%), and 9 (36%), respectively. The most common symptoms at onset of illness were fever (13 [52%]), and dry cough (11 [44%]). Chest CT images showed essential normal in 8 cases (33.3%), unilateral involvement of lungs in 5 cases (20.8%), and bilateral involvement in 11 cases (45.8%). Clinical diagnoses included upper respiratory tract infection (n=8), mild pneumonia (n=15), and critical cases (n=2). Two critical cases (8%) were given invasive mechanical ventilation, corticosteroids, and immunoglobulin. The symptoms in 24 (96%) of 25 patients were alleviated and one patient had been discharged. It was concluded that children were susceptible to COVID-19 like adults, while the clinical presentations and outcomes were more favorable in children. However, children less than 3 years old accounted for majority cases and critical cases lied in this age group, which demanded extra attentions during home caring and hospitalization treatment.", "qid": 47, "docid": "ioauiuu5", "rank": 43, "score": 0.8471099138259888}, {"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": 47, "docid": "dmrtsxik", "rank": 44, "score": 0.8470474481582642}, {"content": "Title: SARS-CoV-2 infection in children - Understanding the immune responses and controlling the pandemic. Content: In December 2019, a cluster of patients with severe pneumonia caused by a novel coronavirus (SARS-CoV-2) emerged in the city of Wuhan, China. The disease is now termed coronavirus disease 2019 (COVID-19). In the early reports, the patients were mainly middle-aged and elderly men, and children appeared to be less susceptible to this infection. With modern and efficient transportation, the disease quickly spread to almost all corners of the world and the mortality far exceeds those caused by severe acute respiratory syndrome coronavirus (SARS) or Middle East respiratory syndrome coronavirus (MERS). As the number of children with COVID-19 gradually increases, the disease has been documented in premature babies, infants, children and adolescents. Severe and fatal cases in children are relatively rare. The burden of disease in children has been relatively low, but the high proportions of asymptomatic or mildly symptomatic infections in children deserve careful attention. Clear understanding of the immune responses to the virus in children and the transmission potential of asymptomatic children are of paramount importance for the development of specific treatments and vaccine in order to effectively control the ongoing pandemic.", "qid": 47, "docid": "dxe7yvix", "rank": 45, "score": 0.8469343781471252}, {"content": "Title: Clinical Characteristics of Children with Coronavirus Disease 2019 in Hubei, China Content: Since December 2019, COVID-19 has occurred unexpectedly and emerged as a health problem worldwide. Despite the rapidly increasing number of cases in subsequent weeks, the clinical characteristics of pediatric cases are rarely described. A cross-sectional multicenter study was carried out in 10 hospitals across Hubei province. A total of 25 confirmed pediatric cases of COVID-19 were collected. The demographic data, epidemiological history, underlying diseases, clinical manifestations, laboratory and radiological data, treatments, and outcomes were analyzed. Of 25 hospitalized patients with COVID-19, the boy to girl ratio was 1.27:1. The median age was 3 years. COVID-19 cases in children aged <3 years, 3.6 years, and \u22656-years patients were 10 (40%), 6 (24%), and 9 (36%), respectively. The most common symptoms at onset of illness were fever (13 [52%]), and dry cough (11 [44%]). Chest CT images showed essential normal in 8 cases (33.3%), unilateral involvement of lungs in 5 cases (20.8%), and bilateral involvement in 11 cases (45.8%). Clinical diagnoses included upper respiratory tract infection (n=8), mild pneumonia (n=15), and critical cases (n=2). Two critical cases (8%) were given invasive mechanical ventilation, corticosteroids, and immunoglobulin. The symptoms in 24 (96%) of 25 patients were alleviated and one patient had been discharged. It was concluded that children were susceptible to COVID-19 like adults, while the clinical presentations and outcomes were more favorable in children. However, children less than 3 years old accounted for majority cases and critical cases lied in this age group, which demanded extra attentions during home caring and hospitalization treatment.", "qid": 47, "docid": "ou80n3p3", "rank": 46, "score": 0.8468934297561646}, {"content": "Title: Clinical features of pediatric patients with coronavirus disease (COVID-19) Content: BACKGROUND: Coronavirus disease 2019 (COVID-19) caused by SARS-CoV-2 has spread around the world, and reports of children with COVID-19 are increasing. OBJECTIVES: To assess clinical profiles of pediatric COVID-19. STUDY DESIGN: A retrospective analysis was undertaken using clinical data of sixteen children (11 months-14 years) diagnosed with COVID-19 between January 1, 2020 and March 17, 2020 at Xiangyang Central Hospital, Hubei province, China. RESULTS: All children had positive epidemiologic histories, 12 (12/16, 75 %) involving family units. The illnesses were either mild (5/16, 31.3 %) or ordinary (11/16, 68.8 %), presenting as follows: asymptomatic (8/16, 50 %), fever and/or cough (8/16, 50 %). Four asymptomatic patients (4/16, 25 %) in ordinary cases had chest computed tomography (CT) abnormalities. Leukocyte counts were normal in 14 cases(88 %), but 2 patients (12.5 %) had leukopenia, and 1 (6.3 %) was lymphopenic. There were 11 patients with chest CT abnormalities, some nodular, others small patchy and others ground-glass opacities. In asymptomatic children, the median time to SRAS-CoV-2 nucleic acid test(NAT) positivity once exposed to a family member with confirmed infection was 15.5 days (range, 10-26 days). The median time to first NAT-negative conversion was 5.5 days (range, 1-23 days). CONCLUSIONS: COVID-19 in children of Xiangyang city is often family acquired and not serious, with favorable outcomes. Asymptomatic children can be diagnosed as pneumonia because of chest CT abnormalities. It is essential to actively screen this segment of the population.", "qid": 47, "docid": "feujr1vv", "rank": 47, "score": 0.8468751907348633}, {"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": 48, "score": 0.8468626737594604}, {"content": "Title: Coronavirus disease 2019 (COVID-19) in children and/or adolescents: a meta-analysis Content: BACKGROUND: To assess the overall prevalence of clinical signs, symptoms, and radiological findings in children and/or adolescents with COVID-19. METHODS: We systematically researched in PubMed, Scopus and Web of Science databases observational studies describing COVID-19 in children and/or adolescents until April 11, 2020. Data regarding clinical and radiological features were extracted from eligible studies and meta-analysis was performed using random-effects modeling. RESULTS: We examined 19 eligible studies for a total of 2855 children and/or adolescents with COVID-19. Approximately 47% of subjects had fever (95% confidence interval [CI] 22-72%; I2 = 98.6%), 37% cough (95%CI 15-63%; I2 = 98.6%), 4% diarrhea (95%CI 0-12%; I2 = 92.2%), 2% nasal congestion (95%CI 0-7%; I2 = 87.7%), 1% dyspnea (95%CI 0-7%; I2 = 91.5%) and 0% abdominal pain (95%CI 0-1%; I2 = 76.3%). Subjects presented mild symptoms in 79% (95%CI 65-91%; I2 = 93.5%) of cases, whereas only 4% (95%CI 1-9%; I2 = 76.4%) were critical. Among those with pneumonia on computed tomography, 26.4% (95%CI 13-41%; I2 = 80.8%) presented a unilateral involvement, 16% (95%CI 5-29%, I2 = 81.2%) had bilateral involvement and 9% (95%CI 0-24%; I2 = 88.7%) had interstitial pneumonia. CONCLUSIONS: Children and/or adolescents tend to have a mild COVID-19 course with a good prognosis. IMPACT: Compared to adults, children and/or adolescents tend to have a mild COVID-19 course with a good prognosis.This study provides new and consistence information on the clinical and radiological characteristics of COVID-19 in pediatrics.This study may help to fight COVID-19 in pediatric population.", "qid": 47, "docid": "hw4kgs6h", "rank": 49, "score": 0.8468616008758545}, {"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": 47, "docid": "828ubhzi", "rank": 50, "score": 0.8467355966567993}, {"content": "Title: Novel coronavirus infection (COVID-19) in children younger than one year: A systematic review of symptoms, management and outcomes Content: AIM: The aim of this systematic review was to evaluate the clinical characteristics of COVID-19 in neonates and children under one year of age. METHODS: A systematic literature review of the MEDLINE, PubMed, CINAHL, Embase and EBSCO databases was carried out for studies from January 1, 2020, to April 7, 2020. We included all papers that addressed clinical manifestations, laboratory results, imaging findings and outcomes in infants and neonates. RESULTS: Our search identified 77 peer-reviewed papers, and 18 papers covering 160 infants were reviewed. One paper was from Vietnam, and the other 17 were from China: eight were cross-sectional studies, eight were case reports, one was a case series, and one was a prospective cohort study. The most common clinical symptoms were fever (54%) and cough (33%). Most infants were treated symptomatically, with frequent use of various empirical medications. Infants and neonates tended to have more severe COVID-19 disease than older children: 11 (7%) were admitted to intensive care and one infant died. The mortality rate was 0.006%, with favourable outcomes in most cases. CONCLUSION: Infants and neonates were more vulnerable to more severe COVID-19 disease than older children, but morbidity and mortality were low.", "qid": 47, "docid": "1n3t23ag", "rank": 51, "score": 0.8467116355895996}, {"content": "Title: SARS-CoV-2 infection in children - Understanding the immune responses and controlling the pandemic Content: In December 2019, a cluster of patients with severe pneumonia caused by a novel coronavirus (SARS-CoV-2) emerged in the city of Wuhan, China. The disease is now termed coronavirus disease 2019 (COVID-19). In the early reports, the patients were mainly middle-aged and elderly men, and children appeared to be less susceptible to this infection. With modern and efficient transportation, the disease quickly spread to almost all corners of the world and the mortality far exceeds that caused by severe acute respiratory syndrome (SARS) coronavirus or Middle East respiratory syndrome (MERS) coronavirus. As the number of children with COVID-19 gradually increases, the disease has been documented in premature babies, infants, children, and adolescents. Severe and fatal cases in children are relatively rare. The burden of disease in children has been relatively low, but the high proportions of asymptomatic or mildly symptomatic infections in children deserve careful attention. A clear understanding of the immune responses to the virus in children and the transmission potential of asymptomatic children is of paramount importance for the development of specific treatments and vaccine in order to effectively control the ongoing pandemic.", "qid": 47, "docid": "t81vxgxu", "rank": 52, "score": 0.8462389707565308}, {"content": "Title: Clinical Characteristics of COVID-19 Infection in Newborns and Pediatrics: A Systematic Review Content: INTRODUCTION: World Health Organization has declared COVID-19 a pandemic and a global health emergency. Thus, it is necessary to clearly characterize clinical manifestations and management of COVID-19 infection in children to provide accurate information for healthcare workers. Accordingly, the present study was designed to review articles published on clinical manifestations and characteristics of children and infants with COVID-19. METHODS: In this systematic review, medical databases including Cochrane Library, Web of Science, Embase, Scopus, SID, Medline, WHO and LitCovid were searched using English and Persian keywords including COVID-19, Pediatrics, Newborn, Coronavirus 2019, 2019-nCoV, SARS-CoV-2. Finally, data of 14 related articles were included in the study. RESULTS: A total of 2228 children, newborns and infants were studied. Clinical manifestation in children may be mild (72%), moderate (22%) or severe (6%), and the most common symptoms include dry cough (91%) and fever (96%). According to the included articles, two children had died, one of which was a 14-year-old boy and his exposure history and underlying disease were unclear, and the other was a male newborn with gestational age of 35 weeks and 5 days, birth weight of 2200, Apgar score of 8, 8 (1 min and 5 min) and his first symptom was increased heart rate. No differences were found between male and female children regarding infection with COVID-19. CONCLUSION: Most pediatrics were infected with COVID-19 due to family cluster or history of close contact. Infected children have relatively milder clinical symptoms compared to infected adults. We should pay special attention to early diagnosis and early treatment in children infected with COVID-19.", "qid": 47, "docid": "33ixlhxc", "rank": 53, "score": 0.8461441993713379}, {"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": 54, "score": 0.8456073999404907}, {"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": 47, "docid": "12sakknb", "rank": 55, "score": 0.8452752828598022}, {"content": "Title: Clinical Characteristics and Outcomes of Hospitalized and Critically Ill Children and Adolescents with Coronavirus Disease 2019 (COVID-19) at a Tertiary Care Medical Center in New York City Content: OBJECTIVE: To describe the clinical profiles and risk factors for critical illness in hospitalized children and adolescents with COVID-19. STUDY DESIGN: Children 1 month to 21 years with COVID-19 from a single tertiary care children's hospital between March 15-April 13, 2020 were included. Demographic and clinical data were collected. RESULTS: 67 children tested positive for COVID-19; 21 (31.3%) were managed as outpatients. Of 46 admitted patients, 33 (72%) were admitted to the general pediatric medical unit and 13 (28%) to the pediatric intensive care unit (PICU). Obesity and asthma were highly prevalent but not significantly associated with PICU admission (p=0.99). Admission to the PICU was significantly associated with higher C-reactive protein, procalcitonin, and pro-B type natriuretic peptide levels and platelet counts (p<0.05 for all). Patients in the PICU were more likely to require high-flow nasal cannula (p=0.0001) and were more likely to have received Remdesivir through compassionate release (p<0.05). Severe sepsis and septic shock syndromes were observed in 7 (53.8%) PICU patients. Acute respiratory distress syndrome (ARDS) was observed in 10 (77%) PICU patients, 6 of whom (46.2%) required invasive mechanical ventilation for a median of 9 days. Of the 13 patients in the PICU, 8 (61.5%) were discharged home, and 4 (30.7%) patients remain hospitalized on ventilatory support at day 14. One patient died after withdrawal of life-sustaining therapy because of metastatic cancer. CONCLUSIONS: We describe a higher than previously recognized rate of severe disease requiring PICU admission in pediatric patients admitted to the hospital with COVID-19.", "qid": 47, "docid": "t5fpm082", "rank": 56, "score": 0.8449949026107788}, {"content": "Title: Children Hospitalized With Severe COVID-19 in Wuhan Content: BACKGROUND: Novel coronavirus disease (COVID-19) is spreading globally. Little is known about the risk factors for the clinical outcomes of COVID-19 in children. METHODS: A retrospective case-control study was taken in children with severe acute respiratory syndrome coronary virus-2 infection in Wuhan Children's Hospital. Risk factors associated with the development of COVID-19 and progression were collected and analyzed. RESULTS: Eight of 260 children diagnosed with severe COVID-19 pneumonia were included in the study. Thirty-five children with COVID-19 infection matched for age, sex and date of admission, and who classified as non-severe type, were randomly selected from the hospital admissions. For cases with severe pneumonia caused by COVID-19, the most common symptoms were dyspnea (87.5%), fever (62.5%) and cough (62.5%). In laboratory, white blood cells count was significantly higher in severe children than non-severe children. Levels of inflammation bio-makers such as hsCRP, IL-6, IL-10 and D-dimer elevated in severe children compared with non-severe children on admission. The level of total bilirubin and uric acid clearly elevated in severe children compared with non-severe children on admission. All of severe children displayed the lesions on chest CT, more lung segments were involved in severe children than in non-severe children, which was only risk factor associated with severe COVID-19 pneumonia in multivariable analysis. CONCLUSIONS: More than 3 lung segments involved were associated with greater risk of development of severe COVID-19 in children. Moreover, the possible risk of the elevation of IL-6, high total bilirubin and D-dimer with univariable analysis could identify patients to be severe earlier.", "qid": 47, "docid": "9cr0bk2a", "rank": 57, "score": 0.8447763323783875}, {"content": "Title: Pediatric COVID-19: Systematic review of the literature Content: OBJECTIVES: There is limited data regarding the demographics and clinical features of SARS-CoV-2 infection in children. This information is especially important as pneumonia is the single leading cause of death in children worldwide. This Systematic Review aims to elucidate a better understanding of the global impact of COVID-19 on the pediatric population. METHODS: A systematic review of the literature was performed in accordance with PRISMA (Preferred Reporting Items for Systematic Reviews and Meta-Analyses) guidelines to gain insight into pediatric COVID-19 epidemiology. Specifically, Pubmed and Google Scholar databases were searched to identify any relevant article with a focus on Pediatric Covid 19, Pediatric Covid-19, Pediatric SARS-COV-2, and Pediatric Coronavirus 19. References within the included articles were reviewed. All articles that met criteria where analyzed for demographics, clinical, laboratory, radiographic, treatment and outcomes data. RESULTS: Ten studies including two case series and 8 retrospective chart reviews, altogether describing a total of 2914 pediatric patients with COVID-19 were included in this systematic review. Of the patients whose data was available, 56% were male, the age range was 1\u00e2\u0080\u00afday to 17\u00e2\u0080\u00afyears, 79% were reported to have no comorbidities, and of the 21% with comorbidities, the most common were asthma, immunosupression, and cardiovascular disease. Of pediatric patients that were tested and positive for an infection with SARS-CoV-2, patients were asymptomatic, 14.9% of the time. Patients presented with cough (48%), fever (47%) and sore throat/pharyngitis (28.6%), more commonly than with upper respiratory symptoms/rhinorrhea/sneezing/nasal congestion (13.7%), vomiting/nausea (7.8%) and diarrhea (10.1%). Median lab values including those for WBC, lymphocyte count and CRP, were within the reference ranges with the exception of procalcitonin levels, which were slightly elevated in children with COVID-19 (median procalcitonin levels ranged from 0.07 to 0.5\u00e2\u0080\u00afng/mL. Computed tomography (CT) results suggest that unilateral CT imaging findings are present 36% of cases while 64% of pediatric patients with COVID-19 had bilateral findings. Of the studies with age specific hospitalization data available, 27.0% of patients hospitalized were infants under 1\u00e2\u0080\u00afyear of age. Various treatment regimens including interferon, antivirals, and hydroxychloroquine therapies have been trialed on the pediatric population but there are currently no studies showing efficacy of one regimen over the other. The mortality rate of children that were hospitalized with COVID-19 was 0.0018%. CONCLUSION: In contrast to adults, most infected children appear to have a milder course and have better outcomes overall. Additional care may be needed for children with comorbidities and younger children. This review also suggests that unilateral CT chest imaging findings were seen in 36.4% pediatric COVID-19 patients. This is particularly concerning as the work-up of pediatric patients with cough may warrant a bronchoscopy to evaluate for airway foreign bodies. Extra precautions need to be taken with personal protective equipment for these cases, as aerosolizing procedures may be a method of viral transmission. LEVEL OF EVIDENCE: 4 (Systematic Review).", "qid": 47, "docid": "fmmm8itx", "rank": 58, "score": 0.8447366952896118}, {"content": "Title: Flash survey on severe acute respiratory syndrome coronavirus-2 infections in paediatric patients on anticancer treatment Content: INTRODUCTION: Since the beginning of COVID-19 pandemic, it is known that the severe course of the disease occurs mostly among the elderly, whereas it is rare among children and young adults. Comorbidities, in particular, diabetes and hypertension, clearly associated with age, besides obesity and smoke, are strongly associated with the need for intensive treatment and a dismal outcome. A weaker immunity of the elderly has been proposed as a possible explanation of this uneven age distribution. Thus, there is concern that children treated for cancer may allso be at risk for an unfavourable course of infection. Along the same line, anecdotal information from Wuhan, China, mentioned a severe course of COVID-19 in a child treated for leukaemia. AIM AND METHODS: We made a flash survey on COVID-19 incidence and severity among children on anticancer treatment. Respondents were asked by email to fill in a short Web-based survey. RESULTS: We received reports from 25 countries, where approximately 10,000 patients at risk are followed up. At the time of the survey, more than 200 of these children were tested, nine of whom were positive for COVID-19. Eight of the nine cases had asymptomatic to mild disease, and one was just diagnosed with COVID-19. We also discuss preventive measures that are in place or should be taken and treatment options in immunocompromised children with COVID-19. CONCLUSION: Thus, even children receiving anticancer chemotherapy may have a mild or asymptomatic course of COVID-19. While we should not underestimate the risk of developing a more severe course of COVID-19 than that observed here, the intensity of preventive measures should not cause delays or obstructions in oncological treatment.", "qid": 47, "docid": "vz4c270q", "rank": 59, "score": 0.8447213172912598}, {"content": "Title: The Epidemiological and Clinical Characteristics of 81 Children with COVID-19 in a Pandemic Hospital in Turkey: an Observational Cohort Study Content: BACKGROUND: Coronavirus disease-2019 (COVID-19) pandemic has affected millions of people throughout the world since December 2019. However, there is a limited amount of data about pediatric patients infected with the disease agent, the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). METHODS: The epidemiological, laboratory, radiological, and treatment features of the pediatric patients who were positive for SARS-CoV-2 based on the reverse-transcription polymerase chain reaction (RT-PCR) test, were investigated retrospectively. RESULTS: The median age of 81 children included in the study was 9.50 years (0\u201317.75 years). The most frequent symptoms at the time of admission were fever (58%), cough (52%), and fatigue or myalgia (19%). The abnormal laboratory findings in these cases were decreased lymphocytes (2.5%, n = 2), leucopenia (5%, n = 4), and increased lactate dehydrogenase (17.2%, n = 14), C-reactive protein (16%, n = 13), procalcitonin (3.7%, n = 3), and D-dimer (12.3%, n = 10). Three (4%) patients had consolidation in chest computed tomography, and three (4%) had ground-glass opacities. None of the patients needed intensive care except for the newborns. The median time to turn SARS-CoV-2 negative in the RT-PCR test was 5 (3\u201310) days. The median length of hospital stay was 5 (4\u201310) days. The time to turn SARS-CoV-2 negative in the RT-PCR test and the length of hospital stay were significantly longer for those aged five years or younger than others (P = 0.037, P = 0.01). CONCLUSION: Compared to adults, COVID-19 is milder and more distinctive in children. As a result, more conservative approaches might be preferred in children for the diagnostic, clinical, and even therapeutic applications.", "qid": 47, "docid": "fyzi38zd", "rank": 60, "score": 0.8434807062149048}, {"content": "Title: [CURRENT KNOWLEDGE ON COVID-19 IN CHILDREN - CAUTIOUS OPTIMISM]. Content: INTRODUCTION The recent outbreak of COVID-19 which began in Wuhan, China in December 2019 and rapidly spread worldwide evolving into a pandemic, poses a global health emergency. As of mid-April over 2 million people have been infected with over 145 thousand casualties. The disease is more severe in the older population, whereas in children lower infection rates and milder symptoms are more common. Severe symptoms in the pediatric population, although uncommon, have been reported mainly in infants younger than 1 year of age. Perinatal transmission is infrequent and associated with a relatively mild illness in the newborn.", "qid": 47, "docid": "9fgq8jhi", "rank": 61, "score": 0.8433927297592163}, {"content": "Title: Clinical Characteristics and Outcomes of Hospitalized and Critically Ill Children and Adolescents with Coronavirus Disease 2019 (COVID-19) at a Tertiary Care Medical Center in New York City Content: OBJECTIVE: To describe the clinical profiles and risk factors for critical illness in hospitalized children and adolescents with COVID-19. STUDY DESIGN: Children 1 month to 21 years with COVID-19 from a single tertiary care children\u2019s hospital between March 15-April 13, 2020 were included. Demographic and clinical data were collected. RESULTS: 67 children tested positive for COVID-19; 21 (31.3%) were managed as outpatients. Of 46 admitted patients, 33 (72%) were admitted to the general pediatric medical unit and 13 (28%) to the pediatric intensive care unit (PICU). Obesity and asthma were highly prevalent but not significantly associated with PICU admission (p=0.99). Admission to the PICU was significantly associated with higher C-reactive protein, procalcitonin, and pro-B type natriuretic peptide levels and platelet counts (p<0.05 for all). Patients in the PICU were more likely to require high-flow nasal cannula (p=0.0001) and were more likely to have received Remdesivir through compassionate release (p<0.05). Severe sepsis and septic shock syndromes were observed in 7 (53.8%) PICU patients. Acute respiratory distress syndrome (ARDS) was observed in 10 (77%) PICU patients, 6 of whom (46.2%) required invasive mechanical ventilation for a median of 9 days. Of the 13 patients in the PICU, 8 (61.5%) were discharged home, and 4 (30.7%) patients remain hospitalized on ventilatory support at day 14. One patient died after withdrawal of life-sustaining therapy because of metastatic cancer. CONCLUSIONS: We describe a higher than previously recognized rate of severe disease requiring PICU admission in pediatric patients admitted to the hospital with COVID-19.", "qid": 47, "docid": "0ifsyct7", "rank": 62, "score": 0.8433837890625}, {"content": "Title: [current Knowledge on Covid-19 in Children - Cautious Optimism] Content: INTRODUCTION: The recent outbreak of COVID-19 which began in Wuhan, China in December 2019 and rapidly spread worldwide evolving into a pandemic, poses a global health emergency. As of mid-April over 2 million people have been infected with over 145 thousand casualties. The disease is more severe in the older population, whereas in children lower infection rates and milder symptoms are more common. Severe symptoms in the pediatric population, although uncommon, have been reported mainly in infants younger than 1 year of age. Perinatal transmission is infrequent and associated with a relatively mild illness in the newborn.", "qid": 47, "docid": "a5jqttue", "rank": 63, "score": 0.8432815074920654}, {"content": "Title: Systematic review of COVID\u201019 in children shows milder cases and a better prognosis than adults Content: AIM: The coronavirus disease 2019 (COVID\u201019) pandemic has affected hundreds of thousands of people. Data on symptoms and prognosis in children are rare. METHODS: A systematic literature review was carried out to identify papers on COVID\u201019, which is caused by the severe acute respiratory syndrome coronavirus 2 (SARS\u2010CoV\u20102), using the MEDLINE and Embase databases between January 1 and March 18, 2020. RESULTS: The search identified 45 relevant scientific papers and letters. The review showed that children have so far accounted for 1%\u20105% of diagnosed COVID\u201019 cases, they often have milder disease than adults and deaths have been extremely rare. Diagnostic findings have been similar to adults, with fever and respiratory symptoms being prevalent, but fewer children seem to have developed severe pneumonia. Elevated inflammatory markers were less common in children, and lymphocytopenia seemed rare. Newborn infants have developed symptomatic COVID\u201019, but evidence of vertical intrauterine transmission was scarce. Suggested treatment included providing oxygen, inhalations, nutritional support and maintaining fluids and electrolyte balances. CONCLUSIONS: The coronavirus disease 2019 has occurred in children, but they seemed to have a milder disease course and better prognosis than adults. Deaths were extremely rare.", "qid": 47, "docid": "sgokzw5i", "rank": 64, "score": 0.842982292175293}, {"content": "Title: Favourable outcome of coronavirus disease 2019 in a 1\u2010year\u2010old girl with acute myeloid leukaemia and severe treatment\u2010induced immunosuppression Content: Since the beginning of coronavirus disease 2019 (COVID-19) pandemic outbreak, it has emerged that the clinical course and outcome of Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2) is definitely more favourable in children than in adults.1 Few cases of infection in children with cancer are described; also in these patients, except for one reported case,2 the disease was largely asymptomatic.3 Nevertheless, the management of COVID-19 in young patients with comorbidities, particularly cancer, remains a challenge for the clinician; further data are required to optimize the clinical approach to these cases.", "qid": 47, "docid": "4cz2hziz", "rank": 65, "score": 0.8424282670021057}, {"content": "Title: Clinical characteristics of a case series of children with coronavirus disease 2019 Content: We reported the clinical characteristics of a case series of 10 patients with coronavirus disease 2019 (COVID-19) aged from 1 year to 18 years. Seven patients had contact with confirmed COVID-19 family members before onset. Fever (4 [40.0%]) and cough (3 [30.0%]) were the most common symptoms. No patient showed leucopenia and lymphopenia on admission. Pneumonia was observed in chest CT images in 5 (50.0%) patients. Five (50.0%) patients received antiviral treatment. No patient had severe complications or developed a severe illness in our study. Our study indicated that COVID-19 children present less severe symptoms and have better outcomes.", "qid": 47, "docid": "nb08i303", "rank": 66, "score": 0.8423389196395874}, {"content": "Title: The Epidemiological and Clinical Characteristics of 81 Children with COVID-19 in a Pandemic Hospital in Turkey: an Observational Cohort Study Content: BACKGROUND: Coronavirus disease-2019 (COVID-19) pandemic has affected millions of people throughout the world since December 2019. However, there is a limited amount of data about pediatric patients infected with the disease agent, the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). METHODS: The epidemiological, laboratory, radiological, and treatment features of the pediatric patients who were positive for SARS-CoV-2 based on the reverse-transcription polymerase chain reaction (RT-PCR) test, were investigated retrospectively. RESULTS: The median age of 81 children included in the study was 9.50 years (0-17.75 years). The most frequent symptoms at the time of admission were fever (58%), cough (52%), and fatigue or myalgia (19%). The abnormal laboratory findings in these cases were decreased lymphocytes (2.5%, n = 2), leucopenia (5%, n = 4), and increased lactate dehydrogenase (17.2%, n = 14), C-reactive protein (16%, n = 13), procalcitonin (3.7%, n = 3), and D-dimer (12.3%, n = 10). Three (4%) patients had consolidation in chest computed tomography, and three (4%) had ground-glass opacities. None of the patients needed intensive care except for the newborns. The median time to turn SARS-CoV-2 negative in the RT-PCR test was 5 (3-10) days. The median length of hospital stay was 5 (4-10) days. The time to turn SARS-CoV-2 negative in the RT-PCR test and the length of hospital stay were significantly longer for those aged five years or younger than others (P = 0.037, P = 0.01). CONCLUSION: Compared to adults, COVID-19 is milder and more distinctive in children. As a result, more conservative approaches might be preferred in children for the diagnostic, clinical, and even therapeutic applications.", "qid": 47, "docid": "onuji0hh", "rank": 67, "score": 0.8421972990036011}, {"content": "Title: Screening of COVID-19 in children admitted to the hospital for acute problems: preliminary data Content: BACKGROUND: The new Coronavirus identified in Whuan at the end of 2019 (SARS-CoV-2) belongs to the Beta Coronavirus genus and is responsible for the new Coronavirus 2019 pandemia (COVID-19). Infected children may be asymptomatic or present fever, dry cough, fatigue or gastrointestinal symptoms. The CDC recommends that clinicians should decide to test patients based on the presence of signs and symptoms compatible with COVID-19. MATERIAL AND METHODS: 42 children (the majority < 5 years of age) were referred, to our Pediatric Department, as possible cases of COVID-19 infection. Blood analysis, chest X-ray, and naso-oropharyngeal swab specimens for viral identification of COVID-19 were requested. RESULTS: None of the screened children resulted positive for COVID-19 infection. At first presentation, the most frequent signs and symptoms were: fever (71.4%), fatigue (35.7%) and cough (30.9%). An high C-reactive protein value and abnormalities of chest X-ray (bronchial wall thickening) were detected in 26.2% and 19% of patients, respectively. Almost half of patients (45.2%) required hospitalization in our Pediatric Unit and one patient in Intensive Care Unit. CONCLUSIONS: Testing people who meet the COVID-19 suspected case definition criteria is essential for clinical management and outbreak control. Children of all ages can get COVID-19, although they appear to be affected less frequently than adults, as reported in our preliminary survey. Further studies are needed to confirm our observations.", "qid": 47, "docid": "xmjyaktl", "rank": 68, "score": 0.8420940637588501}, {"content": "Title: A Mini Review on Current Clinical and Research Findings for Children Suffering from COVID-19 Content: Background: As the novel coronavirus triggering COVID-19 has broken out in Wuhan, China and spread rapidly worldwide, it threatens the lives of thousands of people and poses a global threat on the economies of the entire world. However, infection with COVID-19 is currently rare in children. Objective To discuss the latest findings and research focus on the basis of characteristics of children confirmed with COVID-19, and provide an insight into the future treatment and research direction. Methods: We searched the terms \"COVID-19 OR coronavirus OR SARS-CoV-2\" AND \"Pediatric OR children\" on PubMed, Embase, Cochrane library, NIH, CDC, and CNKI. The authors also reviewed the guidelines published on Chinese CDC and Chinese NHC. Results: We included 25 published literature references related to the epidemiology, clinical manifestation, accessary examination, treatment, and prognosis of pediatric patients with COVID-19. Conclusion: The numbers of children with COVID-19 pneumonia infection are small, and most of them come from family aggregation. Symptoms are mainly mild or even asymptomatic, which allow children to be a risk factor for transmission. Thus, strict epidemiological history screening is needed for early diagnosis and segregation. This holds especially for infants, who are more susceptible to infection than other age groups in pediatric age, but have most likely subtle and unspecific symptoms. They need to be paid more attention to. CT examination is a necessity for screening the suspected cases, because most of the pediatric patients are mild cases, and plain chest X-ray do not usually show the lesions or the detailed features. Therefore, early chest CT examination combined with pathogenic detection is a recommended clinical diagnosis scheme in children. The risk factors which may suggest severe or critical progress for children are: Fast respiratory rate and/or; lethargy and drowsiness mental state and/or; lactate progressively increasing and/or; imaging showed bilateral or multi lobed infiltration, pleural effusion or rapidly expending of lesions in a short period of time and/or; less than 3 months old or those who underly diseases. For those critical pediatric patients with positive SARS-CoV-2 diagnosis, polypnea may be the most common symptom. For treatment, the elevated PCT seen in children in contrast to adults suggests that the underlying coinfection/secondary infection may be more common in pediatric patients and appropriate antibacterial treatment should be considered. Once cytokine storm is found in these patients, anti-autoimmune or blood-purifying therapy should be given in time. Furthermore, effective isolation measures and appropriate psychological comfort need to be provided timely.", "qid": 47, "docid": "f9hyntvf", "rank": 69, "score": 0.8419983983039856}, {"content": "Title: Coronavirus Disease 2019 Case Surveillance \u2014 United States, January 22\u2013May 30, 2020 Content: The coronavirus disease 2019 (COVID-19) pandemic resulted in 5,817,385 reported cases and 362,705 deaths worldwide through May, 30, 2020,\u2020 including 1,761,503 aggregated reported cases and 103,700 deaths in the United States.\u00a7 Previous analyses during February-early April 2020 indicated that age \u226565 years and underlying health conditions were associated with a higher risk for severe outcomes, which were less common among children aged <18 years (1-3). This report describes demographic characteristics, underlying health conditions, symptoms, and outcomes among 1,320,488 laboratory-confirmed COVID-19 cases individually reported to CDC during January 22-May 30, 2020. Cumulative incidence, 403.6 cases per 100,000 persons,\u00b6 was similar among males (401.1) and females (406.0) and highest among persons aged \u226580 years (902.0). Among 599,636 (45%) cases with known information, 33% of persons were Hispanic or Latino of any race (Hispanic), 22% were non-Hispanic black (black), and 1.3% were non-Hispanic American Indian or Alaska Native (AI/AN). Among 287,320 (22%) cases with sufficient data on underlying health conditions, the most common were cardiovascular disease (32%), diabetes (30%), and chronic lung disease (18%). Overall, 184,673 (14%) patients were hospitalized, 29,837 (2%) were admitted to an intensive care unit (ICU), and 71,116 (5%) died. Hospitalizations were six times higher among patients with a reported underlying condition (45.4%) than those without reported underlying conditions (7.6%). Deaths were 12 times higher among patients with reported underlying conditions (19.5%) compared with those without reported underlying conditions (1.6%). The COVID-19 pandemic continues to be severe, particularly in certain population groups. These preliminary findings underscore the need to build on current efforts to collect and analyze case data, especially among those with underlying health conditions. These data are used to monitor trends in COVID-19 illness, identify and respond to localized incidence increase, and inform policies and practices designed to reduce transmission in the United States.", "qid": 47, "docid": "tdxrx9se", "rank": 70, "score": 0.8417531847953796}, {"content": "Title: SARS-CoV-2 Seroprevalence Rates of Children in Louisiana During the State Stay at Home Order. Content: Children (less than 19 years) account for 20% of the US population but currently represent less than 2% of coronavirus disease 2019 (COVID-19) cases. Because infected children often have few or no symptoms and may not be tested, the extent of infection in children is poorly understood. METHODS During the March 18th-May 15th 2020 Louisiana Stay At Home Order, 1690 blood samples from 812 individuals from a Childrens Hospital were tested for antibodies to severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) spike protein. Demographics, COVID-19 testing, and clinical presentation abstracted from medical records were compared with local COVID-19 cases. RESULTS In total, 62 subjects (7.6%) were found to be seropositive. The median age was 11 years with 50.4% female. The presenting complaint of seropositive patients was chronic illness (43.5%). Only 18.2% had a previous positive COVID-19 PCR or antibody test. Seropositivity was significantly associated with parish (counties), race, and residence in a low-income area. Importantly, seropositivity was linearly correlated with cumulative COVID-19 case number for all ages by parish. CONCLUSION In a large retrospective study, the seropositivity prevalence for SARS-CoV-2 in children in Louisiana during the mandated Stay At Home Order was 7.6%. Residence location, race, and lower socioeconomic factors were linked to more frequent seropositivity in children and correlated to regional COVID-19 case rates. Thus, a significant number of children in Louisiana had SARS-CoV-2 infections that went undetected and unreported and may have contributed to virus transmission.", "qid": 47, "docid": "7eyttfre", "rank": 71, "score": 0.8411767482757568}, {"content": "Title: Clinical features of pediatric patients with coronavirus disease (COVID-19) Content: Abstract Background Coronavirus disease 2019 (COVID-19) caused by SARS-CoV-2 has spread around the world, and reports of children with COVID-19 are increasing. Objectives To assess clinical profiles of pediatric COVID-19. Study design A retrospective analysis was undertaken using clinical data of sixteen children (11 months-14 years) diagnosed with COVID-19 between January 1, 2020 and March 17, 2020 at Xiangyang Central Hospital, Hubei province, China. Results All children had positive epidemiologic histories, 12 (12/16, 75 %) involving family units. The illnesses were either mild (5/16, 31.3 %) or ordinary (11/16, 68.8 %), presenting as follows: asymptomatic (8/16, 50 %), fever and/or cough (8/16, 50 %). Four asymptomatic patients (4/16, 25 %) in ordinary cases had chest computed tomography (CT) abnormalities. Leukocyte counts were normal in 14 cases(88 %), but 2 patients (12.5 %) had leukopenia, and 1 (6.3 %) was lymphopenic. There were 11 patients with chest CT abnormalities, some nodular, others small patchy and others ground-glass opacities. In asymptomatic children, the median time to SRAS-CoV-2 nucleic acid test(NAT) positivity once exposed to a family member with confirmed infection was 15.5 days (range, 10\u201326 days). The median time to first NAT-negative conversion was 5.5 days (range, 1\u201323 days). Conclusions COVID-19 in children of Xiangyang city is often family acquired and not serious, with favorable outcomes. Asymptomatic children can be diagnosed as pneumonia because of chest CT abnormalities. It is essential to actively screen this segment of the population.", "qid": 47, "docid": "53xjbu8i", "rank": 72, "score": 0.8411744832992554}, {"content": "Title: Coronavirus Disease 2019 Case Surveillance - United States, January 22-May 30, 2020 Content: The coronavirus disease 2019 (COVID-19) pandemic resulted in 5,817,385 reported cases and 362,705 deaths worldwide through May, 30, 2020,\u0086 including 1,761,503 aggregated reported cases and 103,700 deaths in the United States.\u00a7 Previous analyses during February-early April 2020 indicated that age &#8805;65 years and underlying health conditions were associated with a higher risk for severe outcomes, which were less common among children aged <18 years (1-3). This report describes demographic characteristics, underlying health conditions, symptoms, and outcomes among 1,320,488 laboratory-confirmed COVID-19 cases individually reported to CDC during January 22-May 30, 2020. Cumulative incidence, 403.6 cases per 100,000 persons,\u00b6 was similar among males (401.1) and females (406.0) and highest among persons aged &#8805;80 years (902.0). Among 599,636 (45%) cases with known information, 33% of persons were Hispanic or Latino of any race (Hispanic), 22% were non-Hispanic black (black), and 1.3% were non-Hispanic American Indian or Alaska Native (AI/AN). Among 287,320 (22%) cases with sufficient data on underlying health conditions, the most common were cardiovascular disease (32%), diabetes (30%), and chronic lung disease (18%). Overall, 184,673 (14%) patients were hospitalized, 29,837 (2%) were admitted to an intensive care unit (ICU), and 71,116 (5%) died. Hospitalizations were six times higher among patients with a reported underlying condition (45.4%) than those without reported underlying conditions (7.6%). Deaths were 12 times higher among patients with reported underlying conditions (19.5%) compared with those without reported underlying conditions (1.6%). The COVID-19 pandemic continues to be severe, particularly in certain population groups. These preliminary findings underscore the need to build on current efforts to collect and analyze case data, especially among those with underlying health conditions. These data are used to monitor trends in COVID-19 illness, identify and respond to localized incidence increase, and inform policies and practices designed to reduce transmission in the United States.", "qid": 47, "docid": "n2c2typl", "rank": 73, "score": 0.8407285213470459}, {"content": "Title: Impact of the SARS\u2010CoV\u20102 outbreak on pediatric liver transplant recipients residing in Lombardy, Northern Italy Content: The novel Severe Acute Respiratory Syndrome Coronavirus (SARS\u2010CoV\u20102) disease (COVID\u201019) represents an unprecedented public health issue for the general population and for patients with underlying chronic conditions. Compared to adults, children seem to have a milder course of the disease, with very few requiring medical attention", "qid": 47, "docid": "djrrxxsm", "rank": 74, "score": 0.8402711153030396}, {"content": "Title: Radiation therapy considerations during the COVID\u201019 Pandemic: Literature review and expert opinions Content: COVID-19 is an unprecedented pandemic that has already reached over 2 million confirmed cases globally, with at least 140,000 deaths as reported by the World Health Organization (WHO) as of April 16, 2020 1 . More than 662,000 cases have been reported in the United States with more than 29,000 deaths2 . The overall crude mortality rate now stands at 6.6% (may possibly be lower due to under-testing and under-reporting of total confirmed cases), and is highly dependent on age group, comorbidities, and the locoregional resources medically1 . A report from the United States presented age-stratified COVID-19 associated hospitalization rates among 1,482 patients during March 1-28, 2020, highlighting an alarmingly high rate of 74.5% at age > 50 years with underlining medical conditions3 . Based on a data summary report provided by New York City Health, as of April 14, 2020, the shares of a total of 6839 deaths reached 0.04%, 4.5%, 23.1%, 24.6%, and 47.7% for the age groups of 0-17, 18-44, 45-64, 65-74, and 75+ years old4 . All data suggest that adults at a more advanced age group are facing higher morbidity and mortality risks.", "qid": 47, "docid": "j1j5ghl4", "rank": 75, "score": 0.8401442766189575}, {"content": "Title: COVID-19 in Children: Clinical Approach and Management Content: COVID-19 pandemic caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) is a major public health crisis threatening humanity at this point in time. Transmission of the infection occurs by inhalation of infected droplets or direct contact with soiled surfaces and fomites. It should be suspected in all symptomatic children who have undertaken international travel in the last 14 d, all hospitalized children with severe acute respiratory illness, and asymptomatic direct and high-risk contacts of a confirmed case. Clinical symptoms are similar to any acute respiratory viral infection with less pronounced nasal symptoms. Disease seems to be milder in children, but situation appears to be changing. Infants and young children had relatively more severe illness than older children. The case fatality rate is low in children. Diagnosis can be confirmed by Reverse transcriptase \u2013 Polymerase chain reaction (RT-PCR) on respiratory specimen (commonly nasopharyngeal and oropharyngeal swab). Rapid progress is being made to develop rapid diagnostic tests, which will help ramp up the capacity to test and also reduce the time to getting test results. Management is mainly supportive care. In severe pneumonia and critically ill children, trial of hydroxychloroquine or lopinavir/ritonavir should be considered. As per current policy, children with mild disease also need to be hospitalized; if this is not feasible, these children may be managed on ambulatory basis with strict home isolation. Pneumonia, severe disease and critical illness require admission and aggressive management for acute lung injury and shock and/or multiorgan dysfunction, if present. An early intubation is preferred over non-invasive ventilation or heated, humidified, high flow nasal cannula oxygen, as these may generate aerosols increasing the risk of infection in health care personnel. To prevent post discharge dissemination of infection, home isolation for 1\u20132 wk may be advised. As of now, no vaccine or specific chemotherapeutic agents are approved for children.", "qid": 47, "docid": "bxwbpt2o", "rank": 76, "score": 0.8401330709457397}, {"content": "Title: [Clinical features of coronavirus disease 2019 in children aged <18 years in Jiangxi, China: an analysis of 23 cases] Content: OBJECTIVE: To study the clinical features of coronavirus disease 2019 (COVID-19) in children aged <18 years. METHODS: A retrospective analysis was performed from the medical data of 23 children, aged from 3 months to 17 years and 8 months, who were diagnosed with COVID-19 in Jiangxi, China from January 21 to February 29, 2020. RESULTS: Of the 23 children with COVID-19, 17 had family aggregation. Three children (13%) had asymptomatic infection, 6 (26%) had mild type, and 14 (61%) had common type. Among these 23 children, 16 (70%) had fever, 11 (48%) had cough, 8 (35%) had fever and cough, and 8 (35%) had wet rales in the lungs. The period from disease onset or the first nucleic acid-positive detection of SARS-CoV-2 to the virus nucleic acid negative conversion was 6-24 days (median 12 days). Of the 23 children, 3 had a reduction in total leukocyte count, 2 had a reduction in lymphocytes, 2 had an increase in C-reactive protein, and 2 had an increase in D-dimer. Abnormal pulmonary CT findings were observed in 12 children, among whom 9 had patchy ground-glass opacities in both lungs. All 23 children received antiviral therapy and were recovered. CONCLUSIONS: COVID-19 in children aged <18 years often occurs with family aggregation, with no specific clinical manifestation and laboratory examination results. Most of these children have mild symptoms and a good prognosis. Epidemiological history is of particular importance in the diagnosis of COVID-19 in children aged <18 years.", "qid": 47, "docid": "4qjklght", "rank": 77, "score": 0.8401085138320923}, {"content": "Title: Severe and fatal forms of COVID-19 in children Content: OBJECTIVES: The aim of this study was to describe severe forms of novel coronavirus disease 2019 in children, including patient characteristics, clinical, laboratory, and imaging findings, as well as the disease management and outcomes. METHODS: This was a retrospective, single-center, observational study conducted in a pediatric intensive and high-dependency care unit (PICU, HDU) in an urban hospital in Paris. All patients, aged from 1 month to 18 years, admitted for confirmed or highly suspected SARS-CoV-2 were included. RESULTS: We analyzed the data of 27 children. Comorbidities (n=19, 70%) were mainly neurological (n=7), respiratory, (n=4), or sickle cell disease (n=4). SARS-CoV-2 PCR results were positive in 24 children (nasopharyngeal swabs). The three remaining children had a chest CT scan consistent with COVID-19. Respiratory involvement was observed in 24 patients (89%). Supportive treatments were invasive mechanical ventilation (n=9), catecholamine (n=4), erythropheresis (n=4), renal replacement therapy (n=1), and extracorporeal membrane oxygenation (n=1). Five children died, of whom three were without past medical history. CONCLUSION: This study highlighted the large spectrum of clinical presentation and time course of disease progression as well as the non-negligible occurrence of pediatric life-threatening and fatal cases of COVID-19 mostly in patients with comorbidities. Additional laboratory investigations are needed to further analyze the mechanism underlying the variability of SARS-Cov-2 pathogenicity in children.", "qid": 47, "docid": "zi23n8b4", "rank": 78, "score": 0.839967668056488}, {"content": "Title: COVID-19 bei hospitalisierten Kindern und Jugendlichen: Ein systematischer Review zu publizierten Fallserien (Stand 31.03.2020) und erste Daten aus Deutschland Content: BACKGROUND: The clinical knowledge about the course, complications and treatment of COVID-19 in children and adolescents is so far limited. AIM: This systematic review summarizes the current scientific evidence regarding the clinical presentation of COVID-19 in hospitalized children based on available case series from China. In addition, first data from a nationwide pediatric hospital survey conducted by the German Society for Pediatric Infectious Diseases (DGPI) are presented. METHODS: This study evaluated 12 case series from China with 6\u20132143 children infected with SARS-CoV\u20112, which were identified by a literature search in PubMed up to 31 March 2020. The database of the German nationwide DGPI COVID-19 survey was accessed on 6 April 2020. RESULTS: The median patient age in the case series was between 2 and 7 years and 18\u201345% were infants <1 year of age. The duration of hospital stay was 5\u201320 days. Most commonly reported symptoms were fever and cough; in 40\u2013100% of cases involvement of the lower respiratory tract was reported, usually confirmed by computed tomography (CT). Severe and critical courses of disease were reported in up to 8% of the children including 2 fatalities. So far the German DGPI COVID-19 survey reported 33 hospitalized children up to 6 April 2020, mostly with upper airway infections. Of these children, 45% were infants and 32% had an underlying medical condition. So far 3 children (9%) needed admission to an intensive care unit. CONCLUSION: COVID-19 in hospitalized children usually presented as an uncomplicated febrile upper airway infection or mild pneumonia. Severe cases or fatalities rarely occurred in children. Information on neonates and children with underlying chronic conditions as well as on therapeutic and preventive measures are urgently needed.", "qid": 47, "docid": "i154l4tu", "rank": 79, "score": 0.8396835923194885}, {"content": "Title: COVID-19 bei hospitalisierten Kindern und Jugendlichen: Ein systematischer Review zu publizierten Fallserien (Stand 31.03.2020) und erste Daten aus Deutschland./ [COVID-19 in hospitalized children and adolescents] Content: Background: The clinical knowledge about the course, complications and treatment of COVID-19 in children and adolescents is so far limited. Aim: This systematic review summarizes the current scientific evidence regarding the clinical presentation of COVID-19 in hospitalized children based on available case series from China. In addition, first data from a nationwide pediatric hospital survey conducted by the German Society for Pediatric Infectious Diseases (DGPI) are presented. Methods: This study evaluated 12 case series from China with 6-2143 children infected with SARS-CoV\u00ad2, which were identified by a literature search in PubMed up to 31 March 2020. The database of the German nationwide DGPI COVID-19 survey was accessed on 6 April 2020. Results: The median patient age in the case series was between 2 and 7 years and 18-45% were infants <1 year of age. The duration of hospital stay was 5-20 days. Most commonly reported symptoms were fever and cough; in 40-100% of cases involvement of the lower respiratory tract was reported, usually confirmed by computed tomography (CT). Severe and critical courses of disease were reported in up to 8% of the children including 2 fatalities. So far the German DGPI COVID-19 survey reported 33 hospitalized children up to 6 April 2020, mostly with upper airway infections. Of these children, 45% were infants and 32% had an underlying medical condition. So far 3 children (9%) needed admission to an intensive care unit. Conclusion: COVID-19 in hospitalized children usually presented as an uncomplicated febrile upper airway infection or mild pneumonia. Severe cases or fatalities rarely occurred in children. Information on neonates and children with underlying chronic conditions as well as on therapeutic and preventive measures are urgently needed.", "qid": 47, "docid": "pt03w0wa", "rank": 80, "score": 0.8395030498504639}, {"content": "Title: Clinical Characteristics of 5 COVID-19 Cases With Non-respiratory Symptoms as the First Manifestation in Children Content: An outbreak of the novel coronavirus disease 2019 (COVID-19) occurred in Wuhan, China, in December 2019, which then rapidly spread to more than 80 countries. However, detailed information on the characteristics of COVID-19 in children is still scarce. Five patients with non-respiratory symptoms as the first manifestation were hospitalized from the emergency department, and were later confirmed to have COVID-19, between 23 January and 20 February 2020, at the Wuhan Children's Hospital. SARS-CoV-2 nucleic acid detection was positive for all the patients. Four of the patients were male and one was female, and their ages ranged from 2-months to 5.6 years. All lived in Wuhan. One patient had a clear history of exposure to SARS-CoV-2, one had a suspected history of exposure, while the others had no exposure history. For three of the five patients, the primary onset disease required an emergency operation or treatment, and included intussusception, acute suppurative appendicitis perforation with local peritonitis, and traumatic subdural hemorrhage with convulsion, while for the other two it was acute gastroenteritis (including one patient with hydronephrosis and a stone in his left kidney). During the course of the disease, four of the five patients had a fever, whereas one case had no fever or cough. Two patients had leukopenia, and one also had lymphopenia. In the two cases of severe COVID-19, the levels of CRP, PCT, serum ferritin, IL-6, and IL-10 were significantly increased, whereas the numbers of CD3+, CD4+, CD8+ T lymphocytes, and CD16 + CD56 natural killer cells were decreased. We also found impaired liver, kidney, and myocardial functions; the presence of hypoproteinemia, hyponatremia, and hypocalcemia; and, in one case, abnormal coagulation function. Except for one patient who had a rotavirus infection, all patients tested negative for common pathogens, including the influenza virus, parainfluenza virus, respiratory syncytial virus, adenovirus, enterovirus, mycoplasma, Chlamydia, and Legionella. Chest CT images of all the patients showed patches or ground-glass opacities in the lung periphery or near the pleura, even large consolidations. This case series is the first report to describe the clinical features of COVID-19 with non-respiratory symptoms as the first manifestation in children.", "qid": 47, "docid": "g4250q6l", "rank": 81, "score": 0.8393155336380005}, {"content": "Title: The Epidemiology of Severe Acute Respiratory Syndrome Coronavirus 2 in a Pediatric Healthcare Network in the United States Content: BACKGROUND: Understanding the prevalence and clinical presentation of coronavirus disease 2019 in pediatric patients can help healthcare providers and systems prepare and respond to this emerging pandemic. METHODS: This was a retrospective case series of patients tested for severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) across a pediatric healthcare network, including clinical features and outcomes of those with positive test results. RESULTS: Of 7256 unique children tested for SARS-CoV-2, 424 (5.8%) tested positive. Patients aged 18\u201321 years had the highest test positive rate (11.2%), while those aged 1\u20135 years had the lowest (3.9%). By race, 10.6% (226/2132) of black children tested positive vs 3.3% (117/3592) of white children. By indication for testing, 21.1% (371/1756) of patients with reported exposures or clinical symptoms tested positive vs 3.8% (53/1410) of those undergoing preprocedural or preadmission testing. Of 424 patients who tested positive for SARS-CoV-2, 182 (42.9%) had no comorbidities, 87 (20.5%) had asthma, and 55 (13.0%) were obese. Overall, 52.1% had cough, 51.2% fever, and 14.6% shortness of breath. Seventy-seven (18.2%) SARS-CoV-2\u2013positive patients were hospitalized, of whom 24 (31.2%) required respiratory support. SARS-CoV-2-targeted antiviral therapy was given to 9 patients, and immunomodulatory therapy to 18 patients. Twelve (2.8%) SARS-CoV-2-positive patients required mechanical ventilation, and 2 patients required extracorporeal membrane oxygenation. Two patients died. CONCLUSIONS: In this large cohort of pediatric patients tested for SARS-CoV-2, the rate of infection was low but varied by testing indication. The majority of cases were mild and few children had critical illness.", "qid": 47, "docid": "h1irh7sj", "rank": 82, "score": 0.8392724990844727}, {"content": "Title: COVID-19 in children: Epidemiology, presentation, diagnosis and management Content: The new pandemic coronavirus disease (COVID-19) has affected children, including neonates, who mostly comprise of approximately 2% of total confirmed cases. Most children are asymptomatic or have mild disease and much lower mortality compared to adults for yet unknown reasons. Recovery from illness has largely been universal and <2% have severe disease requiring intensive care. Standardised guidelines from initial studies are now available for diagnosis, treatment, and prevention. Treatment is mostly supportive with no recommendations for any specific drugs so far. As the pandemic evolves, it is expected that more children will be diagnosed and treated with evolving newer regimens. Research should now focus on early diagnosis, better drugs for children, intensive care modalities, and a universal vaccine. New developments will help in better prevention asides from the other precautionary measures already being practiced.", "qid": 47, "docid": "yekcr5ka", "rank": 83, "score": 0.8392202854156494}, {"content": "Title: COVID-19 in children: Epidemiology, presentation, diagnosis and management. Content: The new pandemic coronavirus disease (COVID-19) has affected children, including neonates, who mostly comprise of approximately 2% of total confirmed cases. Most children are asymptomatic or have mild disease and much lower mortality compared to adults for yet unknown reasons. Recovery from illness has largely been universal and <2% have severe disease requiring intensive care. Standardised guidelines from initial studies are now available for diagnosis, treatment, and prevention. Treatment is mostly supportive with no recommendations for any specific drugs so far. As the pandemic evolves, it is expected that more children will be diagnosed and treated with evolving newer regimens. Research should now focus on early diagnosis, better drugs for children, intensive care modalities, and a universal vaccine. New developments will help in better prevention asides from the other precautionary measures already being practiced.", "qid": 47, "docid": "ni4ck8w4", "rank": 84, "score": 0.8392202854156494}, {"content": "Title: Clinical manifestations of children with COVID\u201019: A systematic review Content: BACKGROUND: The coronavirus disease 2019 (COVID\u201019) outbreak is an unprecedented global public health challenge, leading to thousands of deaths every day worldwide. Despite the epidemiological importance, clinical patterns of children with COVID\u201019 remain unclear. The aim of this study was to describe the clinical, laboratorial, and radiological characteristics of children with COVID\u201019. METHODS: The Medline database was searched between December 1st 2019 and April 6th 2020. No language restrictions were applied. Inclusion criteria were (a) studied patients younger than 18 years old; (b) presented original data from cases of COVID\u201019 confirmed by reverse\u2010transcription polymerase chain reaction; and (c) contained descriptions of clinical manifestations, laboratory tests, or radiological examinations. RESULTS: A total of 38 studies (1124 cases) were included. From all the cases, 1117 had their severity classified: 14.2% were asymptomatic, 36.3% were mild, 46.0% were moderate, 2.1% were severe, and 1.2% were critical. The most prevalent symptom was fever (47.5%), followed by cough (41.5%), nasal symptoms (11.2%), diarrhea (8.1%), and nausea/vomiting (7.1%). One hundred forty\u2010five (36.9%) children were diagnosed with pneumonia and 43 (10.9%) upper airway infections were reported. Reduced lymphocyte count was reported in 12.9% of cases. Abnormalities in computed tomography were reported in 63.0% of cases. The most prevalent abnormalities reported were ground\u2010glass opacities, patchy shadows, and consolidations. Only one death was reported. CONCLUSIONS: Clinical manifestations of children with COVID\u201019 differ widely from adult cases. Fever and respiratory symptoms should not be considered a hallmark of COVID\u201019 in children.", "qid": 47, "docid": "5nw3828d", "rank": 85, "score": 0.8390806317329407}, {"content": "Title: Potential Effectiveness and Safety of Antiviral Agents in Children with Coronavirus Disease 2019: A Rapid Review and Meta-Analysis Content: Background: The COVID-19 outbreak presents a new, life-threatening disease. Our aim was to assess the potential effectiveness and safety of antiviral agents for COVID-19 in children. Methods: Electronic databases from their inception to March, 31 2020 were searched for randomized controlled trials, clinical controlled trials and cohort studies of interventions with antiviral agents for children (less than 18 years of age) with COVID-19. Results: A total of 23 studies of indirect evidence with 6008 patients were included. The risks of bias in all studies were moderate to high in general. The effectiveness and safety of antiviral agents for children with COVID-19 is uncertain: For adults with COVID-19, lopinavir/ritonavir had no effect on mortality (risk ratio [RR]= 0.77, 95% confidence interval [CI] 0.45 to 1.30) and probability of negative PCR test (RR=0.98, 95 CI% 0.82 to 1.18). Arbidol had no benefit on probability of negative PCR test (RR=1.27, 95% CI 0.93 to 1.73). Hydroxychloroquine was not associated with increasing the probability of negative PCR result (RR=0.93, 95% CI 0.73 to 1.18). For adults with SARS, interferon was associated with reduced corticosteroid dose (weighted mean difference [WMD]=-0.14 g, 95% CI -0.21 to -0.07) but had no effect on mortality (RR=0.72, 95% CI 0.28 to 1.88); ribavirin did not reduce mortality (RR=0.68, 95% CI % 0.43 to 1.06) and was associated with high risk of severe adverse reactions; and oseltamivir had no effect on mortality (RR=0.87, 95% CI 0.55 to 1.38). Ribavirin combined with interferon was also not effective in adults with MERS and associated with adverse reactions. Conclusions: There is no evidence showing the effectiveness of antiviral agents for children with COVID-19, and the clinical efficacy of existing antiviral agents is still uncertain. We do not suggest clinical routine use of antivirals for COVID-19 in children, with the exception of clinical trials. Keywords: Antiviral agents; children; COVID-19; meta-analysis; rapid review.", "qid": 47, "docid": "xuo2jrfq", "rank": 86, "score": 0.8388280868530273}, {"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": 87, "score": 0.8387902975082397}, {"content": "Title: Covid-19 in children: A brief overview after three months experience Content: Severe Acute Respiratory Syndrome - Coronavirus - 2 (SARS-CoV-2) and its related Coronavirus Disease - 19 (COVID-19) has become a health emergency worldwide. The medical community has been concerned since the beginning of the outbreak about the potential impact of COVID-19 in children, especially in those with underlying chronic diseases. Fortunately, COVID-19 has been reported to be less severe in children than in adults. However, epidemiologic and clinical data are scarce. Children show unique features of SARS-CoV-2 involvement that may account for the low rate of infection and death in this age group. The purpose of this review is to summarize the most relevant evidence of COVID-19 in children highlighting similarities and differences with adults.", "qid": 47, "docid": "fuhvsy2j", "rank": 88, "score": 0.8387419581413269}, {"content": "Title: Covid-19 in children: A brief overview after three months experience. Content: Severe Acute Respiratory Syndrome - Coronavirus - 2 (SARS-CoV-2) and its related Coronavirus Disease - 19 (COVID-19) has become a health emergency worldwide. The medical community has been concerned since the beginning of the outbreak about the potential impact of COVID-19 in children, especially in those with underlying chronic diseases. Fortunately, COVID-19 has been reported to be less severe in children than in adults. However, epidemiologic and clinical data are scarce. Children show unique features of SARS-CoV-2 involvement that may account for the low rate of infection and death in this age group. The purpose of this review is to summarize the most relevant evidence of COVID-19 in children highlighting similarities and differences with adults.", "qid": 47, "docid": "5gvpjxxp", "rank": 89, "score": 0.8387419581413269}, {"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": 47, "docid": "jsyao6qu", "rank": 90, "score": 0.8387361764907837}, {"content": "Title: [Diagnosis and treatment recommendation for pediatric COVID-19 (the second edition)] Content: The coronavirus disease 2019 (COVID-19) has caused a global pandemic. All people including children are generally susceptible to COVID-19, but the condition is relatively mild for children. The diagnosis of COVID-19 is largely based on the epidemiological evidence and clinical manifestations, and confirmed by positive detection of virus nucleic acid in respiratory samples. The main symptoms of COVID-19 in children are fever and cough; the total number of white blood cell count is usually normal or decreased; the chest imaging is characterized by interstitial pneumonia, which is similar to other respiratory virus infections and Mycoplasma pneumoniae infections. Early identification, early isolation, early diagnosis and early treatment are important for clinical management. The treatment of mild or moderate type of child COVID-19 is mainly symptomatic. For severe and critical ill cases, the oxygen therapy, antiviral drugs, antibacterial drugs, glucocorticoids, mechanical ventilation or even extracorporeal membrane oxygenation (ECMO) may be adopted, and the treatment plan should be adjusted timely through multi-disciplinary cooperation.", "qid": 47, "docid": "14dzd7h5", "rank": 91, "score": 0.8386760950088501}, {"content": "Title: [Diagnosis and treatment recommendation for pediatric COVID-19 (the second edition)]. Content: The coronavirus disease 2019 (COVID-19) has caused a global pandemic. All people including children are generally susceptible to COVID-19, but the condition is relatively mild for children. The diagnosis of COVID-19 is largely based on the epidemiological evidence and clinical manifestations, and confirmed by positive detection of virus nucleic acid in respiratory samples. The main symptoms of COVID-19 in children are fever and cough; the total number of white blood cell count is usually normal or decreased; the chest imaging is characterized by interstitial pneumonia, which is similar to other respiratory virus infections and Mycoplasma pneumoniae infections. Early identification, early isolation, early diagnosis and early treatment are important for clinical management. The treatment of mild or moderate type of child COVID-19 is mainly symptomatic. For severe and critical ill cases, the oxygen therapy, antiviral drugs, antibacterial drugs, glucocorticoids, mechanical ventilation or even extracorporeal membrane oxygenation (ECMO) may be adopted, and the treatment plan should be adjusted timely through multi-disciplinary cooperation.", "qid": 47, "docid": "zwv5e1kl", "rank": 92, "score": 0.8386760950088501}, {"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": 93, "score": 0.8385509848594666}, {"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": 94, "score": 0.8385509848594666}, {"content": "Title: Pediatric COVID-19: Systematic review of the literature. Content: OBJECTIVES There is limited data regarding the demographics and clinical features of SARS-CoV-2 infection in children. This information is especially important as pneumonia is the single leading cause of death in children worldwide. This Systematic Review aims to elucidate a better understanding of the global impact of COVID-19 on the pediatric population. METHODS A systematic review of the literature was performed in accordance with PRISMA (Preferred Reporting Items for Systematic Reviews and Meta-Analyses) guidelines to gain insight into pediatric COVID-19 epidemiology. Specifically, Pubmed and Google Scholar databases were searched to identify any relevant article with a focus on Pediatric Covid 19, Pediatric Covid-19, Pediatric SARS-COV-2, and Pediatric Coronavirus 19. References within the included articles were reviewed. All articles that met criteria where analyzed for demographics, clinical, laboratory, radiographic, treatment and outcomes data. RESULTS Ten studies including two case series and 8 retrospective chart reviews, altogether describing a total of 2914 pediatric patients with COVID-19 were included in this systematic review. Of the patients whose data was available, 56% were male, the age range was 1 day to 17 years, 79% were reported to have no comorbidities, and of the 21% with comorbidities, the most common were asthma, immunosupression, and cardiovascular disease. Of pediatric patients that were tested and positive for an infection with SARS-CoV-2, patients were asymptomatic, 14.9% of the time. Patients presented with cough (48%), fever (47%) and sore throat/pharyngitis (28.6%), more commonly than with upper respiratory symptoms/rhinorrhea/sneezing/nasal congestion (13.7%), vomiting/nausea (7.8%) and diarrhea (10.1%). Median lab values including those for WBC, lymphocyte count and CRP, were within the reference ranges with the exception of procalcitonin levels, which were slightly elevated in children with COVID-19 (median procalcitonin levels ranged from 0.07 to 0.5 ng/mL. Computed tomography (CT) results suggest that unilateral CT imaging findings are present 36% of cases while 64% of pediatric patients with COVID-19 had bilateral findings. Of the studies with age specific hospitalization data available, 27.0% of patients hospitalized were infants under 1 year of age. Various treatment regimens including interferon, antivirals, and hydroxychloroquine therapies have been trialed on the pediatric population but there are currently no studies showing efficacy of one regimen over the other. The mortality rate of children that were hospitalized with COVID-19 was 0.0018%. CONCLUSION In contrast to adults, most infected children appear to have a milder course and have better outcomes overall. Additional care may be needed for children with comorbidities and younger children. This review also suggests that unilateral CT chest imaging findings were seen in 36.4% pediatric COVID-19 patients. This is particularly concerning as the work-up of pediatric patients with cough may warrant a bronchoscopy to evaluate for airway foreign bodies. Extra precautions need to be taken with personal protective equipment for these cases, as aerosolizing procedures may be a method of viral transmission. LEVEL OF EVIDENCE 4 (Systematic Review).", "qid": 47, "docid": "4pwxplhh", "rank": 95, "score": 0.8385393619537354}, {"content": "Title: COVID-19 in Children: Clinical Approach and Management Content: COVID-19 pandemic caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) is a major public health crisis threatening humanity at this point in time. Transmission of the infection occurs by inhalation of infected droplets or direct contact with soiled surfaces and fomites. It should be suspected in all symptomatic children who have undertaken international travel in the last 14 d, all hospitalized children with severe acute respiratory illness, and asymptomatic direct and high-risk contacts of a confirmed case. Clinical symptoms are similar to any acute respiratory viral infection with less pronounced nasal symptoms. Disease seems to be milder in children, but situation appears to be changing. Infants and young children had relatively more severe illness than older children. The case fatality rate is low in children. Diagnosis can be confirmed by Reverse transcriptase - Polymerase chain reaction (RT-PCR) on respiratory specimen (commonly nasopharyngeal and oropharyngeal swab). Rapid progress is being made to develop rapid diagnostic tests, which will help ramp up the capacity to test and also reduce the time to getting test results. Management is mainly supportive care. In severe pneumonia and critically ill children, trial of hydroxychloroquine or lopinavir/ritonavir should be considered. As per current policy, children with mild disease also need to be hospitalized; if this is not feasible, these children may be managed on ambulatory basis with strict home isolation. Pneumonia, severe disease and critical illness require admission and aggressive management for acute lung injury and shock and/or multiorgan dysfunction, if present. An early intubation is preferred over non-invasive ventilation or heated, humidified, high flow nasal cannula oxygen, as these may generate aerosols increasing the risk of infection in health care personnel. To prevent post discharge dissemination of infection, home isolation for 1-2 wk may be advised. As of now, no vaccine or specific chemotherapeutic agents are approved for children.", "qid": 47, "docid": "j2omplwn", "rank": 96, "score": 0.8384573459625244}, {"content": "Title: Childhood COVID-19: a multi-center retrospective study Content: OBJECTIVES: To investigate the clinical and epidemiological characteristics of pediatric patients with Coronavirus disease-19 (COVID-19). METHODS: Pediatric patients diagnosed with COVID-19 from January 15 to March 15, 2020, from seven hospitals in Zhejiang Province were collected retrospectively and analyzed. RESULTS: Thirty-two children with COVID-19, ranging from 3 months to 18 years old, were enrolled. Family aggregation occurred in 87.5% of infant and preschool-aged children (7/8), and also school-aged children (14/16), but only 12.5% (1/8) of adolescents (p<0. 05, p<0.001). Most of these patients had mild symptoms, mainly fever (20/32), followed by cough (10/32) and fatigue (4/32). The average duration of viral RNA in respiratory samples and gastrointestinal samples were 15.8 d and 28.9 d, respectively. Detox duration in feces decreased with age, namely 39.8 d, 27.5 d and 20.4 d in infant and preschool children, school children and adolescents respectively (p(0-6, -18)<0. 01, p(0-6, -14)<0. 05). Pneumonia was found in 14 children, without any statistical significance in the incidence of pneumonia between different age groups. Thirty patients were treated with antiviral drugs and all patients were stable and gradually improved after admission. CONCLUSIONS: Most children with COVID-19 had a mild process and good prognosis. More attention should be paid to household contact history investigation in the diagnosis of COVID-19 in young children. Viral RNA lasts longer in gastrointestinal system than the respiratory tract, especially in younger children.", "qid": 47, "docid": "f8psq2r7", "rank": 97, "score": 0.8383758664131165}, {"content": "Title: Current Scenario of COVID-19 in Pediatric Age Group and Physiology of Immune and Thymus response Content: COVID-19 pandemic caused by SARS-CoV-2, continues to manifest with severe acute respiratory syndrome among the adults, however, it offers a convincing indication of less severity and fatality in pediatric age group (0-18 years). The current trend suggests that children may get infected but are less symptomatic with less fatality, which is concordant to earlier epidemic outbreaks of SARS-CoV and MERS-CoV, in 2002 and 2012, respectively. According to the available data, children appear to be at lower risk for COVID-19, as adults constitute for maximum number of the confirmed cases (308,592) and deaths (13,069) as on 22nd March (https://www.worldometers.info/coronavirus). However, rapid publications and information of the adult patients with COVID-19 is in progress and published, on the contrary, almost no comprehensive data or discussion about the COVID-19 in children is available. Therefore, in this review, we outline the epidemiology, clinical symptoms, diagnosis, treatment, prevention, possible immune response and role of thymus in children to combat the COVID-19 outbreak.", "qid": 47, "docid": "o37c3mwe", "rank": 98, "score": 0.8381966352462769}, {"content": "Title: COVID-19 and what pediatric rheumatologists should know: a review from a highly affected country Content: On March 11th, 2020 the World Health Organization declared COVID-19 a global pandemic. The infection, transmitted by 2019 novel coronavirus (2019-nCov), was first discovered in December 2019, in Wuhan, Hubei Province, and then rapidly spread worldwide. Italy was early and severely involved, with a critical spread of the infection and a very high number of victims. Person-to-person spread mainly occurs via respiratory droplets and contact. The median incubation period is 5 days. The spectrum of respiratory symptoms may range from mild to severe, strictly depending on the age of the patient and the underlying comorbidities. In children COVID-19 related disease is less frequent and less aggressive. In Italy 1% of positive cases are under 18 years of age, and no deaths have been recorded before 29 years of age. For patients affected by rheumatic disease, despite the concerns related to the imbalance of their immune response and the effect of immunosuppressive treatments, there are still few data to understand the real consequences of this infection. Major scientific societies have issued recommendations to help rheumatologists in caring their patients. Interestingly, some of the drugs mostly used by rheumatologists appear to be promising in critical COVID-19 infected patients, where the hyperinflammation and cytokine storm seem to drive to the multiorgan failure. Pediatric rheumatologists are expected to play a supporting role in this new front of COVID-19 pandemic, both as general pediatricians treating infected children, and as rheumatologists taking care of their rheumatic patients, as well as offering their experience in the possible alternative use of immunomodulatory drugs.", "qid": 47, "docid": "16rgt4ca", "rank": 99, "score": 0.8381774425506592}, {"content": "Title: COVID-19 and what pediatric rheumatologists should know: a review from a highly affected country Content: On March 11th, 2020 the World Health Organization declared COVID-19 a global pandemic. The infection, transmitted by 2019 novel coronavirus (2019-nCov), was first discovered in December 2019, in Wuhan, Hubei Province, and then rapidly spread worldwide. Italy was early and severely involved, with a critical spread of the infection and a very high number of victims. Person-to-person spread mainly occurs via respiratory droplets and contact. The median incubation period is 5 days. The spectrum of respiratory symptoms may range from mild to severe, strictly depending on the age of the patient and the underlying comorbidities.In children COVID-19 related disease is less frequent and less aggressive. In Italy 1% of positive cases are under 18 years of age, and no deaths have been recorded before 29 years of age. For patients affected by rheumatic disease, despite the concerns related to the imbalance of their immune response and the effect of immunosuppressive treatments, there are still few data to understand the real consequences of this infection. Major scientific societies have issued recommendations to help rheumatologists in caring their patients. Interestingly, some of the drugs mostly used by rheumatologists appear to be promising in critical COVID-19 infected patients, where the hyperinflammation and cytokine storm seem to drive to the multiorgan failure.Pediatric rheumatologists are expected to play a supporting role in this new front of COVID-19 pandemic, both as general pediatricians treating infected children, and as rheumatologists taking care of their rheumatic patients, as well as offering their experience in the possible alternative use of immunomodulatory drugs.", "qid": 47, "docid": "jf2v6shs", "rank": 100, "score": 0.8381774425506592}]}
{"query": "what are the benefits and risks of re-opening schools in the midst of the COVID-19 pandemic?", "hits": [{"content": "Title: Back to school: Safe for children with underlying medical conditions Content: As schools reopen as a result of low community transmission rates of COVID-19, parents and teachers will have understandable concerns about the risks to students and staff.", "qid": 48, "docid": "xu7bazzw", "rank": 1, "score": 0.8940062522888184}, {"content": "Title: Back to school: Safe for children with underlying medical conditions. Content: As schools reopen as a result of low community transmission rates of COVID-19, parents and teachers will have understandable concerns about the risks to students and staff.", "qid": 48, "docid": "6gn2seix", "rank": 2, "score": 0.8940062522888184}, {"content": "Title: Children and the COVID-19 pandemic Content: As a result of the COVID-19 pandemic, many school districts have closed for the remainder of the academic year. These closures are unfortunate because, for many students, schools are their only source of trauma-informed care and supports. When schools reopen, they must develop a comprehensive plan to address the potential mental health needs of their students. (PsycInfo Database Record (c) 2020 APA, all rights reserved).", "qid": 48, "docid": "17a70tu9", "rank": 3, "score": 0.8853164911270142}, {"content": "Title: Children and the COVID-19 pandemic. Content: As a result of the COVID-19 pandemic, many school districts have closed for the remainder of the academic year. These closures are unfortunate because, for many students, schools are their only source of trauma-informed care and supports. When schools reopen, they must develop a comprehensive plan to address the potential mental health needs of their students. (PsycInfo Database Record (c) 2020 APA, all rights reserved).", "qid": 48, "docid": "4nv1kedt", "rank": 4, "score": 0.8853164911270142}, {"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": 5, "score": 0.8845702409744263}, {"content": "Title: The impact of school reopening on the spread of COVID-19 in England Content: Background: In the UK, cases of COVID-19 have been declining since mid-April and there is good evidence to suggest that the effective reproduction number has dropped below 1, leading to a multi-phase relaxation plan for the country to emerge from lockdown. As part of this staggered process, primary schools are scheduled to partially reopen on 1st June. Evidence from a range of sources suggests that children are, in general, only mildly affected by the disease and have low mortality rates, though there is less certainty regarding children's role in transmission. Therefore, there is wide discussion on the impact of reopening schools. Methods: We compare eight strategies for reopening primary and secondary schools in England from 1st June, focusing on the return of particular year groups and the associated epidemic consequences. This is assessed through model simulation, modifying a previously developed dynamic transmission model for SARS-CoV-2. We quantify how the process of reopening schools affected contact patterns and anticipated secondary infections, the relative change in R according to the extent of school reopening, and determine the public health impact via estimated change in clinical cases and its sensitivity to decreases in adherence post strict lockdown. Findings: Whilst reopening schools, in any form, results in more mixing between children, an increase in R and hence transmission of the disease, the magnitude of that increase can be low dependent upon the age-groups that return to school and the behaviour of the remaining population. We predict that reopening schools in a way that allows half class sizes or that is focused on younger children is unlikely to push R above one, although there is noticeable variation between the regions of the country. Given that older children have a greater number of social contacts and hence a greater potential for transmission, our findings suggest reopening secondary schools results in larger increases in case burden than only reopening primary schools; reopening both generates the largest increase and could push R above one in some regions. The impact of less social-distancing in the rest of the population, generally has far larger effects than reopening schools and exacerbates the impacts of reopening. Discussion: Our work indicates that any reopening of schools will result in increased mixing and infection amongst children and the wider population, although the opening of schools alone is unlikely to push the value of R above one. However, impacts of other recent relaxations of lockdown measures are yet to be quantified, suggesting some regions may be closer to the critical threshold that would lead to a growth in cases. Given the uncertainties, in part due to limited data on COVID-19 in children, school reopening should be carefully monitored. Ultimately, the decision about reopening classrooms is a difficult trade-off between increased epidemiological consequences and the emotional, educational and developmental needs of children.", "qid": 48, "docid": "xhyqg5u2", "rank": 6, "score": 0.8806156516075134}, {"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": 7, "score": 0.8781824707984924}, {"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": 8, "score": 0.878158688545227}, {"content": "Title: Little Risk of the COVID-19 Resurgence on Students in China (outside Hubei) Caused by School Reopening Content: Objective: School reopening has not yet started in China where the COVID-19 outbreak has reached ending stage, largely due to a great concern about COVID-19 infections on students. We attempted to quantitatively evaluate the risk of COVID-19 infections on students caused by school reopening. Study design: We collected the data of the numbers of teachers, population size and newly confirmed COVID-19 cases in the past 14 days in typical provinces/cities of China, and then analyzed the risk of COVID-19 infections in schools with respect to each province/city. Methods: A step-by-step procedure was explored to calculate the probability of COVID-19 infections on students as transmitted from infected teachers. Two critical assumptions for analysis were proposed: (i) only locally generated cases were counted while imported cases were omitted; (ii) the secondary attack rate of the COVID-19 virus in schools is similar to that in households in China, ranging from 3-10%. Results: The probability of COVID-19 resurgence within one week on students of primary, middle and high schools in China (outside Hubei) is extremely low (<0.2%) in each province/city, and such probability can be updated daily and weekly based on the newly confirmed cases in the past 14 days. In some areas without newly confirmed cases in the past 14 days, the risk is zero. Conclusions: Our work provides guidance for local governments to make risk level-based policies for school reopening. Currently, the risk of COVID-19 infections on students is extremely low in China (outside Hubei) and therefore school reopening can be initiated without the endanger of infections on students.", "qid": 48, "docid": "7en6cog7", "rank": 9, "score": 0.874758243560791}, {"content": "Title: Expected impact of reopening schools after lockdown on COVID-19 epidemic in Ile-de-France Content: As several countries around the world are planning exit strategies to progressively lift the rigid social restrictions implemented with lockdown, different options are being chosen regarding the closure or reopening of schools. We evaluate the expected impact of reopening schools in lIe-de-France region after the withdrawal of lockdown currently scheduled for May 11, 2020. We explore several scenarios of partial, progressive, or full school reopening, coupled with moderate social distancing interventions and large-scale tracing, testing, and isolation. Accounting for current uncertainty on the role of children in COVID-19 epidemic, we test different hypotheses on children's transmissibility distinguishing between younger children (pre-school and primary school age) and adolescents (middle and high school age). Reopening schools after lifting lockdown will likely lead to an increase in the number of COVID-19 cases in the following 2 months, even with lower transmissibility of children, yet protocols exist that would allow maintaining the epidemic under control without saturating the healthcare system. With pre-schools and primary schools in session starting May 11, ICU occupation would reach at most 72% [55,83]% (95% probability ranges) of a 1,500-bed capacity (here foreseen as the routine capacity restored in the region post-first wave) if no other school level reopens before summer or if middle and high schools reopen one month later through a progressive protocol (increasing attendance week by week). Full attendance of adolescents at school starting in June would overwhelm the ICU system (138% [118,159]% occupation). Reopening all schools on May 11 would likely lead to a second wave similar to the one recently experienced, except if maximum attendance is limited to 50% for both younger children and adolescents. Based on the estimated situation on May 11, no substantial difference in the epidemic risk is predicted between progressive and prompt reopening of pre-schools and primary schools, thus allowing full attendance of younger children mostly in need of resuming learning and development. Reopening would require however large-scale trace and testing to promptly isolate cases, in addition to moderate social distancing interventions. Full attendance in middle and high schools is instead not recommended. Findings are consistent across different assumptions on the relative transmissibility of younger children and for small increase of the reproductive number possibly due to decreasing compliance to lockdown.", "qid": 48, "docid": "qnlf5qfd", "rank": 10, "score": 0.8738414645195007}, {"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": 11, "score": 0.872015655040741}, {"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": 12, "score": 0.8711947798728943}, {"content": "Title: How to Safely Reopen Colleges and Universities During COVID-19: Experiences From Taiwan Content: Reopening colleges and universities during the coronavirus disease 2019 (COVID-19) pandemic poses a special challenge worldwide. Taiwan is one of the few countries where schools are functioning normally. To secure the safety of students and staff, the Ministry of Education in Taiwan established general guidelines for college campuses. The guidelines delineated creation of a task force at each university; school-based risk screening based on travel history, occupation, contacts, and clusters; measures on self-management of health and quarantine; general hygiene measures (including wearing masks indoors); principles on ventilation and sanitization; regulations on school assemblies; a process for reporting suspected cases; and policies on school closing and make-up classes. It also announced that a class should be suspended if 1 student or staff member in it tested positive and that a school should be closed for 14 days if it had 2 or more confirmed cases. As of 18 June 2020, there have been 7 confirmed cases in 6 Taiwanese universities since the start of the pandemic. One university was temporarily closed, adopted virtual classes, and quickly reopened after 14 days of contact tracing and quarantine of possible contacts. Taiwan's experience suggests that, under certain circumstances, safely reopening colleges and universities this fall may be feasible with a combination of strategies that include containment (access control with contact tracing and quarantine) and mitigation (hygiene, sanitation, ventilation, and social distancing) practices.", "qid": 48, "docid": "vgbhyzb9", "rank": 13, "score": 0.869948148727417}, {"content": "Title: School Nurses on the Front Lines of Healthcare: The Approach to Maintaining Student Health and Wellness During COVID-19 School Closures Content: In response to the novel coronavirus disease 2019 (COVID-19) pandemic, most states in the United States enacted statewide school closures, ranging in duration from 1 month to the remainder of the academic year. The extended durations of these closures present unique challenges, as many families rely on the school as a source of physical activity, mental health services, psychosocial support, child care, and food security. While the school doors may be closed, the school nurse can still play a vital role in emergency management. This article discusses challenges and proposes solutions to maintaining student health and wellness during extended school closures due to the COVID-19 pandemic. Furthermore, it is inevitable that until a vaccine for coronavirus is developed and readily available, many schools will continue to see future closures, though likely for shorter periods of time, as they respond to local outbreaks.", "qid": 48, "docid": "xqmxyz7u", "rank": 14, "score": 0.8653591871261597}, {"content": "Title: School closure, COVID-19 and lunch programme: Unprecedented undernutrition crisis in low-middle income countries Content: The coronavirus disease 2019 pandemic has affected nearly 70% of children and teenagers around the world due to school closure policies. School closure is implemented widely in order to prevent viral transmission and its impact on the broader community, based on preliminary recommendations and evidence from influenza. However, there is debate with regard to the effectiveness of school closures. Growing evidence suggests that a child's SARS-CoV-2 infection is often mild or asymptomatic and that children may not be major SARS-CoV-2 transmitters; thus, it is questionable if school closures prevent transmission significantly. This question is important as a majority of children in low- and middle-income countries depend on free school meals; unexpected long-term school closure may adversely impact nutrition and educational outcomes. Food insecurity is expected to be higher during the pandemic. In this viewpoint, we argue for a more thorough exploration of potential adverse impacts of school closures in low- and middle-income countries and recommend actions to ensure that the health and learning needs of vulnerable populations are met in this time of crisis.", "qid": 48, "docid": "7ty971vj", "rank": 15, "score": 0.8646684885025024}, {"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": 16, "score": 0.8569080233573914}, {"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": 48, "docid": "gyilcbr7", "rank": 17, "score": 0.8557525873184204}, {"content": "Title: COVID-19 , School Closings and Weight Gain. Content: We found the publication on \"COVID-19 Related School Closings and Risk of Weight Gain Among Children\" to be interesting.1 Rundle et al. noted that \"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.\"1 In fact, there are several factors relating to nutritional status of the children. We would like to share observations from Thailand, the second country in the timeline of COVID-19.2 In Thailand, school aged children in rural areas where COVID-19 disease outbreak exists are usually underweight.3 Thus, school closing means the children have to live with poor parents adding to economic problems of the family.", "qid": 48, "docid": "qz6w094y", "rank": 18, "score": 0.8537696599960327}, {"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": 48, "docid": "gdz63spj", "rank": 19, "score": 0.8531061410903931}, {"content": "Title: School closure, COVID\u201019 and lunch programme: Unprecedented undernutrition crisis in low\u2010middle income countries Content: The coronavirus disease 2019 pandemic has affected nearly 70% of children and teenagers around the world due to school closure policies. School closure is implemented widely in order to prevent viral transmission and its impact on the broader community, based on preliminary recommendations and evidence from influenza. However, there is debate with regard to the effectiveness of school closures. Growing evidence suggests that a child's SARS\u2010CoV\u20102 infection is often mild or asymptomatic and that children may not be major SARS\u2010CoV\u20102 transmitters; thus, it is questionable if school closures prevent transmission significantly. This question is important as a majority of children in low\u2010 and middle\u2010income countries depend on free school meals; unexpected long\u2010term school closure may adversely impact nutrition and educational outcomes. Food insecurity is expected to be higher during the pandemic. In this viewpoint, we argue for a more thorough exploration of potential adverse impacts of school closures in low\u2010 and middle\u2010income countries and recommend actions to ensure that the health and learning needs of vulnerable populations are met in this time of crisis.", "qid": 48, "docid": "zc2u3hqv", "rank": 20, "score": 0.8503265976905823}, {"content": "Title: Education and the COVID-19 pandemic Content: The COVID-19 pandemic is a huge challenge to education systems. This Viewpoint offers guidance to teachers, institutional heads, and officials on addressing the crisis. What preparations should institutions make in the short time available and how do they address students' needs by level and field of study? Reassuring students and parents is a vital element of institutional response. In ramping up capacity to teach remotely, schools and colleges should take advantage of asynchronous learning, which works best in digital formats. As well as the normal classroom subjects, teaching should include varied assignments and work that puts COVID-19 in a global and historical context. When constructing curricula, designing student assessment first helps teachers to focus. Finally, this Viewpoint suggests flexible ways to repair the damage to students' learning trajectories once the pandemic is over and gives a list of resources.", "qid": 48, "docid": "06mqd6vg", "rank": 21, "score": 0.8431049585342407}, {"content": "Title: How Much May COVID-19 School Closures Increase Childhood Obesity? Content: In a recent paper entitled, \"COVID-19 Related School Closings and Risk of Weight Gain Among Children\" Rundle et al. (2020) proposed the COVID-19 pandemic may increase obesity among American children because the pandemic, \"will likely double out-of-school time this year for many children in the United States and will exacerbate the risk factors for weight gain associated with summer recess\" (pg. 1). I add support to Rundle et al.'s argument by demonstrating that doubling of out-of-school time alone may lead to a sizable increase in childhood obesity.", "qid": 48, "docid": "8ew7rv5q", "rank": 22, "score": 0.843059778213501}, {"content": "Title: Helping children cope with the COVID-19 pandemic Content: Numerous societal changes in response to the COVID-19 pandemic, such as school closings and event cancellations, have caused anxiety and fear for children and young people. There are ways to help young people cope with the current situation including establishing an open dialogue, creating a structured daily routine with a schedule with assigned roles, and using social media and video conferencing to remain socially connected.", "qid": 48, "docid": "rfsituum", "rank": 23, "score": 0.8427008390426636}, {"content": "Title: Helping children cope with the COVID-19 pandemic. Content: Numerous societal changes in response to the COVID-19 pandemic, such as school closings and event cancellations, have caused anxiety and fear for children and young people. There are ways to help young people cope with the current situation including establishing an open dialogue, creating a structured daily routine with a schedule with assigned roles, and using social media and video conferencing to remain socially connected.", "qid": 48, "docid": "6d832az2", "rank": 24, "score": 0.8427008390426636}, {"content": "Title: Education, the science of learning, and the COVID-19 crisis Content: In the COVID-19 crisis, the science of learning has two different responsibilities: first, to offer guidance about how best to deal with the impact of the current situation, including lockdown and home-schooling; and second, to consider bigger questions about what this large-scale educational experiment might mean for the future. The first part of this Viewpoint summarises advice for parents on mental health, and on becoming stand-in-teachers. The second part, taking the longer view, considers the potential negative impact of the COVID-19 crisis in increasing inequality in education; but also the potential positive impact of driving innovations in technology use for educating children.", "qid": 48, "docid": "v83dwt6k", "rank": 25, "score": 0.8421289920806885}, {"content": "Title: Education and the COVID-19 pandemic Content: The COVID-19 pandemic is a huge challenge to education systems. This Viewpoint offers guidance to teachers, institutional heads, and officials on addressing the crisis. What preparations should institutions make in the short time available and how do they address students\u2019 needs by level and field of study? Reassuring students and parents is a vital element of institutional response. In ramping up capacity to teach remotely, schools and colleges should take advantage of asynchronous learning, which works best in digital formats. As well as the normal classroom subjects, teaching should include varied assignments and work that puts COVID-19 in a global and historical context. When constructing curricula, designing student assessment first helps teachers to focus. Finally, this Viewpoint suggests flexible ways to repair the damage to students\u2019 learning trajectories once the pandemic is over and gives a list of resources.", "qid": 48, "docid": "744a3hga", "rank": 26, "score": 0.8401318192481995}, {"content": "Title: Echoes of 2009 H1N1 Influenza Pandemic in the COVID Pandemic Content: The severe acute respiratory syndrome-related coronavirus-2 (SARS-CoV2) pandemic that has engulfed the globe has had incredible effects on health care systems and economic activity. Social distancing and school closures have played a central role in public health efforts to counter the coronavirus disease 2019 (COVID)-19 pandemic. The most recent global pandemic prior to COVID-19 was the 2009 pandemic, hemagglutinin type 1 and neuraminidase type 1 (H1N1) influenza. The course of events in 2009 offer some rich lessons that could be applied to the current COVID-19 pandemic. This commentary highlights some of the most relevant points and a discussion of possible outcomes of the COVID-19 pandemic.", "qid": 48, "docid": "iw48r2za", "rank": 27, "score": 0.8401082158088684}, {"content": "Title: Echoes of 2009 H1N1 Influenza Pandemic in the COVID Pandemic Content: Abstract The severe acute respiratory syndrome\u2013related coronavirus-2 (SARS-CoV2) pandemic that has engulfed the globe has had incredible effects on health care systems and economic activity. Social distancing and school closures have played a central role in public health efforts to counter the coronavirus disease 2019 (COVID)-19 pandemic. The most recent global pandemic prior to COVID-19 was the 2009 pandemic, hemagglutinin type 1 and neuraminidase type 1 (H1N1) influenza. The course of events in 2009 offer some rich lessons that could be applied to the current COVID-19 pandemic. This commentary highlights some of the most relevant points and a discussion of possible outcomes of the COVID-19 pandemic. \u00a9 2020 Elsevier Inc.", "qid": 48, "docid": "si7oucep", "rank": 28, "score": 0.840072512626648}, {"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": 48, "docid": "8jvljcuh", "rank": 29, "score": 0.8393157720565796}, {"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": 48, "docid": "lgf0nwgx", "rank": 30, "score": 0.8393157720565796}, {"content": "Title: Coronavirus Disease 2019, School Closures, and Children\u2019s Mental Health Content: Coronavirus disease 2019 (COVID-19), which was first identified in Wuhan, China, in late December of 2019 is rapidly spreading across the globe. The South Korean government has ordered the closure of all schools, as part of its attempts to use social distancing measures to prevent the spread of COVID-19. The effects of the school closures on reducing contagion are generally positive; however, the measure is controversial because of the socioeconomic ripple effect that accompanies it. The author briefly reviewed the existing literature on the mental health aspects of disasters and presents the issues related to school closures due to pandemics, from medical and socioeconomic perspectives and in terms of children\u2019s mental health. The results of this review suggest that research on children\u2019s mental health in relation to the adoption of school closures as a pandemic mitigation strategy is urgently needed.", "qid": 48, "docid": "y0ufxwhq", "rank": 31, "score": 0.8392598628997803}, {"content": "Title: COVID-19 and schooling in South Africa: Who should go back to school first? Content: The COVID-19 pandemic is the largest social and economic shock of our lifetimes. As governments grapple with their responses to the virus, more than half the world\u2019s countries have closed their schools and severely limited almost all forms of public life. This will have a profound impact on children, both now and in the decade to come. As many countries start to send children back to school, a question arises: who should go back to school first? This Viewpoint addresses that question in the context of a middle-income country, South Africa. Based on a review of much of the evidence available at the time of publication, it concludes that the youngest children are least susceptible to harm from COVID-19, are less likely to spread the virus than adults, and also have the most to lose by being out of school. Hence, they should be the ones to return to school first.", "qid": 48, "docid": "rmefwih2", "rank": 32, "score": 0.8389790058135986}, {"content": "Title: The effect of the COVID-19 lockdown on parents: A call to adopt urgent measures Content: The COVID-19 health crisis is strongly affecting the mental health of the general population. In particular, the pandemic may be producing psychological distress and collateral concerns for parents in lockdown, due to unstable financial circumstances, school closures, and suspended educational services for children. A call for measures to increase family-based interventions during the emergency is urgently needed to forestall psychopathological trajectories and prevent the exacerbation of vulnerable conditions. (PsycInfo Database Record (c) 2020 APA, all rights reserved).", "qid": 48, "docid": "jtxqybzu", "rank": 33, "score": 0.8379546403884888}, {"content": "Title: The effect of the COVID-19 lockdown on parents: A call to adopt urgent measures. Content: The COVID-19 health crisis is strongly affecting the mental health of the general population. In particular, the pandemic may be producing psychological distress and collateral concerns for parents in lockdown, due to unstable financial circumstances, school closures, and suspended educational services for children. A call for measures to increase family-based interventions during the emergency is urgently needed to forestall psychopathological trajectories and prevent the exacerbation of vulnerable conditions. (PsycInfo Database Record (c) 2020 APA, all rights reserved).", "qid": 48, "docid": "p9pggrq9", "rank": 34, "score": 0.8379546403884888}, {"content": "Title: Prevent the resurgence of infectious disease with asymptomatic carriers Content: As many countries reached the peak of the COVID-19 outbreak, there is debate on how to reopen the economy without causing a significant resurgence. Here we show, using a microsimulation model, that how to reopen safely depends on what percentage of COVID-19 cases can be detected by testing. The higher the detection rate, the less restrictive the reopen plan needs to be. If 70% of cases can be detected, schools and businesses can reopen if 2-layer quarantine is imposed on each confirmed case. Our results suggest that increasing the detection rate is essential to prevent the resurgence of COVID-19.", "qid": 48, "docid": "r2mwzzaw", "rank": 35, "score": 0.8377532958984375}, {"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": 36, "score": 0.8374512791633606}, {"content": "Title: Collective impacts on a global education emergency: The power of network response Content: The COVID-19 pandemic is an emergency of an exceptional scale, with major impacts on education globally and with significant new challenges for education in existing humanitarian contexts. This Viewpoint reflects on the immediate challenges of continuing education in humanitarian contexts and on the experience of the Inter-agency Network for Education in Emergencies (INEE) as a network supporting collective action of Education in Emergencies (EiE) practitioners globally. It also looks forward at INEE\u2019s plans to support quality distance education and issues to consider on the reopening of schools. It concludes with reflections on the needs and risks for EiE longer term.", "qid": 48, "docid": "5lntnce0", "rank": 37, "score": 0.8369081020355225}, {"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": 38, "score": 0.8363185524940491}, {"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": 39, "score": 0.8360746502876282}, {"content": "Title: COVID-19 causes unprecedented educational disruption: Is there a road towards a new normal? Content: COVID-19 confronts the education system with a new and massive crisis. What should a \u201cnew normal\u201d look like for future generations? How can countries use the innovativeness of the recovery period to \u201cbuild back better\u201d? This Viewpoint highlights the UNESCO-led Global Coalition for Education initiative, which is seeking solutions to support learners and teachers, as well as governments throughout the recovery process, with a principal focus on inclusion, equity, and gender equality. The Viewpoint also argues that the current crisis is an opportunity for stronger international collaboration, which might provide a better focus and deliver solutions, including digital tools. Resilience and adaptability will be crucial for the next generations to navigate through the present\u2014and any future\u2014pandemic.", "qid": 48, "docid": "zg51e060", "rank": 40, "score": 0.8359450101852417}, {"content": "Title: COVID-19 as a catalyst for educational change Content: The massive damages of COVID-19 may be incalculable. But in the spirit of never wasting a good crisis, COVID-19 represents an opportunity to rethink education. The rethinking should not be about improving schooling, but should focus on the what, how, and where of learning. This article highlights some of the questions that schools can ask as they reimagine post-COVID education.", "qid": 48, "docid": "w3ohzxn5", "rank": 41, "score": 0.8355716466903687}, {"content": "Title: Inequities in access to education: Lessons from the COVID\u201019 pandemic Content: The COVID\u201019 pandemic has brought attention to the stark inequities in public education worldwide, with the United Nations sharing these statistics: Schools closed in 191 countries, affecting 1.5 billion students and 63 million primary and secondary school teachers. Half of students did not have access to a computer, and 40% did not have internet access. A total of 56 million children live in areas that are not served by mobile networks \u2014 for example, in sub\u2010Saharan Africa. In the United States, about 7 million school\u2010aged children are in homes without home internet service.", "qid": 48, "docid": "6fptiwmy", "rank": 42, "score": 0.8345329761505127}, {"content": "Title: Initial Coronavirus Disease\u20132019 Closure Strategies Adopted by a Convenience Sample of US School Districts: Directions for Future Research Content: School closures are an important strategy to mitigate the impacts of a pandemic. But an optimal approach to transitioning from in-person to distance learning approaches is lacking. We analyzed a convenience sample of public K-12 schools in the early weeks of the COVID-19 pandemic in the United States. This initial snapshot provides some insights to inform future research into the variation of strategies across school districts, and would benefit from more rigorous methods to determine true correlations between demographic and geographic factors. Additionally, many of these strategies have evolved in response to ongoing and prolonged public health social distancing measures implemented after this analysis was conducted.", "qid": 48, "docid": "6n0ce55n", "rank": 43, "score": 0.8337907791137695}, {"content": "Title: Initial Coronavirus Disease-2019 Closure Strategies Adopted by a Convenience Sample of US School Districts: Directions for Future Research Content: School closures are an important strategy to mitigate the impacts of a pandemic. But an optimal approach to transitioning from in-person to distance learning approaches is lacking. We analyzed a convenience sample of public K-12 schools in the early weeks of the COVID-19 pandemic in the United States. This initial snapshot provides some insights to inform future research into the variation of strategies across school districts, and would benefit from more rigorous methods to determine true correlations between demographic and geographic factors. Additionally, many of these strategies have evolved in response to ongoing and prolonged public health social distancing measures implemented after this analysis was conducted.", "qid": 48, "docid": "xecvlxhg", "rank": 44, "score": 0.8337907791137695}, {"content": "Title: Education as the path to a sustainable recovery from COVID-19 Content: COVID-19 has disrupted education for millions of children across the globe. The education community is re-imagining and re-designing to build back better. This Viewpoint takes the principles behind UNESCO\u2019s Futures of Education initiative to highlight their importance in post-COVID-19 recovery. The pandemic has shown how communities can come together to educate children. The article argues that, post-COVID-19, education systems should recognize community-driven support systems, use technology to overcome the digital divide in learning, and focus more on SDG 4.7 and its links to climate crises.", "qid": 48, "docid": "gneuzgts", "rank": 45, "score": 0.833163857460022}, {"content": "Title: COVID-19 projections for reopening Connecticut Content: Closure of schools and the statewide \"Stay Safe, Stay Home\" order have effectively reduced COVID-19 transmission in Connecticut, with model projections estimating incidence at about 1,300 new infections per day. If close interpersonal contact increases quickly in Connecticut following reopening on May 20, the state is at risk of a substantial increase of COVID-19 infections, hospitalizations, and deaths by late Summer 2020. Real-time metrics including case counts, hospitalizations, and deaths may fail to provide enough advance warning to avoid resurgence. Substantial uncertainty remains in our knowledge of cumulative COVID-19 incidence, the proportion of infected individuals who are asymptomatic, infectiousness of children, the effects of testing and contact tracing on isolation of infected individuals, and how contact patterns may change following reopening.", "qid": 48, "docid": "1109fcvc", "rank": 46, "score": 0.8327083587646484}, {"content": "Title: Impact of COVID-19 Second Wave on Healthcare Networks in the United States Content: The risk of overwhelming healthcare systems from a second wave of COVID-19 is yet to be quantified. Here, we investigate the impact of different reopening scenarios of states around the U.S. on COVID-19 hospitalized cases and the risk of overwhelming the healthcare system while considering resources at the county level. We show that the second wave might involve an unprecedented impact on the healthcare system if an increasing number of the population becomes susceptible and/or if the various protective measures are discontinued. Furthermore, we explore the ability of different mitigation strategies in providing considerable relief to the healthcare system. The results can aid healthcare planners, policymakers, and state officials in making decisions on additional resources required and on when to return to normalcy.", "qid": 48, "docid": "8kv7io05", "rank": 47, "score": 0.8325357437133789}, {"content": "Title: Child protection in the time of COVID-19 Content: As the number of cases of coronavirus disease 2019 (COVID-19) caused by the virus SARS-CoV-2 rises exponentially in Australia with consequences for the health system and society at large, we need to remember that during this pandemic that necessary social distancing measures, effective school closures and rising unemployment levels may lead to an increased risk for child abuse and neglect.", "qid": 48, "docid": "e3tgppzf", "rank": 48, "score": 0.8317096829414368}, {"content": "Title: Reopening Colleges and Universities During the COVID-19 Pandemic Content: In their article, Cheng and colleagues present the plan for reopening colleges and universities in Taiwan. There are important differences between Taiwan and other countries, but residential colleges and universities present similar challenges to pandemic control for all. Considering how well Taiwan has managed COVID-19 overall, the editorialists believe that the plan for safely reopening colleges and universities in Taiwan offers important principles.", "qid": 48, "docid": "hn4wg94k", "rank": 49, "score": 0.8315767049789429}, {"content": "Title: School Opening Delay Effect on Transmission Dynamics of Coronavirus Disease 2019 in Korea: Based on Mathematical Modeling and Simulation Study Content: BACKGROUND: Nonpharmaceutical intervention strategy is significantly important to mitigate the coronavirus disease 2019 (COVID-19) spread. One of the interventions implemented by the government is a school closure. The Ministry of Education decided to postpone the school opening from March 2 to April 6 to minimize epidemic size. We aimed to quantify the school closure effect on the COVID-19 epidemic. METHODS: The potential effects of school opening were measured using a mathematical model considering two age groups: children (aged 19 years and younger) and adults (aged over 19). Based on susceptible-exposed-infectious-recovered model, isolation and behavior-changed susceptible individuals are additionally considered. The transmission parameters were estimated from the laboratory confirmed data reported by the Korea Centers for Disease Control and Prevention from February 16 to March 22. The model was extended with estimated parameters and estimated the expected number of confirmed cases as the transmission rate increased after school opening. RESULTS: Assuming the transmission rate between children group would be increasing 10 fold after the schools open, approximately additional 60 cases are expected to occur from March 2 to March 9, and approximately additional 100 children cases are expected from March 9 to March 23. After March 23, the number of expected cases for children is 28.4 for 7 days and 33.6 for 14 days. CONCLUSION: The simulation results show that the government could reduce at least 200 cases, with two announcements by the Ministry of education. After March 23, although the possibility of massive transmission in the children's age group is lower, group transmission is possible to occur.", "qid": 48, "docid": "x0yiv35v", "rank": 50, "score": 0.8309854865074158}, {"content": "Title: How risk communication could have reduced controversy about school closures in Australia during the COVID-19 pandemic Content: Although there has been consistent evidence indicating that school closures have only limited efficacy in reducing community transmission of coronavirus disease 2019 (COVID-19), the question of whether children should be kept home from school has attracted extensive and often divisive public debate in Australia. In this article we analyse the factors that drove high levels of concern among parents, teachers and the public and led to both demands for school closures in late March 2020, and to many parents' reluctance to return their children to school in May 2020. We discuss how the use of well-established principles of risk communication might have reduced much of this community concern. Then we set out a range of practical suggestions for communication practices that build trust and hence diminish concerns in relation to managing schools over the long term of the COVID-19 pandemic.", "qid": 48, "docid": "pvus33s7", "rank": 51, "score": 0.8304548859596252}, {"content": "Title: How risk communication could have reduced controversy about school closures in Australia during the COVID-19 pandemic. Content: Although there has been consistent evidence indicating that school closures have only limited efficacy in reducing community transmission of coronavirus disease 2019 (COVID-19), the question of whether children should be kept home from school has attracted extensive and often divisive public debate in Australia. In this article we analyse the factors that drove high levels of concern among parents, teachers and the public and led to both demands for school closures in late March 2020, and to many parents' reluctance to return their children to school in May 2020. We discuss how the use of well-established principles of risk communication might have reduced much of this community concern. Then we set out a range of practical suggestions for communication practices that build trust and hence diminish concerns in relation to managing schools over the long term of the COVID-19 pandemic.", "qid": 48, "docid": "u3isdii7", "rank": 52, "score": 0.8304548859596252}, {"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": 53, "score": 0.830368161201477}, {"content": "Title: How much leeway is there to relax COVID-19 control measures? Content: Following successful widespread non-pharmaceutical interventions aiming to control COVID-19, many jurisdictions are moving towards reopening economies and borders. Given that little immunity has developed in most populations, re-establishing higher contact rates within and between populations carries substantial risks. Using a Bayesian epidemiological model, we estimate the leeway to reopen in a range of national and regional jurisdictions that have experienced different COVID-19 epidemics. We estimate the risks associated with different levels of reopening and the likely burden of new cases due to introductions from other jurisdictions. We find widely varying leeway to reopen, high risks of exceeding past peak sizes, and high possible burdens per introduced case per week, up to hundreds in some jurisdictions. We recommend a cautious approach to reopening economies and borders, coupled with strong monitoring for changes in transmission.", "qid": 48, "docid": "4df5l01l", "rank": 54, "score": 0.8298232555389404}, {"content": "Title: No evidence of secondary transmission of COVID-19 from children attending school in Ireland, 2020 Content: As many countries begin to lift some of the restrictions to contain COVID-19 spread, lack of evidence of transmission in the school setting remains. We examined Irish notifications of SARS-CoV2 in the school setting before school closures on 12 March 2020 and identified no paediatric transmission. This adds to current evidence that children do not appear to be drivers of transmission, and we argue that reopening schools should be considered safe accompanied by certain measures.", "qid": 48, "docid": "i804iorq", "rank": 55, "score": 0.8285971879959106}, {"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": 48, "docid": "05jzxdy8", "rank": 56, "score": 0.828467845916748}, {"content": "Title: Dataset of Ex-pat Teachers in Southeast Asia's Intention to Leave due to the COVID-19 pandemic Content: The COVID-19 pandemic exerted an adverse influence on the global education system, especially since starting school lockdown. The growth of teacher unemployment figures climbed double-digit and spawned these unexpected sequels. For instance, while native teachers seemed indisposed to leave the profession with the aim of seeking another more profited and seasonal jobs, many ex-pat teachers presented themselves with moving or stayed dilemma in the way the government salvaged their situation. In preference with the ex-pat teacher's case, we elucidated further throughout an e-survey in the International Baccalaureate community on Facebook from 4 to 11 April 2020 for 18,000 ex-pat teachers, who are teaching at Southeast Asia. This dataset includes 307 responses of ex-pat teachers who are staying in Singapore, Thailand, Vietnam, the Philippines, and Indonesia during the pandemic. The dataset comprises (i) Survey partakers' Demographics; (ii) Ex-pat teachers' perceptions in the relation of national, regional and school plans were afoot to the pandemic; (iii) The degree of attachment of ex-pat teacher to their current society, the ex-pat community, friends, and families during the pandemic time; (iv) Ex-pat teachers' embryo intention to reconsider their current teaching location.", "qid": 48, "docid": "qb31rxnn", "rank": 57, "score": 0.8270896673202515}, {"content": "Title: COVID-19 pandemic: Impact caused by school closure and national lockdown on pediatric visits and admissions for viral and non-viral infections, a time series analysis Content: A time series analysis of 871,543 pediatric emergency visits revealed that the COVID-19 lockdown and school closure were associated with a significant decrease in infectious diseases disseminated through airborne or fecal-oral transmissions: common cold, gastro-enteritis, bronchiolitis, acute otitis. No change was found for urinary tract infections.", "qid": 48, "docid": "vdlvp880", "rank": 58, "score": 0.8270822763442993}, {"content": "Title: They stumble that run fast: the economic and COVID-19 transmission impacts of reopening industries in the US Content: COVID-19 has laid bare the United States economically and epidemiologically. Decisions must be made as how and when to reopen industries. Here we quantify economic and health risk tradeoffs of reopening by industry for each state in the US. To estimate total economic impact, we summed income loss due to unemployment and profit loss. We assess transmission risk by: (1) workplace size, (2) human interactions, (3) inability to work from home, and (4) industry size. We found that the industry with the highest estimated economic impact from COVID-19 was manufacturing in 40 states; the industry with the largest transmission risk index was accommodation and food services in 41 states, and the industry with the highest economic impact per unit of transmission risk, interpreted as the value of reopening, was manufacturing in 37 states. Researchers and decision makers must work together to consider both health and economics when making tough decisions.", "qid": 48, "docid": "2gzip67i", "rank": 59, "score": 0.827043890953064}, {"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": 60, "score": 0.8270083069801331}, {"content": "Title: Closure of Universities Due to Coronavirus Disease 2019 (COVID-19): Impact on Education and Mental Health of Students and Academic Staff Content: The novel coronavirus disease 2019 (COVID-19), originated in Wuhan city of China, has spread rapidly around the world, sending billions of people into lockdown. The World Health Organization (WHO) declared the coronavirus epidemic a pandemic. In light of rising concern about the current COVID-19 pandemic, a growing number of universities across the world have either postponed or canceled all campus events such as workshops, conferences, sports, and other activities. Universities are taking intensive measures to prevent and protect all students and staff members from the highly infectious disease. Faculty members are already in the process of transitioning to online teaching platforms. In this review, the author will highlight the potential impact of the terrible COVID-19 outbreak on the education and mental health of students and academic staff.", "qid": 48, "docid": "gz1yqaun", "rank": 61, "score": 0.826681911945343}, {"content": "Title: SDG 4 and the COVID-19 emergency: Textbooks, tutoring, and teachers Content: COVID-19 once again revealed the inherent weaknesses in relying on classroom-based schooling and ICT to sustain learning, a danger already familiar from earlier man-made and natural disasters. A lack of textbooks and lack of guidance for caregivers to support home-based learning limited the effectiveness of efforts to provide continuity of learning. These same elements are the key to preparing better for the next crisis and keeping SDG 4 on track.", "qid": 48, "docid": "0aq7cpu8", "rank": 62, "score": 0.8265776634216309}, {"content": "Title: COVID 19: Disruptive impacts and transformative opportunities in undergraduate nurse education Content: \u2022 COVID 19. \u2022 Education. \u2022 Transformation. \u2022 Opportunities. \u2022 Challenges.", "qid": 48, "docid": "dxwx4g8m", "rank": 63, "score": 0.8257417678833008}, {"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": 64, "score": 0.825329065322876}, {"content": "Title: How Much May COVID\u201019 School Closures Increase Childhood Obesity? Content: In a recent paper entitled, \u201cCOVID\u201019 Related School Closings and Risk of Weight Gain Among Children\u201d Rundle et al. (2020) proposed the COVID\u201019 pandemic may increase obesity among American children because the pandemic, \u201cwill likely double out\u2010of\u2010school time this year for many children in the United States and will exacerbate the risk factors for weight gain associated with summer recess\u201d (pg. 1). I add support to Rundle et al.\u2019s argument by demonstrating that doubling of out\u2010of\u2010school time alone may lead to a sizable increase in childhood obesity.", "qid": 48, "docid": "1rw80tde", "rank": 65, "score": 0.8249942660331726}, {"content": "Title: Preparing Students for a More Public Health-Aware Market in Response to COVID-19 Content: The COVID-19 pandemic has made the public more aware of public health and the role its professionals play in addressing the pandemic. Schools and programs in public health have a new opportunity to recruit, train, and sustain the public health workforce. Academic public health can further educate the public and prepare students for meaningful careers through interprofessional education and practice-based learning.", "qid": 48, "docid": "8ykrh75b", "rank": 66, "score": 0.8248531818389893}, {"content": "Title: Preparing Students for a More Public Health-Aware Market in Response to COVID-19. Content: The COVID-19 pandemic has made the public more aware of public health and the role its professionals play in addressing the pandemic. Schools and programs in public health have a new opportunity to recruit, train, and sustain the public health workforce. Academic public health can further educate the public and prepare students for meaningful careers through interprofessional education and practice-based learning.", "qid": 48, "docid": "6gwqo21j", "rank": 67, "score": 0.8248531818389893}, {"content": "Title: Challenges of COVID-19 in children in low- and middle-income countries Content: As the coronavirus pandemic extends to low and middle income countries (LMICs), there are growing concerns about the risk of coronavirus disease (COVID-19) in populations with high prevalence of comorbidities, the impact on health and economies more broadly and the capacity of existing health systems to manage the additional burden of COVID-19. The direct effects of COVID are less of a concern in children, who seem to be largely asymptomatic or to develop mild illness as occurs in high income countries; however children in LMICs constitute a high proportion of the population and may have a high prevalence of risk factors for severe lower respiratory infection such as HIV or malnutrition. Further diversion of resources from child health to address the pandemic among adults may further impact on care for children. Poor living conditions in LMICs including lack of sanitation, running water and overcrowding may facilitate transmission of SARS-CoV-2. The indirect effects of the pandemic on child health are of considerable concern, including increasing poverty levels, disrupted schooling, lack of access to school feeding schemes, reduced access to health facilities and interruptions in vaccination and other child health programs. Further challenges in LMICs include the inability to implement effective public health measures such as social distancing, hand hygiene, timely identification of infected people with self-isolation and universal use of masks. Lack of adequate personal protective equipment, especially N95 masks is a key concern for health care worker protection. While continued schooling is crucial for children in LMICs, provision of safe environments is especially challenging in overcrowded resource constrained schools. The current crisis is a harsh reminder of the global inequity in health in LMICs. The pandemic highlights key challenges to the provision of health in LMICs, but also provides opportunities to strengthen child health broadly in such settings.", "qid": 48, "docid": "kf68lraw", "rank": 68, "score": 0.8246564865112305}, {"content": "Title: Medical students and COVID-19: the need for pandemic preparedness Content: The COVID-19 pandemic has prompted unprecedented global disruption. For medical schools, this has manifested as examination and curricular restructuring as well as significant changes to clinical attachments. With the available evidence suggesting that medical students' mental health status is already poorer than that of the general population, with academic stress being a chief predictor, such changes are likely to have a significant effect on these students. In addition, there is an assumption that these students are an available resource in terms of volunteerism during a crisis. This conjecture should be questioned; however, as those engaging in such work without sufficient preparation are susceptible to moral trauma and adverse health outcomes. This, in conjunction with the likelihood of future pandemics, highlights the need for 'pandemic preparedness' to be embedded in the medical curriculum.", "qid": 48, "docid": "hm388jjb", "rank": 69, "score": 0.8246164321899414}, {"content": "Title: A COVID-19 Reopening Readiness Index: The Key to Opening up the Economy Content: With respect to reopening the economy as a result of the COVID-19 restrictions, governmental response and messaging have been inconsistent, and policies have varied by state as this is a uniquely polarizing topic. Considering the urgent need to return to normalcy, a method was devised to determine the degree of progress any state has made in containing the spread of COVID-19. Using various measures for each state including mortality, hospitalizations, testing capacity, number of infections and infection rate has allowed for the creation of a composite COVID -19 Reopening Readiness Index. This index can serve as a comprehensive reliable and simple-to-use metric to assess the level of containment in any state and to determine the level of risk in further opening. As states struggle to contain the outbreak and at the same time face great pressure in resuming economic activity, an index that provides a data-driven and objective insight is urgently needed.", "qid": 48, "docid": "1faxyx9x", "rank": 70, "score": 0.8238650560379028}, {"content": "Title: How to manage the post pandemic opening? A Pontryagin Maximum Principle approach Content: The COVID-19 pandemic has completely disrupted the operation of our societies. Its elusive transmission process, characterized by an unusually long incubation period, as well as a high contagion capacity, has forced many countries to take quarantine and social isolation measures that conspire against the performance of national economies. This situation confronts decision makers in different countries with the alternative of reopening the economies, thus facing the unpredictable cost of a rebound of the infection. This work tries to offer an initial theoretical framework to handle this alternative.", "qid": 48, "docid": "dsmdqp2o", "rank": 71, "score": 0.8237082958221436}, {"content": "Title: Returning to School: Separation Problems and Anxiety in the Age of Pandemics Content: The shift to the postpandemic school environment will cause dramatic changes and is likely to increase separation problems. In this article, we look at the anxiety problems that some parents and their children might experience when school reopens after the COVID-19 lockdown. Using a behavioral theory of development, we provide suggestions for how to handle the departure and separation problems that may emerge as parents drop their children off at school. Many parents are unsure about how to handle anxiety or fear as their children return to school or have to visit other environments outside their homes. Social distancing has caused families to develop stronger dependencies at home and to create new routines that vary, in many instances greatly, from their prepandemic routines. Families are adjusting to the new \u201cnormal.\u201d They are keeping their children busy with schoolwork as best they can. In particular, families have likely developed close attachment relationships. Families have been struggling with an unprecedented lockdown, and for many parents and their children, this extended period of family confinement and severe restrictions has been especially stressful, and the timing for returning to school is uncertain. We emphasize here that parents can be responsive to their children\u2019s needs, plan ahead, provide reassurance, and depart firmly without vacillating, and we provide other tips to avoid inadvertently shaping children\u2019s negative or anxiety behaviors as they go back to school. We offer some specific advice for parents and teachers to follow to prevent the departure and separation problems that typically develop during challenging behavioral interactions in school settings.", "qid": 48, "docid": "66c2qobr", "rank": 72, "score": 0.823593258857727}, {"content": "Title: Medical Education Adaptations: Really Good Stuff for Educational Transition during a Pandemic. Content: In response to the COVID-19 pandemic, educators around the globe are scrambling to adapt in ways that facilitate the ongoing knowledge and skill development of the next generation of health professionals while social distancing and other measures are dramatically disrupting standard practices.", "qid": 48, "docid": "kzoc2ssy", "rank": 73, "score": 0.8233629465103149}, {"content": "Title: Child protection in the time of COVID\u201019 Content: As the number of cases of coronavirus disease 2019 (COVID\u201019) caused by the virus SARS\u2010CoV\u20102 rises exponentially in Australia with consequences for the health system and society at large, we need to remember that during this pandemic that necessary social distancing measures, effective school closures and rising unemployment levels may lead to an increased risk for child abuse and neglect.", "qid": 48, "docid": "6cfrnmau", "rank": 74, "score": 0.8222811222076416}, {"content": "Title: Provide and Protect the Essential Components Content: This article takes a look at the current educational climate during the worldwide COVID-19 pandemic, specifically the place that physical education has during this time. It explores the importance of maintaining standards-based learning and the essential components of physical education.", "qid": 48, "docid": "v8bxdyon", "rank": 75, "score": 0.822147011756897}, {"content": "Title: Leveraging a public-public partnership in Los Angeles County to address COVID-19 for children, youth, and families in underresourced communities Content: There is growing concern about the mental health and social impact of COVID-19 on underresourced children, youth, and families given widespread social disruption, school closures, economic impact, and loss of lives. In this commentary we describe how an existing public-public partnership between a large county mental health department and a state university responded to COVID-19. This partnership, originally designed to address workforce needs, rapidly pivoted to support providers through a trauma- and resilience-informed approach to mitigating adverse mental health effects among youth and families in Los Angeles County. (PsycInfo Database Record (c) 2020 APA, all rights reserved).", "qid": 48, "docid": "eif9xnke", "rank": 76, "score": 0.8211416006088257}, {"content": "Title: Leveraging a public-public partnership in Los Angeles County to address COVID-19 for children, youth, and families in underresourced communities. Content: There is growing concern about the mental health and social impact of COVID-19 on underresourced children, youth, and families given widespread social disruption, school closures, economic impact, and loss of lives. In this commentary we describe how an existing public-public partnership between a large county mental health department and a state university responded to COVID-19. This partnership, originally designed to address workforce needs, rapidly pivoted to support providers through a trauma- and resilience-informed approach to mitigating adverse mental health effects among youth and families in Los Angeles County. (PsycInfo Database Record (c) 2020 APA, all rights reserved).", "qid": 48, "docid": "8s3395wa", "rank": 77, "score": 0.8211416006088257}, {"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": 48, "docid": "z4mj4xgv", "rank": 78, "score": 0.8210632801055908}, {"content": "Title: Post-Coronavirus Disease 2019 Health Care and University: From Efficiency to Resilience. Content: After the initial emergency responses deployed to control the coronavirus disease 2019 (COVID-19) pandemic in the first half of 2020, we should now start thinking about long-term strategies and concepts for pandemic and disaster governance such as resilience. In this context, COVID-19 health care and education are especially important because they are essential public goods that determine what kind of a society we live in, during the pandemic and afterward. So for, the focus has been a tactical efficiency perspective that prioritized instrumental, logistical, or pragmatic aspects in planetary health and university education, with much less attention paid to social justice, history of inequity, and power asymmetries that affect the pandemic impacts in society. For a resilient COVID-19 response, we need to address not only medical, technical, and logistical challenges, but also the social disparities that are inherited from the prepandemic world that are negatively affecting the current pandemic outcomes.", "qid": 48, "docid": "1nnjrjwh", "rank": 79, "score": 0.8209517002105713}, {"content": "Title: Post-Coronavirus Disease 2019 Health Care and University: From Efficiency to Resilience Content: After the initial emergency responses deployed to control the coronavirus disease 2019 (COVID-19) pandemic in the first half of 2020, we should now start thinking about long-term strategies and concepts for pandemic and disaster governance such as resilience. In this context, COVID-19 health care and education are especially important because they are essential public goods that determine what kind of a society we live in, during the pandemic and afterward. So for, the focus has been a tactical efficiency perspective that prioritized instrumental, logistical, or pragmatic aspects in planetary health and university education, with much less attention paid to social justice, history of inequity, and power asymmetries that affect the pandemic impacts in society. For a resilient COVID-19 response, we need to address not only medical, technical, and logistical challenges, but also the social disparities that are inherited from the prepandemic world that are negatively affecting the current pandemic outcomes.", "qid": 48, "docid": "cw0ewwdm", "rank": 80, "score": 0.8209516406059265}, {"content": "Title: Lower State COVID-19 Deaths and Cases with Earlier School Closure in the U.S. Content: This study quantifies the relationship between school closure timing and COVID-19 deaths and cases in the general population in all U.S. states. COVID-19 has higher symptomatic infection rates among the elderly, suggesting school closures could be unrelated to transmission. However, predicting daily cumulative COVID-19 deaths by state, earlier school closure is related to fewer deaths per capita and slower growth in deaths per capita. Results are similar for COVID-19 cases per capita.", "qid": 48, "docid": "0ytk77fm", "rank": 81, "score": 0.8199896216392517}, {"content": "Title: On Leadership: Responding to COVID-19: Short- and long-term challenges Content: In the early days of the COVID-19 outbreak, school district leaders\u2019 most immediate priority was to ensure that students have access to regular meals. However, efforts to provide a range of other social services must follow close behind. As a start, superintendents can look to their data systems to help them identify those students and families that are most likely to need social services to make it through this phase and beyond. But even while racing to ensure students\u2019 health and safety, they cannot afford to ignore the longer-term challenges that their districts will face, given not just the need to move instruction online but also given that COVID-19 is all but guaranteed to do serious damage to state and local economies.", "qid": 48, "docid": "o56km9qw", "rank": 82, "score": 0.8199073076248169}, {"content": "Title: Willingness to Accept Tradeoffs among Covid-19 Cases, Social-Distancing Restrictions, and Economic Impact: A Nationwide US Study Content: We designed a discrete-choice experiment to quantify the extent to which US adults would accept greater risk of infection with SARS-CoV-2 in return for lifting social-distancing restrictions and diminishing the economic impact of the COVID-19 pandemic. 5953 adults representing all 50 states had 4 distinctly different preference patterns. About 37% were risk minimizers reluctant to accept any increases in risk of contracting the virus. Another group (26%) was primarily concerned about time required for economic recovery, accepting increases in COVID-19 risk levels up to 16% to shorten recovery from 3 to 2 years. The remaining two groups diverged on the relative importance of reopening nonessential businesses. The larger group (26%) strongly preferred delaying reopening while the smaller group (13%) would accept COVID-19 risks well beyond 20% to avoid a delay in reopening. Political affiliation, race, household income and employment status were predictive of group membership.", "qid": 48, "docid": "clxe1gzb", "rank": 83, "score": 0.819877028465271}, {"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": 84, "score": 0.8193983435630798}, {"content": "Title: Cost Benefit Analysis of Limited Reopening Relative to a Herd Immunity Strategy or Shelter in Place for SARS-CoV-2 in the United States Content: BACKGROUND: Fierce debate about the health and financial tradeoffs presented by different COVID-19 pandemic mitigation strategies highlights the need for rigorous quantitative evaluation of policy options. OBJECTIVE: To quantify the economic value of the costs and benefits of a policy of continued limited reopening with social distancing relative to alternative COVID-19 response strategies in the United States. DESIGN: We estimate the number and value of quality-adjusted life-years (QALY) gained from mortality averted, with a value of $125,000 per QALY, and compare these benefits to the associated costs in terms of plausible effects on US GDP under a policy of continued limited reopening with social distancing relative to a policy of full reopening toward herd immunity. Using the same QALY value assumptions, we further evaluate cost-effectiveness of a return to Shelter-in-Place relative to a policy of limited reopening. SETTING: United States MEASUREMENTS: QALY and cost as percent of GDP of limited reopening with continued social distancing relative to a strategy of full reopening aimed at achieving herd immunity; a limited reopening \u201cbudget\u201d measured in the number of months before this strategy fails to demonstrate cost-effectiveness relative to a full reopening; a shelter-in-place \u201cthreshold\u201d measured in the number of lives saved at which a month of sheltering in place demonstrates cost effectiveness relative to the limited reopening strategy. RESULTS: QALY benefits from mortality averted by continued social distancing and limited reopening relative to a policy of full reopening exceed projected GDP costs if an effective vaccine or therapeutic can be developed within 11.1 months from late May 2020. White House vaccine projections fall within this date, supporting a partial reopening strategy. One month of shelter-in-place restrictions provides QALY benefits from averted mortality that exceed the associated GDP costs relative to limited reopening if the restrictions prevent at least 154,586 additional COVID-19 deaths over the course of the pandemic. Current models of disease progression suggest that limited reopening will not cause this many additional deaths, again supporting a limited reopening strategy. LIMITATION: Limited horizon of COVID-19 mortality projections; infection fatality ratio stable across strategies, ignoring both the potential for ICU overload to increase mortality and the deployment of partially effective therapeutics to decrease mortality; effect on GDP modeled as constant within a given phase of the pandemic; accounts for age and sex distribution of QALYs, but not effect of comorbidities; only considers impact from QALY lost due to mortality and from changes in GDP, excluding numerous other considerations, such as non-fatal COVID-19 morbidity, reduced quality of life caused by prolonged social distancing, or educational regression associated with prolonged school closures and restrictions. CONCLUSIONS: A limited reopening to achieve partial mitigation of COVID-19 is cost effective relative to a full reopening if an effective therapeutic or vaccine can be deployed within 11.1 months of late May 2020. One additional month of shelter-in-place restrictions should only be imposed if it saves at least 154,586 lives per month before the development of an effective therapeutic or vaccine relative to limited reopening.", "qid": 48, "docid": "wkcdv0h4", "rank": 85, "score": 0.8192288279533386}, {"content": "Title: Repeat SARS-CoV-2 Testing Models for Residential College Populations Content: Residential colleges are considering re-opening under uncertain futures regarding the COVID-19 pandemic. We consider repeat SARS-CoV-2 testing models for the purpose of containing outbreaks in the residential campus community. The goal of repeat testing is to rapidly detect and isolate new infections as they occur to block transmission that would otherwise occur on campus and, of arguably greater importance, off. The models allow for the evolution of test sensitivity with time from infection, scheduled on-campus resident screening at a given frequency, imported infections from off campus throughout the school year, and a lag from testing until student isolation due to laboratory turnaround and student relocation delay. For early- (late-) transmission of SARS-CoV-2 by age of infection, we find that weekly screening cannot reliably contain outbreaks with reproductive numbers above 1.4 (1.6) if more than one imported exposure per 10,000 students occurs daily. Screening every three days can contain outbreaks providing the reproductive number remains below 1.75 (2.3) if transmission happens earlier (later) with time from infection, but at the cost of greatly increased false positive rates requiring more isolation quarters for students testing positive. Testing frequently while minimizing the delay from testing until isolation for those found positive are the most controllable levers for preventing large residential college outbreaks.", "qid": 48, "docid": "fmh3r8n4", "rank": 86, "score": 0.8190357685089111}, {"content": "Title: Hopelessness, helplessness and resilience: The importance of safeguarding our trainees' mental wellbeing during the COVID-19 pandemic Content: \u2022 The COVID-19 pandemic may put the mental wellbeing of trainees at risk. \u2022 Hopelessness, helplessness and burnout are important to be aware of. \u2022 We need to foster an open culture of trust and support. \u2022 We need to promote resilience in colleagues/trainees where possible.", "qid": 48, "docid": "c4dlym34", "rank": 87, "score": 0.8187057375907898}, {"content": "Title: The global viralization of policies to contain the spreading of the COVID-19 pandemic: analyses of school closures and first reported cases. Content: Background With the exposure to the COVID-19 pandemic, countries swiftly implemented a variety of health policies. In this work we examine how rapid countries responded to this pandemic using two events: the day in which the first case of COVID-19 was reported, and first day in which countries used school closure as one of the measures to avoid outbreaks. Methods We compiled information from multiple sources, from December 31st 2019 to June 1st 2020, to trace when 172 countries reported their first COVID-19 case and implemented school closure to contain outbreaks. We applied cross-national Weibull survival analysis to evaluate the global speed of detection of first COVID-19 reported cases and school closure. We also assessed how health systems, globalization, economic development, political systems, and economic integration to China, Republic of Korea and Italy increased the speed of adoption. Results Ten days after the World Health Organization (WHO) declared COVID-19 to be an international emergency, countries were 28 (95% CI: 12,77) times more likely to report first COVID-19 cases and 42 (95% CI: 22,90) times more likely to close schools. One standard deviation increase in the epidemic security index rises the rate of report first cases by 37% (Hazard Ratio (HR) 1.37 (95% CI: 1.09,1.72) and delays the adoption for school closures by 36% (HR 0.64 (95% CI:0.50,0.82). One standard deviation increase in the globalization index augments the adoption for school closures by 74% (HR 1.74 (95% CI:1.34,2.24). Conclusion. After the WHO declared a global emergency, countries were unprecedently acting very rapidly. While countries more globally integrated were swifter in closing schools, countries with better designed health systems to tackle epidemics were slower in adopting it. More studies are needed to assess how the speed of school closures and other policies will affect the development of the pandemic.", "qid": 48, "docid": "5kbrsos9", "rank": 88, "score": 0.8186075687408447}, {"content": "Title: Undue burdens in the time of coronavirus Content: Beginning early in March of this year, postsecondary schools across the country responded to the COVID-19 pandemic by quickly reconfiguring classroom instruction to exclusively online education", "qid": 48, "docid": "1dnvgblt", "rank": 89, "score": 0.8184795379638672}, {"content": "Title: A Community Hospital's Response to the COVID-19 Pandemic Content: The novel coronavirus 2019-nCoV (COVID-19) has disrupted and altered the way health care is delivered in the United States and across the world. Patient care guidelines and isolation recommendations continue to hastily change, demonstrating the key role of nursing professional development practitioners in educating and preparing frontline staff to provide safe patient care during the COVID-19 pandemic. This article describes a community hospital's strategic educational response to a highly contagious respiratory pandemic. Initiatives to increase staff education and conserve personal protective equipment are discussed.", "qid": 48, "docid": "a36gnqjz", "rank": 90, "score": 0.8183112144470215}, {"content": "Title: A Community Hospital's Response to the COVID-19 Pandemic. Content: The novel coronavirus 2019-nCoV (COVID-19) has disrupted and altered the way health care is delivered in the United States and across the world. Patient care guidelines and isolation recommendations continue to hastily change, demonstrating the key role of nursing professional development practitioners in educating and preparing frontline staff to provide safe patient care during the COVID-19 pandemic. This article describes a community hospital's strategic educational response to a highly contagious respiratory pandemic. Initiatives to increase staff education and conserve personal protective equipment are discussed.", "qid": 48, "docid": "vm2kbzk1", "rank": 91, "score": 0.8183112144470215}, {"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": 48, "docid": "k30mv20e", "rank": 92, "score": 0.8177206516265869}, {"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": 48, "docid": "q0ubeurh", "rank": 93, "score": 0.8177206516265869}, {"content": "Title: Teaching Public Health Will Never Be the Same. Content: Students will likely be flocking to public health courses and programs in upcoming semesters. The coronavirus disease 2019 (COVID-19) pandemic has piqued the interest of many in society, among them college students. Students who have an interest in health, medicine, or science now may see public health as a viable career option, especially with numerous public health researchers being featured in stories and social media around the globe. Although this is an important moment for our field and discipline, universities training future public health professionals will need to recalibrate how they approach their teaching in the aftermath of the COVID-19 pandemic. (Am J Public Health. Published online ahead of print May 14, 2020: e1-e2. doi:10.2105/AJPH.2020.305710).", "qid": 48, "docid": "h6oxqpi0", "rank": 94, "score": 0.8174917697906494}, {"content": "Title: Medical students and COVID-19: the need for pandemic preparedness Content: The COVID-19 pandemic has prompted unprecedented global disruption. For medical schools, this has manifested as examination and curricular restructuring as well as significant changes to clinical attachments. With the available evidence suggesting that medical students\u2019 mental health status is already poorer than that of the general population, with academic stress being a chief predictor, such changes are likely to have a significant effect on these students. In addition, there is an assumption that these students are an available resource in terms of volunteerism during a crisis. This conjecture should be questioned; however, as those engaging in such work without sufficient preparation are susceptible to moral trauma and adverse health outcomes. This, in conjunction with the likelihood of future pandemics, highlights the need for \u2018pandemic preparedness\u2019 to be embedded in the medical curriculum.", "qid": 48, "docid": "tl8iam1o", "rank": 95, "score": 0.816875159740448}, {"content": "Title: Imagining what education can be post-COVID-19 Content: This Viewpoint argues that the COVID-19 crisis offers a unique chance to imagine more equitable societies and education systems. It is also a call to action, to take meaningful action to bring about that desired future.", "qid": 48, "docid": "pktvx20k", "rank": 96, "score": 0.8166779279708862}, {"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": 97, "score": 0.8162474036216736}, {"content": "Title: Medical Students in the Time of COVID-19: opportunities and challenges Content: The spread of COVID-19 has had a substantial impact on healthcare systems around the world. Increased pressure has led to doctors being called out of retirement, as well as a call for volunteers in healthcare settings and within the community. Medical education has been transformed within the space of weeks, with clinical placements cancelled and teaching and examinations moved to an online format. This raises the question of what the role of medical students is during this pandemic.", "qid": 48, "docid": "389djar8", "rank": 98, "score": 0.8162192106246948}, {"content": "Title: Preparing for the Next Wave of COVID-19: Resilience in the Face of a Spreading Pandemic Content: COVID-19 painfully demonstrates how little resilience our societies have to novel viruses. Societies, decision makers, and scientists lack (1) a comprehensive understanding of the complexity of viral outbreaks and their impact on society; (2) intervention portfolios; and (3) a global crisis and resilience policy, all of which are required to develop appropriate measures and to improve societal resilience. We highlight COVID-19 immunity as one key benchmark in preparation for the next wave of the pandemic. Specifically, using network scenarios, we demonstrate the substantial advantage of reintegrating health care workers with acquired COVID-19 immunity in epidemic hotspots, which would not only enable their safe contribution to the health care system but also drastically contain further spread.", "qid": 48, "docid": "5le1f8kx", "rank": 99, "score": 0.8156224489212036}, {"content": "Title: COVID-19 and schooling: evaluation, assessment and accountability in times of crises\u2014reacting quickly to explore key issues for policy, practice and research with the school barometer Content: The crisis caused by the COVID-19 virus has far-reaching effects in the field of education, as schools were closed in March 2020 in many countries around the world. In this article, we present and discuss the School Barometer, a fast survey (in terms of reaction time, time to answer and dissemination time) that was conducted in Germany, Austria and Switzerland during the early weeks of the school lockdown to assess and evaluate the current school situation caused by COVID-19. Later, the School Barometer was extended to an international survey, and some countries conducted the survey in their own languages. In Germany, Austria and Switzerland, 7116 persons participated in the German language version: 2222 parents, 2152 students, 1949 school staff, 655 school leaders, 58 school authority and 80 members of the school support system. The aim was to gather, analyse and present data in an exploratory way to inform policy, practice and further research. In this article, we present some exemplary first results and possible implications for policy, practice and research. Furthermore, we reflect on the strengths and limitations of the School Barometer and fast surveys as well as the methodological options for data collection and analysis when using a short monitoring survey approach. Specifically, we discuss the methodological challenges associated with survey data of this kind, including challenges related to hypothesis testing, the testing of causal effects and approaches to ensure reliability and validity. By doing this, we reflect on issues of assessment, evaluation and accountability in times of crisis.", "qid": 48, "docid": "zwhbzdm2", "rank": 100, "score": 0.8155597448348999}]}
{"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": 0.8841696977615356}, {"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": 2, "score": 0.877723753452301}, {"content": "Title: SARS-CoV-2-specific T cells exhibit unique features characterized by robust helper function, lack of terminal differentiation, and high proliferative potential Content: Convalescing COVID-19 patients mount robust T cell responses against SARS-CoV-2, suggesting an important role for T cells in viral clearance. To date, the phenotypes of SARS-CoV-2-specific T cells remain poorly defined. Using 38-parameter CyTOF, we phenotyped longitudinal specimens of SARS-CoV-2-specific CD4+ and CD8+ T cells from four individuals who recovered from mild COVID-19. SARS-CoV-2-specific CD4+ T cells were exclusively Th1 cells, and predominantly Tcm with phenotypic features of robust helper function. SARS-CoV-2-specific CD8+ T cells were predominantly atypical Temra cells in a state of less terminal differentiation and therefore capable of expansion. Subsets of SARS-CoV-2-specific T cells exhibit features of being long-lived and capable of homeostatic proliferation consistent with their persistence for over two months. Our results suggest that long-lived and robust T cell immunity is generated following natural SARS-CoV-2 infection, and support an important role for SARS-CoV-2-specific T cells in host control of COVID-19.", "qid": 49, "docid": "lec1kplh", "rank": 3, "score": 0.8718041181564331}, {"content": "Title: Detection of SARS-CoV-2-Specific Humoral and Cellular Immunity in COVID-19 Convalescent Individuals Content: The World Health Organization has declared SARS-CoV-2 virus outbreak a worldwide pandemic. However, there is very limited understanding on the immune responses, especially adaptive immune responses to SARS-CoV-2 infection. Here, we collected blood from COVID-19 patients who have recently become virus-free, and therefore were discharged, and detected SARS-CoV-2-specific humoral and cellular immunity in eight newly discharged patients. Follow-up analysis on another cohort of six patients 2 weeks post discharge also revealed high titers of immunoglobulin G (IgG) antibodies. In all 14 patients tested, 13 displayed serum-neutralizing activities in a pseudotype entry assay. Notably, there was a strong correlation between neutralization antibody titers and the numbers of virus-specific T cells. Our work provides 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 also has implications in developing an effective vaccine to SARS-CoV-2 infection.", "qid": 49, "docid": "53j3ly3v", "rank": 4, "score": 0.8704522848129272}, {"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": 5, "score": 0.8699148893356323}, {"content": "Title: Differences in antibody kinetics and functionality between severe and mild SARS-CoV-2 infections. Content: We determined and compared the humoral immune response in severe, hospitalized and mild, non-hospitalized COVID-19 patients. Severe patients (n=38) develop a robust antibody response to SARS-CoV-2, including IgG and IgA antibodies. The geometric mean 50% virus neutralization titer is 1:240. SARS-CoV-2 infected hospital personnel (n=24), who developed mild symptoms necessitating leave of absence, self-isolation, but not hospitalization, 75 % develop antibodies, but with low/absent virus neutralization (60% < 1:20). While severe COVID-19 patients develop a strong antibody response, mild SARS-CoV-2 infections induce a modest antibody response. Long term monitoring will show whether these responses predict protection against future infections.", "qid": 49, "docid": "yuwrr4vg", "rank": 6, "score": 0.8674216270446777}, {"content": "Title: Detection of SARS-CoV-2-specific humoral and cellular immunity in COVID-19 convalescent individuals Content: Summary The World Health Organization has declared SARS-CoV-2 virus outbreak a world-wide pandemic. However, there is very limited understanding on the immune responses, especially adaptive immune responses to SARS-CoV-2 infection. Here, we collected blood from COVID-19 patients who have recently become virus-free and therefore were discharged, and detected SARS-CoV-2-specific humoral and cellular immunity in 8 newly discharged patients. Follow-up analysis on another cohort of 6 patients 2 weeks post discharge also revealed high titers of IgG antibodies. In all 14 patients tested, 13 displayed serum neutralizing activities in a pseudotype entry assay. Notably, there was a strong correlation between neutralization antibody titers and the numbers of virus-specific T cells. Our work provides 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 developing an effective vaccine to SARS-CoV-2 infection.", "qid": 49, "docid": "0tn06al2", "rank": 7, "score": 0.8673182725906372}, {"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": 49, "docid": "88px7oq2", "rank": 8, "score": 0.8670056462287903}, {"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": 9, "score": 0.8666431903839111}, {"content": "Title: Reappearance of Effector T Cells Predicts Successful Recovery from COVID-19 Content: Background: Elucidating the role of T cell responses in COVID-19 is of utmost importance to understand the clearance of SARS-CoV-2 infection. Methods: 90 individuals were enrolled in this study, 30 hospitalized COVID-19 patients and 60 age- and gender-matched healthy controls (HC). Using two comprehensive 11-color flow cytometric panels conforming to Good Laboratory Practice (GLP) and approved for clinical diagnostics, we longitudinally examined cell count differences in lymphocyte populations and T cell activation in COVID-19 patients. Findings: Absolute numbers of lymphocyte subsets were differentially decreased in COVID-19 patients according to clinical severity. In severe disease (SD) patients, all lymphocyte subsets were reduced, whilst in mild disease (MD) NK, NKT and {gamma}{delta} T cells were at the level of HC. Additionally, we provide evidence of T cell activation in MD but not SD, when compared to HC. Interestingly, follow up samples revealed a marked increase in effector T cells and memory subsets in convalescing but not in non-convalescing patients. Interpretation: Our data suggest that activation and expansion of innate and adaptive lymphocytes play a major role in COVID-19. Additionally, recovery is associated with formation of T cell memory as suggested by the missing formation of effector and central memory T cells in SD but not in MD. Our data imply that the presence of SARS-CoV-2 responsive T cells contributes to convalescence in MD. Thus, understanding the T cell-response in the context of clinical severity might serve as foundation to overcome the lack of effective anti-viral immune response in severely affected COVID-19 patients and can offer prognostic value as biomarker for disease outcome and control.", "qid": 49, "docid": "5lhvix51", "rank": 10, "score": 0.8663698434829712}, {"content": "Title: Broad and strong memory CD4+ and CD8+ T cells induced by SARS-CoV-2 in UK convalescent COVID-19 patients Content: COVID-19 is an ongoing global crisis in which the development of effective vaccines and therapeutics will depend critically on understanding the natural immunity to the virus, including the role of SARS-CoV-2-specific T cells. We have conducted a study of 42 patients following recovery from COVID-19, including 28 mild and 14 severe cases, comparing their T cell responses to those of 16 control donors. We assessed the immune memory of T cell responses using IFN\u03b3 based assays with overlapping peptides spanning SARS-CoV-2 apart from ORF1. We found the breadth, magnitude and frequency of memory T cell responses from COVID-19 were significantly higher in severe compared to mild COVID-19 cases, and this effect was most marked in response to spike, membrane, and ORF3a proteins. Total and spike-specific T cell responses correlated with the anti-Spike, anti-Receptor Binding Domain (RBD) as well as anti-Nucleoprotein (NP) endpoint antibody titre (p<0.001, <0.001 and =0.002). We identified 39 separate peptides containing CD4+ and/or CD8+ epitopes, which strikingly included six immunodominant epitope clusters targeted by T cells in many donors, including 3 clusters in spike (recognised by 29%, 24%, 18% donors), two in the membrane protein (M, 32%, 47%) and one in the nucleoprotein (Np, 35%). CD8+ responses were further defined for their HLA restriction, including B*4001-restricted T cells showing central memory and effector memory phenotype. In mild cases, higher frequencies of multi-cytokine producing M- and NP-specific CD8+ T cells than spike-specific CD8+ T cells were observed. They furthermore showed a higher ratio of SARS-CoV-2-specific CD8+ to CD4+ T cell responses. Immunodominant epitope clusters and peptides containing T cell epitopes identified in this study will provide critical tools to study the role of virus-specific T cells in control and resolution of SARS-CoV-2 infections. The identification of T cell specificity and functionality associated with milder disease, highlights the potential importance of including non-spike proteins within future COVID-19 vaccine design.", "qid": 49, "docid": "qo3cfytq", "rank": 11, "score": 0.8638068437576294}, {"content": "Title: A longitudinal study of immune cells in severe COVID-19 patients. Content: Little is known about the time-dependent immune responses in severe COVID-19. Data of 15 consecutive patients were sequentially recorded from intensive care unit admission. Lymphocyte subsets and total monocyte and subsets counts were monitored as well as the expression of HLA-DR. For 5 patients, SARS-CoV-2-specific T-cell polyfunctionality was assessed against Spike and Nucleoprotein SARS-CoV-2 peptides. Non-specific inflammation markers were increased in all patients. Median monocyte HLA-DR expression was below the 8,000 AB/C threshold defining acquired immunodepression. A V trend curve for lymphopenia, monocyte numbers, and HLA-DR expression was observed with a nadir between days 11-14 after the onset of symptoms. Intermediate CD14++CD16+ monocytes increased early with a reduction in classic CD14++CD16- monocytes. Polyfunctional SARS-Cov-2-specific CD4 T-cells were present and functional, whereas virus-specific CD8 T-cells were less frequent and not efficient. We report a temporal variation of both innate and adaptive immunity in severe COVID-19 patients, helpful in guiding therapeutic decisions (e.g. anti-inflammatory vs. immunostimulatory ones). We describe a defect in virus-specific CD8 T-cells, a potential biomarker of clinical severity. These combined data also provide helpful knowledge for vaccine design.", "qid": 49, "docid": "pukl3vhs", "rank": 12, "score": 0.8635784983634949}, {"content": "Title: Breadth of concomitant immune responses underpinning viral clearance and patient recovery in a non-severe case of COVID-19 Content: We report the kinetics of the immune response in relation to clinical and virological features of a patient with mild-to-moderate coronavirus disease-19 (COVID-19) requiring hospitalisation. Increased antibody-secreting cells, follicular T-helper cells, activated CD4+ and CD8+ T-cells and IgM/IgG SARS-CoV-2-binding antibodies were detected in blood, prior to symptomatic recovery. These immunological changes persisted for at least 7 days following full resolution of symptoms, indicating substantial anti-viral immunity in this non-severe COVID-19.", "qid": 49, "docid": "kqanoog7", "rank": 13, "score": 0.8631683588027954}, {"content": "Title: Reappearance of effector T cells is associated with recovery from COVID-19 Content: BACKGROUND: Elucidating the role of T cell responses in COVID-19 is of utmost importance to understand the clearance of SARS-CoV-2 infection. METHODS: 30 hospitalized COVID-19 patients and 60 age- and gender-matched healthy controls (HC) participated in this study. We used two comprehensive 11-colour flow cytometric panels conforming to Good Laboratory Practice and approved for clinical diagnostics. FINDINGS: Absolute numbers of lymphocyte subsets were differentially decreased in COVID-19 patients according to clinical severity. In severe disease (SD) patients, all lymphocyte subsets were reduced, whilst in mild disease (MD) NK, NKT and \u00ce\u00b3\u00ce\u00b4 T cells were at the level of HC. Additionally, we provide evidence of T cell activation in MD but not SD, when compared to HC. Follow up samples revealed a marked increase in effector T cells and memory subsets in convalescing but not in non-convalescing patients. INTERPRETATION: Our data suggest that activation and expansion of innate and adaptive lymphocytes play a major role in COVID-19. Additionally, recovery is associated with formation of T cell memory as suggested by the missing formation of effector and central memory T cells in SD but not in MD. Understanding T cell-responses in the context of clinical severity might serve as foundation to overcome the lack of effective anti-viral immune response in severely affected COVID-19 patients and can offer prognostic value as biomarker for disease outcome and control. FUNDING: Funded by State of Lower Saxony grant 14-76,103-184CORONA-11/20 and German Research Foundation, Excellence Strategy - EXC2155\"RESIST\"-Project ID39087428, and DFG-SFB900/3-Project ID158989968, grants SFB900-B3, SFB900-B8.", "qid": 49, "docid": "871812f7", "rank": 14, "score": 0.8627235889434814}, {"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": 15, "score": 0.8626805543899536}, {"content": "Title: Reduction and Functional Exhaustion of T Cells in Patients With Coronavirus Disease 2019 (COVID-19) Content: Background: The outbreak of coronavirus disease 2019 (COVID-19) caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) has posed great threat to human health. T cells play a critical role in antiviral immunity but their numbers and functional state in COVID-19 patients remain largely unclear. Methods: We retrospectively reviewed the counts of T cells and serum cytokine concentration from data of 522 patients with laboratory-confirmed COVID-19 and 40 healthy controls. In addition, the expression of T cell exhaustion markers were measured in 14 COVID-19 cases. Results: The number of total T cells, CD4+ and CD8+ T cells were dramatically reduced in COVID-19 patients, especially in patients requiring Intensive Care Unit (ICU) care. Counts of total T cells, CD8+ T cells or CD4+ T cells lower than 800, 300, or 400/\u00b5L, respectively, were negatively correlated with patient survival. T cell numbers were negatively correlated to serum IL-6, IL-10, and TNF-&#945; concentration, with patients in the disease resolution period showing reduced IL-6, IL-10, and TNF-&#945; concentrations and restored T cell counts. T cells from COVID-19 patients had significantly higher levels of the exhausted marker PD-1. Increasing PD-1 and Tim-3 expression on T cells was seen as patients progressed from prodromal to overtly symptomatic stages. Conclusions: T cell counts are reduced significantly in COVID-19 patients, and the surviving T cells appear functionally exhausted. Non-ICU patients with total T cells counts lower than 800/\u00b5L may still require urgent intervention, even in the immediate absence of more severe symptoms due to a high risk for further deterioration in condition.", "qid": 49, "docid": "gqdyddtg", "rank": 16, "score": 0.861876368522644}, {"content": "Title: Reappearance of effector T cells is associated with recovery from COVID-19 Content: BACKGROUND: Elucidating the role of T cell responses in COVID-19 is of utmost importance to understand the clearance of SARS-CoV-2 infection. METHODS: 30 hospitalized COVID-19 patients and 60 age- and gender-matched healthy controls (HC) participated in this study. We used two comprehensive 11-colour flow cytometric panels conforming to Good Laboratory Practice and approved for clinical diagnostics. FINDINGS: Absolute numbers of lymphocyte subsets were differentially decreased in COVID-19 patients according to clinical severity. In severe disease (SD) patients, all lymphocyte subsets were reduced, whilst in mild disease (MD) NK, NKT and \u03b3\u03b4 T cells were at the level of HC. Additionally, we provide evidence of T cell activation in MD but not SD, when compared to HC. Follow up samples revealed a marked increase in effector T cells and memory subsets in convalescing but not in non-convalescing patients. INTERPRETATION: Our data suggest that activation and expansion of innate and adaptive lymphocytes play a major role in COVID-19. Additionally, recovery is associated with formation of T cell memory as suggested by the missing formation of effector and central memory T cells in SD but not in MD. Understanding T cell-responses in the context of clinical severity might serve as foundation to overcome the lack of effective anti-viral immune response in severely affected COVID-19 patients and can offer prognostic value as biomarker for disease outcome and control. FUNDING: Funded by State of Lower Saxony grant 14\u201376,103\u2013184CORONA-11/20 and German Research Foundation, Excellence Strategy \u2013 EXC2155\u201cRESIST\u201d\u2013Project ID39087428, and DFG-SFB900/3\u2013Project ID158989968, grants SFB900-B3, SFB900-B8.", "qid": 49, "docid": "9iuesnxo", "rank": 17, "score": 0.861568808555603}, {"content": "Title: Reduction and Functional Exhaustion of T Cells in Patients With Coronavirus Disease 2019 (COVID-19) Content: Background: The outbreak of coronavirus disease 2019 (COVID-19) caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) has posed great threat to human health. T cells play a critical role in antiviral immunity but their numbers and functional state in COVID-19 patients remain largely unclear. Methods: We retrospectively reviewed the counts of T cells and serum cytokine concentration from data of 522 patients with laboratory-confirmed COVID-19 and 40 healthy controls. In addition, the expression of T cell exhaustion markers were measured in 14 COVID-19 cases. Results: The number of total T cells, CD4(+) and CD8(+) T cells were dramatically reduced in COVID-19 patients, especially in patients requiring Intensive Care Unit (ICU) care. Counts of total T cells, CD8(+) T cells or CD4(+) T cells lower than 800, 300, or 400/\u03bcL, respectively, were negatively correlated with patient survival. T cell numbers were negatively correlated to serum IL-6, IL-10, and TNF-\u03b1 concentration, with patients in the disease resolution period showing reduced IL-6, IL-10, and TNF-\u03b1 concentrations and restored T cell counts. T cells from COVID-19 patients had significantly higher levels of the exhausted marker PD-1. Increasing PD-1 and Tim-3 expression on T cells was seen as patients progressed from prodromal to overtly symptomatic stages. Conclusions: T cell counts are reduced significantly in COVID-19 patients, and the surviving T cells appear functionally exhausted. Non-ICU patients with total T cells counts lower than 800/\u03bcL may still require urgent intervention, even in the immediate absence of more severe symptoms due to a high risk for further deterioration in condition.", "qid": 49, "docid": "aqcllik0", "rank": 18, "score": 0.8614305257797241}, {"content": "Title: Persistent SARS-CoV-2 presence is companied with defects in adaptive immune system in non-severe COVID-19 patients Content: Background: COVID-19 has been widely spreading. We aim to examine adaptive immune cells in non-severe patients with persistent SARS-CoV-2 shedding. Methods 37 non-severe patients with persistent SARS-CoV-2 presence transferred to Zhongnan hospital of Wuhan University were retrospectively recruited to PP (persistently positive) group, which was further allocated to PPP group (n=19) and PPN group (n=18), according to their testing results after 7 days (N=negative). Epidemiological, demographic, clinical and laboratory data were collected and analyzed. Data from age- and sex-matched non-severe patients at disease onset (PA [positive on admission] patients, n=37), and lymphocyte subpopulation measurements from matched 54 healthy subjects were extracted for comparison. Results Compared with PA patients, PP patients had much improved laboratory findings, including WBCs, neutrophils, lymphocytes, neutrophil-to-lymphocyte ratio, albumin, AST, CRP, SAA, and IL-6. The absolute numbers of CD3+ T cells, CD4+ T cells, and NK cells were significantly higher in PP group than that in PA group, and were comparable to that in healthy controls. PPP subgroup had markedly reduced B cells and T cells compared to PPN group and healthy subjects. Finally, paired results of these lymphocyte subpopulations from 10 PPN patients demonstrated that the number of T cells and B cells significantly increased when the SARS-CoV-2 tests turned negative. Conclusion Persistent SARS-CoV-2 presence in non-severe COVID-19 patients is associated with reduced numbers of adaptive immune cells. Monitoring lymphocyte subpopulations could be clinically meaningful in identifying fully recovered COVID-19 patients. Abbreviations COVID-19: Coronavirus disease 2019; SARS-CoV-2: Severe acute respiratory syndrome coronavirus 2; HC: Healthy controls.", "qid": 49, "docid": "0tkx7aas", "rank": 19, "score": 0.8609178066253662}, {"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": 20, "score": 0.8598896861076355}, {"content": "Title: Longitudinal evaluation and decline of antibody responses in SARS-CoV-2 infection Content: Antibody (Ab) responses to SARS-CoV-2 can be detected in most infected individuals 10-15 days following the onset of COVID-19 symptoms. However, due to the recent emergence of this virus in the human population it is not yet known how long these Ab responses will be maintained or whether they will provide protection from re-infection. Using sequential serum samples collected up to 94 days post onset of symptoms (POS) from 65 RT-qPCR confirmed SARS-CoV-2-infected individuals, we show seroconversion in >95% of cases and neutralizing antibody (nAb) responses when sampled beyond 8 days POS. We demonstrate that the magnitude of the nAb response is dependent upon the disease severity, but this does not affect the kinetics of the nAb response. Declining nAb titres were observed during the follow up period. Whilst some individuals with high peak ID50 (>10,000) maintained titres >1,000 at >60 days POS, some with lower peak ID50 had titres approaching baseline within the follow up period. A similar decline in nAb titres was also observed in a cohort of seropositive healthcare workers from Guy's and St Thomas' Hospitals. We suggest that this transient nAb response is a feature shared by both a SARS-CoV-2 infection that causes low disease severity and the circulating seasonal coronaviruses that are associated with common colds. This study has important implications when considering widespread serological testing, Ab protection against re-infection with SARS-CoV-2 and the durability of vaccine protection.", "qid": 49, "docid": "7n6pva1l", "rank": 21, "score": 0.8589990735054016}, {"content": "Title: Next Generation Sequencing of T and B cell receptor repertoires from COVID-19 patients showed signatures associated with severity of disease Content: Summary We profiled adaptive immunity in COVID-19 patients with active infection or after recovery and created a repository of currently >14 million B and T cell receptor (BCR, TCR) sequences from blood of these patients. The B cell response showed converging IGHV3-driven BCR clusters closely associated with SARS-CoV-2 antibodies. Clonality and skewing of TCR repertoires was associated with interferon type I and III responses, early CD4+ and CD8+ T cell activation and counterregulation by the coreceptors BTLA, Tim-3, PD-1, TIGIT and CD73. Tfh, Th17-like and nonconventional (but not classical anti-viral) Th1 cell polarizations were induced. SARS-CoV-2-specific T cell responses were driven by TCR clusters shared between patients with a characteristic trajectory of clonotypes and traceability over the disease course. Our data provide fundamental insight into adaptive immunity to SARS-CoV-2 with the actively updated repository providing a resource for the scientific community urgently needed to inform therapeutic concepts and vaccine development.", "qid": 49, "docid": "tb8k979g", "rank": 22, "score": 0.8588910102844238}, {"content": "Title: SARS-CoV-2 viral load and antibody responses: the case for convalescent plasma therapy Content: Most patients with COVID-19 lack antibody to SARS-CoV-2 in the first 10 days of illness while the virus drives disease pathogenesis. SARS-CoV-2 antibody deficiency in the setting of a tissue viral burden suggests that using an antibody as a therapeutic agent would augment the antiviral immune response. In this issue of the JCI, Wang and collaborators describe the kinetics of viral load and antibody responses of 23 individuals with COVID-19 with mild and severe disease. The researchers found: 1) individuals with mild and severe disease produced neutralizing IgG to SARS-CoV-2 10 days after disease onset; 2) SARS-CoV-2 persisted longer in those with severe disease; and 3) there was cross-reactivity between antibodies to SARS-CoV-1 and SARS-CoV-2, but only antibodies from patients with COVID-19 neutralized SARS-CoV-2. These observations provide important information on the serological response to SARS-CoV-2 of hospitalized patients with COVID-19 that can inform the use of convalescent plasma therapy.", "qid": 49, "docid": "tckjc7os", "rank": 23, "score": 0.8586490154266357}, {"content": "Title: SARS-CoV-2 viral load and antibody responses: the case for convalescent plasma therapy. Content: Most patients with COVID-19 lack antibody to SARS-CoV-2 in the first 10 days of illness while the virus drives disease pathogenesis. SARS-CoV-2 antibody deficiency in the setting of a tissue viral burden suggests that using an antibody as a therapeutic agent would augment the antiviral immune response. In this issue of the JCI, Wang and collaborators describe the kinetics of viral load and antibody responses of 23 individuals with COVID-19 with mild and severe disease. The researchers found: 1) individuals with mild and severe disease produced neutralizing IgG to SARS-CoV-2 10 days after disease onset; 2) SARS-CoV-2 persisted longer in those with severe disease; and 3) there was cross-reactivity between antibodies to SARS-CoV-1 and SARS-CoV-2, but only antibodies from patients with COVID-19 neutralized SARS-CoV-2. These observations provide important information on the serological response to SARS-CoV-2 of hospitalized patients with COVID-19 that can inform the use of convalescent plasma therapy.", "qid": 49, "docid": "xp09u1tq", "rank": 24, "score": 0.8586490154266357}, {"content": "Title: Deep immune profiling of COVID-19 patients reveals patient heterogeneity and distinct immunotypes with implications for therapeutic interventions Content: COVID-19 has become a global pandemic. Immune dysregulation has been implicated, but immune responses remain poorly understood. We analyzed 71 COVID-19 patients compared to recovered and healthy subjects using high dimensional cytometry. Integrated analysis of ~200 immune and >30 clinical features revealed activation of T cell and B cell subsets, but only in some patients. A subgroup of patients had T cell activation characteristic of acute viral infection and plasmablast responses could reach >30% of circulating B cells. However, another subgroup had lymphocyte activation comparable to uninfected subjects. Stable versus dynamic immunological signatures were identified and linked to trajectories of disease severity change. These analyses identified three \u201cimmunotypes\u201d associated with poor clinical trajectories versus improving health. These immunotypes may have implications for therapeutics and vaccines.", "qid": 49, "docid": "wcmxmahq", "rank": 25, "score": 0.8584869503974915}, {"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": 49, "docid": "aed6psww", "rank": 26, "score": 0.8578149676322937}, {"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": 27, "score": 0.857304573059082}, {"content": "Title: Relative COVID-19 viral persistence and antibody kinetics Content: Importance: The COVID-19 antibody response is a critical indicator for evaluating immunity and also serves as the knowledge base for vaccine development. The picture is still not clear because of many limitations including testing tools, time of sampling, and the unclear impact of varying clinical status. In addition to these problems, antibody levels may not be equivalent to protective capacity. Objective: To define the key factor for the different patterns of COVID-19 antibody response. Design: We elucidated the antibody response with time-series throat and serum samples for viral loads and antibody levels, then used a neutralization test to evaluate protectiveness. Setting: A medical center that typically cares for patients with moderate to severe diseases. Because of the low prevalence of COVID-19 in Taiwan and local government policy, however, we also admit COVID-19 patients with mild disease or even those without symptoms for inpatient care. Participants: RT-PCR-confirmed COVID-19 patients. Results: We found that only patients with relative persistence of virus at pharynx displayed strong antibody responses that were proportional to the pharyngeal viral load. They also had proportional neutralization titers per unit of serum. Although antibody levels decreased around 2 weeks after symptom onset, the neutralization efficacy per unit antibody remained steady and even continued to increase over time. The antibody response in patients with rapid virus clearance was weak, but the neutralization efficacy per unit antibody in these patients was comparable to those with persistent presence of virus. The deceased were with higher viral load, higher level of antibody, and higher neutralization titers in the serum, but the neutralization capacity per unit antibody is relatively low. Conclusions and Relevance: Strong antibody response depends on the relative persistence of the virus, instead of the absolute virus amount. The antibody response is still weak if large amount of virus is cleared quickly. The neutralization efficacy per unit antibody is comparable between high and low antibody patterns. Strong antibody response contains more inefficient and maybe even harmful antibodies. Low antibody response is also equipped with a capable B cell pool of efficient antibodies, which may expand with next virus encounter and confer protection.", "qid": 49, "docid": "nj5xe91b", "rank": 28, "score": 0.8569040894508362}, {"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": 29, "score": 0.8568432927131653}, {"content": "Title: Long-term infection of SARS-CoV-2 changed the body's immune status Content: The outbreak of SARS-CoV-2-associated pneumonia, a disease called COVID-19, has caused a pandemic worldwide. To investigate the immune responses after infection of SARS-CoV-2 in non-critical patients may help to better understand the disease progression. We collected 334 confirmed COVID-19 cases including 212 still in hospital with nucleic acid test positive on halfway for SARS-CoV-2 and 122 discharged from hospital, compared specific antibodies, immune cells, and cytokine changes between the hospitalized and discharged patients. The hospitalized patients had a longer illness time compared with discharged patients. Analysis of viral loads explained long-term or persistent infection of SARS-CoV-2, which existed with the median time of 18.5 days of the positive nucleic acid test. Serum analysis showed that the specific anti-N IgG antibody was positive in all detected patients after infection of two weeks. Neutrophils, Monocytes, NK cells, and CD4(+) T cells significantly increased, while total lymphocytes and CD8(+) T cells decreased from non-critical hospitalized patients after longer-term infection. Further analysis of the cytokines showed that IL-6, TNF-\u03b1, IFN-\u03b3, IL-2, IL-4, and IL-10 from the hospitalized patients were significantly higher, indicating a potential of the increased CD4(+) T cell differentiation.", "qid": 49, "docid": "ppo5rv67", "rank": 30, "score": 0.8560322523117065}, {"content": "Title: Analysis of adaptive immune cell populations and phenotypes in the patients infected by SARS-CoV-2 Content: Coronavirus disease-2019 (COVID-19), caused by SARS-CoV-2, has rapidly spread to most of countries in the world, threatening the health and lives of many people. Unfortunately, information regarding the immunological characteristics in COVID-19 patients remains limited. Here we collected the blood samples from 18 healthy donors (HD) and 38 COVID-19 patients to analyze changes in the adaptive immune cell populations and phenotypes. In comparison to HD, the lymphocyte percentage was slightly decreased, the percentages of CD4 and CD8 T cells in lymphocytes are similar, whereas B cell percentage increased in COVID-19 patients. T cells, especially CD8 T cells, showed an enhanced expression of late activation marker CD25 and exhaustion marker PD-1. Importantly, SARS-CoV-2 induced an increased percentage of T follicular helpher (Tfh)- and germinal center B-like (GCB-like) cells in the blood. However, the parameters in COVD-19 patients remained unchanged across various age groups. Therefore, we demonstrated that the T and B cells can be activated normally and exhibit functional features. These data provide a clue that the adaptive immunity in most people could be primed to induce a significant immune response against SARS-CoV-2 infection upon receiving standard medical care.", "qid": 49, "docid": "zjgswsjj", "rank": 31, "score": 0.8557489514350891}, {"content": "Title: SARS-CoV-2-reactive interferon-\u00ce\u00b3-producing CD8+ T cells in patients hospitalized with coronavirus disease 2019 Content: There is limited information on severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) T-cell immune responses in patients with coronavirus disease 2019 (COVID-19). Both CD4+ and CD8+ T cells may be instrumental in resolution of and protection from SARS-CoV-2 infection. Here, we tested 25 hospitalized patients either with microbiologically documented COVID-19 (n = 19) or highly suspected of having the disease (n = 6) for presence of SARS-CoV-2-reactive CD69+ expressing interferon-\u00ce\u00b3 (IFN-\u00ce\u00b3) producing CD8+ T cells using flow-cytometry for intracellular cytokine staining assay. Two sets of overlapping peptides encompassing the SARS-CoV-2 Spike glycoprotein N-terminal 1 to 643 amino acid sequence and the entire sequence of SARS-CoV-2 M protein were used simultaneously as antigenic stimulus. Ten patients (40%) had detectable responses, displaying frequencies ranging from 0.15 to 2.7% (median of 0.57 cells/\u00b5L; range, 0.43-9.98 cells/\u00b5L). The detection rate of SARS-CoV-2-reactive IFN-\u00ce\u00b3 CD8+ T cells in patients admitted to intensive care was comparable (P = .28) to the rate in patients hospitalized in other medical wards. No correlation was found between SARS-CoV-2-reactive IFN-\u00ce\u00b3 CD8+ T-cell counts and SARS-CoV-2 S-specific antibody levels. Likewise, no correlation was observed between either SARS-CoV-2-reactive IFN-\u00ce\u00b3 CD8+ T cells or S-specific immunoglobulin G-antibody titers and blood cell count or levels of inflammatory biomarkers. In summary, in this descriptive, preliminary study we showed that SARS-CoV-2-reactive IFN-\u00ce\u00b3 CD8+ T cells can be detected in a non-negligible percentage of patients with moderate to severe forms of COVID-19. Further studies are warranted to determine whether quantitation of these T-cell subsets may provide prognostic information on the clinical course of COVID-19.", "qid": 49, "docid": "3cy35zkx", "rank": 32, "score": 0.8536755442619324}, {"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": 33, "score": 0.8534396886825562}, {"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": 34, "score": 0.8528352379798889}, {"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": 35, "score": 0.8528352379798889}, {"content": "Title: Long-term coexistence of SARS-CoV-2 with antibody response in COVID-19 patients Content: Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection causing coronavirus disease 2019 (COVID-19) has spread worldwide. Whether antibodies are important for the adaptive immune responses against SARS-CoV-2 infection needs to be determined. Here, 26 cases of COVID-19 in Jinan, China, were examined and shown to be mild or with common clinical symptoms, and no case of severe symptoms was found among these patients. Strikingly, a subset of these patients had SARS-CoV-2 and virus-specific IgG coexist for an unexpectedly long time, with two cases for up to 50 days. One COVID-19 patient who did not produce any SARS-CoV-2-bound IgG successfully cleared SARS-CoV-2 after 46 days of illness, revealing that without antibody-mediated adaptive immunity, innate immunity alone may still be powerful enough to eliminate SARS-CoV-2. This report may provide a basis for further analysis of both innate and adaptive immunity in SARS-CoV-2 clearance, especially in nonsevere cases.", "qid": 49, "docid": "x1k6ao9h", "rank": 36, "score": 0.852818489074707}, {"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": 37, "score": 0.8527873754501343}, {"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": 38, "score": 0.8524207472801208}, {"content": "Title: Reduction and Functional Exhaustion of T Cells in Patients with Coronavirus Disease 2019 (COVID-19) Content: BACKGROUND The outbreak of coronavirus disease 2019 (COVID-19) caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) has posed great threat to human health, which has been declared a public health emergency of international concern (PHEIC) by the WHO. T cells play a critical role in antiviral immunity but their numbers and functional state in COVID-19 patients remain largely unclear. METHODS We retrospectively reviewed the counts of total T cells, CD4+, CD8+ T cell subsets, and serum cytokine concentration from inpatient data of 522 patients with laboratory-confirmed COVID-19, admitted into two hospitals in Wuhan from December 2019 to January 2020, and 40 healthy controls, who came to the hospitals for routine physical examination. In addition, the expression of T cell exhaustion markers PD-1 and Tim-3 were measured by flow cytometry in the peripheral blood of 14 COVID-19 cases. RESULTS The number of total T cells, CD4+ and CD8+ T cells were dramatically reduced in COVID-19 patients, especially among elderly patients (\u226560 years of age) and in patients requiring Intensive Care Unit (ICU) care. Counts of total T cells, CD8+T cells or CD4+T cells lower than 800/\u03bcL, 300/\u03bcL, or 400/\u03bcL, respectively, are negatively correlated with patient survival. Statistical analysis demonstrated that T cell numbers are negatively correlated to serum IL-6, IL-10 and TNF-\u03b1 concentration, with patients in decline period showing reduced IL-6, IL-10 and TNF-\u03b1 concentrations and restored T cell counts. Finally, T cells from COVID-19 patients have significantly higher levels of the exhausted marker PD-1 as compared to health controls. Moreover, increasing PD-1 and Tim-3 expression on T cells could be seen as patients progressed from prodromal to overtly symptomatic stages, further indicative of T cell exhaustion. CONCLUSIONS T cell counts are reduced significantly in COVID-19 patients, and the surviving T cells appear functionally exhausted. Non-ICU patients, with total T cells, CD8+T cells CD4+T cells counts lower than 800/\u03bcL, 300/\u03bcL, and 400/\u03bcL, respectively, may still require aggressive intervention even in the immediate absence of more severe symptoms due to a high risk for further deterioration in condition.", "qid": 49, "docid": "yj25zkx6", "rank": 39, "score": 0.852111279964447}, {"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": 40, "score": 0.8519390821456909}, {"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": 41, "score": 0.8516925573348999}, {"content": "Title: Targets of T Cell Responses to SARS-CoV-2 Coronavirus in Humans with COVID-19 Disease and Unexposed Individuals Content: Understanding adaptive immunity to SARS-CoV-2 is important for vaccine development, interpreting coronavirus disease 2019 (COVID-19) pathogenesis, and calibration of pandemic control measures. Using HLA class I and II predicted peptide \"megapools,\" circulating SARS-CoV-2-specific CD8+ and CD4+ T cells were identified in \u00e2\u0088\u00bc70% and 100% of COVID-19 convalescent patients, respectively. CD4+ T cell responses to spike, the main target of most vaccine efforts, were robust and correlated with the magnitude of the anti-SARS-CoV-2 IgG and IgA titers. The M, spike, and N proteins each accounted for 11%-27% of the total CD4+ response, with additional responses commonly targeting nsp3, nsp4, ORF3a, and ORF8, among others. For CD8+ T cells, spike and M were recognized, with at least eight SARS-CoV-2 ORFs targeted. Importantly, we detected SARS-CoV-2-reactive CD4+ T cells in \u00e2\u0088\u00bc40%-60% of unexposed individuals, suggesting cross-reactive T cell recognition between circulating \"common cold\" coronaviruses and SARS-CoV-2.", "qid": 49, "docid": "wxti06ng", "rank": 42, "score": 0.8514043092727661}, {"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": 43, "score": 0.8511091470718384}, {"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": 44, "score": 0.8507611751556396}, {"content": "Title: High levels of SARS-CoV-2 specific T-cells with restricted functionality in patients with severe course of COVID-19 Content: Patients infected with SARS-CoV-2 differ in the severity of disease. In this study, SARS-CoV-2 specific T-cells and antibodies were characterized in patients with different COVID-19 related disease severity. Despite severe lymphopenia affecting all major lymphocyte subpopulations, patients with severe disease mounted significantly higher levels of SARS-CoV-2 specific T-cells as compared to convalescent individuals. SARS-CoV-2 specific CD4 T-cells dominated over CD8 T-cells and closely correlated with the number of plasmablasts and SARS-CoV-2 specific IgA- and IgG-levels. Unlike in convalescents, SARS-CoV-2 specific T-cells in patients with severe disease showed marked alterations in phenotypical and functional properties, which also extended to CD4 and CD8 T-cells in general. Given the strong induction of specific immunity to control viral replication in patients with severe disease, the functionally altered phenotype may result from the need for contraction of specific and general immunity to counteract excessive immunopathology in the lung.", "qid": 49, "docid": "jr6yaomi", "rank": 45, "score": 0.850217342376709}, {"content": "Title: Targets of T cell responses to SARS-CoV-2 coronavirus in humans with COVID-19 disease and unexposed individuals Content: Summary Understanding adaptive immunity to SARS-CoV-2 is important for vaccine development, interpreting coronavirus disease 2019 (COVID-19) pathogenesis, and calibration of pandemic control measures. Using HLA class I and II predicted peptide \u2018megapools\u2019, circulating SARS-CoV-2\u2212specific CD8+ and CD4+ T cells were identified in \u223c70% and 100% of COVID-19 convalescent patients, respectively. CD4+ T cell responses to spike, the main target of most vaccine efforts, were robust and correlated with the magnitude of the anti-SARS-CoV-2 IgG and IgA titers. The M, spike and N proteins each accounted for 11-27% of the total CD4+ response, with additional responses commonly targeting nsp3, nsp4, ORF3a and ORF8, among others. For CD8+ T cells, spike and M were recognized, with at least eight SARS-CoV-2 ORFs targeted. Importantly, we detected SARS-CoV-2\u2212reactive CD4+ T cells in \u223c40-60% of unexposed individuals, suggesting cross-reactive T cell recognition between circulating \u2018common cold\u2019 coronaviruses and SARS-CoV-2.", "qid": 49, "docid": "isivkz8b", "rank": 46, "score": 0.8497425317764282}, {"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": 47, "score": 0.8497412204742432}, {"content": "Title: T cell responses to whole SARS coronavirus in humans. Content: Effective vaccines should confer long-term protection against future outbreaks of severe acute respiratory syndrome (SARS) caused by a novel zoonotic coronavirus (SARS-CoV) with unknown animal reservoirs. We conducted a cohort study examining multiple parameters of immune responses to SARS-CoV infection, aiming to identify the immune correlates of protection. We used a matrix of overlapping peptides spanning whole SARS-CoV proteome to determine T cell responses from 128 SARS convalescent samples by ex vivo IFN-gamma ELISPOT assays. Approximately 50% of convalescent SARS patients were positive for T cell responses, and 90% possessed strongly neutralizing Abs. Fifty-five novel T cell epitopes were identified, with spike protein dominating total T cell responses. CD8(+) T cell responses were more frequent and of a greater magnitude than CD4(+) T cell responses (p < 0.001). Polychromatic cytometry analysis indicated that the virus-specific T cells from the severe group tended to be a central memory phenotype (CD27(+)/CD45RO(+)) with a significantly higher frequency of polyfunctional CD4(+) T cells producing IFN-gamma, TNF-alpha, and IL-2, and CD8(+) T cells producing IFN-gamma, TNF-alpha, and CD107a (degranulation), as compared with the mild-moderate group. Strong T cell responses correlated significantly (p < 0.05) with higher neutralizing Ab. The serum cytokine profile during acute infection indicated a significant elevation of innate immune responses. Increased Th2 cytokines were observed in patients with fatal infection. Our study provides a roadmap for the immunogenicity of SARS-CoV and types of immune responses that may be responsible for the virus clearance, and should serve as a benchmark for SARS-CoV vaccine design and evaluation.", "qid": 49, "docid": "xhnqywqb", "rank": 48, "score": 0.848429799079895}, {"content": "Title: Restoration of leukomonocyte counts is associated with viral clearance in COVID-19 hospitalized patients Content: Background: Viral clearance is one important indicator for the recovery of SARS-CoV-2 infected patients. Suboptimal T and B cell responses can delay viral clearance in MERS and SARS patients. The role of leukomonocytes in viral clearance of COVID-19 patients is not yet well defined.Methods: From January 26 to February 28, 2020, an observational study was launched at Zhongnan Hospital of Wuhan University, Wuhan, China. We enrolled 25 laboratory-confirmed COVID-19 patients, whose throat-swab specimens were tested positive for SARS-CoV-2 infection by qRT-PCR. We comprehensively analyzed clinical records, counts of lymphocyte subsets including CD3+, CD4+, CD8+ T cells, B cells and NK cells in the patients who successfully cleared SARS-CoV-2, and compared to those that failed to, after a standardized treatment of 8-14 days. Findings: In 25 enrolled COVID-19 patients, lymphopeniawas a common feature. After the treatment, 14 patients were tested negative for SARS-CoV-2. The patients that cleared the infection had restored the numbers of CD3+, CD4+, CD8+ T cellsand B cells as compared to the still viral RNA positive patients, while the recovered patients had a higher count of leukomonocytes. Conclusions: By comparison of leukomonocytes counts in COVID-19 patients at different stages of the disease, we found that CD3+, CD4+, CD8+ T cells and B cells appear to play important roles in viral clearance. The restoration of leukomonocytes counts from peripheral blood can be used as prognosis for the recovery of an COVID-19 infection. We propose that restoration of leukomonocytes counts can be added to the COVID-19 diagnostic guidanceas a criterion for releasing and discharging patients.", "qid": 49, "docid": "cv32u0ox", "rank": 49, "score": 0.8482465744018555}, {"content": "Title: Serological surveys in Reunion Island of the first hospitalized patients revealed that long-lived immunoglobulin G antibodies specific against SARS-CoV2 virus are rapidly vanishing in severe cases Content: Both cellular and humoral immunities are critically important to control COVID19 infection but little is known about the kinetics of those responses and, in particular, in patients who will go on to develop a severe form of the disease over several weeks. We herein report the first set of data of our prospective cohort study of 90 hospitalized cases. Serological surveys were thoroughly performed over 2 month period by assessing IgG and IgM responses by immunofluorescence, immunoblot, Western blot and conventional ELISA using clinical RUN isolates of SARS-CoV-2 immobilized on 96 well plates. While the IgM and, unexpectedly, the IgG responses were readily detected early during the course of the disease (5-7 days post-first symptoms), our results (n=3-5 and over the full dilution set of the plasma 1/200 to 1/12800) demonstrated a significant decrease (over 2.5-fold) of IgG levels in severe (ICU) hospitalized patients (exemplified in patient 1) by WB and ELISA. In contrast, mild non-ICU patients had a steady and yet robust rise in their specific IgG levels against the virus. Interestingly, both responses (IgM and IgG) were initially against the nucleocapsid (50kDa band on the WB) and spreading to other major viral protein S and domains (S1 and S2. In conclusion, serological testing may be helpful for the diagnosis of patients with negative RT-PCR results and for the identification of asymptomatic cases. Moreover, medical care and protections should be maintained particularly for recovered patients (severe cases) who may remain at risk of relapsing or reinfection. Experiments to ascertain T cell responses but although their kinetics overtime are now highly warranted. All in all, these studies will help to delineate the best routes for vaccination.", "qid": 49, "docid": "4aawkp8p", "rank": 50, "score": 0.8475589156150818}, {"content": "Title: SARS-CoV-2 seroconversion in health care workers Content: Background The correlates of protection against SARS-CoV-2 and their longevity remain unclear. Studies in severely ill individuals have identified robust cellular and humoral immune responses against the virus. Asymptomatic infection with SARS-CoV-2 has also been described, but it is unknown whether this is sufficient to produce antibody responses. Methods We performed a cross-sectional study recruiting 554 health care workers from University Hospitals Birmingham NHS Foundation Trust who were at work and asymptomatic. Participants were tested for current infection with SARS-CoV-2 by nasopharyngeal swab for real-time polymerase chain reaction and for seroconversion by the measurement of anti-SARS-CoV-2 spike glycoprotein antibodies by enzyme linked immunosorbent assay. Results were interpreted in the context of previous, self-reported symptoms of illness consistent with COVID-19. Results The point prevalence of infection with SARS-CoV-2, determined by the detection of SARS-CoV-2 RNA on nasopharnygeal swab was 2.39% (n=13/544). Serum was available on 516 participants. The overall rate of seroconversion in the cohort was 24.4% (n=126/516). Individuals who had previously experienced a symptomatic illness consistent with COVID-19 had significantly greater seroconversion rates than those who had remained asymptomatic (37.5% vs 17.1%, {chi}2 =21.1034, p<0.0001). In the week preceding peak COVID-19-related mortality at UHBFT, seroconversion rates amongst those who were suffering from symptomatic illnesses peaked at 77.8%. Prior symptomatic illness generated quantitatively higher antibody responses than asymptomatic seroconversion. Seroconversion rates were highest amongst those working in housekeeping (34.5%), acute medicine (33.3%) and general internal medicine (30.3%) with lower rates observed in participants working in intensive care (14.8%) and emergency medicine (13.3%). Conclusions In a large cross-sectional seroprevalence study of health-care workers, we demonstrate that asymptomatic seroconversion occurs, however prior symptomatic illness is associated with quantitatively higher antibody responses. The identification that the potential for seroconversion in health-care workers can associate differentially with certain hospital departments may inform future infection control and occupational health practices.", "qid": 49, "docid": "2a12nsnl", "rank": 51, "score": 0.8473666310310364}, {"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": 49, "docid": "nacxjt2f", "rank": 52, "score": 0.8471077084541321}, {"content": "Title: Long-term Co-existence of Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2) with Antibody Response in Non-severe Coronavirus Disease 2019 (COVID-19) Patients Content: Severe acute respiratory syndrome coronavirus 2 infection causing coronavirus disease 2019 has spread worldwide. Whether antibodies are important for the adaptive immune responses against SARS-CoV-2 infection needs to be determined. Here, 26 cases of COVID-19 in Jinan, China, were examined and shown to be mild or with common clinical symptoms and no cases of severe symptoms were found among these patients. A striking feature of some patients is that SARS-CoV-2 could exist in patients who have virus-specific IgG antibodies for a very long period, with one case for up to 36 days. One COVID-19 patient who did not produce any SARS-CoV-2-bound IgG successfully cleared SARS-CoV-2 after 46 days of illness, revealing that without antibody-mediated adaptive immunity, innate immunity may still be powerful enough to eliminate SARS-CoV-2. Overall, this report may provide a basis for further analysis of both innate and adaptive immunity in SARS-CoV-2 clearance, especially in non-severe cases. This study also has implications for understanding the pathogenesis and treatment of SARS-CoV-2.", "qid": 49, "docid": "12edypl7", "rank": 53, "score": 0.8468750715255737}, {"content": "Title: Lack of peripheral memory B cell responses in recovered patients with severe acute respiratory syndrome: a six-year follow-up study. Content: Six years have passed since the outbreak of severe acute respiratory syndrome (SARS). Previous studies indicated that specific Abs to SARS-related coronavirus (SARS-CoV) waned over time in recovered SARS patients. It is critical to find out whether a potential anamnestic response, as seen with other viral infections, exists to protect a person from reinfection in case of another SARS outbreak. Recovered SARS patients were followed up to 6 y to estimate the longevity of specific Ab. The specific memory B cell and T cell responses to SARS-CoV Ags were measured by means of ELISPOT assay. Factors in relation to humoral and cellular immunity were investigated. Six years postinfection, specific IgG Ab to SARS-CoV became undetectable in 21 of the 23 former patients. No SARS-CoV Ag-specific memory B cell response was detected in either 23 former SARS patients or 22 close contacts of SARS patients. Memory T cell responses to a pool of SARS-CoV S peptides were identified in 14 of 23 (60.9%) recovered SARS patients, whereas there was no such specific response in either close contacts or healthy controls. Patients with more severe clinical manifestations seemed to present a higher level of Ag-specific memory T cell response. SARS-specific IgG Ab may eventually vanish and peripheral memory B cell responses are undetectable in recovered SARS patients. In contrast, specific T cell anamnestic responses can be maintained for at least 6 y. These findings have applications in preparation for the possible reemergence of SARS.", "qid": 49, "docid": "xdpxkxkc", "rank": 54, "score": 0.8465427160263062}, {"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": 49, "docid": "7k24r3p5", "rank": 55, "score": 0.8462420701980591}, {"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": 49, "docid": "38mhmxvd", "rank": 56, "score": 0.8461250066757202}, {"content": "Title: Identification of IgG antibody response to SARS-CoV-2 spike protein and its receptor binding domain does not predict rapid recovery from COVID-19 Content: Diagnostic testing and evaluation of patient immunity against the novel severe acute respiratory syndrome (SARS) corona virus that emerged last year (SARS-CoV-2) are essential for health and economic crisis recovery of the world. It is suggested that potential acquired immunity against SARS-CoV-2 from prior exposure may be determined by detecting the presence of circulating IgG antibodies against viral antigens, such as the spike glycoprotein and its receptor binding domain (RBD). Testing our asymptomatic population for evidence of COVID-19 immunity would also offer valuable epidemiologic data to aid health care policies and health care management. Currently, there are over 100 antibody tests that are being used around the world without approval from the FDA or similar regulatory bodies, and they are mostly for rapid and qualitative assessment, with different degrees of error rates. ELISA-based testing for sensitive and rigorous quantitative assessment of SARS-CoV-2 antibodies can potentially offer mechanistic insights into the COVID-19 disease and aid communities uniquely challenged by limited financial resources and access to commercial testing products. Employing recombinant SARS-CoV-2 RBD and spike protein generated in the laboratory, we devised a quantitative ELISA for the detection of circulating serum antibodies. Serum from twenty SARS-CoV-2 RT-PCR confirmed COVID-19 hospitalized patients were used to detect circulating IgG titers against SARS-CoV-2 spike protein and RBD. Quantitative detection of IgG antibodies to the spike glycoprotein or the RBD in patient samples was not always associated with faster recovery, compared to patients with borderline antibody response to the RBD. One patient who did not develop antibodies to the RBD completely recovered from COVID-19. In surveying 99 healthy donor samples (procured between 2017-February 2020), we detected RBD antibodies in one donor from February 2020 collection with three others exhibiting antibodies to the spike protein but not the RBD. Collectively, our study suggests that more rigorous and quantitative analysis, employing large scale sample sets, is required to determine whether antibodies to SARS-CoV-2 spike protein or RBD is associated with protection from COVID-19 disease. It is also conceivable that humoral response to SARS-CoV-2 spike protein or RBD works in association with adaptive T cell response to determine clinical sequela and severity of COVID-19 disease.", "qid": 49, "docid": "y1afswkm", "rank": 57, "score": 0.8460966944694519}, {"content": "Title: Longitudinal high-throughput TCR repertoire profiling reveals the dynamics of T cell memory formation after mild COVID-19 infection Content: COVID-19 is a global pandemic caused by the SARS-CoV-2 coronavirus. T cell response is a critical part of both individual and herd immunity to SARS-CoV-2 and the efficacy of developed vaccines. However neither the dynamics and cross-reactivity of the SARS-CoV-2-specific T cell response nor the diversity of resulting immune memory are well understood. In this study we use longitudinal high-throughput T cell receptor sequencing to track changes in the T cell repertoire following two mild cases of COVID-19 infection. In both donors we identified SARS-CoV-2-responding CD4+ and CD8+ T cell clones. We describe characteristic motifs in TCR sequences of COVID-19-reactive clones, suggesting the existence of immunodominant epitopes. We show that in both donors the majority of infection-reactive clonotypes acquire memory phenotypes. Certain CD4+ clones were detected in the memory fraction at the pre-infection timepoint, suggesting participation of pre-existing cross-reactive memory T cells in the immune response to SARS-CoV-2.", "qid": 49, "docid": "fglyfz8p", "rank": 58, "score": 0.8454980850219727}, {"content": "Title: Immune phenotyping based on neutrophil-to-lymphocyte ratio and IgG predicts disease severity and outcome for patients with COVID-19 Content: Background: A recently emerging respiratory disease named coronavirus disease 2019 (COVID-19) has quickly spread across the world. This disease is initiated by severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2) and uncontrolled cytokine storm, but it remains unknown as to whether a robust antibody response is related to clinical deterioration and poor outcome in laboratory-confirmed COVID-19 patients. Methods: Anti-SARS-CoV-2 IgG and IgM antibodies were determined by chemiluminescence analysis (CLIA) in COVID-19 patients from a single center in Wuhan. Median IgG and IgM levels in acute and convalescent-phase sera (within 35 days) for all included patients were calculated and compared among severe and nonsevere patients. Immune response phenotyping based on late IgG levels and neutrophil-to-lymphocyte ratio (NLR) was characterized to stratify patients with different disease severities and outcome. Laboratory parameters in patients with different immune response phenotypes and disease severities were analyzed. Findings: A total of 222 patients were included in this study. IgG was first detected on day 4 of illness, and its peak levels occurred in the fourth week. Severe cases were more frequently found in patients with high IgG levels, compared to those who with low IgG levels (51.8% versus 32.3%; p=0.008). Severity rates for patients with NLRhiIgGhi, NLRhiIgGlo, NLRloIgGhi, and NLRloIgGlo phenotype was 72.3%, 48.5%, 33.3%, and 15.6%, respectively (p<0.0001). Furthermore, severe patients with NLRhiIgGhi, NLRhiIgGlo had higher proinflammatory cytokines levels including IL-2, IL-6 and IL-10, and decreased CD4+ T cell count compared to those with NLRloIgGlo phenotype (p<0.05). Recovery rate for severe patients with NLRhiIgGhi, NLRhiIgGlo, NLRloIgGhi, and NLRloIgGlo phenotype was 58.8% (20/34), 68.8% (11/16), 80.0% (4/5), and 100% (12/12), respectively (p=0.0592). Dead cases only occurred in NLRhiIgGhi and NLRhiIgGlo phenotypes. Interpretation: COVID-19 severity is associated with increased IgG response, and an immune response phenotyping based on late IgG response and NLR could act as a simple complementary tool to discriminate between severe and nonsevere COVID-19 patients, and further predict their clinical outcome.", "qid": 49, "docid": "68193u0a", "rank": 59, "score": 0.8454281091690063}, {"content": "Title: In-depth phenotyping of human peripheral blood mononuclear cells in convalescent COVID-19 patients following a mild versus severe disease course Content: Background: Covid-19, the disease caused by infection with SARS-CoV-2, has developed to a pandemic causing more than 239, 000 deaths worldwide as of 6th May according to the World Health Organization (WHO). It presents with a highly variable disease course ranging from a large proportion of asymptomatic cases to severe respiratory failure in 17-29% of cases even in the absence of apparent comorbidities 1, 2. This implies a diverse host immune response to SARS-CoV-2. The immunological characteristics underlying these divergent disease courses, however, still remain elusive. While insights into abrogations of innate immunity begin to emerge, adaptive immune responses towards SARS-CoV-2 are poorly investigated, although they serve as immune signatures of protection and vaccine responses. We therefore set out to characterize immune signatures of convalescent COVID-19 patients stratified according to their disease severity. Methods: We performed high-dimensional flow cytometric profiling of peripheral blood mononuclear cells of convalescent COVID-19 patients who we stratified according to their disease severity by a physician-assisted questionnaire based assessment of COVID-19 symptoms. Results: Surprisingly, we did not observe any difference in the relative proportions of any major immune cell type in convalescent patients presenting with different severity of COVID-19 disease except for a reduction in monocytes. The frequency of Tnaive T cells was significantly reduced in CD4+ and CD8+ T cells, whereas other T cell differentiations states (TCM, TEM, TEMRA) remained relatively unaffected by COVID-19 severity as assessed approximately two weeks after infection. Conclusions In our COVID-19 patient cohort, which is characterized by absence of comorbidities and therapeutic interventions other than symptomatic antipyretics, the immunophenotype is similar irrespective of a highly variable disease severity. Convalescence is therefore associated with a rather uniform immune signature. Abrogations, which were previously identified in the innate and adaptive immune compartment of COVID-19 patients should be scrutinized for direct associations with a preconditioned immune system shaped and made vulnerable for SARS-CoV-2 by preexisting comorbidities.", "qid": 49, "docid": "j008qh26", "rank": 60, "score": 0.8444110155105591}, {"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": 61, "score": 0.8442838788032532}, {"content": "Title: Longitudinal high-throughput TCR repertoire profiling reveals the dynamics of T cell memory formation after mild COVID-19 infection Content: COVID-19 is a global pandemic caused by the SARS-CoV-2 coronavirus. The T cell response is a critical part of both individual and herd immunity to SARS-CoV-2 and the efficacy of developed vaccines. However neither the dynamics and cross-reactivity of the SARS-CoV-2-specific T cell response nor the diversity of resulting immune memory are well understood. In this study we use longitudinal high-throughput T cell receptor sequencing to track changes in the T cell repertoire following two mild cases of COVID-19 infection. In both donors we identified SARS-CoV-2-responding CD4+ and CD8+ T cell clones. We describe characteristic motifs in TCR sequences of COVID-19-reactive clones, suggesting the existence of immunodominant epitopes. We show that in both donors the majority of infection-reactive clonotypes acquire memory phenotypes. Certain CD4+ clones were detected in the memory fraction at the pre-infection timepoint, suggesting participation of pre-existing cross-reactive memory T cells in the immune response to SARS-CoV-2.", "qid": 49, "docid": "4akxfetl", "rank": 62, "score": 0.8441104888916016}, {"content": "Title: Marked T cell activation, senescence, exhaustion and skewing towards TH17 in patients with COVID-19 pneumonia Content: The immune system of patients infected by SARS-CoV-2 is severely impaired. Detailed investigation of T cells and cytokine production in patients affected by COVID-19 pneumonia are urgently required. Here we show that, compared with healthy controls, COVID-19 patients' T cell compartment displays several alterations involving na\u00efve, central memory, effector memory and terminally differentiated cells, as well as regulatory T cells and PD1+CD57+ exhausted T cells. Significant alterations exist also in several lineage-specifying transcription factors and chemokine receptors. Terminally differentiated T cells from patients proliferate less than those from healthy controls, whereas their mitochondria functionality is similar in CD4+ T cells from both groups. Patients display significant increases of proinflammatory or anti-inflammatory cytokines, including T helper type-1 and type-2 cytokines, chemokines and galectins; their lymphocytes produce more tumor necrosis factor (TNF), interferon-\u00ce\u00b3, interleukin (IL)-2 and IL-17, with the last observation implying that blocking IL-17 could provide a novel therapeutic strategy for COVID-19.", "qid": 49, "docid": "kn8orioi", "rank": 63, "score": 0.8440233469009399}, {"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": 64, "score": 0.8439902663230896}, {"content": "Title: Primary exposure to SARS-CoV-2 protects against reinfection in rhesus macaques Content: Coronavirus disease 2019 (COVID-19), which is caused by infection with the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), has become a global pandemic. It currently remains unclear whether convalescing patients have a risk of reinfection. We generated a rhesus macaque model of SARS-CoV-2 infection that was characterized by interstitial pneumonia and systemic viral dissemination mainly in the respiratory and gastrointestinal tracts. Rhesus macaques reinfected with the identical SARS-CoV-2 strain during the early recovery phase of the initial SARS-CoV-2 infection did not show detectable viral dissemination, clinical manifestations of viral disease, or histopathological changes. Comparing the humoral and cellular immunity between primary infection and rechallenge revealed notably enhanced neutralizing antibody and immune responses. Our results suggest that primary SARS-CoV-2 exposure protects against subsequent reinfection in rhesus macaques.", "qid": 49, "docid": "tdorhy8x", "rank": 65, "score": 0.8439127206802368}, {"content": "Title: Primary exposure to SARS-CoV-2 protects against reinfection in rhesus macaques. Content: Coronavirus disease 2019 (COVID-19), which is caused by infection with the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), has become a global pandemic. It currently remains unclear whether convalescing patients have a risk of reinfection. We generated a rhesus macaque model of SARS-CoV-2 infection that was characterized by interstitial pneumonia and systemic viral dissemination mainly in the respiratory and gastrointestinal tracts. Rhesus macaques reinfected with the identical SARS-CoV-2 strain during the early recovery phase of the initial SARS-CoV-2 infection did not show detectable viral dissemination, clinical manifestations of viral disease, or histopathological changes. Comparing the humoral and cellular immunity between primary infection and rechallenge revealed notably enhanced neutralizing antibody and immune responses. Our results suggest that primary SARS-CoV-2 exposure protects against subsequent reinfection in rhesus macaques.", "qid": 49, "docid": "5dbuxvc4", "rank": 66, "score": 0.8439127206802368}, {"content": "Title: Immune Characteristics of Patients with Coronavirus Disease 2019 (COVID-19) Content: Up to now, little is known about the detailed immune profiles of COVID-19 patients from admission to discharge. In this study we retrospectively reviewed the clinical and laboratory characteristics of 18 COVID-19 patients from January 30, 2020 to February 21, 2020. These patients were divided into two groups; group 1 had a severe acute respiratory syndrome coronavirus 2 nucleic acid-positive duration for more than 15 days (n = 6) and group 2 had a nucleic acid-positive duration for less than 15 days (n = 12). Group 1 patients had lower level of peripheral blood lymphocytes (0.40 vs. 0.78 \u00d710(9)/L, p = 0.024) and serum potassium (3.36 vs. 3.79 mmol/L, p = 0.043) on admission but longer hospitalization days (23.17 vs. 15.75 days, p < 0.001) compared to Group 2 patients. Moreover, baseline level of lymphocytes (r = -0.62, p = 0.006) was negatively correlated with the nucleic acid-positive duration. Additionally, lymphocytes (420.83 vs. 1100.56 /\u03bcL), T cells (232.50 vs. 706.78 /\u03bcL), CD4(+) T cells (114.67 vs. 410.44 /\u03bcL), and CD8(+) T cells (94.83 vs. 257.44 /\u03bcL) in the peripheral blood analyzed by flow cytometry were significantly different between Group 1and Group 2. Furthermore, there was also a negative correlation between lymphocytes (r = -0.54, p = 0.038) or T cells (r = -0.55, p = 0.034) at diagnosis and the nucleic acid-positive duration, separately. In conclusion, the patients with nucleic acid-positive \u2265 15 days had significantly decreased lymphocytes, T cell and its subsets compared to those who remained positive for less than 15 days.", "qid": 49, "docid": "9a46n47u", "rank": 67, "score": 0.8436390161514282}, {"content": "Title: Prevalence of IgG antibodies to SARS-CoV-2 in Wuhan -implications for the ability to produce long-lasting protective antibodies against SARS-CoV-2 Content: Background It is to be determined whether people infected with SARS-CoV-2 will develop long-term immunity against SARS-CoV-2 and retain long-lasting protective antibodies after the infection is resolved. This study was to explore to explore the outcomes of IgG antibodies to SARS-CoV-2 in four groups of individuals in Wuhan, China. Methods We included the following four groups of individuals who received both COVID-19 IgM/IgG tests and RT-PCR tests for SARS-CoV-2 from February 29, 2020 to April 29, 2020: 1470 hospitalized patients with COVID-19 from Leishenshan Hospital, Zhongnan Hospital of Wuhan University, and Wuhan No. 7 Hospital, 3832 healthcare providers without COVID-19 diagnosis, 19555 general workers, and 1616 other patients to be admitted to the hospital (N=26473). COVID-19 patients who received IgM/IgG tests <21 days after symptom onset were excluded. Results IgG prevalence was 89.8% (95% CI 88.2-91.3%) in COVID-19 patients, 4.0% (95% CI 3.4-4.7%) in healthcare providers, 4.6 (95% CI 4.3-4.9 %) in general workers, and 1.0% in other patients (p all <0.001 for comparisons with COVID-19 patients). IgG prevalence increased significantly by age among healthcare workers and general workers. Prevalence of IgM antibodies to SARS-CoV-2 was 31.4% in COVID-19 patients, 1.5% in healthcare providers, 1.3% in general workers, and 0.2% in other patients. Conclusions Very few healthcare providers had IgG antibodies to SARS-CoV-2, though a significant proportion of them had been infected with the virus. After SARS-CoV-2 infection, people are unlikely to produce long-lasting protective antibodies against this virus.", "qid": 49, "docid": "066rysjh", "rank": 68, "score": 0.8435977697372437}, {"content": "Title: Clinical characteristics of the recovered COVID-19 patients with re-detectable positive RNA test Content: Background It has been reported that several cases recovered from COVID-19 tested positive for SARS-CoV-2 after discharge (re-detectable positive, RP), however the clinical characteristics, significance and potential cause of RP patients remained elusive. Methods A total of 262 COVID-19 patients were discharged from January 23 to February 25, 2020, and were enrolled for analysis of their clinical parameters. The RP and non-RP (NRP) patients were grouped according to the disease severity during their hospitalization period. The clinical characterization at re-admission to the hospital was analyzed. SARS-CoV-2 RNA and plasma antibody levels were detected using high-sensitive detection methods. Findings Up to March 10, 2020, all of patients were followed up for at least 14 days, and 38/262 of RP patients (14.5%) were present. The RP patients were characterized by being less than 14-years old and having mild and moderate conditions as compared to NRP patients, while no severe patients became RP. Retrospectively, the RP patients displayed fewer symptoms, more sustained remission of CT imaging and earlier RNA negative-conversion but similar plasma antibody levels during their hospitalization period as compared to those NRP patients. When re-admitted to the hospital, these RP patients showed no obvious clinical symptoms or disease progression indicated by normal or improving CT imaging and inflammatory cytokine levels. All 21 close contacts of RP patients were tested negative for SARS-CoV-2 RNA, and no suspicious clinical symptoms were reported. However, 18/24 of RNA-negative samples detected by the commercial kit were tested to be positive for virus RNA using a hyper-sensitive method, suggesting the carrier status of virus possibly existed in patients recovered from COVID-19. Interpretation Our results showed that young and mild COVID-19 patients seem to be RP patients after discharge, who show no obviously clinical symptoms and disease progression upon re-admission. More sensitive RNA detection methods are required to monitor these patients during follow-up. Our findings provide empirical information and evidence for the effective management of COVID-19 patients during their convalescent phase.", "qid": 49, "docid": "58sc6xgq", "rank": 69, "score": 0.8431676626205444}, {"content": "Title: Longitudinal immunological analyses reveal inflammatory misfiring in severe COVID-19 patients Content: Recent studies have provided insights into the pathogenesis of coronavirus disease 2019 (COVID-19)1-4. Yet, longitudinal immunological correlates of disease outcome remain unclear. Here, we serially analysed immune responses in 113 COVID-19 patients with moderate (non-ICU) and severe (ICU) disease. Immune profiling revealed an overall increase in innate cell lineages with a concomitant reduction in T cell number. We identify an association between early, elevated cytokines and worse disease outcomes. Following an early increase in cytokines, COVID-19 patients with moderate disease displayed a progressive reduction in type-1 (antiviral) and type-3 (antifungal) responses. In contrast, patients with severe disease maintained these elevated responses throughout the course of disease. Moreover, severe disease was accompanied by an increase in multiple type 2 (anti-helminths) effectors including, IL-5, IL-13, IgE and eosinophils. Unsupervised clustering analysis of plasma and peripheral blood leukocyte data identified 4 immune signatures, representing (A) growth factors, (B) type-2/3 cytokines, (C) mixed type-1/2/3 cytokines, and (D) chemokines that correlated with three distinct disease trajectories of patients. The immune profile of patients who recovered with moderate disease was enriched in tissue reparative growth factor signature (A), while the profile for those with worsened disease trajectory had elevated levels of all four signatures. Thus, we identified development of a maladapted immune response profile associated with severe COVID-19 outcome and early immune signatures that correlate with divergent disease trajectories.", "qid": 49, "docid": "06gbt9t0", "rank": 70, "score": 0.84305340051651}, {"content": "Title: The laboratory tests and host immunity of COVID-19 patients with different severity of illness Content: BACKGROUNDThe coronavirus disease 2019 (COVID-19), infected by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), has caused a severe outbreak throughout the world. The host immunity of COVID-19 patients is unknown.METHODSThe routine laboratory tests and host immunity in COVID-19 patients with different severity of illness were compared after patient admission.RESULTSA total of 65 SARS-CoV-2-positive patients were classified as having mild (n = 30), severe (n = 20), and extremely severe (n = 15) illness. Many routine laboratory tests, such as ferritin, lactate dehydrogenase, and D-dimer, were increased in severe and extremely severe patients. The absolute numbers of CD4+ T cells, CD8+ T cells, and B cells were gradually decreased with increased severity of illness. The activation markers such as HLA-DR and CD45RO expressed on CD4+ and CD8+ T cells were increased in severe and extremely severe patients compared with mild patients. The costimulatory molecule CD28 had opposite results. The percentage of natural Tregs was decreased in extremely severe patients. The percentage of IFN-\u00ce\u00b3-producing CD8+ T cells was increased in both severe and extremely severe patients compared with mild patients. The percentage of IFN-\u00ce\u00b3-producing CD4+ T cells was increased in extremely severe patients. IL-2R, IL-6, and IL-10 were all increased in extremely severe patients. The activation of DC and B cells was decreased in extremely severe patients.CONCLUSIONThe number and function of T cells are inconsistent in COVID-19 patients. The hyperfunction of CD4+ and CD8+ T cells is associated with the pathogenesis of extremely severe SARS-CoV-2 infection.FUNDINGThis work was funded by the National Mega Project on Major Infectious Disease Prevention (2017ZX10103005-007) and the Fundamental Research Funds for the Central Universities (2019kfyRCPY098).", "qid": 49, "docid": "c2en7ie9", "rank": 71, "score": 0.8430274128913879}, {"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": 72, "score": 0.8425655961036682}, {"content": "Title: The laboratory tests and host immunity of COVID-19 patients with different severity of illness. Content: BACKGROUND The Coronavirus Disease-2019 (COVID-19), infected by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), has caused a severe outbreak in China. The host immunity of COVID-19 patients is unknown. METHODS The routine laboratory tests and host immunity in COVID-19 patients with different severity of illness were compared after patient admission. RESULTS A total of 65 SARS-CoV-2-positive patients were classified as mild (n=30), severe (n=20), and extremely severe (n=15) illness. Many routine laboratory tests such as ferritin, lactate dehydrogenase and D-dimer were increased in severe and extremely severe patients. The absolute numbers of CD4+ T cells, CD8+ T cells and B cells were all gradually decreased with increased severity of illness. The activation markers such as HLA-DR and CD45RO expressed on CD4+ and CD8+ T cells were increased in severe and extremely severe patients compared with mild patients. The co-stimulatory molecule CD28 had opposite results. The percentage of natural regulatory T cells was decreased in extremely severe patients. The percentage of IFN-\u03b3 producing CD8+ T cells was increased in both severe and extremely severe patients compared with mild patients. The percentage of IFN-\u03b3 producing CD4+ T cells was increased in extremely severe patients. The IL-2R, IL-6, and IL-10 were all increased in extremely severe patients. The activation of DC and B cells was decreased in extremely severe patients. CONCLUSIONS The number and function of T cells are inconsistent in COVID-19 patients. The hyperfunction of CD4+ and CD8+ T cells is associated with the pathogenesis of extremely severe SARS-CoV-2 infection.", "qid": 49, "docid": "bbs7zocu", "rank": 73, "score": 0.8418396711349487}, {"content": "Title: Marked T cell activation, senescence, exhaustion and skewing towards TH17 in patients with COVID-19 pneumonia Content: The immune system of patients infected by SARS-CoV-2 is severely impaired. Detailed investigation of T cells and cytokine production in patients affected by COVID-19 pneumonia are urgently required. Here we show that, compared with healthy controls, COVID-19 patients\u2019 T cell compartment displays several alterations involving na\u00efve, central memory, effector memory and terminally differentiated cells, as well as regulatory T cells and PD1(+)CD57(+) exhausted T cells. Significant alterations exist also in several lineage-specifying transcription factors and chemokine receptors. Terminally differentiated T cells from patients proliferate less than those from healthy controls, whereas their mitochondria functionality is similar in CD4(+) T cells from both groups. Patients display significant increases of proinflammatory or anti-inflammatory cytokines, including T helper type-1 and type-2 cytokines, chemokines and galectins; their lymphocytes produce more tumor necrosis factor (TNF), interferon-\u03b3, interleukin (IL)-2 and IL-17, with the last observation implying that blocking IL-17 could provide a novel therapeutic strategy for COVID-19.", "qid": 49, "docid": "55yxh5er", "rank": 74, "score": 0.8417451977729797}, {"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": 75, "score": 0.8417271971702576}, {"content": "Title: CoViD-19 Immunopathology and Immunotherapy Content: New evidence on the T-cell immuno-pathology in patient\u2019s with Corona Virus Disease 2019 (CoViD-19) was reported by Diao et al. in MedRxiv (doi: 10.1101/2020.02.18.20024364) [1]. It reports observations on 522 patients with confirmed CoViD-19 symptomatology, compared to 40 control subjects. In brief, notable T cytopoenia was recorded by flow cytometry in the CD4+ and the CD8+ populations, which were significantly yet inversely correlated with remarkably increased serum levels of the pro-inflammatory cytokines IL-6, IL-10 and TNF-a. Flow cytometry established a progressive increase in the expression of programmed cell death marker-1 (PD-1) and T cell immunoglobulin and mucin domain 3 (Tim-3) as patients (n=14) deteriorated from prodromal to symptomatic CoViD-19 requiring intensive care. Here, we interpret these observations of Diao et al from our current understanding of T cell immunophysiology and immunopathology following an immune challenge in the form of sustained viral infection, as is the case in CoViD-19, with emphasis on exhausted T cells (Tex). Recent clinical trials to rescue Tex show promising outcomes. The relevance of these interventions for the prevention and treatment of CoViD-19 is discussed. Taken together, the data of Diao et al could proffer the first glimpse of immunopathology and possible immunotherapy for patients with CoViD-19.", "qid": 49, "docid": "qopf1uig", "rank": 76, "score": 0.841460108757019}, {"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": 49, "docid": "yzffm05r", "rank": 77, "score": 0.8413975238800049}, {"content": "Title: Imiquimod - A toll like receptor 7 agonist - Is an IDEAL OPTION for MANAGEMENT of COVID 19 Content: According to numerous recent publications, the COVID-19 patients have lymphopenia, higher infection-related biomarkers and several elevated inflammatory cytokines (i.e. tumor necrosis factor (TNF)-\u03b1, interleukin IL-2R and IL-6). The total number of B cells, T cells and NK cells are significantly decreased. RNA viruses, SARS-CoV-2 included, hit the innate immune system in order to cause infection, through TLRs 3, 7 and 8. Imiquimod is an immune-stimulator that activates TLR 7 and can be used to enhance the innate and adaptive immunity. Preclinical and clinical trials are proposed.", "qid": 49, "docid": "5lvrb7s3", "rank": 78, "score": 0.8411722779273987}, {"content": "Title: Complex Immune Dysregulation in COVID-19 Patients with Severe Respiratory Failure Content: Summary Proper management of COVID-19 mandates better understanding of disease pathogenesis. The sudden clinical deterioration 7\u20138 days after initial symptom onset suggests that severe respiratory failure (SRF) in COVID-19 is driven by a unique pattern of immune dysfunction. We studied immune responses of 54 COVID-19 patients, 28 of whom had SRF. All patients with SRF displayed either macrophage activation syndrome (MAS) or very low human leukocyte antigen D related (HLA-DR) expression accompanied by profound depletion of CD4 lymphocytes, CD19 lymphocytes, and natural killer (NK) cells. Tumor necrosis factor-\u03b1 (TNF-\u03b1) and interleukin-6 (IL-6) production by circulating monocytes was sustained, a pattern distinct from bacterial sepsis or influenza. SARS-CoV-2 patient plasma inhibited HLA-DR expression, and this was partially restored by the IL-6 blocker Tocilizumab; off-label Tocilizumab treatment of patients was accompanied by increase in circulating lymphocytes. Thus, the unique pattern of immune dysregulation in severe COVID-19 is characterized by IL-6-mediated low HLA-DR expression and lymphopenia, associated with sustained cytokine production and hyper-inflammation.", "qid": 49, "docid": "e9mepqvn", "rank": 79, "score": 0.8411251306533813}, {"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": 49, "docid": "w98i9l5i", "rank": 80, "score": 0.8410202860832214}, {"content": "Title: Convalescent donor SARS-COV-2-specific cytotoxic T lymphocyte infusion as a possible treatment option for COVID-19 patients with severe disease - has not received enough attention till date. Content: One of the hallmarks of COVID-19 is a reduction in lymphocyte counts, and the degree of reduction correlates with disease severity. Studies have shown a linear negative correlation between peripheral blood CD8+ T cells counts and viral copy numbers in nasopharynx and disease severity. In addition, CD8+ T cells are reported to be functionally 'exhausted'. Currently, there is no proven treatment for COVID-19. Cytotoxic T cells are key to fighting intracellular viruses. In the context of haematopoietic stem cell transplantation, a variety of viral infections have been successfully treated using off-the-shelf HLA-matched virus-specific cytotoxic T cells. A similar strategy using convalescent donor CD8+ T cells appears to be the need of the hour and has not received enough attention till date.", "qid": 49, "docid": "0rn439n7", "rank": 81, "score": 0.8407955169677734}, {"content": "Title: Aberrant hyperactivation of cytotoxic T-cell as a potential determinant of COVID-19 severity Content: OBJECTIVES: We hypothesized that immune response may contribute to progression of coronavirus disease-19 (COVID-19) at the second week of illness. Therefore, we compared cell-mediated immune (CMI) responses between severe and mild COVID-19 cases. METHODS: We examined peripheral blood mononuclear cells of laboratory-confirmed COVID-19 patients from their first and third weeks of illness. Severe pneumonia was defined as an oxygen saturation &#8804;93% at room air. Expressions of molecules related to T-cell activation and functions were analyzed by flow cytometry. RESULTS: The population dynamics of T cells at the first week were not different between the two groups. However, total numbers of CD4+ and CD8+ T cells tended to be lower in the severe group at the third week of illness. Expressions of Ki-67, PD-1, perforin, and granzyme B in CD4+ or CD8+ T cells were significantly higher in the severe group than in the mild group at the third week. In contrast to the mild group, the levels of their expression did not decrease in the severe group. CONCLUSIONS: Severe COVID-19 had a higher degree of proliferation, activation, and cytotoxicity of T-cells at the late phase of illness without cytotoxic T-cell contraction, which might contribute to the development of severe COVID-19.", "qid": 49, "docid": "32fho74f", "rank": 82, "score": 0.8407078385353088}, {"content": "Title: Aberrant hyperactivation of cytotoxic T-cell as a potential determinant of COVID-19 severity Content: Abstract Objectives We hypothesized that immune response may contribute to progression of coronavirus disease-19 (COVID-19) at the second week of illness. Therefore, we compared cell-mediated immune (CMI) responses between severe and mild COVID-19 cases. Methods We examined peripheral blood mononuclear cells of laboratory-confirmed COVID-19 patients from their first and third weeks of illness. Severe pneumonia was defined as an oxygen saturation \u2264 93% at room air. Expressions of molecules related to T-cell activation and functions were analyzed by flow cytometry. Results The population dynamics of T cells at the first week were not different between the two groups. However, total numbers of CD4+ and CD8 + T cells tended to be lower in the severe group at the third week of illness. Expressions of Ki-67, PD-1, perforin, and granzyme B in CD4+ or CD8+ T cells were significantly higher in the severe group than in the mild group at the third week. In contrast to the mild group, the levels of their expression did not decrease in severe group. Conclusions Severe COVID-19 had higher degree of proliferation, activation, and cytotoxicity of T-cells at the late phase of illness without cytotoxic T-cell contraction, which might contribute to the development of severe COVID-19.", "qid": 49, "docid": "m67acbzd", "rank": 83, "score": 0.8404697179794312}, {"content": "Title: COVID\u201019 crossing paths with AIDS in the homeless Content: The coronavirus disease of 2019 (COVID-19) pandemic has created new challenges and magnified existing ones for immunocompromised individuals who may be at risk for worse clinical outcomes. Severe COVID-19 has been associated with a hyperimmune response characterized by a surge in cytokine release defined as a cytokine release syndrome (CRS) (1). Among immunocompromised patients, the inability to mount an immune response may be protective against a poor outcome. This article is protected by copyright. All rights reserved.", "qid": 49, "docid": "5ufo0ygl", "rank": 84, "score": 0.8399757146835327}, {"content": "Title: When COVID-19 Crosses Paths with AIDS in the Homeless Content: The coronavirus disease of 2019 (COVID-19) pandemic has created new challenges and magnified existing ones for immunocompromised individuals who may be at risk for worse clinical outcomes. Severe COVID-19 has been associated with a hyperimmune response characterized by a surge in cytokine release defined as a cytokine release syndrome (CRS) (1). Among immunocompromised patients, the inability to mount an immune response may be protective against a poor outcome. This article is protected by copyright. All rights reserved.", "qid": 49, "docid": "o09428gh", "rank": 85, "score": 0.8399757146835327}, {"content": "Title: Recurrent pneumonia in a patient with new coronavirus infection after discharge from hospital for insufficient antibody production: a case report Content: BACKGROUND: The rapid spread of coronavirus disease 2019 (COVID-19) was declared as an emerging public health threat by the World Health Organization. As various measures have been taken successfully to combat the epidemic caused by SARS-CoV-2, a growing number of fully recovered patients have been discharged from hospitals. However, some of them have relapsed. Little is known about the causes that triggered the relapse. CASE PRESENTATION: We report a case of a 40 years old man who suffered from recurrent pulmonary infection with progression of lesions on chest computed tomography (CT), elevated levels of ferritin and IL2R, reduced lymphocyte count and positive oropharyngeal swab test for SARS-CoV-2 again after 5 days discharge from hospital. The anti-SARS-CoV-2 antibody level of this patient was very low at the time of relapse, suggesting a weak humoral immune response to the virus. Total exon sequencing revealed mutations in TRNT1 gene, which may be responsible for B cell immunodeficiency. Therefore, uncleared SARS-CoV-2 at his first discharge was likely to lead to his recurrence. However, viral superinfection and non-infectious organizing pneumonia could not be completely excluded. CONCLUSION: COVID-19 relapse may occur in a part of discharged patients with low titers of anti-SARS-CoV-2 antibodies. These patients should be maintained in isolation for longer time even after discharge. A more sensitive method to detect SARS-CoV-2 needs to be established and serological testing for specific antibodies may be used as a reference to determine the duration of isolation.", "qid": 49, "docid": "vsh9rdct", "rank": 86, "score": 0.8391582369804382}, {"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": 87, "score": 0.8388392925262451}, {"content": "Title: Clinical characteristics of rehospitalized patients with COVID-19 in China Content: This study aims to observe the clinical characteristics of recovered patients from Coronavirus Disease 2019 (COVID-19) with positive in reverse transcription-polymerase chain reaction (RT-PCR) or serum antibody. The profile, clinical symptoms, laboratory outcomes, and radiologic assessments were extracted on 11 patients, who tested positive for COVID-19 with RT-PCR or serum antibody after discharged and was admitted to Hubei No. 3 People's Hospital of Jianghan University for a second treatment in March 2020. The average interval time between the first discharge and the second admission measured 16.00 \u00b1 7.14 days, ranging from 6 to 27 days. In the second hospitalization, one patient was positive for RT-PCR and serum antibody immunoglobulin M (IgM)-immunoglobulin G (IgG), five patients were positive for both IgM and IgG but negative for RT-PCR. Three patients were positive for both RT-PCR and IgG but negative for IgM. The main symptoms were cough (54.55%), fever (27.27%), and feeble (27.27%) in the second hospitalization. Compared with the first hospitalization, there were significant decreases in gastrointestinal symptoms (5 vs 0, P = .035), elevated levels of both white blood cell count (P = .036) and lymphocyte count (P = .002), remarkedly decreases in C-reactive protein and serum amyloid A (P < .05) in the second hospitalization. Additionally, six patients' chest computed tomography (CT) exhibited notable improvements in acute exudative lesions. There could be positive results for RT-PCR analysis or serum IgM-IgG in discharged patients, even with mild clinical symptoms, however, their laboratory outcomes and chest CT images would not indicate the on-going development in those patients.", "qid": 49, "docid": "evonlumf", "rank": 88, "score": 0.8384363055229187}, {"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": 89, "score": 0.8380283117294312}, {"content": "Title: Cross-reactivity of neutralizing antibody and its correlation with circulating T follicular cells in recovered COVID-19 individuals Content: Seroconversion appeared early after COVID-19 onset, and convalescent sera therapy benefit some critical patients. However, neutralizing antibody (nAb) in convalescents is largely unknown. We found that 97.01% (65/67) of COVID-19 convalescents maintained IgG antibodies with high binding and avidity to SARS-CoV-2 spike subunits S1 and S2, and 95.52% (64/67) had neutralization activity against SARS-CoV-2 pesudovirus, one month after discharge (median ID50, 2.75; IQR, 2.34-3.08). Some sera exhibited cross-neutralization against SARS-CoV (76.12%), MERS-CoV (17.91%), or both (10.45%). Interestingly, individuals recovered from severe disease (severe group) had nAbs with binding and neutralization titers higher than non-severe group. Severe group appeared a rapid increase of lymphocytes and a high proportion of circulating CXCR3+ Tfh cells. Interestingly, the later were spike-specific and positively correlated with SARS-CoV-2 nAb titers. All subjects had no autoimmunity. Our findings provide novel insights into nAb responses in COVID-19 convalescents and facilitate treatment and vaccine development for SARS-CoV-2 infection.", "qid": 49, "docid": "70jg65o2", "rank": 90, "score": 0.8379785418510437}, {"content": "Title: Kinetics of viral load and antibody response in relation to COVID-19 severity Content: The SARS-CoV-2 is the causative agent for COVID-19 pneumonia. Little is known about the kinetics, tissue distribution, cross-reactivity and neutralization antibody response in COVID-19 patients. Two groups of RT-PCR confirmed COVID-19 patients were enrolled in this study, including 12 severe patients in ICUs who needed mechanical ventilation and 11 mild patients in isolation wards. Serial clinical samples were collected for laboratory detection. Results showed that most of the severe patients had viral shedding in a variety of tissues for 20~40 days post onset of disease (8/12, 66.7%); while the majority of mild patients had viral shedding restricted to the respiratory tract and had no detectable virus RNA after 10 days post-onset (9/11, 81.8%). Mild patients showed significantly lower IgM response compared with that of the severe group. IgG responses were detected in most patients in both severe and mild groups at 9 days post onset and remained high level throughout the study. Antibodies cross-reactive to SARS-CoV and SARS-CoV-2 were detected in COVID-19 patients but not in MERS patients. High-levels of neutralizing antibodies were induced after about 10 days post onset in both severe and mild patients which were higher in the severe group. SARS-CoV-2 pseudotype neutralization test and focus reduction neutralization test with authentic virus showed consistent results. Sera from COVID-19 patients, but not convalescent SARS and MERS patients inhibited SARS-CoV-2 entry. Anti-SARS-CoV-2 S and N IgG level exhibited moderate correlation with neutralization titers in patients' plasma. This study improves our understanding of immune response in human after SARS-CoV-2 infection.", "qid": 49, "docid": "vtvdk8qj", "rank": 91, "score": 0.8377845883369446}, {"content": "Title: Kinetics of viral load and antibody response in relation to COVID-19 severity. Content: The SARS-CoV-2 is the causative agent for COVID-19 pneumonia. Little is known about the kinetics, tissue distribution, cross-reactivity and neutralization antibody response in COVID-19 patients. Two groups of RT-PCR confirmed COVID-19 patients were enrolled in this study, including 12 severe patients in ICUs who needed mechanical ventilation and 11 mild patients in isolation wards. Serial clinical samples were collected for laboratory detection. Results showed that most of the severe patients had viral shedding in a variety of tissues for 20~40 days post onset of disease (8/12, 66.7%); while the majority of mild patients had viral shedding restricted to the respiratory tract and had no detectable virus RNA after 10 days post-onset (9/11, 81.8%). Mild patients showed significantly lower IgM response compared with that of the severe group. IgG responses were detected in most patients in both severe and mild groups at 9 days post onset and remained high level throughout the study. Antibodies cross-reactive to SARS-CoV and SARS-CoV-2 were detected in COVID-19 patients but not in MERS patients. High-levels of neutralizing antibodies were induced after about 10 days post onset in both severe and mild patients which were higher in the severe group. SARS-CoV-2 pseudotype neutralization test and focus reduction neutralization test with authentic virus showed consistent results. Sera from COVID-19 patients, but not convalescent SARS and MERS patients inhibited SARS-CoV-2 entry. Anti-SARS-CoV-2 S and N IgG level exhibited moderate correlation with neutralization titers in patients' plasma. This study improves our understanding of immune response in human after SARS-CoV-2 infection.", "qid": 49, "docid": "ehe1uj7i", "rank": 92, "score": 0.8377845883369446}, {"content": "Title: CD8+ T cell cross-reactivity against SARS-CoV-2 conferred by other coronavirus strains and influenza virus Content: While individuals infected with coronavirus disease 2019 (COVID-19) manifested a broad range in susceptibility and severity to the disease, the pre-existing immune memory of related pathogens can influence the disease outcome. Here, we investigated the potential extent of T cell cross-reactivity against severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) that can be conferred by other coronaviruses and influenza virus, and generated a map of public and private predicted CD8+ T cell epitopes between coronaviruses. Moreover, to assess the potential risk of self-reactivity and/or diminished T cell response for peptides identical or highly similar to the host, we identified predicted epitopes with high sequence similarity with human proteome. Lastly, we compared predicted epitopes from coronaviruses with epitopes from influenza virus deposited in IEDB to support vaccine development against different virus strains. We believe the comprehensive in silico profile of private and public predicted epitopes across coronaviruses and influenza viruses will facilitate design of vaccines capable of protecting against various viral infections.", "qid": 49, "docid": "x8asawcv", "rank": 93, "score": 0.8375190496444702}, {"content": "Title: Clinical Characteristics on 25 Discharged Patients with COVID-19 Virus Returning Content: Here we report the clinical features of 25 discharged patients with COVID-19 recovery. Our analysis indicated that there was a significant inverse correlation existed between serum D-Dimer level and the duration of antiviral treatment, while lymphocyte concentration significantly positively correlated with the duration of virus reversal.", "qid": 49, "docid": "jarnavwl", "rank": 94, "score": 0.8369476795196533}, {"content": "Title: Sex, age, and hospitalization drive antibody responses in a COVID-19 convalescent plasma donor population Content: Convalescent plasma is currently one of the leading treatments for COVID-19, but there is a paucity of data identifying therapeutic efficacy. A comprehensive analysis of the antibody responses in potential plasma donors and an understanding of the clinical and demographic factors that drive variant antibody responses is needed. Among 126 potential convalescent plasma donors, the humoral immune response was evaluated by a SARS-CoV-2 virus neutralization assay using Vero-E6-TMPRSS2 cells, commercial IgG and IgA ELISA to Spike (S) protein S1 domain (Euroimmun), IgA, IgG and IgM indirect ELISAs to the full-length S or S-receptor binding domain (S-RBD), and an IgG avidity assay. Multiple linear regression and predictive models were utilized to assess the correlations between antibody responses with demographic and clinical characteristics. IgG titers were greater than either IgM or IgA for S1, full length S, and S-RBD in the overall population. Of the 126 plasma samples, 101 (80%) had detectable neutralizing titers. Using neutralization titer as the reference, the sensitivity of the IgG ELISAs ranged between 95-98%, but specificity was only 20-32%. Male sex, older age, and hospitalization with COVID-19 were all consistently associated with increased antibody responses across the serological assays. Neutralizing antibody titers were reduced over time in contrast to overall antibody responses. There was substantial heterogeneity in the antibody response among potential convalescent plasma donors, but sex, age and hospitalization emerged as factors that can be used to identify individuals with a high likelihood of having strong antiviral antibody levels.", "qid": 49, "docid": "8uanfma5", "rank": 95, "score": 0.8368985652923584}, {"content": "Title: Human coronavirus reinfection dynamics: lessons for SARS-CoV-2 Content: In the current SARS-CoV-2 pandemic a key unsolved question is the quality and duration of acquired immunity in recovered individuals. This is crucial to solve, however SARS-CoV-2 has circulated for under five months, precluding a direct study. We therefore monitored 10 subjects over a time span of 35 years (1985-2020), providing a total of 2473 follow up person-months, and determined a) their antibody levels following infection by any of the four seasonal human coronaviruses, and b) the time period after which reinfections by the same virus can occur. An alarmingly short duration of protective immunity to coronaviruses was found by both analyses. We saw frequent reinfections at 12 months post-infection and a substantial reduction in antibody levels as soon as 6 months post-infection.", "qid": 49, "docid": "u5nxm9tu", "rank": 96, "score": 0.8366727828979492}, {"content": "Title: SARS-CoV-2 infection protects against rechallenge in rhesus macaques Content: An understanding of protective immunity to SARS-CoV-2 is critical for vaccine and public health strategies aimed at ending the global COVID-19 pandemic. A key unanswered question is whether infection with SARS-CoV-2 results in protective immunity against re-exposure. We developed a rhesus macaque model of SARS-CoV-2 infection and observed that macaques had high viral loads in the upper and lower respiratory tract, humoral and cellular immune responses, and pathologic evidence of viral pneumonia. Following initial viral clearance, animals were rechallenged with SARS-CoV-2 and showed 5 log10 reductions in median viral loads in bronchoalveolar lavage and nasal mucosa compared with primary infection. Anamnestic immune responses following rechallenge suggested that protection was mediated by immunologic control. These data show that SARS-CoV-2 infection induced protective immunity against re-exposure in nonhuman primates.", "qid": 49, "docid": "t3sjv4hv", "rank": 97, "score": 0.836550772190094}, {"content": "Title: SARS-CoV-2 infection protects against rechallenge in rhesus macaques Content: An understanding of protective immunity to SARS-CoV-2 is critical for vaccine and public health strategies aimed at ending the global COVID-19 pandemic. A key unanswered question is whether infection with SARS-CoV-2 results in protective immunity against re-exposure. We developed a rhesus macaque model of SARS-CoV-2 infection and observed that macaques had high viral loads in the upper and lower respiratory tract, humoral and cellular immune responses, and pathologic evidence of viral pneumonia. Following initial viral clearance, animals were rechallenged with SARS-CoV-2 and showed 5 log(10) reductions in median viral loads in bronchoalveolar lavage and nasal mucosa compared with primary infection. Anamnestic immune responses following rechallenge suggested that protection was mediated by immunologic control. These data show that SARS-CoV-2 infection induced protective immunity against re-exposure in nonhuman primates.", "qid": 49, "docid": "car394ou", "rank": 98, "score": 0.8363833427429199}, {"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": 99, "score": 0.8362208604812622}, {"content": "Title: Monoclonal Antibodies and Vaccines: Q and A Content: The second reason is even more salient: the great majority of people who have recovered during the COVID-19 pandemic did so because they raised their own neutralizing antibodies to the virus There is, for example, a canine coronavirus vaccine available, although one has to note immediately that it\u2019s for an enteric virus, not a respiratory one, and that it itself is of no use whatsoever (in dogs or in people) against the COVID-19 epidemic", "qid": 49, "docid": "pg9ykf23", "rank": 100, "score": 0.8355105519294739}]}
{"query": "what is known about an mRNA vaccine for the SARS-CoV-2 virus?", "hits": [{"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": 50, "docid": "l9l6z1o0", "rank": 1, "score": 0.8796883821487427}, {"content": "Title: RNA to the rescue: RNA is one of the most promising targets for drug development given its wide variety of uses Content: The race for a vaccine against SARS-CoV-2 has accelerated research on RNA-based therapeutics. Beyond vaccines, RNA also shows great potential for cancer therapies.", "qid": 50, "docid": "avxexjl5", "rank": 2, "score": 0.8776324391365051}, {"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": 3, "score": 0.873192548751831}, {"content": "Title: Current Insight into the Novel Coronavirus Disease 2019 (COVID-19) Content: SARS-CoV-2 is a novel strain of coronavirus that has not been previously identified in humans. It has been declared a pandemic and has infected at least 1,844,683 individuals and caused 117,021 deaths as of 14th April 2020. Transmission among humans occurs via close contact with an infected individual that produces respiratory droplets. Patients have been shown to undergo acute respiratory distress syndrome, which is defined as cytokine storm. The diagnosis relies on detection of nucleic acid, IgG/IgM antibodies, and a chest radiograph of the suspected individuals. The genome of SARS-CoV-2 is similar to other coronaviruses that comprise of ten open reading frames (ORFs). SARS-CoV-2 spike protein exhibits higher affinity to ACE2 receptor as compared with SARS-CoV. Repurposing drugs like favipiravir, remdesivir, chloroquine, and TMPRSS2 protease inhibitors have been shown to be effective for the treatment of COVID-19. Personal protective measures should be followed to prevent SARS-CoV-2 infection. In addition, a clinical trial of SARS-CoV-2 vaccine, mRNA-1273, has been started. This chapter provides a glimpse of advancements made in the area of SARS-CoV-2 infection by proving recent clinical and research trials in the field.", "qid": 50, "docid": "zv0ysi8m", "rank": 4, "score": 0.8700913786888123}, {"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": 50, "docid": "t0cw7l2a", "rank": 5, "score": 0.8679882287979126}, {"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": 6, "score": 0.8672193288803101}, {"content": "Title: SARS-CoV-2 transcriptome analysis and molecular cataloguing of immunodominant epitopes for multi-epitope based vaccine design Content: SARS-CoV-2 is a single-stranded RNA virus that has caused more than 0.29 million deaths worldwide as of May 2020, and influence of COVID-19 pandemic is increasing continuously in the absence of approved vaccine and drug. Moreover, very limited information is available about SARS-CoV-2 expressed regions and immune responses. In this paper an effort has been made, to facilitate vaccine development by proposing multiple epitopes as potential vaccine candidates by utilising SARS-CoV-2 transcriptome data. Here, publicly available RNA-seq data of SARS-CoV-2 infection in NHBE and A549 human cell lines were used to construct SARS-CoV-2 transcriptome to understand disease pathogenesis and immune responses. In the first step, epitope prediction, MHC class I and II gene identification for epitopes, population coverage, antigenicity, immunogenicity, conservation and crossreactivity analysis with host antigens were performed by using SARS-CoV-2 transcriptome, and in the second step, structural compatibility of identified T-and B-cell epitopes were evaluated with MHC molecules and B-cell receptors through molecular docking studies. Quantification of MHC gene expression was also performed that indicated high variation in allele types and expression level of MHC genes with respect to cell lines. In A549 cell line, HLA-A*30:01:01:01 and HLA-B*44:03:01:01 were highly expressed, whereas 92 variants of HLA-A*24 genes such as HLA-A*24:02:01:01, HLA-A*24:286, HLA-A*24:479Q, HLA-A*24:02:134 and HLA-A*24:02:116 were highly expressed in NHBE cell lines. Prevalence of HLA-A*24 alleles was suggested as risk factors for H1N1 infection, and associated with type-1 diabetes. HLA-C*03:03, linked with male infertility factors was also highly expressed in SARS-CoV-2 infected NHBE cell lines. Finally, three potential T-cell and five B-cell epitopes were selected for molecular docking studies with twenty-two MHC molecules and two B-cell receptors respectively. The results of in silico analysis indicated that proposed epitopes have high potential to recognize immune response of SARS-CoV-2 infection. This study will facilitate in vitro and in vivo vaccine related research studies.", "qid": 50, "docid": "oiepgu0v", "rank": 7, "score": 0.8645169138908386}, {"content": "Title: Vaccination strategies to combat novel corona virus SARS-CoV-2 Content: The 2019-novel coronavirus disease (COVID-19) is caused by SARS-CoV-2 is transmitted from human to human has recently reported in China. Now COVID-19 has been spread all over the world and declared epidemics by WHO. It has caused a Public Health Emergency of International Concern. The elderly and people with underlying diseases are susceptible to infection and prone to serious outcomes, which may be associated with acute respiratory distress syndrome (ARDS) and cytokine storm. Due to the rapid increase of SARS-CoV-2 infections and unavailability of antiviral therapeutic agents, developing an effective SAR-CoV-2 vaccine is urgently required. SARS-CoV-2 which is genetically similar to SARS-CoV and Middle East respiratory syndrome coronavirus (MERS-CoV) is an enveloped, single and positive-stranded RNA virus with a genome comprising 29,891 nucleotides, which encode the 12 putative open reading frames responsible for the synthesis of viral structural and nonstructural proteins which are very similar to SARS-CoV and MERS-CoV proteins. In this review we have summarized various vaccine candidates i.e., nucleotide, subunit and vector based as well as attenuated and inactivated forms, which have already been demonstrated their prophylactic efficacy against MERS-CoV and SARS-CoV, so these candidates could be used as a potential tool for the development of a safe and effective vaccine against SARS-CoV-2.", "qid": 50, "docid": "eq2ahtlc", "rank": 8, "score": 0.8637803792953491}, {"content": "Title: Universal coronavirus vaccines: the time to start is now Content: The continued explosive spread of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) despite aggressive public health measures has triggered an unprecedented international vaccine effort. However, correlates of protection, which can help guide intelligent vaccine design, are not known for SARS-CoV-2. Research on influenza immunity and vaccine development may provide valuable lessons for coronavirus efforts, especially considering similarities in rapid evolutionary potential. The apparent inevitability of future novel coronavirus outbreaks must prompt work on a universal coronavirus vaccine.", "qid": 50, "docid": "yrrz7oef", "rank": 9, "score": 0.8630953431129456}, {"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": 10, "score": 0.8623927235603333}, {"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": 11, "score": 0.8621906042098999}, {"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": 12, "score": 0.8617412447929382}, {"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": 13, "score": 0.8606890439987183}, {"content": "Title: Expected immune recognition of COVID-19 virus by memory from earlier infections with common coronaviruses in a large part of the world population Content: SARS-CoV-2 is the coronavirus agent of the COVID-19 pandemic causing high mortalities. In contrast, the widely spread human coronaviruses OC43, HKU1, 229E, and NL63 tend to cause only mild symptoms. The present study shows, by in silico analysis, that these common human viruses are expected to induce immune memory against SARS-CoV-2 by sharing protein fragments (antigen epitopes) for presentation to the immune system by MHC class I. A list of such epitopes is provided. The number of these epitopes and the prevalence of the common coronaviruses suggest that a large part of the world population has some degree of specific immunity against SARS-CoV-2 already, even without having been infected by that virus. For inducing protection, booster vaccinations enhancing existing immunity are less demanding than primary vaccinations against new antigens. Therefore, for the discussion on vaccination strategies against COVID-19, the available immune memory against related viruses should be part of the consideration.", "qid": 50, "docid": "majelie8", "rank": 14, "score": 0.859390139579773}, {"content": "Title: Sequence analysis of SARS-CoV-2 genome reveals features important for vaccine design Content: As the SARS-CoV-2 pandemic is rapidly progressing, the need for the development of an effective vaccine is critical. A promising approach for vaccine development is to generate, through codon pair deoptimization, an attenuated virus. This approach carries the advantage that it only requires limited knowledge specific to the virus in question, other than its genome sequence. Therefore, it is well suited for emerging viruses for which we may not have extensive data. We performed comprehensive in silico analyses of several features of SARS-CoV-2 genomic sequence (e.g., codon usage, codon pair usage, dinucleotide/junction dinucleotide usage, RNA structure around the frameshift region) in comparison with other members of the coronaviridae family of viruses, the overall human genome, and the transcriptome of specific human tissues such as lung, which are primarily targeted by the virus. Our analysis identified the spike (S) and nucleocapsid (N) proteins as promising targets for deoptimization and suggests a roadmap for SARS-CoV-2 vaccine development, which can be generalizable to other viruses.", "qid": 50, "docid": "2fn25l6m", "rank": 15, "score": 0.8589946627616882}, {"content": "Title: No current evidence supporting risk of using Ibuprofen in patients with COVID-19 Content: SARS-CoV-2 is a novel RNA virus that infects cells expressing the angiotensin-converting enzyme (ACE2) receptor and is associated with an acute respiratory disease named COVID-19. It has been hypothesized that ACE2 expression can be increased by Ibuprofen leading to a higher risk for severe COVID-19 (1). Despite the reasonable mechanistic background and results from studies suggesting that Ibuprofen may be associated with complications of community-acquired pneumonia in children (2,3), there is no current evidence that this NSAID aggravates a SARS-CoV-2 infection in any age group.", "qid": 50, "docid": "0upp8cv5", "rank": 16, "score": 0.8580822348594666}, {"content": "Title: COVID-19: How has the scientific community risen to the challenge? Content: As the novel coronavirus SARS-CoV-2 spreads around the world, scientists have raced to develop vaccines and tests in order to curb the infection.", "qid": 50, "docid": "humoykni", "rank": 17, "score": 0.8578668832778931}, {"content": "Title: SARS Vaccine Development Content: Developing effective and safe vaccines is urgently needed to prevent infection by severe acute respiratory syndrome (SARS)\u2013associated coronavirus (SARS-CoV). The inactivated SARS-CoV vaccine may be the first one available for clinical use because it is easy to generate; however, safety is the main concern. The spike (S) protein of SARS-CoV is the major inducer of neutralizing antibodies, and the receptor-binding domain (RBD) in the S1 subunit of S protein contains multiple conformational neutralizing epitopes. This suggests that recombinant proteins containing RBD and vectors encoding the RBD sequence can be used to develop safe and effective SARS vaccines.", "qid": 50, "docid": "c18arb6s", "rank": 18, "score": 0.856330156326294}, {"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": 50, "docid": "znx5p3yp", "rank": 19, "score": 0.8563050031661987}, {"content": "Title: The biological characteristics of SARS-CoV-2 Spike protein Pro330-Leu650 Content: SARS-CoV-2 is the cause of the worldwide outbreak of COVID-19 that has been characterized as a pandemic by the WHO. Since the first report of COVID-19 on December 31, 2019, 179,111 cases were confirmed in 160 countries/regions with 7,426 deaths as of March 17, 2020. However, there have been no vaccines approved in the world to date. In this study, we analyzed the biological characteristics of the SARS-CoV-2 Spike protein, Pro330-Leu650 (SARS-CoV-2-SPL), using biostatistical methods. SARS-CoV-2-SPL possesses a receptor-binding region (RBD) and important B (Ser438-Gln506, Thr553-Glu583, Gly404-Aps427, Thr345-Ala352, and Lys529-Lys535) and T (9 CD4 and 11 CD8 T cell antigenic determinants) cell epitopes. High homology in this region between SARS-CoV-2 and SARS-CoV amounted to 87.7%, after taking the biological similarity of the amino acids into account and eliminating the receptor-binding motif (RBM). The overall topology indicated that the complete structure of SARS-CoV-2-SPL was with RBM as the head, and RBD as the trunk and the tail region. SARS-CoV-2-SPL was found to have the potential to elicit effective B and T cell responses. Our findings may provide meaningful guidance for SARS-CoV-2 vaccine design.", "qid": 50, "docid": "vhl5adaw", "rank": 20, "score": 0.8562982082366943}, {"content": "Title: The biological characteristics of SARS-CoV-2 spike protein Pro330-Leu650 Content: SARS-CoV-2 is the cause of the worldwide outbreak of COVID-19 that has been characterized as a pandemic by the WHO. Since the first report of COVID-19 on December 31, 2019, 179,111 cases were confirmed in 160 countries/regions with 7426 deaths as of March 17, 2020. However, there have been no vaccines approved in the world to date. In this study, we analyzed the biological characteristics of the SARS-CoV-2 Spike protein, Pro330-Leu650 (SARS-CoV-2-SPL), using biostatistical methods. SARS-CoV-2-SPL possesses a receptor-binding region (RBD) and important B (Ser438-Gln506, Thr553-Glu583, Gly404-Aps427, Thr345-Ala352, and Lys529-Lys535) and T (9 CD4 and 11 CD8 T cell antigenic determinants) cell epitopes. High homology in this region between SARS-CoV-2 and SARS-CoV amounted to 87.7%, after taking the biological similarity of the amino acids into account and eliminating the receptor-binding motif (RBM). The overall topology indicated that the complete structure of SARS-CoV-2-SPL was with RBM as the head, and RBD as the trunk and the tail region. SARS-CoV-2-SPL was found to have the potential to elicit effective B and T cell responses. Our findings may provide meaningful guidance for SARS-CoV-2 vaccine design.", "qid": 50, "docid": "ufmzv9f4", "rank": 21, "score": 0.856274425983429}, {"content": "Title: DNA vaccine protection against SARS-CoV-2 in rhesus macaques Content: The global COVID-19 pandemic caused by the SARS-CoV-2 virus has made the development of a vaccine a top biomedical priority. In this study, we developed a series of DNA vaccine candidates expressing different forms of the SARS-CoV-2 Spike (S) protein and evaluated them in 35 rhesus macaques. Vaccinated animals developed humoral and cellular immune responses, including neutralizing antibody titers comparable to those found in convalescent humans and macaques infected with SARS-CoV-2. Following vaccination, all animals were challenged with SARS-CoV-2, and the vaccine encoding the full-length S protein resulted in >3.1 and >3.7 log(10) reductions in median viral loads in bronchoalveolar lavage and nasal mucosa, respectively, as compared with sham controls. Vaccine-elicited neutralizing antibody titers correlated with protective efficacy, suggesting an immune correlate of protection. These data demonstrate vaccine protection against SARS-CoV-2 in nonhuman primates.", "qid": 50, "docid": "w9zyshzb", "rank": 22, "score": 0.8550287485122681}, {"content": "Title: DNA vaccine protection against SARS-CoV-2 in rhesus macaques Content: The global COVID-19 pandemic caused by the SARS-CoV-2 virus has made the development of a vaccine a top biomedical priority. In this study, we developed a series of DNA vaccine candidates expressing different forms of the SARS-CoV-2 Spike (S) protein and evaluated them in 35 rhesus macaques. Vaccinated animals developed humoral and cellular immune responses, including neutralizing antibody titers comparable to those found in convalescent humans and macaques infected with SARS-CoV-2. Following vaccination, all animals were challenged with SARS-CoV-2, and the vaccine encoding the full-length S protein resulted in >3.1 and >3.7 log10 reductions in median viral loads in bronchoalveolar lavage and nasal mucosa, respectively, as compared with sham controls. Vaccine-elicited neutralizing antibody titers correlated with protective efficacy, suggesting an immune correlate of protection. These data demonstrate vaccine protection against SARS-CoV-2 in nonhuman primates.", "qid": 50, "docid": "pfjq2m42", "rank": 23, "score": 0.8548822402954102}, {"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": 50, "docid": "ymoigqdw", "rank": 24, "score": 0.8548272848129272}, {"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": 50, "docid": "du2zxq96", "rank": 25, "score": 0.8546782732009888}, {"content": "Title: Epitope-Based Peptide Vaccine Against Severe Acute Respiratory Syndrome-Coronavirus-2 Nucleocapsid Protein: An in silico Approach Content: With an increasing fatality rate, severe acute respiratory syndrome-coronavirus-2 (SARS-CoV-2) has emerged as a promising threat to human health worldwide. SARS-CoV-2 is a member of the Coronaviridae family, which is transmitted from animal to human and because of being contagious, further it transmitted human to human. Recently, the World Health Organization (WHO) has announced the infectious disease caused by SARS-CoV-2, which is known as coronavirus disease-2019 (COVID-2019) as a global pandemic. But, no specific medications are available for the treatment of COVID-19 so far. As a corollary, there is a need for a potential vaccine to impede the progression of the disease. Lately, it has been documented that the nucleocapsid (N) protein of SARS-CoV-2 is responsible for viral replication as well as interferes with host immune responses. We have comparatively analyzed the sequences of N protein of SARS-CoV-2 for the identification of core attributes and analyzed the ancestry through phylogenetic analysis. Subsequently, we have predicted the most immunogenic epitope for T-cell as well as B-cell. Importantly, our investigation mainly focused on major histocompatibility complex (MHC) class I potential peptides and NTASWFTAL interacted with most human leukocyte antigen (HLA) that are encoded by MHC class I molecules. Further, molecular docking analysis unveiled that NTASWFTAL possessed a greater affinity towards HLA and also available in a greater range of the population. Our study provides a consolidated base for vaccine design and we hope that this computational analysis will pave the way for designing novel vaccine candidates.", "qid": 50, "docid": "6m9llyta", "rank": 26, "score": 0.8536615967750549}, {"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": 50, "docid": "ccau1qwc", "rank": 27, "score": 0.8530319333076477}, {"content": "Title: A proposed role for the SARS-CoV-2 nucleocapsid protein in the formation and regulation of biomolecular condensates Content: To date, the recently discovered SARS-CoV-2 virus has afflicted >6.9 million people worldwide and disrupted the global economy. Development of effective vaccines or treatments for SARS-CoV-2 infection will be aided by a molecular-level understanding of SARS-CoV-2 proteins and their interactions with host cell proteins. The SARS-CoV-2 nucleocapsid (N) protein is highly homologous to the N protein of SARS-CoV, which is essential for viral RNA replication and packaging into new virions. Emerging models indicate that nucleocapsid proteins of other viruses can form biomolecular condensates to spatiotemporally regulate N protein localization and function. Our bioinformatic analyses, in combination with pre-existing experimental evidence, suggest that the SARS-CoV-2 N protein is capable of forming or regulating biomolecular condensates in vivo by interaction with RNA and key host cell proteins. We discuss multiple models, whereby the N protein of SARS-CoV-2 may harness this activity to regulate viral life cycle and host cell response to viral infection.", "qid": 50, "docid": "n2biqjmf", "rank": 28, "score": 0.8529244065284729}, {"content": "Title: Recombinant SARS-CoV-2 spike proteins for sero-surveillance and epitope mapping Content: The newly emergent SARS-CoV-2 coronavirus is closely related to SARS-CoV which emerged in 2002. Studies on coronaviruses in general, and SARS in particular, have identified the virus spike protein (S) as being central to virus tropism, to the generation of a protective antibody response and to the unambiguous detection of past infections. As a result of this centrality SARS-CoV-2 S protein has a role in many aspects of research from vaccines to diagnostic tests. We describe a number of recombinant forms of SARS-CoV-2 S expressed in commonly available expression systems and their preliminary use in diagnostics and epitope mapping. These sources may find use in the current and future analysis of the virus and the Covid-19 disease it causes.", "qid": 50, "docid": "e20gtx0z", "rank": 29, "score": 0.8525431156158447}, {"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": 50, "docid": "9qneslip", "rank": 30, "score": 0.8521314263343811}, {"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": 50, "docid": "023h20vk", "rank": 31, "score": 0.85211181640625}, {"content": "Title: Potential Treatments for COVID-19; a Narrative Literature Review. Content: SARS-CoV-2 is a newly emerging human infectious coronavirus that causes COVID-19, which has been recognized as a pandemic by the World Health Organization (WHO) on March 11th. There is still no vaccine or definitive treatment for this virus because its pathogenesis and proliferation pathways are still unknown. Therefore, in this article, new potential COVID-19 therapies are briefly reviewed.", "qid": 50, "docid": "yympgnfe", "rank": 32, "score": 0.8520553708076477}, {"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": 33, "score": 0.8513737916946411}, {"content": "Title: Immunoinformatics-guided designing of epitope-based subunit vaccine against the SARS Coronavirus-2 (SARS-CoV-2) Content: SARS Coronavirus-2 (SARS-CoV-2) pandemic has become a global issue which has raised the concern of scientific community to design and discover a counter-measure against this deadly virus which has caused deaths of numerous infected people upon infection and spreading. To date, no effective vaccine is available which can combat the infection caused by this virus. This study was conducted to design possible epitope-based subunit vaccines against the SARS-CoV-2 virus using the approaches of reverse vaccinology and immunoinformatics. Upon continual computational experimentation three possible vaccine constructs were designed and one vaccine construct was selected as the best vaccine based on molecular docking study which is supposed to effectively act against SARS-CoV-2. Thereafter, molecular dynamics simulation and in silico codon adaptation experiments were carried out in order to check biological stability and find effective mass production strategy of the selected vaccine. This study should contribute to uphold the present efforts of the researches to secure a definitive treatment for this lethal disease.", "qid": 50, "docid": "s9k5ej8l", "rank": 34, "score": 0.8513453006744385}, {"content": "Title: A review on Promising vaccine development progress for COVID-19 disease Content: Abstract The emergence of the strain of coronavirus SARS-CoV-2 (severe acute respiratory syndrome coronavirus 2) that causes corona virus disease 2019 (COVID-19) and its impact on in the world have made imperative progress to develop an effective and safe vaccine. Despite several measures undertaken, the spread of this virus is ongoing. So far, more than 1,560,000 cases and 1000,000 deaths occurred in the world. Efforts have been made to develop vaccines against human coronavirus (CoV) infections such as MERS and SARS. However, currently, no approved vaccine exists for these coronavirus strains. Such Previous research efforts to develop a coronavirus vaccine in the years following the 2003 pandemic have opened the door for the scientist to design a new vaccine for the COVID-19. Both SARS-CoV and SARS-CoV-2 has a high degree of genetic similarity and bind to the same host cell ACE2 receptor. By using different vaccine development platforms including whole virus vaccines, recombinant protein subunit vaccines, and nucleic acid vaccines several candidates displayed efficacy in vitro studies but few progressed to clinical trials. This review provides a brief introduction of the general features of SARS-CoV-2 and discusses the current progress of ongoing advances in designing vaccine development efforts to counter COVID-19.", "qid": 50, "docid": "gkcan78j", "rank": 35, "score": 0.8513349294662476}, {"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": 50, "docid": "wfjdxgxh", "rank": 36, "score": 0.8509624004364014}, {"content": "Title: Potential Treatments for COVID-19; a Narrative Literature Review Content: SARS-CoV-2 is a newly emerging human infectious coronavirus that causes COVID-19, which has been recognized as a pandemic by the World Health Organization (WHO) on March 11(th). There is still no vaccine or definitive treatment for this virus because its pathogenesis and proliferation pathways are still unknown. Therefore, in this article, new potential COVID-19 therapies are briefly reviewed.", "qid": 50, "docid": "y29kct7v", "rank": 37, "score": 0.8507175445556641}, {"content": "Title: SARS-CoV-2 spike glycoprotein vaccine candidate NVX-CoV2373 elicits immunogenicity in baboons and protection in mice Content: The COVID-19 pandemic continues to spread throughout the world with an urgent need for a safe and protective vaccine to effectuate herd immunity to control the spread of SARS-CoV-2. Here, we report the development of a SARS-CoV-2 subunit vaccine (NVX-CoV2373) produced from the full-length spike (S) protein, stabilized in the prefusion conformation. Purified NVX-CoV2373 S form 27.2nm nanoparticles that are thermostable and bind with high affinity to the human angiotensin-converting enzyme 2 (hACE2) receptor. In mice and baboons, low-dose NVX-CoV2373 with saponin-based Matrix-M adjuvant elicits high titer anti-S IgG that is associated with blockade of hACE2 receptor binding, virus neutralization, and protection against SARS-CoV-2 challenge in mice with no evidence of vaccine-associated enhanced respiratory disease (VAERD). NVX-CoV2373 vaccine also elicits multifunctional CD4+ and CD8+ T cells, CD4+ T follicular helper T cells (Tfh), and the generation of antigen-specific germinal center (GC) B cells in the spleen. These results support the ongoing phase 1/2 clinical evaluation of the safety and immunogenicity of NVX-CoV2327 with Matrix-M (NCT04368988).", "qid": 50, "docid": "2nruf2g7", "rank": 38, "score": 0.8505492210388184}, {"content": "Title: From SARS-CoV to SARS-CoV-2: safety and broad-spectrum are important for coronavirus vaccine development Content: The global pandemic of COVID-19 caused by SARS-CoV-2 (also known as 2019-nCoV and HCoV-19) has posed serious threats to public health and economic stability worldwide, thus calling for development of vaccines against SARS-CoV-2 and other emerging and reemerging coronaviruses. Since SARS-CoV-2 and SARS-CoV have high similarity of their genomic sequences and share the same cellular receptor (ACE2), it is essential to learn the lessons and experiences from the development of SARS-CoV vaccines for the development of SARS-CoV-2 vaccines. In this review, we summarized the current knowledge on the advantages and disadvantages of the SARS-CoV vaccine candidates and prospected the strategies for the development of safe, effective and broad-spectrum coronavirus vaccines for prevention of infection by currently circulating SARS-CoV-2 and other emerging and reemerging coronaviruses that may cause future epidemics or pandemics.", "qid": 50, "docid": "8zzi6gu9", "rank": 39, "score": 0.849932074546814}, {"content": "Title: Modified Vaccinia Ankara Based SARS-CoV-2 Vaccine Expressing Full-Length Spike Induces Strong Neutralizing Antibody Response Content: There is a great need for the development of vaccines for preventing SARS-CoV-2 infection and mitigating the COVID-19 pandemic. Here, we developed two modified vaccinia Ankara (MVA) based vaccines which express either a membrane anchored full-length spike protein (MVA/S) stabilized in a prefusion state or the S1 region of the spike (MVA/S1) which forms trimers and is secreted. Both immunogens contained the receptor-binding domain (RBD) which is a known target of antibody-mediated neutralization. Following immunizations with MVA/S or MVA/S1, both spike protein recombinants induced strong IgG antibodies to purified full-length SARS-CoV-2 spike protein. The MVA/S induced a robust antibody response to purified RBD, S1 and S2 whereas MVA/S1 induced an antibody response to the S1 region outside of the RBD region. Both vaccines induced an antibody response in the lung and that was associated with induction of bronchus-associated lymphoid tissue. MVA/S but not MVA/S1 vaccinated mice generated robust neutralizing antibody responses against SARS-CoV-2 that strongly correlated with RBD antibody binding titers. Mechanistically, S1 binding to ACE-2 was strong but reduced following prolonged pre-incubation at room temperature suggesting confirmation changes in RBD with time. These results demonstrate MVA/S is a potential vaccine candidate against SARS-CoV-2 infection.", "qid": 50, "docid": "byt52ym3", "rank": 40, "score": 0.8499307632446289}, {"content": "Title: Knowledge-based repositioning of the anti-HCV direct antiviral agent Sofosbuvir as SARS-CoV-2 treatment Content: The new human coronavirus named SARS-CoV-2 is a positive-sense RNA virus for which no specific drugs are currently available. A knowledge-based analysis strongly suggests a possible repositioning of the anti-HCV direct antiviral agent (DAA) Sofosbuvir as treatment for SARS-CoV-2. Indeed, the RNA-dependent RNA-polymerases (RdRp) of the two viruses show high sequence and structural homology, supporting the likelihood of binding the Sofosbuvir molecule with similar efficiency. Such a repositioning would allow the containment of the SARS-CoV-2 pandemic and limit the progression of disease to potentially deadly COVID19.", "qid": 50, "docid": "fspxett8", "rank": 41, "score": 0.8499172925949097}, {"content": "Title: Noncanonical junctions in subgenomic RNAs of SARS-CoV-2 lead to variant open reading frames Content: SARS-CoV-2, a positive-sense RNA virus in the family Coronaviridae, has caused the current worldwide pandemic, known as coronavirus disease 2019 or COVID-19. The definition of SARS-CoV-2 open reading frames is a key step in delineating targets for vaccination and treatment for COVID-19. Here, we report an integrative analysis of three independent direct RNA sequencing datasets of the SARS-CoV-2 transcriptome. We find strong evidence for variant open reading frames (ORFs) encoded by SARS-CoV-2 RNA. A variant transcript for the matrix protein (M) lacking its N-terminal transmembrane domain, initiated by a TTG start codon, is produced by a strong transcriptional regulatory sequence (TRS)-mediated junction within the M ORF and represents up to 19% of all M ORFs. Sporadic non-canonical junctions in the spike (S) ORF lead to N-terminal truncations that remove the N-terminal and receptor-binding domains from up to 25% of S ORFs. Surprisingly, nearly all ORFs from ORF1a identified in these transcriptome sequences were variant. These ORFs contain the first 200-800 amino acids of ORF1a and may represent a mechanism to regulate the relative abundance of ORF1a nonstructural proteins. We show there is strong transcriptome and junctional support for variant ORF1a ORFs in independent direct RNA sequencing and short-read RNA sequencing datasets, and further show that up to 1/3 of these ORFs are expected to have C-terminal fusions with downstream genes. Finally, we show that currently unannotated ORFs are abundant in the SARS-CoV-2 transcriptome. Together, these analyses help to elucidate the diverse coding potential of SARS-CoV-2.", "qid": 50, "docid": "8y9gaoqb", "rank": 42, "score": 0.8497062921524048}, {"content": "Title: Replication-competent vesicular stomatitis virus vaccine vector protects against SARS-CoV-2-mediated pathogenesis Content: Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) has caused millions of human infections and hundreds of thousands of deaths. Accordingly, an effective vaccine is of critical importance in mitigating coronavirus induced disease 2019 (COVID-19) and curtailing the pandemic. We developed a replication-competent vesicular stomatitis virus (VSV)-based vaccine by introducing a modified form of the SARS-CoV-2 spike gene in place of the native glycoprotein gene (VSV-eGFP-SARS-CoV-2). Immunization of mice with VSV-eGFP-SARS-CoV-2 elicits high titers of antibodies that neutralize SARS-CoV-2 infection and target the receptor binding domain that engages human angiotensin converting enzyme-2 (ACE2). Upon challenge with a human isolate of SARS-CoV-2, mice expressing human ACE2 and immunized with VSV-eGFP-SARS-CoV-2 show profoundly reduced viral infection and inflammation in the lung indicating protection against pneumonia. Finally, passive transfer of sera from VSV-eGFP-SARS-CoV-2-immunized animals protects na\u00efve mice from SARS-CoV-2 challenge. These data support development of VSV-eGFP-SARS-CoV-2 as an attenuated, replication-competent vaccine against SARS-CoV-2.", "qid": 50, "docid": "enli9n34", "rank": 43, "score": 0.8494471311569214}, {"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": 50, "docid": "7qd8z5e7", "rank": 44, "score": 0.8490726947784424}, {"content": "Title: The Architecture of SARS-CoV-2 Transcriptome Content: SARS-CoV-2 is a betacoronavirus responsible for the COVID-19 pandemic. Although the SARS-CoV-2 genome was reported recently, its transcriptomic architecture is unknown. Utilizing two complementary sequencing techniques, we present a high-resolution map of the SARS-CoV-2 transcriptome and epitranscriptome. DNA nanoball sequencing shows that the transcriptome is highly complex owing to numerous discontinuous transcription events. In addition to the canonical genomic and 9 subgenomic RNAs, SARS-CoV-2 produces transcripts encoding unknown ORFs with fusion, deletion, and/or frameshift. Using nanopore direct RNA sequencing, we further find at least 41 RNA modification sites on viral transcripts, with the most frequent motif, AAGAA. Modified RNAs have shorter poly(A) tails than unmodified RNAs, suggesting a link between the modification and the 3' tail. Functional investigation of the unknown transcripts and RNA modifications discovered in this study will open new directions to our understanding of the life cycle and pathogenicity of SARS-CoV-2.", "qid": 50, "docid": "6quqydr6", "rank": 45, "score": 0.8488319516181946}, {"content": "Title: Immunoinformatics-guided designing of epitope-based subunit vaccines against the SARS Coronavirus-2 (SARS-CoV-2) Content: SARS Coronavirus-2 (SARS-CoV-2) pandemic has become a global issue which has raised the concern of scientific community to design and discover a counter-measure against this deadly virus. So far, the pandemic has caused the death of hundreds of thousands of people upon infection and spreading. To date, no effective vaccine is available which can combat the infection caused by this virus. Therefore, this study was conducted to design possible epitope-based subunit vaccines against the SARS-CoV-2 virus using the approaches of reverse vaccinology and immunoinformatics. Upon continual computational experimentation, three possible vaccine constructs were designed and one vaccine construct was selected as the best vaccine based on molecular docking study which is supposed to effectively act against the SARS-CoV-2. Thereafter, the molecular dynamics simulation and in silico codon adaptation experiments were carried out in order to check biological stability and find effective mass production strategy of the selected vaccine. This study should contribute to uphold the present efforts of the researches to secure a definitive preventative measure against this lethal disease.", "qid": 50, "docid": "fr536bc9", "rank": 46, "score": 0.8486740589141846}, {"content": "Title: Self-amplifying RNA SARS-CoV-2 lipid nanoparticle vaccine induces equivalent preclinical antibody titers and viral neutralization to recovered COVID-19 patients Content: The spread of the SARS-CoV-2 into a global pandemic within a few months of onset motivates the development of a rapidly scalable vaccine. Here, we present a self-amplifying RNA encoding the SARS-CoV-2 spike protein encapsulated within a lipid nanoparticle as a vaccine and demonstrate induction of robust neutralization of a pseudo-virus, proportional to quantity of specific IgG and of higher quantities than recovered COVID-19 patients. These data provide insight into the vaccine design and evaluation of immunogenicity to enable rapid translation to the clinic.", "qid": 50, "docid": "6ubk3rv7", "rank": 47, "score": 0.8486135601997375}, {"content": "Title: The SARS-CoV-2 Coronavirus and the COVID-19 Outbreak Content: The SARS-CoV-2, a newly identified \u00df-coronavirus, is the causative agent of the third large-scale pandemic from the last two decades. The outbreak started in December 2019 in Wuhan City, Hubei province in China. The patients presented clinical symptoms of dry cough, fever, dyspnea, and bilateral lung infiltrates on imaging. By February 2020, The World Health Organization (WHO) named the disease as Coronavirus Disease 2019 (COVID-19). The Coronavirus Study Group (CSG) of the International Committee on Taxonomy of Viruses (ICTV) recognized and designated this virus as severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). The SARS-CoV-2 uses the same host receptor, angiotensin-converting enzyme 2 (ACE2), used by SARS-CoV to infect humans. One hypothesis of SARSCoV-2 origin indicates that it is likely that bats serve as reservoir hosts for SARSCoV-2, being the intermediate host not yet determined. The predominant route of transmission of SARS-CoV-2 is from human to human. As of May 10th 2020, the number of worldwide confirmed COVID-19 cases is over 4 million, while the number of global deaths is around 279.000 people. The United States of America (USA) has the highest number of COVID-19 cases with over 1.3 million cases followed by Spain, Italy, United Kingdom, Russia, France and Germany with over 223.000, 218.000, 215.000, 209.000, 176.000, and 171.000 cases, respectively.", "qid": 50, "docid": "7re3jgya", "rank": 48, "score": 0.8482530117034912}, {"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.", "qid": 50, "docid": "zn182czp", "rank": 49, "score": 0.8481251001358032}, {"content": "Title: SARS-CoV-2 RNA polymerase as target for antiviral therapy Content: A new human coronavirus named SARS-CoV-2 was identified in several cases of acute respiratory syndrome in Wuhan, China in December 2019. On March 11 2020, WHO declared the SARS-CoV-2 infection to be a pandemic, based on the involvement of 169 nations. Specific drugs for SARS-CoV-2 are obviously not available. Currently, drugs originally developed for other viruses or parasites are currently in clinical trials based on empiric data. In the quest of an effective antiviral drug, the most specific target for an RNA virus is the RNA-dependent RNA-polymerase (RdRp) which shows significant differences between positive-sense and negative-sense RNA viruses. An accurate evaluation of RdRps from different viruses may guide the development of new drugs or the repositioning of already approved antiviral drugs as treatment of SARS-CoV-2. This can accelerate the containment of the SARS-CoV-2 pandemic and, hopefully, of future pandemics due to other emerging zoonotic RNA viruses.", "qid": 50, "docid": "c0jfa5jd", "rank": 50, "score": 0.8480277061462402}, {"content": "Title: SARS CoV subunit vaccine: antibody-mediated neutralisation and enhancement. Content: 1. A SARS vaccine was produced based on recombinant native full-length Spike-protein trimers (triSpike) and efficient establishment of a vaccination procedure in rodents. 2. Antibody-mediated enhancement of SARS-CoV infection with anti-SARS-CoV Spike immune-serum was observed in vitro. 3. Antibody-mediated infection of SARS-CoV triggers entry into human haematopoietic cells via an Fc\u03b3R-dependent and ACE2-, pH-, cysteine-protease-independent pathways. 4. The antibody-mediated enhancement phenomenon is not a mandatory component of the humoral immune response elicited by SARS vaccines, as pure neutralising antibody only could be obtained. 5. Occurrence of immune-mediated enhancement of SARS-CoV infection raises safety concerns regarding the use of SARS-CoV vaccine in humans and enables new ways to investigate SARS pathogenesis (tropism and immune response deregulation).", "qid": 50, "docid": "xbgmch1q", "rank": 51, "score": 0.8480039238929749}, {"content": "Title: Self-amplifying RNA SARS-CoV-2 lipid nanoparticle vaccine candidate induces high neutralizing antibody titers in mice Content: The spread of the SARS-CoV-2 into a global pandemic within a few months of onset motivates the development of a rapidly scalable vaccine. Here, we present a self-amplifying RNA encoding the SARS-CoV-2 spike protein encapsulated within a lipid nanoparticle (LNP) as a vaccine. We observe remarkably high and dose-dependent SARS-CoV-2 specific antibody titers in mouse sera, as well as robust neutralization of both a pseudo-virus and wild-type virus. Upon further characterization we find that the neutralization is proportional to the quantity of specific IgG and of higher magnitude than recovered COVID-19 patients. saRNA LNP immunizations induce a Th1-biased response in mice, and there is no antibody-dependent enhancement (ADE) observed. Finally, we observe high cellular responses, as characterized by IFN-\u00ce\u00b3 production, upon re-stimulation with SARS-CoV-2 peptides. These data provide insight into the vaccine design and evaluation of immunogenicity to enable rapid translation to the clinic.", "qid": 50, "docid": "oiu80002", "rank": 52, "score": 0.8475392460823059}, {"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": 50, "docid": "f5xs0tv2", "rank": 53, "score": 0.8474944233894348}, {"content": "Title: Computational methods to develop potential neutralizing antibody Fab region against SARS-CoV-2 as therapeutic and diagnostic tool Content: SARS-CoV-2, a global pandemic originated from Wuhan city of China in the month of December 2019. There is an urgency to identify potential antibodies to neutralize the virus and also as a diagnostic tool candidate. At present palliative treatments using existing antiviral drugs are under trails to treat SARS-CoV-2.Whole Genome sequence of Wuhan market sample of SARS-CoV-2 was obtained from NCBI Gene ID MN908947.3.Spike protein sequence PDB ID 6VSB obtained from RCSB database. Spike protein sequence had shown top V gene match with IGLV1-44*01, IGLV1-47*02 and has VL type chain. Whole Genome sequence had shown top V gene match with IGHV1-38-4*01 and has VH type chain. VD chain had shown link to allele HLA-A0206 80%, HLA-A0217 80%, HLA-A2301 75%, HLA-A0203 75%, HLA-A0202 70% and HLA-A0201 55% of binding levels. Some conserved regions of spike protein had shown strong binding affinity with HLA-A-0*201, HLA-A24, HLA-B-5701 and HLA-B-5703 alpha chains. Synthetic Fab construct BCR type antibody IgG (CR5840) had shown Polyspecific binding activity with spike glycoprotein when compared with available Anti-SARS antibody CR3022.Thus we propose CR5840 Fab constructed antibody as potential neutralizing antibody for SARS-CoV-2. Based on germline analysis we also propose cytotoxic T lymphocyte epitope peptide selective system as effective tool for the development of SARS-CoV-2 vaccine.", "qid": 50, "docid": "2jrichn5", "rank": 54, "score": 0.8472186326980591}, {"content": "Title: Optimization of a DNA vaccine against SARS. Content: Severe acute respiratory syndrome coronavirus (SARS-CoV) first appeared in Southern China in November 2002, and then quickly spread to 33 countries on five continents along international air travel routes. Although the SARS epidemic has been contained, there is a clear need for a safe and effective vaccine should an outbreak of a SARS-CoV infection reappear in human population. In this study, we tested four DNA-vaccine constructs: (1) pLL70, containing cDNA for the SARS-CoV spike (S) gene; (2) pcDNA-SS, containing codon-optimized S gene for SARS-CoV S protein (residues 12-1255) fused with a leader sequence derived from the human CD5 gene; (3) pcDNA-St, containing the gene encoding the N-portion of the codon-optimized S gene (residues 12-532) with the CD5 leader sequence; (4) pcDNA-St-VP22C, containing the gene encoding the N-portion of the codon-optimized S protein with the CD5 leader sequence fused with the C-terminal 138 amino acids of the bovine herpesvirus-1 (BHV-1) major tegument protein VP22. Each of these plasmids was intradermally administered to C57BL/6 mice in three separate immunizations. Analysis of humoral and cellular immune responses in immunized mice demonstrated that pcDNA-SS and pcDNA-St-VP22C are the most immunogenic SARS vaccine candidates.", "qid": 50, "docid": "6derrgno", "rank": 55, "score": 0.847216784954071}, {"content": "Title: SARS vaccine: progress and challenge. Content: Severe acute respiratory syndrome (SARS) emerged in 2002 as a severe and highly contagious infectious disease that rapidly spread to a number of different countries. The collaborative efforts of the global scientific community have provided, within a short period of time, substantial insights into the molecular biology and immunology of SARS-CoV. Although the outbreak has been contained, there is continuous concern that the virus may resurface into the human population through seasonal changes, animal reservoirs or laboratory accidents. The severe morbidity and mortality associated with SARS make it imperative that an effective vaccine be developed to prevent reemergence and epidemics in the future.", "qid": 50, "docid": "9t9yzuyz", "rank": 56, "score": 0.8471176028251648}, {"content": "Title: Molecular biology of severe acute respiratory syndrome coronavirus Content: The worldwide epidemic of severe acute respiratory syndrome (SARS) in 2003 was caused by a novel coronavirus called SARS-CoV. Coronaviruses and their closest relatives possess extremely large plus-strand RNA genomes and employ unique mechanisms and enzymes in RNA synthesis that separate them from all other RNA viruses. The SARS epidemic prompted a variety of studies on multiple aspects of the coronavirus replication cycle, yielding both rapid identification of the entry mechanisms of SARS-CoV into host cells and valuable structural and functional information on SARS-CoV proteins. These recent advances in coronavirus research have important implications for the development of anti-SARS drugs and vaccines.", "qid": 50, "docid": "y64i8ui3", "rank": 57, "score": 0.8470959067344666}, {"content": "Title: The SARS-CoV-2 Coronavirus and the COVID-19 Outbreak. Content: The SARS-CoV-2, a newly identified \u03b2-coronavirus, is the causative agent of the third large-scale pandemic from the last two decades. The outbreak started in December 2019 in Wuhan City, Hubei province in China. The patients presented clinical symptoms of dry cough, fever, dyspnea, and bilateral lung infiltrates on imaging. By February 2020, The World Health Organization (WHO) named the disease as Coronavirus Disease 2019 (COVID-19). The Coronavirus Study Group (CSG) of the International Committee on Taxonomy of Viruses (ICTV) recognized and designated this virus as severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). The SARS-CoV-2 uses the same host receptor, angiotensin-converting enzyme 2 (ACE2), used by SARS-CoV to infect humans. One hypothesis of SARSCoV-2 origin indicates that it is likely that bats serve as reservoir hosts for SARSCoV-2, being the intermediate host not yet determined. The predominant route of transmission of SARS-CoV-2 is from human to human. As of May 10th 2020, the number of worldwide confirmed COVID-19 cases is over 4 million, while the number of global deaths is around 279.000 people. The United States of America (USA) has the highest number of COVID-19 cases with over 1.3 million cases followed by Spain, Italy, United Kingdom, Russia, France and Germany with over 223.000, 218.000, 215.000, 209.000, 176.000, and 171.000 cases, respectively.", "qid": 50, "docid": "1enb2vxv", "rank": 58, "score": 0.8470938205718994}, {"content": "Title: A Guide to COVID-19: a global pandemic caused by the novel coronavirus SARS-CoV-2 Content: The emergence of the SARS-CoV-2 strain of the human coronavirus has thrown the world into the midst of a new pandemic. In the human body, the virus causes COVID-19, a disease characterized by shortness of breath, fever, and pneumonia, which can be fatal in vulnerable individuals. SARS-CoV-2 has characteristics of past human coronaviruses, with close genomic similarities to SARS-CoV, the virus that causes the disease SARS. Like these related coronaviruses, SARS-CoV-2 is transmitted through the inhalation of droplets and interaction with contaminated surfaces. Across the world, laboratories are developing candidate vaccines for the virus - with vaccine trials underway in the United States and the United Kingdom - and considering various drugs for possible treatments and prophylaxis. Here, we provide an overview of SARS-CoV-2 by analyzing its virology, epidemiology, and modes of transmission while examining the current progress of testing procedures and possible treatments through drugs and vaccines.", "qid": 50, "docid": "wq7ljx2f", "rank": 59, "score": 0.8470920324325562}, {"content": "Title: Self-amplifying RNA SARS-CoV-2 lipid nanoparticle vaccine candidate induces high neutralizing antibody titers in mice Content: The spread of the SARS-CoV-2 into a global pandemic within a few months of onset motivates the development of a rapidly scalable vaccine. Here, we present a self-amplifying RNA encoding the SARS-CoV-2 spike protein encapsulated within a lipid nanoparticle (LNP) as a vaccine. We observe remarkably high and dose-dependent SARS-CoV-2 specific antibody titers in mouse sera, as well as robust neutralization of both a pseudo-virus and wild-type virus. Upon further characterization we find that the neutralization is proportional to the quantity of specific IgG and of higher magnitude than recovered COVID-19 patients. saRNA LNP immunizations induce a Th1-biased response in mice, and there is no antibody-dependent enhancement (ADE) observed. Finally, we observe high cellular responses, as characterized by IFN-\u03b3 production, upon re-stimulation with SARS-CoV-2 peptides. These data provide insight into the vaccine design and evaluation of immunogenicity to enable rapid translation to the clinic.", "qid": 50, "docid": "1c15qxb8", "rank": 60, "score": 0.8470880389213562}, {"content": "Title: In vivo structural characterization of the whole SARS-CoV-2 RNA genome identifies host cell target proteins vulnerable to re-purposed drugs Content: SARS-CoV-2 is an RNA virus of the Coronaviridae family that is the causal pathogen of the ongoing Coronavirus Disease 2019 pandemic. There are currently no antiviral drugs or vaccines to treat COVID-19, and the failure to identify effective interventions can be blamed on our incomplete understanding of the nature of this virus and its host cell infection process. Here, we experimentally determined structural maps of the SARS-CoV-2 RNA genome in infected human cells and also characterized in vitro refolded RNA structures for SARS-CoV-2 and 6 other coronaviruses. Our in vivo data confirms several structural elements predicted from theoretical analysis and goes much further in revealing many previously unknown structural features that functionally impact viral translation and discontinuous transcription in cells. Importantly, we harnessed our in vivo structure data alongside a deep-learning tool and accurately predicted several dozen functionally related host cell proteins that bind to the SARS-CoV-2 RNA genome, none of which were known previously. Thus, our in vivo structural study lays a foundation for coronavirus RNA biology and indicates promising directions for the rapid development of therapeutics to treat COVID-19. HIGHLIGHTS We mapped the in vivo structure and built secondary structural models of the SARS-CoV-2 RNA genome We discovered functionally impactful structural features in the RNA genomes of multiple coronaviruses We predicted and validated host cell proteins that bind to the SARS-CoV-2 RNA genome based on our in vivo RNA structural data using a deep-learning tool", "qid": 50, "docid": "oc3qaeiy", "rank": 61, "score": 0.8470259308815002}, {"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": 50, "docid": "j6gn8exx", "rank": 62, "score": 0.8470239639282227}, {"content": "Title: Preliminary Identification of Potential Vaccine Targets for the COVID-19 Coronavirus (SARS-CoV-2) Based on SARS-CoV Immunological Studies Content: The beginning of 2020 has seen the emergence of COVID-19 outbreak caused by a novel coronavirus, Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2). There is an imminent need to better understand this new virus and to develop ways to control its spread. In this study, we sought to gain insights for vaccine design against SARS-CoV-2 by considering the high genetic similarity between SARS-CoV-2 and SARS-CoV, which caused the outbreak in 2003, and leveraging existing immunological studies of SARS-CoV. By screening the experimentally-determined SARS-CoV-derived B cell and T cell epitopes in the immunogenic structural proteins of SARS-CoV, we identified a set of B cell and T cell epitopes derived from the spike (S) and nucleocapsid (N) proteins that map identically to SARS-CoV-2 proteins. As no mutation has been observed in these identified epitopes among the 120 available SARS-CoV-2 sequences (as of 21 February 2020), immune targeting of these epitopes may potentially offer protection against this novel virus. For the T cell epitopes, we performed a population coverage analysis of the associated MHC alleles and proposed a set of epitopes that is estimated to provide broad coverage globally, as well as in China. Our findings provide a screened set of epitopes that can help guide experimental efforts towards the development of vaccines against SARS-CoV-2.", "qid": 50, "docid": "ojs5e7n9", "rank": 63, "score": 0.8467670679092407}, {"content": "Title: Structure of the full SARS-CoV-2 RNA genome in infected cells Content: SARS-CoV-2 is a betacoronavirus with a single-stranded, positive-sense, 30-kilobase RNA genome responsible for the ongoing COVID-19 pandemic. Currently, there are no antiviral drugs or vaccines with proven efficacy, and development of these treatments are hampered by our limited understanding of the molecular and structural biology of the virus. Like many other RNA viruses, RNA structures in coronaviruses regulate gene expression and are crucial for viral replication. Although genome and transcriptome data were recently reported, there is to date little experimental data on predicted RNA structures in SARS-CoV-2 and most putative regulatory sequences are uncharacterized. Here we report the secondary structure of the entire SARS-CoV-2 genome in infected cells at single nucleotide resolution using dimethyl sulfate mutational profiling with sequencing (DMS-MaPseq). Our results reveal previously undescribed structures within critical regulatory elements such as the genomic transcription-regulating sequences (TRSs). Contrary to previous studies, our in-cell data show that the structure of the frameshift element, which is a major drug target, is drastically different from prevailing in vitro models. The genomic structure detailed here lays the groundwork for coronavirus RNA biology and will guide the design of SARS-CoV-2 RNA-based therapeutics.", "qid": 50, "docid": "2y49kcwu", "rank": 64, "score": 0.8467337489128113}, {"content": "Title: The Architecture of SARS-CoV-2 Transcriptome Content: Summary SARS-CoV-2 is a betacoronavirus responsible for the COVID-19 pandemic. Although the SARS-CoV-2 genome was reported recently, its transcriptomic architecture is unknown. Utilizing two complementary sequencing techniques, we present a high-resolution map of the SARS-CoV-2 transcriptome and epitranscriptome. DNA nanoball sequencing shows that the transcriptome is highly complex owing to numerous discontinuous transcription events. In addition to the canonical genomic and 9 subgenomic RNAs, SARS-CoV-2 produces transcripts encoding unknown ORFs with fusion, deletion, and/or frameshift. Using nanopore direct RNA sequencing, we further find at least 41 RNA modification sites on viral transcripts, with the most frequent motif, AAGAA. Modified RNAs have shorter poly(A) tails than unmodified RNAs, suggesting a link between the modification and the 3\u2032 tail. Functional investigation of the unknown transcripts and RNA modifications discovered in this study will open new directions to our understanding of the life cycle and pathogenicity of SARS-CoV-2.", "qid": 50, "docid": "ypsh3rjv", "rank": 65, "score": 0.8467258214950562}, {"content": "Title: Taking aim at a fast-moving target: Targets to watch for SARS-CoV-2 and COVID-19 Content: Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) is characterized as a betacoronavirus and recognized as the seventh discrete coronavirus species capable of causing human disease. This new coronavirus causes febrile respiratory illness and on March 11, 2020, was characterized as a global pandemic. Investigators have accelerated the search for a vaccine to prevent infection and for agents to treat it. This article presents those drug targets that (as of March 20, 2020) are currently under active investigation for the treatment of COVID-19, the disease caused by SARS-CoV-2 infection.", "qid": 50, "docid": "ybzfhp8p", "rank": 66, "score": 0.8466165661811829}, {"content": "Title: Preliminary identification of potential vaccine targets for the COVID-19 coronavirus (SARS-CoV-2) based on SARS-CoV immunological studies Content: The beginning of 2020 has seen the emergence of COVID-19 outbreak caused by a novel coronavirus, Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2). There is an imminent need to better understand this new virus and to develop ways to control its spread. In this study, we sought to gain insights for vaccine design against SARS-CoV-2 by considering the high genetic similarity between SARS-CoV-2 and SARS-CoV, which caused the outbreak in 2003, and leveraging existing immunological studies of SARS-CoV. By screening the experimentally-determined SARS-CoV-derived B cell and T cell epitopes in the immunogenic structural proteins of SARS-CoV, we identified a set of B cell and T cell epitopes derived from the spike (S) and nucleocapsid (N) proteins that map identically to SARS-CoV-2 proteins. As no mutation has been observed in these identified epitopes among the available SARS-CoV-2 sequences (as of 9 February 2020), immune targeting of these epitopes may potentially offer protection against this novel virus. For the T cell epitopes, we performed a population coverage analysis of the associated MHC alleles and proposed a set of epitopes that is estimated to provide broad coverage globally, as well as in China. Our findings provide a screened set of epitopes that can help guide experimental efforts towards the development of vaccines against SARS-CoV-2.", "qid": 50, "docid": "7i52vltp", "rank": 67, "score": 0.8462527394294739}, {"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": 50, "docid": "t8q99tlq", "rank": 68, "score": 0.8457712531089783}, {"content": "Title: Do COVID-19 and SARS Gene Complexities and Variations Help Overcome the Knowledge Gap? Content: A whole new pathogen, to which humans have virtually no pre-existing immunity, has caused fear all over the world. Severe acute respiratory syndrome coronavirus (SARS CoV-2) is one of the types of human novel-coronavirus of the family coronavirus. The nature of transmission of the virus makes it one of the most infectious pathogenic diseases that has ever existed. Though the human coronaviruses have existed since the discovery of the human coronavirus 229E (HCoV-229E) and human coronavirus OC43 (HCoV-OC43) in 1960, it has been a challenge to develop an effective cure as well as vaccine for the diseases associated with coronaviruses. Commonly, human coronaviruses cause illnesses such as intestinal and respiratory tract illnesses. Nevertheless, the symptoms reflected after infection from the coronaviruses take some time before being identified. Thus, viruses can replicate and cause more harm to the human body before being detected. Moreover, research continues to explain why some gene variations in some individuals increase the risk of some infectious diseases, while others are not affected. Looking at gene variations in people infected with Coronavirus Disease 2019 (COVID-19) and studying how genes influence people's response to infection will help to develop a vaccine that will help strengthen the immune system. Knowing how the human genes respond to the virus COVID-19 will help to cure people more effectively.", "qid": 50, "docid": "96p0ktoz", "rank": 69, "score": 0.8456894159317017}, {"content": "Title: Sofosbuvir as a potential alternative to treat the SARS-CoV-2 epidemic Content: As of today, there is no antiviral for the treatment of the SARS-CoV-2 infection, and the development of a vaccine might take several months or even years. The structural superposition of the hepatitis C virus polymerase bound to sofosbuvir, a nucleoside analog antiviral approved for hepatitis C virus infections, with the SARS-CoV polymerase shows that the residues that bind to the drug are present in the latter. Moreover, a multiple alignment of several SARS-CoV-2, SARS and MERS-related coronaviruses polymerases shows that these residues are conserved in all these viruses, opening the possibility to use sofosbuvir against these highly infectious pathogens.", "qid": 50, "docid": "okqkgrxi", "rank": 70, "score": 0.8453838229179382}, {"content": "Title: A Hypothesis on the role of the human immune system in covid-19 Content: The COVID-19 pandemic has not spared any continent. The disease has affected more than 7,500,000 individuals globally and killed approximately 450,000 individuals. The disease is caused by a very small virus named severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), which is an enveloped single-stranded RNA virus with a spike-like structure on its envelope that can interact with the angiotensin-converting enzyme 2 (ACE2) receptor after cleavage. ACE2 receptors are present in the human lungs and other organs. SARS-CoV-2 is a new virus that belongs to the subgenus Sarbecovirus; viruses in this subgenus have spread widely in the previous years and caused outbreaks of severe acute respiratory syndromes.", "qid": 50, "docid": "akt4glln", "rank": 71, "score": 0.8453605771064758}, {"content": "Title: A hypothesis on the role of the human immune system in covid-19 Content: The COVID-19 pandemic has not spared any continent. The disease has affected more than 7,500,000 individuals globally and killed approximately 450,000 individuals. The disease is caused by a very small virus named severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), which is an enveloped single-stranded RNA virus with a spike-like structure on its envelope that can interact with the angiotensin-converting enzyme 2 (ACE2) receptor after cleavage. ACE2 receptors are present in the human lungs and other organs. SARS-CoV-2 is a new virus that belongs to the subgenus Sarbecovirus; viruses in this subgenus have spread widely in the previous years and caused outbreaks of severe acute respiratory syndromes.", "qid": 50, "docid": "4oe0veq9", "rank": 72, "score": 0.8453605771064758}, {"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": 73, "score": 0.8452720642089844}, {"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": 74, "score": 0.8452720642089844}, {"content": "Title: Potential Treatments for COVID-19;a Narrative Literature Review Content: SARS-CoV-2 is a newly emerging human infectious coronavirus that causes COVID-19, which has been recognized as a pandemic by the World Health Organization (WHO) on March 11(th) There is still no vaccine or definitive treatment for this virus because its pathogenesis and proliferation pathways are still unknown Therefore, in this article, new potential COVID-19 therapies are briefly reviewed", "qid": 50, "docid": "3sewe0np", "rank": 75, "score": 0.8451206684112549}, {"content": "Title: Trained Immunity: a Tool for Reducing Susceptibility to and the Severity of SARS-CoV-2 Infection Content: SARS-CoV-2 infection is mild in the majority of individuals but progresses into severe pneumonia in a small proportion of patients. The increased susceptibility to severe disease in the elderly and individuals with co-morbidities argues for an initial defect in anti-viral host defense mechanisms. Long-term boosting of innate immune responses, also termed \"trained immunity,\" by certain live vaccines (BCG, oral polio vaccine, measles) induces heterologous protection against infections through epigenetic, transcriptional, and functional reprogramming of innate immune cells. We propose that induction of trained immunity by whole-microorganism vaccines may represent an important tool for reducing susceptibility to and severity of SARS-CoV-2.", "qid": 50, "docid": "g5ovvjc6", "rank": 76, "score": 0.844595730304718}, {"content": "Title: ACE-2 och coronavirus \u00ad en fr\u00e5ga om balans och dynamik?/ [ACE2 and coronavirus - a question of balance and dynamics?] Content: The new SARS-CoV-2 virus enters cells via angiotensin-converting enzyme 2 (ACE2). ACE2 counteracts ACE and angiotensin II in the renin-angiotensin-aldosterone system (RAAS) and has critical functions in the lung and cardiovascular system. SARS-CoV was found to down-regulate ACE2, leaving angiotensin II unbalanced in affected organs. A similar effect of SARS-CoV-2 could partly explain risk factors and symptoms, and could potentially be treatable.", "qid": 50, "docid": "wqpt073e", "rank": 77, "score": 0.8445221185684204}, {"content": "Title: [ACE2 and coronavirus - a question of balance and dynamics?] Content: The new SARS-CoV-2 virus enters cells via angiotensin-converting enzyme 2 (ACE2). ACE2 counteracts ACE and angiotensin II in the renin-angiotensin-aldosterone system (RAAS) and has critical functions in the lung and cardiovascular system. SARS-CoV was found to down-regulate ACE2, leaving angiotensin II unbalanced in affected organs. A similar effect of SARS-CoV-2 could partly explain risk factors and symptoms, and could potentially be treatable.", "qid": 50, "docid": "e97zvah8", "rank": 78, "score": 0.8445221185684204}, {"content": "Title: ChAdOx1 nCoV-19 vaccination prevents SARS-CoV-2 pneumonia in rhesus macaques Content: Severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2) emerged in December 20191,2 and is responsible for the COVID-19 pandemic3. Vaccines are an essential countermeasure urgently needed to control the pandemic4. Here, we show that the adenovirus-vectored vaccine ChAdOx1 nCoV-19, encoding the spike protein of SARS-CoV-2, is immunogenic in mice, eliciting a robust humoral and cell-mediated response. This response was not Th2 dominated, as demonstrated by IgG subclass and cytokine expression profiling. A single vaccination with ChAdOx1 nCoV-19 induced a humoral and cellular immune response in rhesus macaques. We observed a significantly reduced viral load in bronchoalveolar lavage fluid and respiratory tract tissue of vaccinated animals challenged with SARS-CoV-2 compared with control animals, and no pneumonia was observed in vaccinated rhesus macaques. Importantly, no evidence of immune-enhanced disease following viral challenge in vaccinated animals was observed. ChAdOx1 nCoV-19 is currently under investigation in a phase I clinical trial. Safety, immunogenicity and efficacy against symptomatic PCR-positive COVID-19 disease will now be assessed in randomised controlled human clinical trials.", "qid": 50, "docid": "uexahhdr", "rank": 79, "score": 0.8439944982528687}, {"content": "Title: D614G mutation of SARS-CoV-2 spike protein enhances viral infectivity Content: Coronavirus disease 2019 (COVID-19) is caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). The spike (S) protein that mediates SARS-CoV-2 entry into host cells is a major target for vaccines and therapeutics. Thus, insights into its sequence variations are key to understanding the infection and antigenicity of SARS-CoV-2. A dominant mutational variant at position 614 of the S protein (aspartate to glycine, D614G mutation) was observed in the SARS-CoV-2 genome sequence obtained from the Nextstrain database. Using a pseudovirus-based assay, we identified that S-D614 and S-G614 protein pseudotyped viruses share a common receptor, human angiotensin-converting enzyme 2 (ACE2), which could be blocked by recombinant ACE2 with the fused Fc region of human IgG1. However, S-D614 and S-G614 protein demonstrated functional differences. First, S-G614 protein could be cleaved by serine protease elastase-2 more efficiently. Second, S-G614 pseudovirus infected 293T-ACE2 cells significantly more efficiently than did the S-D614 pseudovirus, especially in the presence of elastase-2. Third, an elastase inhibitor approved for clinical use blocked elastase-enhanced S-G614 pseudovirus infection. Moreover, 93% (65/70) convalescent sera from patients with COVID-19 could neutralize both S-D614 and S-G614 pseudoviruses with comparable efficiencies, but about 7% (5/70) convalescent sera showed reduced neutralizing activity against the S-G614 pseudovirus. These findings have important implications for SARS-CoV-2 transmission and immune interventions.", "qid": 50, "docid": "nd2hfja7", "rank": 80, "score": 0.8439131379127502}, {"content": "Title: [Theoretical prediction of the antigenic epitopes of severe acute respiratory syndrome (SARS-CoV) proteins and evaluation of their diagnostic value]. Content: Analysis of the sequence of a number of proteins of the virus causing severe acute respiratory syndrome (SARS-CoV) was used to theoretically predict antigenic epitopes. Nine sequences, encoding for the predicted epitopes in spike, nucleocapside, and membranous SARS CoV proteins, were synthesized by polymyrase chain reaction and cloned into the pGEX 4-T2 vector. The resultant plasmids were expressed in the E. coil cells and purified by glutathione-Sepharose affinity chromatography.", "qid": 50, "docid": "mllzgvdq", "rank": 81, "score": 0.8438751697540283}, {"content": "Title: Could an endo-lysosomal ion channel be the Achilles heel of SARS-CoV2? Content: The ongoing SARS-CoV2 outbreak has developed into a global pandemic. Despite previous outbreaks of SARS-CoV and the related MERS-CoV in recent years, neither a vaccine nor any other medication for an effective treatment are currently available. Endo-lysosomal two-pore cation channels have now emerged as potential novel targets for SARS-CoV treatment.", "qid": 50, "docid": "nbmbh34l", "rank": 82, "score": 0.8437947630882263}, {"content": "Title: Identification of SARS-CoV-2 Vaccine Epitopes Predicted to Induce Long-term Population-Scale Immunity Content: Summary Here we propose a SARS-CoV-2 vaccine design concept based on identification of highly conserved regions of the viral genome and newly acquired adaptations, both predicted to generate epitopes presented on MHC class I and II across the vast majority of the population. We further prioritize genomic regions that generate highly dissimilar peptides from the human proteome, and are also predicted to produce B cell epitopes. We propose sixty-five 33mer peptide sequences, a subset of which can be tested using DNA or mRNA delivery strategies. These include peptides 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 newly evolved furin cleavage site thought to increase membrane fusion. Validation and implementation of this vaccine concept could specifically target specific vulnerabilities of SARS-CoV-2 and should engage a robust adaptive immune response in the vast majority of the population.", "qid": 50, "docid": "4ab3d00h", "rank": 83, "score": 0.8437507152557373}, {"content": "Title: Prospects of Replication-Deficient Adenovirus Based Vaccine Development against SARS-CoV-2 Content: The current appearance of the new SARS coronavirus 2 (SARS-CoV-2) and it quickly spreading across the world poses a global health emergency. The serious outbreak position is affecting people worldwide and requires rapid measures to be taken by healthcare systems and governments. Vaccinations represent the most effective strategy to prevent the epidemic of the virus and to further reduce morbidity and mortality with long-lasting effects. Nevertheless, currently there are no licensed vaccines for the novel coronaviruses. Researchers and clinicians from all over the world are advancing the development of a vaccine against novel human SARS-CoV-2 using various approaches. Herein, we aim to present and discuss the progress and prospects in the field of vaccine research towards SARS-CoV-2 using adenovirus (AdV) replication deficient-based strategies, with a comprehension that may support research and combat this recent world health emergency.", "qid": 50, "docid": "cofi4cue", "rank": 84, "score": 0.843411386013031}, {"content": "Title: Prospects of Replication-Deficient Adenovirus Based Vaccine Development against SARS-CoV-2. Content: The current appearance of the new SARS coronavirus 2 (SARS-CoV-2) and it quickly spreading across the world poses a global health emergency. The serious outbreak position is affecting people worldwide and requires rapid measures to be taken by healthcare systems and governments. Vaccinations represent the most effective strategy to prevent the epidemic of the virus and to further reduce morbidity and mortality with long-lasting effects. Nevertheless, currently there are no licensed vaccines for the novel coronaviruses. Researchers and clinicians from all over the world are advancing the development of a vaccine against novel human SARS-CoV-2 using various approaches. Herein, we aim to present and discuss the progress and prospects in the field of vaccine research towards SARS-CoV-2 using adenovirus (AdV) replication deficient-based strategies, with a comprehension that may support research and combat this recent world health emergency.", "qid": 50, "docid": "gw6po8qg", "rank": 85, "score": 0.8434113264083862}, {"content": "Title: SARS-CoV-2 Infection and the Liver Content: A novel strain of coronoviridae (SARS-CoV-2) was reported in Wuhan China in December 2019. Initially, infection presented with a broad spectrum of symptoms which typically included muscle aches, fever, dry cough, and shortness of breath. SARS-CoV-2 enters cells via ACE2 receptors which are abundant throughout the respiratory tract. However, there is evidence that these receptors are abundant throughout the body, and just as abundant in cholangiocytes as alveolar cells, posing the question of possible direct liver injury. While liver enzymes and function tests do seem to be deranged in some patients, it is questionable if the injury is due to direct viral damage, drug-induced liver injury, hypoxia, or microthromboses. Likely, the injury is multifactoral, and management of infected patients with pre-existing liver disease should be taken into consideration. Ultimately, a vaccine is needed to aid in reducing cases of SARS-CoV-2 and providing immunity to the general population. However, while considering the types of vaccines available, safety concerns, particularly of RNA- or DNA-based vaccines, need to be addressed.", "qid": 50, "docid": "w3z7mxu7", "rank": 86, "score": 0.8432801365852356}, {"content": "Title: Structure, Function, and Antigenicity of the SARS-CoV-2 Spike Glycoprotein Content: The emergence of SARS-CoV-2 has resulted in >90,000 infections and >3,000 deaths. Coronavirus spike (S) glycoproteins promote entry into cells and are the main target of antibodies. We show that SARS-CoV-2 S uses ACE2 to enter cells and that the receptor-binding domains of SARS-CoV-2 S and SARS-CoV S bind with similar affinities to human ACE2, correlating with the efficient spread of SARS-CoV-2 among humans. We found that the SARS-CoV-2 S glycoprotein harbors a furin cleavage site at the boundary between the S1/S2 subunits, which is processed during biogenesis and sets this virus apart from SARS-CoV and SARS-related CoVs. We determined cryo-EM structures of the SARS-CoV-2 S ectodomain trimer, providing a blueprint for the design of vaccines and inhibitors of viral entry. Finally, we demonstrate that SARS-CoV S murine polyclonal antibodies potently inhibited SARS-CoV-2 S mediated entry into cells, indicating that cross-neutralizing antibodies targeting conserved S epitopes can be elicited upon vaccination.", "qid": 50, "docid": "im2np7s1", "rank": 87, "score": 0.8430957198143005}, {"content": "Title: How did we get here? Short history of COVID-19 and other coronavirus-related epidemics Content: The COVID-19 epidemic was not the first coronavirus epidemic of this century and represents one of the increasing number of zoonoses from wildlife to impact global health. SARS CoV-2, the virus causing the COVID-19 epidemic is distinct from, but closely resembles SARS CoV-1, which was responsible for the severe acute respiratory syndrome (SARS) outbreak in 2002. SARS CoV-1 and 2 share almost 80% of genetic sequences and use the same host cell receptor to initiate viral infection. However, SARS predominantly affected individuals in close contact with infected animals and health care workers. In contrast, CoV-2 exhibits robust person to person spread, most likely by means of asymptomatic carriers, which has resulted in greater spread of disease, overall morbidity and mortality, despite its lesser virulence. We review recent coronavirus-related epidemics and distinguish clinical and molecular features of CoV-2, the causative agent for COVID-19, and review the current status of vaccine trials.", "qid": 50, "docid": "j5j3hxxw", "rank": 88, "score": 0.8430494070053101}, {"content": "Title: Structure, Function, and Antigenicity of the SARS-CoV-2 Spike Glycoprotein Content: The emergence of SARS-CoV-2 has resulted in >90,000 infections and >3,000 deaths. Coronavirus spike (S) glycoproteins promote entry into cells and are the main target of antibodies. We show that SARS-CoV-2 S uses ACE2 to enter cells and that the receptor-binding domains of SARS-CoV-2 S and SARS-CoV S bind with similar affinities to human ACE2, correlating with the efficient spread of SARS-CoV-2 among humans. We found that the SARS-CoV-2 S glycoprotein harbors a furin cleavage site at the boundary between the S(1)/S(2) subunits, which is processed during biogenesis and sets this virus apart from SARS-CoV and SARS-related CoVs. We determined cryo-EM structures of the SARS-CoV-2 S ectodomain trimer, providing a blueprint for the design of vaccines and inhibitors of viral entry. Finally, we demonstrate that SARS-CoV S murine polyclonal antibodies potently inhibited SARS-CoV-2 S mediated entry into cells, indicating that cross-neutralizing antibodies targeting conserved S epitopes can be elicited upon vaccination.", "qid": 50, "docid": "trlni6iq", "rank": 89, "score": 0.8428442478179932}, {"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": 50, "docid": "wzv8n34v", "rank": 90, "score": 0.8424299955368042}, {"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": 91, "score": 0.8420734405517578}, {"content": "Title: The architecture of SARS-CoV-2 transcriptome Content: SARS-CoV-2 is a betacoronavirus that is responsible for the COVID-19 pandemic. The genome of SARS-CoV-2 was reported recently, but its transcriptomic architecture is unknown. Utilizing two complementary sequencing techniques, we here present a high-resolution map of the SARS-CoV-2 transcriptome and epitranscriptome. DNA nanoball sequencing shows that the transcriptome is highly complex owing to numerous recombination events, both canonical and noncanonical. In addition to the genomic RNA and subgenomic RNAs common in all coronaviruses, SARS-CoV-2 produces a large number of transcripts encoding unknown ORFs with fusion, deletion, and/or frameshift. Using nanopore direct RNA sequencing, we further find at least 41 RNA modification sites on viral transcripts, with the most frequent motif being AAGAA. Modified RNAs have shorter poly(A) tails than unmodified RNAs, suggesting a link between the internal modification and the 3\u2032 tail. Functional investigation of the unknown ORFs and RNA modifications discovered in this study will open new directions to our understanding of the life cycle and pathogenicity of SARS-CoV-2. Highlights We provide a high-resolution map of SARS-CoV-2 transcriptome and epitranscriptome using nanopore direct RNA sequencing and DNA nanoball sequencing. The transcriptome is highly complex owing to numerous recombination events, both canonical and noncanonical. In addition to the genomic and subgenomic RNAs common in all coronaviruses, SARS-CoV-2 produces transcripts encoding unknown ORFs. We discover at least 41 potential RNA modification sites with an AAGAA motif.", "qid": 50, "docid": "wt4pxu08", "rank": 92, "score": 0.8419660329818726}, {"content": "Title: The SARS-CoV-2 receptor-binding domain elicits a potent neutralizing response without antibody-dependent enhancement Content: The SARS-coronavirus 2 (SARS-CoV-2) spike (S) protein mediates entry of SARS-CoV-2 into cells expressing the angiotensin-converting enzyme 2 (ACE2). The S protein engages ACE2 through its receptor-binding domain (RBD), an independently folded 197-amino acid fragment of the 1273-amino acid S-protein protomer. Antibodies to the RBD domain of SARS-CoV (SARS-CoV-1), a closely related coronavirus which emerged in 2002-2003, have been shown to potently neutralize SARS-CoV-1 S-protein-mediated entry, and the presence of anti-RBD antibodies correlates with neutralization in SARS-CoV-2 convalescent sera. Here we show that immunization with the SARS-CoV-2 RBD elicits a robust neutralizing antibody response in rodents, comparable to 100 \u00b5g/ml of ACE2-Ig, a potent SARS-CoV-2 entry inhibitor. Importantly, anti-sera from immunized animals did not mediate antibody-dependent enhancement (ADE) of S-protein-mediated entry under conditions in which Zika virus ADE was readily observed. These data suggest that an RBD-based vaccine for SARS-CoV-2 could be safe and effective.", "qid": 50, "docid": "fnguelau", "rank": 93, "score": 0.8418892025947571}, {"content": "Title: Making sense of mutation: what D614G means for the COVID-19 pandemic remains unclear Content: Abstract Korber et al. (2020) found that a SARS-CoV-2 variant in the spike protein, D614G, rapidly became dominant around the world. While clinical and in vitro data suggest that D614G changes the virus phenotype, the impact of the mutation on transmission, disease, and vaccine and therapeutic development are largely unknown.", "qid": 50, "docid": "rwxhdg8r", "rank": 94, "score": 0.8418329954147339}, {"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": 95, "score": 0.8418145179748535}, {"content": "Title: SARS-CoV-2 Vaccines: Status Report Content: SARS-CoV-2, the causal agent of COVID-19, first emerged in late 2019 in China. It has since infected more than 870,000 individuals and caused more than 43,000 deaths globally. Here, we discuss therapeutic and prophylactic interventions for SARS-CoV-2 with a focus on vaccine development and its challenges. Vaccines are being rapidly developed but will likely come too late to affect the first wave of a potential pandemic. Nevertheless, critical lessons can be learned for the development of vaccines against rapidly emerging viruses. Importantly, SARS-CoV-2 vaccines will be essential to reducing morbidity and mortality if the virus establishes itself in the population.", "qid": 50, "docid": "7yq8zqxq", "rank": 96, "score": 0.8415931463241577}, {"content": "Title: Amantadine as a drug to mitigate the effects of COVID-19 Content: The SARS-CoV-2 virus has spread around the world. At this time, there is no vaccine that can help people prevent the spread of coronavirus. We are proposing amantadine as a drug that can be used to mitigate the effects of the virus. It is demonstrated by docking models how amantadine can exert its action on Coronavirus viroporin E.", "qid": 50, "docid": "l0g04qgr", "rank": 97, "score": 0.8414086103439331}, {"content": "Title: Growth, detection, quantification, and inactivation of SARS-CoV-2 Content: Severe acute respiratory syndrome coronavirus (SARS-CoV)-2 is the agent responsible for the coronavirus disease 2019 (COVID-19) global pandemic. SARS-CoV-2 is closely related to SARS-CoV, which caused the 2003 SARS outbreak but disappeared rapidly. Although numerous reagents were developed to study SARS-CoV infections, few have been applicable to evaluating SARS-CoV-2 infection and immunity. Current limitations in studying SARS-CoV-2 include few validated assays with fully replication-competent wild-type virus. We have developed protocols to propagate, quantify, and work with infectious SARS-CoV-2. Here, we describe: (1) virus stock generation, (2) RT-qPCR quantification of SARS-CoV-2 RNA; (3) detection of SARS-CoV-2 antigen by flow cytometry, (4) quantification of infectious SARS-CoV-2 by focus-forming and plaque assays; and 5) validated protocols for virus inactivation. Collectively, these methods can be adapted to a variety of experimental designs, which should accelerate our understanding of SARS-CoV-2 biology and the development of effective countermeasures against COVID-19.", "qid": 50, "docid": "ahu7lda5", "rank": 98, "score": 0.8412846326828003}, {"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": 50, "docid": "ygwdldae", "rank": 99, "score": 0.8410415649414062}, {"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": 50, "docid": "buwz6lu3", "rank": 100, "score": 0.8409094214439392}]}
{"query": "has social distancing had an impact on slowing the spread of COVID-19?", "hits": [{"content": "Title: Enacting national social distancing policies corresponds with dramatic reduction in COVID19 infection rates Content: The outbreak the SARS-CoV-2 (CoV-2) virus has resulted in over 2.5 million cases of COVID19, greatly stressing global healthcare infrastructure. Lacking medical prophylactic measures to combat disease spread, many nations have adopted social distancing policies in order to mitigate transmission of CoV-2. While mathematical models have suggested the efficacy of social distancing to curb the spread of CoV-2, there is a lack of systematic studies to quantify the real-world efficacy of these approaches. Here, we quantify the spread rate of COVID19 before and after national social distancing measures were implemented in 26 nations and compare this to the changes in COVID19 spread rate over equivalent time periods in 27 nations that did not enact social distancing policies. We find that social distancing policies significantly reduced the COVID19 spread rate. Using mixed linear regression models we estimate that social distancing policies reduced the spread of COVID19 by 66%. These data suggest that social distancing policies may be a powerful tool to prevent spread of COVID19 in real-world scenarios.", "qid": 10, "docid": "vdrd74nz", "rank": 1, "score": 0.9170806407928467}, {"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": 2, "score": 0.9145655632019043}, {"content": "Title: Social Distancing Has Merely Stabilized COVID-19 in the US Content: Social distancing measures, with varying degrees of restriction, have been imposed around the world in order to stem the spread of COVID-19. In this work we analyze the effect of current social distancing measures in the United States. We quantify the reduction in doubling rate, by state, that is associated with social distancing. We find that social distancing is associated with a statistically-significant reduction in the doubling rate for all but three states. At the same time, we do not find significant evidence that social distancing has resulted in a reduction in the number of daily confirmed cases. Instead, social distancing has merely stabilized the spread of the disease. We provide an illustration of our findings for each state, including point estimates of the effective reproduction number, R, both with and without social distancing. We also discuss the policy implications of our findings.", "qid": 10, "docid": "all7ocnd", "rank": 3, "score": 0.9091168642044067}, {"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": 4, "score": 0.9068474769592285}, {"content": "Title: Early Mandated Social Distancing is a Strong Predictor of Reduction in Highest Number of New COVID-19 cases per Day within Various Geographic Regions Content: Mandated social distancing has been globally applied to limit the spread of corona virus disease 2019 (COVID-19) from highly pathogenic severe acute respiratory syndrome (SARS) -associated coronavirus 2 (SARS-CoV-2). The benefit of this community-based intervention in limiting COVID-19 has not been proven nor quantified. We examined the effect of timing of mandated social distancing on the rate of COVID-19 in 119 geographic regions derived from 41 states within United States and 78 countries. We found that highest number of new COVID-19 cases per day per million persons was significantly associated with total number of COVID-19 cases per million persons on the day before mandated social distancing (Beta;=0.66, p<0.0001). Our findings suggest that the initiation of mandated social distancing for each doubling in number of existing COVID-19 cases would result in eventual peak with 58% higher number of COVID-19 infections per day. Subgroup analysis on those regions where the highest number of new COVID-19 cases per day have peaked increased Beta to .85 (p<0.0001). We demonstrate that initiating mandated social distancing at a 10 times smaller number of COVID-19 cases will reduce the number of daily new COVID-19 cases at peak by 80% highlighting the importance of this community-based intervention.", "qid": 10, "docid": "xcxjc3po", "rank": 5, "score": 0.9062066674232483}, {"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": 6, "score": 0.905366837978363}, {"content": "Title: Dynamics of COVID-19 under social distancing measures are driven by transmission network structure Content: In the absence of pharmaceutical interventions, social distancing is being used worldwide to curb the spread of COVID-19. The impact of these measures has been inconsistent, with some regions rapidly nearing disease elimination and others seeing delayed peaks or nearly flat epidemic curves. Here we build a stochastic epidemic model to examine the effects of COVID-19 clinical progression and transmission network structure on the outcomes of social distancing interventions. We find that the strength of within-household transmission is a critical determinant of success, governing the timing and size of the epidemic peak, the rate of decline, individual risks of infection, and the success of partial relaxation measures. The structure of residual external connections, driven by workforce participation and essential businesses, interacts to determine outcomes. These findings can improve future predictions of the timescale and efficacy of interventions needed to control similar outbreaks, and highlight the need for better quantification and control of household transmission.", "qid": 10, "docid": "v941u1t1", "rank": 7, "score": 0.9040749073028564}, {"content": "Title: Mobile phone location data reveal the effect and geographic variation of social distancing on the spread of the COVID-19 epidemic Content: The emergence of SARS-CoV-2 and the coronavirus infectious disease (COVID-19) has become a pandemic. Social (physical) distancing is a key non-pharmacologic control measure to reduce the transmission rate of SARS-COV-2, but high-level adherence is needed. Using daily travel distance and stay-at-home time derived from large-scale anonymous mobile phone location data provided by Descartes Labs and SafeGraph, we quantify the degree to which social distancing mandates have been followed in the U.S. and its effect on growth of COVID-19 cases. The correlation between the COVID-19 growth rate and travel distance decay rate and dwell time at home change rate was -0.586 (95% CI: -0.742 ~ -0.370) and 0.526 (95% CI: 0.293 ~ 0.700), respectively. Increases in state-specific doubling time of total cases ranged from 1.04 ~ 6.86 days to 3.66 ~ 30.29 days after social distancing orders were put in place, consistent with mechanistic epidemic prediction models. Social distancing mandates reduce the spread of COVID-19 when they are followed.", "qid": 10, "docid": "esa5700v", "rank": 8, "score": 0.9022261500358582}, {"content": "Title: Association between mobility patterns and COVID-19 transmission in the USA: a mathematical modelling study Content: BACKGROUND: Within 4 months of COVID-19 first being reported in the USA, it spread to every state and to more than 90% of all counties. During this period, the US COVID-19 response was highly decentralised, with stay-at-home directives issued by state and local officials, subject to varying levels of enforcement. The absence of a centralised policy and timeline combined with the complex dynamics of human mobility and the variable intensity of local outbreaks makes assessing the effect of large-scale social distancing on COVID-19 transmission in the USA a challenge. METHODS: We used daily mobility data derived from aggregated and anonymised cell (mobile) phone data, provided by Teralytics (Z\u00fcrich, Switzerland) from Jan 1 to April 20, 2020, to capture real-time trends in movement patterns for each US county, and used these data to generate a social distancing metric. We used epidemiological data to compute the COVID-19 growth rate ratio for a given county on a given day. Using these metrics, we evaluated how social distancing, measured by the relative change in mobility, affected the rate of new infections in the 25 counties in the USA with the highest number of confirmed cases on April 16, 2020, by fitting a statistical model for each county. FINDINGS: Our analysis revealed that mobility patterns are strongly correlated with decreased COVID-19 case growth rates for the most affected counties in the USA, with Pearson correlation coefficients above 0\u00b77 for 20 of the 25 counties evaluated. Additionally, the effect of changes in mobility patterns, which dropped by 35\u201363% relative to the normal conditions, on COVID-19 transmission are not likely to be perceptible for 9\u201312 days, and potentially up to 3 weeks, which is consistent with the incubation time of severe acute respiratory syndrome coronavirus 2 plus additional time for reporting. We also show evidence that behavioural changes were already underway in many US counties days to weeks before state-level or local-level stay-at-home policies were implemented, implying that individuals anticipated public health directives where social distancing was adopted, despite a mixed political message. INTERPRETATION: This study strongly supports a role of social distancing as an effective way to mitigate COVID-19 transmission in the USA. Until a COVID-19 vaccine is widely available, social distancing will remain one of the primary measures to combat disease spread, and these findings should serve to support more timely policy making around social distancing in the USA in the future. FUNDING: None.", "qid": 10, "docid": "swwrokfm", "rank": 9, "score": 0.9022139310836792}, {"content": "Title: Association between mobility patterns and COVID-19 transmission in the USA: a mathematical modelling study Content: BACKGROUND: Within 4 months of COVID-19 first being reported in the USA, it spread to every state and to more than 90% of all counties. During this period, the US COVID-19 response was highly decentralised, with stay-at-home directives issued by state and local officials, subject to varying levels of enforcement. The absence of a centralised policy and timeline combined with the complex dynamics of human mobility and the variable intensity of local outbreaks makes assessing the effect of large-scale social distancing on COVID-19 transmission in the USA a challenge. METHODS: We used daily mobility data derived from aggregated and anonymised cell (mobile) phone data, provided by Teralytics (Z\u00fcrich, Switzerland) from Jan 1 to April 20, 2020, to capture real-time trends in movement patterns for each US county, and used these data to generate a social distancing metric. We used epidemiological data to compute the COVID-19 growth rate ratio for a given county on a given day. Using these metrics, we evaluated how social distancing, measured by the relative change in mobility, affected the rate of new infections in the 25 counties in the USA with the highest number of confirmed cases on April 16, 2020, by fitting a statistical model for each county. FINDINGS: Our analysis revealed that mobility patterns are strongly correlated with decreased COVID-19 case growth rates for the most affected counties in the USA, with Pearson correlation coefficients above 0\u00b77 for 20 of the 25 counties evaluated. Additionally, the effect of changes in mobility patterns, which dropped by 35-63% relative to the normal conditions, on COVID-19 transmission are not likely to be perceptible for 9-12 days, and potentially up to 3 weeks, which is consistent with the incubation time of severe acute respiratory syndrome coronavirus 2 plus additional time for reporting. We also show evidence that behavioural changes were already underway in many US counties days to weeks before state-level or local-level stay-at-home policies were implemented, implying that individuals anticipated public health directives where social distancing was adopted, despite a mixed political message. INTERPRETATION: This study strongly supports a role of social distancing as an effective way to mitigate COVID-19 transmission in the USA. Until a COVID-19 vaccine is widely available, social distancing will remain one of the primary measures to combat disease spread, and these findings should serve to support more timely policy making around social distancing in the USA in the future. FUNDING: None.", "qid": 10, "docid": "jhavycsq", "rank": 10, "score": 0.9015647172927856}, {"content": "Title: Quantifying human mobility behavior changes in response to non-pharmaceutical interventions during the COVID-19 outbreak in the United States Content: Ever since the first case of the novel coronavirus disease (COVID-19) was confirmed in Wuhan, China, social distancing has been promoted worldwide, including the United States. It is one of the major community mitigation strategies, also known as non-pharmaceutical interventions. However, our understanding is remaining limited in how people practice social distancing. In this study, we construct a Social Distancing Index (SDI) to evaluate people's mobility pattern changes along with the spread of COVID-19. We utilize an integrated dataset of mobile device location data for the contiguous United States plus Alaska and Hawaii over a 100-day period from January 1, 2020 to April 9, 2020. The major findings are: 1) the declaration of the national emergency concerning the COVID-19 outbreak greatly encouraged social distancing and the mandatory stay-at-home orders in most states further strengthened the practice; 2) the states with more confirmed cases have taken more active and timely responses in practicing social distancing; 3) people in the states with fewer confirmed cases did not pay much attention to maintaining social distancing and some states, e.g., Wyoming, North Dakota, and Montana, already began to practice less social distancing despite the high increasing speed of confirmed cases; 4) some counties with the highest infection rates are not performing much social distancing, e.g., Randolph County and Dougherty County in Georgia, and some counties began to practice less social distancing right after the increasing speed of confirmed cases went down, e.g., in Blaine County, Idaho, which may be dangerous as well.", "qid": 10, "docid": "gwh3vc9y", "rank": 11, "score": 0.9010869264602661}, {"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": 10, "docid": "aiah8kkn", "rank": 12, "score": 0.8979419469833374}, {"content": "Title: Effects of Government Mandated Social Distancing Measures on Cumulative Incidence of COVID-19 in the United States and its Most Populated Cities Content: COVID-19, caused by the SARS-CoV-2 virus, has quickly spread throughout the world, necessitating assessment of the most effective containment methods. Very little research exists on the effects of social distancing measures on this pandemic. The purpose of this study was to examine the effects of government implemented social distancing measures on the cumulative incidence rates of COVID-19 in the United States on a state level, and in the 25 most populated cities, while adjusting for socio-demographic risk factors. The social distancing variables assessed in this study were: days to closing of non-essential business; days to stay home orders; days to restrictions on gathering, days to restaurant closings and days to school closing. Using negative binomial regression, adjusted rate ratios and 95% confidence intervals were calculated comparing two levels of a binary variable: above median value, and median value and below for days to implementing a social distancing measure. For city level data, the effects of these social distancing variables were also assessed in high (above median value) vs low (median value and below) population density cities. For the state level analysis, days to school closing was associated with cumulative incidence, with an adjusted rate ratio of 1.59 (95% CI:1.03,2.44), p=0.04 at 35 days. Some results were counterintuitive, including inverse associations between cumulative incidence and days to closure of non-essential business and restrictions on gatherings. This finding is likely due to reverse causality, where locations with slower growth rates initially chose not to implement measures, and later implemented measures when they absolutely needed to respond to increasing rates of infection. Effects of social distancing measures seemed to vary by population density in cities. Our results suggest that the effect of social distancing measures may differ between states and cities and between locations with different population densities. States and cities need individual approaches to containment of an epidemic, with an awareness of their own structure in terms of crowding and socio-economic variables. In an effort to reduce infection rates, cities may want to implement social distancing in advance of state mandates.", "qid": 10, "docid": "in3pyyue", "rank": 13, "score": 0.8974422216415405}, {"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": 14, "score": 0.8972986340522766}, {"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": 15, "score": 0.8943851590156555}, {"content": "Title: COVID-19 related social distancing measures and reduction in city mobility Content: In the absence of any pharmacological intervention, one approach to slowing the COVID-19 pandemic is reducing the contact rate in the population through social distancing. Governments the world over have instituted different measures to increase social distancing but information on their effectiveness in reducing mobility is lacking. We analyzed the mobility data from 41 cities to look at the effect of these interventions. The median mobility across cities on March 2, 2020 was 100% (IQR: 94%, 107%), which decreased to a median of 10% (IQR: 7%, 17%) on March 26, 2020. We found that the mobility decreased on average by 3.4% (95%CI: 3.3%, 3.6%) per day from March 2 through March 26. Social distancing measures decreased the mobility by an additional 23% (95%CI: 20%, 27%). Our study provides initial evidence for the reduction in mobility in cities instituting social distancing measures.", "qid": 10, "docid": "71b6ai77", "rank": 16, "score": 0.8937314748764038}, {"content": "Title: Social distancing: A non-pharmacological intervention for COVID-19 Content: Social distancing is one of the non-pharmacological measures to contain the infection of COVID-19. At this point in time, no vaccine is available to prevent the infection, no effective drugs are available to prevent and treat the disease, and none of the communities have acquired herd immunity. Various models have shown positive impact of social distancing, provided its implementation on vast majority of the population over a long period of time. Its effect is manifold. Besides flattening the curve, it impacts the political, fiscal, social, economic aspects of the society, along with socially vulnerable and economically underprivileged population. It becomes obsolete after the population develops herd immunity subsequent to widespread infection in the community, or after effective mass immunisation or specific drugs for its control, cure and prevention are available widely.", "qid": 10, "docid": "omygp8bu", "rank": 17, "score": 0.8917151093482971}, {"content": "Title: Social distancing: A non-pharmacological intervention for COVID-19. Content: Social distancing is one of the non-pharmacological measures to contain the infection of COVID-19. At this point in time, no vaccine is available to prevent the infection, no effective drugs are available to prevent and treat the disease, and none of the communities have acquired herd immunity. Various models have shown positive impact of social distancing, provided its implementation on vast majority of the population over a long period of time. Its effect is manifold. Besides flattening the curve, it impacts the political, fiscal, social, economic aspects of the society, along with socially vulnerable and economically underprivileged population. It becomes obsolete after the population develops herd immunity subsequent to widespread infection in the community, or after effective mass immunisation or specific drugs for its control, cure and prevention are available widely.", "qid": 10, "docid": "3cke9x69", "rank": 18, "score": 0.8917151093482971}, {"content": "Title: Dynamic coupling between the COVID epidemic timeline and the behavioral response to PAUSE in New York State counties Content: By many expert opinions, the COVID 19 epidemic is still much in its developing stages. While awaiting for effective clinical answers for the outbreak, the best approach remains that of social distancing. This raises a few crucial questions related to the extent to which social distancing measures were (1) well timed, (2) necessary and (3) efficient. By investigating correlations between epidemic measures such as daily infection rate, and social mobility measures (as reported by Apple and Google), our study aims to establish whether data identifies social distancing measures as a primary player in controlling the outbreak in New York State.", "qid": 10, "docid": "k8eqzr6w", "rank": 19, "score": 0.8908005952835083}, {"content": "Title: A Decision Analytic Approach for Social Distancing Policies During the COVID-19 Pandemic Content: The COVID-19 pandemic has become a crucial public health issue in many countries including the United States. In the absence of the right vaccine strain and sufficient antiviral stockpiles on hand, nonpharmaceutical interventions have become valuable public health tools at the early stages of the pandemic and they are employed by many countries across the globe. These interventions are designed to increase social distancing between individuals to reduce the transmission of the virus and eventually dampen the burden on the healthcare system. The virus transmissibility is a function of the average number of contacts individuals have in their communities and it is highly dependent on population density and daily mobility patterns, along with other social factors. These show significant variation across the United States. In this article, we study the effectiveness of social distancing measures in communities with different population density. Specifically, first we show how the empirical estimation of reproduction number differs for two completely different states, thus the experience of the COVID-19 outbreak is drastically different, suggesting different outbreak growth rates in practice. Second, we develop an age-structured compartmental model for simulating the disease spread to demonstrate the variation in the observed outbreak characteristics. We find that early trigger and late trigger options present a trade-off between the peak magnitude and the overall death toll of the outbreak which may also vary across different populations.", "qid": 10, "docid": "baq47reg", "rank": 20, "score": 0.8895190954208374}, {"content": "Title: The differential impact of physical distancing strategies on social contacts relevant for the spread of COVID-19 Content: Physical distancing measures are intended to mitigate the spread of COVID-19. However, the impact these measures have on social contact and disease transmission patterns remains unclear. We ran the first comparative contact survey (N=53,708) across eight countries (Belgium, France, Germany, Italy, Netherlands, Spain, United Kingdom, United States) for the period March 13 - April 13, 2020. Our results show that social contact numbers mainly decreased after governments issued physical distancing guidelines rather than after announcing national lockdown measures. Compared to pre-COVID levels, social contact numbers decreased by 48% - 85% across countries. Except in Italy, these reductions were smaller than those observed in Wuhan (China). However, they sufficed to bring the R0 below one in almost every context considered. Finally, in all countries studied, the numbers of contacts decreased more rapidly among older people than among younger people, indicating higher levels of protection for groups at greater risk.", "qid": 10, "docid": "u9fmokcf", "rank": 21, "score": 0.8892627954483032}, {"content": "Title: How long does a lockdown need to be? Content: Social distancing, often in the form of lockdown, has been adopted by many countries as a way to contrast the spreading of COVID-19. We discuss the temporal aspects of social distancing in contrasting an epidemic diffusion. We argue that a strategy based uniquely on social distancing requires to maintain the relative measures for a very long time, while a more articulate strategy, which also uses early detection and prompt isolation, can be both more efficient on reducing the epidemic peak and allow to relax the social distancing measures after a much shorter time. We consider in more detail the situation in Italy, simulating the effect of different strategies through a recently introduced SIR-type epidemiological model. The short answer to the question in the title is:\"it depends on what else you do\".", "qid": 10, "docid": "gilpb3oy", "rank": 22, "score": 0.8885610103607178}, {"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": 23, "score": 0.8884575963020325}, {"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": 24, "score": 0.8874253630638123}, {"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": 25, "score": 0.8872627019882202}, {"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": 26, "score": 0.887237548828125}, {"content": "Title: Social Distancing is Effective at Mitigating COVID-19 Transmission in the United States Content: COVID-19 is present in every state and over 90 percent of all counties in the United States. Decentralized government efforts to reduce spread, combined with the complex dynamics of human mobility and the variable intensity of local outbreaks makes assessing the effect of large-scale social distancing on COVID-19 transmission in the U.S. is a challenge. We generate a novel metric to represent social distancing behavior derived from mobile phone data, and examine its relationship with COVID-19 case reports at the county level. Our analysis reveals that social distancing is strongly correlated with decreased COVID-19 case growth rates for the 25 most affected counties in the United States, with a lag period consistent with the incubation time of SARS-CoV-2. We also demonstrate evidence that social distancing was already under way in many U.S. counties before county and state-level policies were implemented. This study strongly supports social distancing as an effective way to mitigate COVID-19 transmission in the United States.", "qid": 10, "docid": "noyx53ej", "rank": 27, "score": 0.8869234919548035}, {"content": "Title: An analysis of the ethics of lockdown in India Content: Over the past 6 months, coronavirus-induced disease (COVID-19) has spread across 212 countries, affecting millions of people. As it has no known cure, social distancing is highly recommended for prevention of spread of the disease. Here, we have described the impact of the social distancing measures implemented by the Government of India on various sections of the society, especially the vulnerable sections. Furthermore, we have presented an analysis of these measures, according to the World Health Organization\u00b4s Guidance for Managing Ethical Issues in Infectious Disease Outbreaks (2016); we have also applied principles, as applicable, from the Indian Council of Medical Research\u2019s National Ethical Guidelines for Biomedical and Health Research Involving Human Participants (2017). Finally, we have presented several measures that should have been adopted before and in addition to implementing the lockdown to improve its effectiveness.", "qid": 10, "docid": "qipttim3", "rank": 28, "score": 0.8866472244262695}, {"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": 29, "score": 0.8865129947662354}, {"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 of 2020 to contain the spread of novel coronavirus disease 2019 (COVID-19). These included large event bans, school closures, closures of entertainment venues, gyms, bars, and restaurant dining areas, and shelter-in-place orders (SIPOs). 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 by 5.4 percentage points after 1-5 days, 6.8 after 6-10 days, 8.2 after 11-15 days, and 9.1 after 16-20 days. Holding the amount of voluntary social distancing constant, these results imply 10 times greater spread by April 27 without SIPOs (10 million cases) and more than 35 times greater spread without any of the four measures (35 million). Our paper illustrates the potential danger of exponential spread in the absence of interventions, providing relevant information to strategies for restarting economic activity. [Editor's Note: This Fast Track Ahead Of Print article is the accepted version of the peer-reviewed manuscript. The final edited version will appear in an upcoming issue of Health Affairs.].", "qid": 10, "docid": "h6ngg7ea", "rank": 30, "score": 0.8860172033309937}, {"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 of 2020 to contain the spread of novel coronavirus disease 2019 (COVID-19). These included large event bans, school closures, closures of entertainment venues, gyms, bars, and restaurant dining areas, and shelter-in-place orders (SIPOs). 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 by 5.4 percentage points after 1-5 days, 6.8 after 6-10 days, 8.2 after 11-15 days, and 9.1 after 16-20 days. Holding the amount of voluntary social distancing constant, these results imply 10 times greater spread by April 27 without SIPOs (10 million cases) and more than 35 times greater spread without any of the four measures (35 million). Our paper illustrates the potential danger of exponential spread in the absence of interventions, providing relevant information to strategies for restarting economic activity. [Editor's Note: This Fast Track Ahead Of Print article is the accepted version of the peer-reviewed manuscript. The final edited version will appear in an upcoming issue of Health Affairs.].", "qid": 10, "docid": "ereh4ub8", "rank": 31, "score": 0.8860172033309937}, {"content": "Title: Association of County-Level Socioeconomic and Political Characteristics with Engagement in Social Distancing for COVID-19 Content: The U.S. is the epicenter of the coronavirus disease 2019 (COVID-19) pandemic. In response, governments have implemented measures to slow transmission through \"social distancing.\" However, the practice of social distancing may depend on prevailing socioeconomic conditions and beliefs. Using 15-17 million anonymized cell phone records, we find that lower per capita income and greater Republican orientation were associated with significantly reduced social distancing among U.S. counties. These associations persisted after adjusting for county-level sociodemographic and labor market characteristics as well as state fixed effects. These results may help policymakers and health professionals identify communities that are most vulnerable to transmission and direct resources and communications accordingly.", "qid": 10, "docid": "lb0fd7ig", "rank": 32, "score": 0.8855667114257812}, {"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": 10, "docid": "zkjiixuq", "rank": 33, "score": 0.8851474523544312}, {"content": "Title: Effect of the social distancing measures on the spread of COVID-19 in 10 highly infected countries Content: Abstract From the end of 2019, an unprecedented novel coronavirus, which was named COVID-19 by the World Health Organization (WHO) emerged from Wuhan city, China. Despite rigorous global containment and quarantine efforts, the incidence of COVID-19 has continued to rise, with over 4 million confirmed-cases and over 300,000 deaths worldwide until mid-May. This study aims to present the effect of the promulgation of social distancing measures on the spread of COVID-19 in the cases of 10 highly infected countries. The authors focus on the statistics of the COVID-19 confirmed-cases and deaths in 10 highly infected countries, including The U.S., Spain, Italy, The U.K., France, Germany, Russia, Turkey, Iran and China, and the response to the pandemic of these countries in the period from January 11 to May 2, 2020. The relationships between the social distancing measures and the statistics of COVID-19 confirmed-cases and deaths were analyzed in order to elucidate the effectiveness of the social distancing measures on the spread of COVID-19 in 10 highly infected countries. The results showed it took1\u20134 weeks since the highest level of social distancing measures promulgation until the daily confirmed-cases and deaths showed signs of decreasing. The effectiveness of the social distancing measures on the spread of COVID-19 was different between the 10 focused countries. This variation is due to the difference in the levels of promulgated social distancing measures, as well as the difference in the COVID-19 spread situation at the time of promulgation between the countries.", "qid": 10, "docid": "mhmno6vb", "rank": 34, "score": 0.8849946856498718}, {"content": "Title: The Benefits and Costs of Social Distancing in Rich and Poor Countries Content: Social distancing is the primary policy prescription for combating the COVID-19 pandemic, and has been widely adopted in Europe and North America. We estimate the value of disease avoidance using an epidemiological model that projects the spread of COVID-19 across rich and poor countries. Social distancing measures that\"flatten the curve\"of the disease to bring demand within the capacity of healthcare systems are predicted to save many lives in high-income countries, such that practically any economic cost is worth bearing. These social distancing policies are estimated to be less effective in poor countries with younger populations less susceptible to COVID-19, and more limited healthcare systems, which were overwhelmed before the pandemic. Moreover, social distancing lowers disease risk by limiting people's economic opportunities. Poorer people are less willing to make those economic sacrifices. They place relatively greater value on their livelihood concerns compared to contracting COVID-19. Not only are the epidemiological and economic benefits of social distancing much smaller in poorer countries, such policies may exact a heavy toll on the poorest and most vulnerable. Workers in the informal sector lack the resources and social protections to isolate themselves and sacrifice economic opportunities until the virus passes. By limiting their ability to earn a living, social distancing can lead to an increase in hunger, deprivation, and related mortality and morbidity. Rather than a blanket adoption of social distancing measures, we advocate for the exploration of alternative harm-reduction strategies, including universal mask adoption and increased hygiene measures.", "qid": 10, "docid": "4u7qtoz7", "rank": 35, "score": 0.8847941160202026}, {"content": "Title: On the benefits of flattening the curve: A perspective() Content: The many variations on a graphic illustrating the impact of non-pharmaceutical measures to mitigate pandemic influenza that have appeared in recent news reports about COVID-19 suggest a need to better explain the mechanism by which social distancing reduces the spread of infectious diseases. And some reports understate one benefit of reducing the frequency or proximity of interpersonal encounters, a reduction in the total number of infections. In hopes that understanding will increase compliance, we describe how social distancing a) reduces the peak incidence of infections, b) delays the occurrence of this peak, and c) reduces the total number of infections during epidemics. In view of the extraordinary efforts underway to identify existing medications that are active against SARS-CoV-2 and to develop new antiviral drugs, vaccines and antibody therapies, any of which may have community-level effects, we also describe how pharmaceutical interventions affect transmission.", "qid": 10, "docid": "zukjh1hr", "rank": 36, "score": 0.8840759992599487}, {"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": 37, "score": 0.8838372826576233}, {"content": "Title: Social Distancing as a Health Behavior: County-Level Movement in the United States During the COVID-19 Pandemic Is Associated with Conventional Health Behaviors Content: BACKGROUND: Social distancing-when people limit close contact with others outside their household-is a primary intervention available to combat the COVID-19 pandemic. The importance of social distancing is unlikely to change until effective treatments or vaccines become widely available. However, relatively little is known about how best to promote social distancing. Applying knowledge from social and behavioral research on conventional health behaviors (e.g., smoking, physical activity) to support public health efforts and research on social distancing is promising, but empirical evidence supporting this approach is needed. PURPOSE: We examined whether one type of social distancing behavior-reduced movement outside the home-was associated with conventional health behaviors. METHOD: We examined the association between GPS-derived movement behavior in 2,858 counties in USA from March 1 to April 7, 2020 and the prevalence of county-level indicators influenced by residents' conventional health behaviors. RESULTS: Changes in movement were associated with conventional health behaviors, and the magnitude of these associations were similar to the associations among the conventional health behaviors. Counties with healthier behaviors-particularly less obesity and greater physical activity-evidenced greater reduction in movement outside the home during the initial phases of the pandemic in the USA. CONCLUSIONS: Social distancing, in the form of reduced movement outside the home, is associated with conventional health behaviors. Existing scientific literature on health behavior and health behavior change can be more confidently used to promote social distancing behaviors during the COVID-19 pandemic.", "qid": 10, "docid": "cm41gpx1", "rank": 38, "score": 0.8837554454803467}, {"content": "Title: A simplified model for expected development of the SARS-CoV-2 (Corona) spread in Germany and US after social distancing Content: Widespread opinions and discussion exist regarding the efficiency of social distancing after crucial spread of the SARS-CoV-2 virus during the actual Covid-19 pandemic. While Germany has released a federal law that prohibits any type of direct contact for more than 2 people other countries including the US released curfews. People are now wondering whether these measures are helpful to stop or hamper the Covid-19 pandemic and to limit the spread of the new corona virus. A quantitative statement on this question depends on many parameters that are difficult to grasp mathematically and cannot therefore be made conclusively (they include consistent adherence to the measures decided, the estimated number of unreported cases, the possible limitation by test capacities, possible mutations of the virus, etc ...). However, it turns out that a reduction in the actual daily new infection rate (actual daily growth rate of reported cases, in short: infection rate) from the current value of 30-35% in the US to 10% would be extremely effective in stopping the spread of the virus. The severe restrictions in Germany which closed any public events, schools and universities a week ago might already have contributed to a reduction of the growth rate of reported cases below 30%.", "qid": 10, "docid": "0o79m08j", "rank": 39, "score": 0.8834303617477417}, {"content": "Title: The science of social distancing and total lock down: Does it work? whom does it benefit? Content: COVID-19 is spiralling like wild fire and has caused a global mayhem. Many lives have already been lost, and the global economy is at stake. In the absence of vaccine, social distancing and total lock down is the current mainstay in efforts to mitigate and flatten the epidemic curves. Several countries across the globe are currently implementing social distancing and total lock downs. However, what is social distancing and lock down? Does it work? Whom does it benefit? We expound on these questions and conclude that social distancing and lock down benefit the local and international community alike. Moreover, we hypothesis that evacuations may facilitate international spread of a highly contagious disease of pandemic potential.", "qid": 10, "docid": "45k6tp0b", "rank": 40, "score": 0.8832128643989563}, {"content": "Title: On the benefits of flattening the curve: A perspective Content: The many variations on a graphic illustrating the impact of non-pharmaceutical measures to mitigate pandemic influenza that have appeared in recent news reports about COVID-19 suggest a need to better explain the mechanism by which social distancing reduces the spread of infectious diseases. And some reports understate one benefit of reducing the frequency or proximity of interpersonal encounters, a reduction in the total number of infections. In hopes that understanding will increase compliance, we describe how social distancing (a) reduces the peak incidence of infections, (b) delays the occurrence of this peak, and (c) reduces the total number of infections during epidemics. In view of the extraordinary efforts underway to identify existing medications that are active against SARS-CoV-2 and to develop new antiviral drugs, vaccines and antibody therapies, any of which may have community-level effects, we also describe how pharmaceutical interventions affect transmission.", "qid": 10, "docid": "883y61q5", "rank": 41, "score": 0.8831192255020142}, {"content": "Title: Effects of Population Co-location Reduction on Cross-county Transmission Risk of COVID-19 in the United States Content: The rapid spread of COVID-19 in the United States has imposed a major threat to public health, the real economy, and human well-being. With the absence of effective vaccines, the preventive actions of social distancing and travel reduction are recognized as essential non-pharmacologic approaches to control the spread of COVID-19. Prior studies demonstrated that human movement and mobility drove the spatiotemporal distribution of COVID-19 in China. Little is known, however, about the patterns and effects of co-location reduction on cross-county transmission risk of COVID-19. This study utilizes Facebook co-location data for all counties in the United States from March to early May 2020. The analysis examines the synchronicity and time lag between travel reduction and pandemic growth trajectory to evaluate the efficacy of social distancing in ceasing the population co-location probabilities, and subsequently the growth in weekly new cases. The results show that the mitigation effects of co-location reduction appear in the growth of weekly new cases with one week of delay. Furthermore, significant segregation is found among different county groups which are categorized based on numbers of cases. The results suggest that within-group co-location probabilities remain stable, and social distancing policies primarily resulted in reduced cross-group co-location probabilities (due to travel reduction from counties with large number of cases to counties with low numbers of cases). These findings could have important practical implications for local governments to inform their intervention measures for monitoring and reducing the spread of COVID-19, as well as for adoption in future pandemics. Public policy, economic forecasting, and epidemic modeling need to account for population co-location patterns in evaluating transmission risk of COVID-19 across counties.", "qid": 10, "docid": "ekw3nlw3", "rank": 42, "score": 0.882379949092865}, {"content": "Title: Effect of the social distancing measures on the spread of COVID-19 in 10 highly infected countries Content: From the end of 2019, an unprecedented novel coronavirus, which was named COVID-19 by the World Health Organization (WHO) emerged from Wuhan city, China. Despite rigorous global containment and quarantine efforts, the incidence of COVID-19 has continued to rise, with over 4 million confirmed-cases and over 300,000 deaths worldwide until mid-May. This study aims to present the effect of the promulgation of social distancing measures on the spread of COVID-19 in the cases of 10 highly infected countries. The authors focus on the statistics of the COVID-19 confirmed-cases and deaths in 10 highly infected countries, including The U.S., Spain, Italy, The U.K., France, Germany, Russia, Turkey, Iran and China, and the response to the pandemic of these countries in the period from January 11 to May 2, 2020. The relationships between the social distancing measures and the statistics of COVID-19 confirmed-cases and deaths were analyzed in order to elucidate the effectiveness of the social distancing measures on the spread of COVID-19 in 10 highly infected countries. The results showed it took1-4 weeks since the highest level of social distancing measures promulgation until the daily confirmed-cases and deaths showed signs of decreasing. The effectiveness of the social distancing measures on the spread of COVID-19 was different between the 10 focused countries. This variation is due to the difference in the levels of promulgated social distancing measures, as well as the difference in the COVID-19 spread situation at the time of promulgation between the countries.", "qid": 10, "docid": "1r8dhqi5", "rank": 43, "score": 0.8823515772819519}, {"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": 44, "score": 0.8818625211715698}, {"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": 45, "score": 0.8818625211715698}, {"content": "Title: Social Distancing as a Health Behavior: County-Level Movement in the United States During the COVID-19 Pandemic Is Associated with Conventional Health Behaviors Content: BACKGROUND: Social distancing\u2014when people limit close contact with others outside their household\u2014is a primary intervention available to combat the COVID-19 pandemic. The importance of social distancing is unlikely to change until effective treatments or vaccines become widely available. However, relatively little is known about how best to promote social distancing. Applying knowledge from social and behavioral research on conventional health behaviors (e.g., smoking, physical activity) to support public health efforts and research on social distancing is promising, but empirical evidence supporting this approach is needed. PURPOSE: We examined whether one type of social distancing behavior\u2014reduced movement outside the home\u2014was associated with conventional health behaviors. METHOD: We examined the association between GPS-derived movement behavior in 2,858 counties in USA from March 1 to April 7, 2020 and the prevalence of county-level indicators influenced by residents\u2019 conventional health behaviors. RESULTS: Changes in movement were associated with conventional health behaviors, and the magnitude of these associations were similar to the associations among the conventional health behaviors. Counties with healthier behaviors\u2014particularly less obesity and greater physical activity\u2014evidenced greater reduction in movement outside the home during the initial phases of the pandemic in the USA. CONCLUSIONS: Social distancing, in the form of reduced movement outside the home, is associated with conventional health behaviors. Existing scientific literature on health behavior and health behavior change can be more confidently used to promote social distancing behaviors during the COVID-19 pandemic.", "qid": 10, "docid": "rziqtdp0", "rank": 46, "score": 0.8817494511604309}, {"content": "Title: Impact of non-pharmaceutical interventions against COVID-19 in Europe: a quasi-experimental study Content: The current epidemic of COVID-19 is unparalleled in recent history as are the social distancing interventions that have led to a significant halt on the economic and social life of so many countries. However, there is very little empirical evidence about which social distancing measures have the most impact. We report a quasi-experimental study of the impact of various interventions for control of the outbreak. Data on case numbers and deaths were taken from the daily published figures by the European Centre for Disease Control and dates of initiation of various control strategies from the Institute of Health Metrics and Evaluation website and published sources. Our primary analyses were modelled in R using Bayesian generalised additive mixed models (GAMM). We found that closure of education facilities, prohibiting mass gatherings and closure of some non-essential businesses were associated with reduced incidence whereas stay at home orders, closure of all non-businesses and requiring the wearing of facemasks or coverings in public was not associated with any independent additional impact. Our results could help inform strategies for coming out of lockdown.", "qid": 10, "docid": "3yi44xfe", "rank": 47, "score": 0.8816976547241211}, {"content": "Title: Correcting misperceptions of exponential coronavirus growth increases support for social distancing Content: The most effective way to stem the spread of a pandemic such as coronavirus disease 2019 (COVID-19) is social distancing, but the introduction of such measures is hampered by the fact that a sizeable part of the population fails to see their need. Three studies conducted during the mass spreading of the virus in the United States toward the end of March 2020 show that this results partially from people's misperception of the virus's exponential growth in linear terms and that overcoming this bias increases support for social distancing. Study 1 shows that American participants mistakenly perceive the virus's exponential growth in linear terms (conservatives more so than liberals). Studies 2 and 3 show that instructing people to avoid the exponential growth bias significantly increases perceptions of the virus's growth and thereby increases support for social distancing. Together, these results show the importance of statistical literacy to recruit support for fighting pandemics such as the coronavirus.", "qid": 10, "docid": "7t8yzbr7", "rank": 48, "score": 0.881432294845581}, {"content": "Title: Correcting misperceptions of exponential coronavirus growth increases support for social distancing. Content: The most effective way to stem the spread of a pandemic such as coronavirus disease 2019 (COVID-19) is social distancing, but the introduction of such measures is hampered by the fact that a sizeable part of the population fails to see their need. Three studies conducted during the mass spreading of the virus in the United States toward the end of March 2020 show that this results partially from people's misperception of the virus's exponential growth in linear terms and that overcoming this bias increases support for social distancing. Study 1 shows that American participants mistakenly perceive the virus's exponential growth in linear terms (conservatives more so than liberals). Studies 2 and 3 show that instructing people to avoid the exponential growth bias significantly increases perceptions of the virus's growth and thereby increases support for social distancing. Together, these results show the importance of statistical literacy to recruit support for fighting pandemics such as the coronavirus.", "qid": 10, "docid": "c84lpxrn", "rank": 49, "score": 0.881432294845581}, {"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": 10, "docid": "tnecig63", "rank": 50, "score": 0.8813539743423462}, {"content": "Title: Effects of social distancing on the spreading of COVID-19 inferred from mobile phone data Content: A better understanding of how the COVID-19 epidemic responds to social distancing efforts is required for the control of future outbreaks and to calibrate partial lock-downs. We present quantitative relationships between key parameters characterizing the COVID-19 epidemiology and social distancing efforts of nine selected European countries. Epidemiological parameters were extracted from the number of daily deaths data, while mitigation efforts are estimated from mobile phone tracking data. The decrease of the basic reproductive number (R0) as well as the duration of the initial exponential expansion phase of the epidemic strongly correlates with the magnitude of mobility reduction. Utilizing these relationships we decipher the relative impact of the timing and the extent of social distancing on the total death burden of the epidemic.", "qid": 10, "docid": "gz18sxzc", "rank": 51, "score": 0.8806816935539246}, {"content": "Title: Diminishing Marginal Benefit of Social Distancing in Balancing COVID-19 Medical Demand-to-Supply Content: Social distancing has been adopted as a non-pharmaceutical intervention to prevent the COVID-19 pandemic from overwhelming the medical resources across the United States (US). The catastrophic socio-economic impacts of this intervention could outweigh its benefits if the timing and duration of implementation are left uncontrolled and ill-strategized. Here we investigate the dynamics of social distancing on age-stratified US population and benchmark its effectiveness in reducing the burden on hospital and ICU beds. Our findings highlight the diminishing marginal benefit of social distancing, characterized by a linear decrease in medical demands against an exponentially increasing social distancing duration. We determine an optimal intermittent social-to-no-distancing ratio of 5:1 corresponding to ~80% reduction in healthcare demands; beyond this ratio, benefit of social distancing diminishes to a negligible level. COVID-19 Medical Forecast: https://eece.wustl.edu/chakrabarty-group/covid/", "qid": 10, "docid": "rzh7ja6a", "rank": 52, "score": 0.8804550766944885}, {"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": 53, "score": 0.8796154260635376}, {"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": 10, "docid": "vnc1iay1", "rank": 54, "score": 0.8780834674835205}, {"content": "Title: Analyzing situational awareness through public opinion to predict adoption of social distancing amid pandemic COVID-19 Content: COVID-19 pandemic has affected over 100 countries in a matter of weeks. People's response toward social distancing in the emerging pandemic is uncertain. In this study, we evaluated the influence of information (formal and informal) sources on situational awareness of the public for adopting health-protective behaviors such as social distancing. For this purpose, a questionnaire-based survey was conducted. The hypothesis proposed suggests that adoption of social distancing practices is an outcome of situational awareness which is achieved by the information sources. Results suggest that information sources, formal (P = .001) and informal (P = 0.007) were found to be significantly related to perceived understanding. Findings also indicate that social distancing is significantly influenced by situational awareness, P = .000. It can, therefore, be concluded that an increase in situational awareness in times of public health crisis using formal information sources can significantly increase the adoption of protective health behavior and in turn contain the spread of infectious diseases.", "qid": 10, "docid": "e8gga4oh", "rank": 55, "score": 0.8769869804382324}, {"content": "Title: Pandemic Politics: Timing State-Level Social Distancing Responses to COVID-19 Content: Social distancing policies are critical but economically painful measures to flatten the curve against emergent infectious diseases. As the novel coronavirus that causes COVID-19 spread throughout the United States in early 2020, the federal government issued social distancing recommendations but left to the states the most difficult and consequential decisions restricting behavior, such as canceling events, closing schools and businesses, and issuing stay-at-home orders. We present an original dataset of state-level social distancing policy responses to the epidemic and explore how political partisanship, COVID-19 caseload, and policy diffusion explain the timing of governors' decisions to mandate social distancing. An event history analysis of five social distancing policies across all fifty states reveals the most important predictors are political: all else equal, Republican governors and governors from states with more Trump supporters were slower to adopt social distancing policies. These delays are likely to produce significant, on-going harm to public health.", "qid": 10, "docid": "g8lsrojl", "rank": 56, "score": 0.8769473433494568}, {"content": "Title: Targeted adaptive isolation strategy for COVID-19 pandemic Content: We investigate the effects of social distancing in controlling the impact of the COVID-19 epidemic using a simple susceptible-infected-removed epidemic model. We show that an alternative or complementary approach based on targeted isolation of the vulnerable sub-population may provide a more efficient and robust strategy at a lower economic and social cost within a shorter timeframe resulting in a collectively immune population.", "qid": 10, "docid": "qpufvt3o", "rank": 57, "score": 0.8767021298408508}, {"content": "Title: Targeted adaptive isolation strategy for Covid-19 pandemic Content: We investigate the effects of social distancing in controlling the impact of the COVID-19 epidemic using a simple susceptible-infected-removed epidemic model. We show that an alternative or complementary approach based on targeted isolation of the vulnerable sub-population may provide a more efficient and robust strategy at a lower economic and social cost within a shorter timeframe resulting in a collectively immune population.", "qid": 10, "docid": "80d9p4j8", "rank": 58, "score": 0.876702070236206}, {"content": "Title: Social distancing, population density, and spread of COVID-19 in England: a longitudinal study Content: BACKGROUND: The UK government introduced social distancing measures between 16-22 March 2020, aiming to slow down transmission of COVID-19. AIM: To explore the spreading of COVID-19 in relation to population density after the introduction of social distancing measures. DESIGN & SETTING: Longitudinal design with 5-weekly COVID-19 incidence rates per 100 000 people for 149 English Upper Tier Local Authorities (UTLAs), between 16 March and 19 April 2020. METHOD: Multivariable multilevel model to analyse weekly incidence rates per 100 000 people; time was level-1 unit and UTLA level-2 unit. Population density was divided into quartiles. The model included an interaction between week and population density. Potential confounders were percentage aged &#8805;65, percentage non-white British, and percentage in two highest classes of the National Statistics Socioeconomic Classification. Co-variates were male life expectancy at birth, and COVID-19 prevalence rate per 100 000 people on March 15. Confounders and co-variates were standardised around the mean. RESULTS: Incidence rates per 100 000 people peaked in the week of March 30-April 5, showing higher adjusted incidence rate per 100 000 people (46.2; 95% confidence interval [CI] = 40.6 to 51.8) in most densely populated ULTAs (quartile 4) than in less densely populated ULTAs (quartile 1: 33.3, 95% CI = 27.4 to 37.2; quartile 2: 35.9, 95% CI = 31.6 to 40.1). Thereafter, incidence rate dropped in the most densely populated ULTAs resulting in rate of 22.4 (95% CI = 16.9 to 28.0) in the week of April 13-19; this was lower than in quartiles 1, 2, and 3, respectively 31.4 (95% CI = 26.5 to 36.3), 34.2 (95% CI = 29.9 to 38.5), and 43.2 (95% CI = 39.0 to 47.4). CONCLUSION: After the introduction of social distancing measures, the incidence rates per 100 000 people dropped stronger in most densely populated ULTAs.", "qid": 10, "docid": "lezcbgx9", "rank": 59, "score": 0.8765042424201965}, {"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": 60, "score": 0.876488208770752}, {"content": "Title: Impacts of State-Level Policies on Social Distancing in the United States Using Aggregated Mobility Data during the COVID-19 Pandemic Content: Social distancing has emerged as the primary mitigation strategy to combat the COVID-19 pandemic in the United States. However, large-scale evaluation of the public's response to social distancing campaigns has been lacking. We used anonymized and aggregated mobility data from Google Location History users to estimate the impact of social distancing recommendations on bulk mobility among users who have opted into this service. We found that state-of-emergency declarations resulted in approximately a 10% reduction in time spent away from places of residence. Implementation of one or more social distancing policies resulted in an additional 25% reduction in mobility the following week. Subsequent shelter-in-place mandates provided an additional 29% reduction. Our findings provide evidence that state-wide mandates are effective in promoting social distancing within this study group.", "qid": 10, "docid": "f6rx4h3r", "rank": 61, "score": 0.8763315081596375}, {"content": "Title: Mathematical modeling of COVID-19 containment strategies with considerations for limited medical resources Content: The outbreak of SARS-CoV-2 in China has spread around the world, infecting millions and causing governments to implement strict policies to counteract the spread of the disease. One of the most effective strategies in reducing the severity of the pandemic is social distancing, where members of the population systematically reduce their interactions with others to limit the transmission rate of the virus. However, the implementation of social distancing can be difficult and costly, making it imperative that both policy makers and the citizenry understand the potential benefits if done correctly and the risks if not. In this work, a mathematical model is developed to study the effects of social distancing on the spread of the SARS-CoV-2 virus in Canada. The model is based upon a standard epidemiological SEIRD model that has been stratified to directly incorporate the proportion of individuals who are following social distancing protocols. The model parameters characterizing the disease are estimated from current epidemiological data on COVID-19 using machine learning techniques. The results of the model show that social distancing policies in Canada have already saved thousands of lives and that the prolonged adherence to social distancing guidelines could save thousands more. Importantly, our model indicates that social distancing can significantly delay the onset of infection peaks, allowing more time for the production of a vaccine or additional medical resources. Furthermore, our results stress the importance of easing social distancing restrictions gradually, rather than all at once, in order to prevent a second wave of infections. Model results are compared to the current capacity of the Canadian healthcare system by examining the current and future number of ventilators available for use, emphasizing the need for the increased production of additional medical resources.", "qid": 10, "docid": "51g3vhcx", "rank": 62, "score": 0.8753036260604858}, {"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": 63, "score": 0.8752988576889038}, {"content": "Title: COVID-19 and social distancing Content: AIM: COVID-19 has spread rapidly worldwide since it began, greatly affecting peoples' lives, social economies and medical systems. At present, little is known about the disease, and vaccines are still under development. Therefore, in the face of severe outbreaks, previous effective experience can help people better protect themselves and their families. The aim of this article is to discuss the social distancing measures for COVID-19. SUBJECTS AND METHODS: Literature and document search. RESULTS: Recent research and a novel coronavirus pneumonia prediction model revealed social distancing measures and wearing masks are required to mitigate hospital system overload and prevent pathogen exposure. After a series of social distancing measures, there are 309 cities with zero cases and 34 cities with confirmed cases in China as of April 13, 2020. CONCLUSION: From China's experience with novel coronavirus pneumonia, we know that social distancing is the most effective measure at present. We need to win more time to allow limited medical resources to save lives.", "qid": 10, "docid": "5tx03o6h", "rank": 64, "score": 0.875220775604248}, {"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": 65, "score": 0.8750306367874146}, {"content": "Title: Social Distancing During the COVID\u201019 Pandemic: Who Are the Present and Future Non\u2010compliers? Content: Social distancing is an effective means for containing the spread of COVID\u201019, but only so if we all participate. Who are the individuals who are the least likely to adhere to social distancing recommendations, presently and in the long\u2010term? Such knowledge is important for policymakers looking to sustain the public's buy\u2010in to social distancing. Using survey data from sample U.S. residents (n = 1,449), we show that some demographic factors (gender, age, race, political party) help predict intent to adhere to social distancing. Yet demographic factors are relatively poor predictors compared to individual attitudes and media diets. We argue that public officials should make efforts to inform and persuade the public of the importance of social distancing, targeting mediums like TV and radio where audiences are less likely to currently engage in social distancing or are less likely to envision themselves sustaining strict social distancing for several weeks or months. This article is protected by copyright. All rights reserved.", "qid": 10, "docid": "6mnjt0t8", "rank": 66, "score": 0.8739956617355347}, {"content": "Title: The effect of social distance measures on COVID-19 epidemics in Europe: an interrupted time series analysis Content: Following the introduction of unprecedented \u201cstay-at-home\u201d national policies, the COVID-19 pandemic recently started declining in Europe. Our research aims were to characterize the changepoint in the flow of the COVID-19 epidemic in each European country and to evaluate the association of the level of social distancing with the observed decline in the national epidemics. Interrupted time series analyses were conducted in 28 European countries. Social distance index was calculated based on Google Community Mobility Reports. Changepoints were estimated by threshold regression, national findings were analyzed by Poisson regression, and the effect of social distancing in mixed effects Poisson regression model. Our findings identified the most probable changepoints in 28 European countries. Before changepoint, incidence of new COVID-19 cases grew by 24% per day on average. From the changepoint, this growth rate was reduced to 0.9%, 0.3% increase, and to 0.7% and 1.7% decrease by increasing social distancing quartiles. The beneficial effect of higher social distance quartiles (i.e., turning the increase into decline) was statistically significant for the fourth quartile. Notably, many countries in lower quartiles also achieved a flat epidemic curve. In these countries, other plausible COVID-19 containment measures could contribute to controlling the first wave of the disease. The association of social distance quartiles with viral spread could also be hindered by local bottlenecks in infection control. Our results allow for moderate optimism related to the gradual lifting of social distance measures in the general population, and call for specific attention to the protection of focal micro-societies enriching high-risk elderly subjects, including nursing homes and chronic care facilities.", "qid": 10, "docid": "1abupl36", "rank": 67, "score": 0.8733087778091431}, {"content": "Title: The Effectiveness of Social Distancing in Mitigating COVID-19 Spread: a modelling analysis Content: Background The novel coronavirus COVID19 has been classified by the World Health Organisation as a pandemic due to its worldwide spread. The ability of countries to contain and control transmission is critical in the absence of a vaccine. We evaluated a range of social distancing measures to determine which strategies are most effective in reducing the peak daily infection rate, and consequential pressure on the health care system. Methods Using COVID19 transmission data from the outbreak source in Hubei Province, China, collected prior to activation of containment measures, we adapted an established individual based simulation model of the city of Newcastle, Australia, population 272,409. Simulation of virus transmission in this community model without interventions provided a baseline from which to compare alternative social distancing strategies. The infection history of each individual was determined, as was the time infected. From this model generated data, the rate of growth in cases, the magnitude of the epidemic peak, and the outbreak duration were obtained. Findings The application of all four social distancing interventions: school closure, workplace non-attendance, increased case isolation, and community contact reduction is highly effective in flattening the epidemic curve, reducing the maximum daily case numbers, and lengthening outbreak duration. These were also found to be effective even after 10 weeks delay from index case arrivals. The most effective single intervention was found to be increasing case isolation, to 100 percent of children and 90 percent of adults. Interpretation As strong social distancing intervention strategies had the most effect in reducing the epidemic peak, this strategy may be considered when weaker strategies are first tried and found to be less effective. Questions arise as to the duration of strong social distancing measures, given they are highly disruptive to society. Tradeoffs may need to be made between the effectiveness of social distancing strategies and population willingness to adhere to them.", "qid": 10, "docid": "qqsefagq", "rank": 68, "score": 0.8729328513145447}, {"content": "Title: COVID-19 social distancing in the Kingdom of Saudi Arabia: Bold measures in the face of political, economic, social and religious challenges Content: Abstract Social distancing at its various levels has been a key measure to mitigate the transmission of COVID-19. The implementation of strict measures for social distancing is challenging, including in the Kingdom of Saudi Arabia (KSA) due to its level of urbanizations, its social and religious norms and its annual hosting of high visibility international religious mass gatherings. KSA started introducing decisive social distancing measures early before the first case of COVID-19 was confirmed in the Kingdom. These ranged from suspension or cancelations of religious, entertainment and sporting mass gatherings and events such as the Umrah, shutting of educational establishments and mosques and postponing all non-essential gatherings, to imposing a partial curfew. These measures were taken in spite of their socio-economic, political and religious challenges in the interest of public and global health. The effect of these actions on the epidemic curve of the Kingdom and on the global fight against COVID-19 remains to be seen. However, given the current COVID-19 situation, further bold and probably unpopular measures are likely to be introduced in the future.", "qid": 10, "docid": "44kpu8nw", "rank": 69, "score": 0.8727059960365295}, {"content": "Title: The effect of social distance measures on COVID-19 epidemics in Europe: an interrupted time series analysis Content: Following the introduction of unprecedented \"stay-at-home\" national policies, the COVID-19 pandemic recently started declining in Europe. Our research aims were to characterize the changepoint in the flow of the COVID-19 epidemic in each European country and to evaluate the association of the level of social distancing with the observed decline in the national epidemics. Interrupted time series analyses were conducted in 28 European countries. Social distance index was calculated based on Google Community Mobility Reports. Changepoints were estimated by threshold regression, national findings were analyzed by Poisson regression, and the effect of social distancing in mixed effects Poisson regression model. Our findings identified the most probable changepoints in 28 European countries. Before changepoint, incidence of new COVID-19 cases grew by 24% per day on average. From the changepoint, this growth rate was reduced to 0.9%, 0.3% increase, and to 0.7% and 1.7% decrease by increasing social distancing quartiles. The beneficial effect of higher social distance quartiles (i.e., turning the increase into decline) was statistically significant for the fourth quartile. Notably, many countries in lower quartiles also achieved a flat epidemic curve. In these countries, other plausible COVID-19 containment measures could contribute to controlling the first wave of the disease. The association of social distance quartiles with viral spread could also be hindered by local bottlenecks in infection control. Our results allow for moderate optimism related to the gradual lifting of social distance measures in the general population, and call for specific attention to the protection of focal micro-societies enriching high-risk elderly subjects, including nursing homes and chronic care facilities.", "qid": 10, "docid": "4z3r8hoe", "rank": 70, "score": 0.8721816539764404}, {"content": "Title: Social distancing, population density, and spread of COVID-19 in England: a longitudinal study. Content: BACKGROUND The UK government introduced social distancing measures between 16-22 March 2020, aiming to slow down transmission of COVID-19. AIM To explore the spreading of COVID-19 in relation to population density after the introduction of social distancing measures. DESIGN & SETTING Longitudinal design with 5-weekly COVID-19 incidence rates per 100 000 people for 149 English Upper Tier Local Authorities (UTLAs), between 16 March and 19 April 2020. METHOD Multivariable multilevel model to analyse weekly incidence rates per 100 000 people; time was level-1 unit and UTLA level-2 unit. Population density was divided into quartiles. The model included an interaction between week and population density. Potential confounders were percentage aged \u226565, percentage non-white British, and percentage in two highest classes of the National Statistics Socioeconomic Classification. Co-variates were male life expectancy at birth, and COVID-19 prevalence rate per 100 000 people on March 15. Confounders and co-variates were standardised around the mean. RESULTS Incidence rates per 100 000 people peaked in the week of March 30-April 5, showing higher adjusted incidence rate per 100 000 people (46.2; 95% confidence interval [CI] = 40.6 to 51.8) in most densely populated ULTAs (quartile 4) than in less densely populated ULTAs (quartile 1: 33.3, 95% CI = 27.4 to 37.2; quartile 2: 35.9, 95% CI = 31.6 to 40.1). Thereafter, incidence rate dropped in the most densely populated ULTAs resulting in rate of 22.4 (95% CI = 16.9 to 28.0) in the week of April 13-19; this was lower than in quartiles 1, 2, and 3, respectively 31.4 (95% CI = 26.5 to 36.3), 34.2 (95% CI = 29.9 to 38.5), and 43.2 (95% CI = 39.0 to 47.4). CONCLUSION After the introduction of social distancing measures, the incidence rates per 100 000 people dropped stronger in most densely populated ULTAs.", "qid": 10, "docid": "qrhzum9v", "rank": 71, "score": 0.8711872696876526}, {"content": "Title: Statewide Interventions and Covid-19 Mortality in the United States: An Observational Study Content: BACKGROUND: Social distancing is encouraged to mitigate viral spreading during outbreaks. However, the association between distancing and patient-centered outcomes in Covid-19 has not been demonstrated. In the United States social distancing orders are implemented at the state level with variable timing of onset. Emergency declarations and school closures were two early statewide interventions. METHODS: To determine whether later distancing interventions were associated with higher mortality, we performed a state-level analysis in 55,146 Covid-19 non-survivors. We tested the association between timing of emergency declarations and school closures with 28-day mortality using multivariable negative binomial regression. Day 1 for each state was set to when they recorded &#8805; 10 deaths. We performed sensitivity analyses to test model assumptions. RESULTS: At time of analysis, 37 of 50 states had &#8805; 10 deaths and 28 follow-up days. Both later emergency declaration (adjusted mortality rate ratio [aMRR] 1.05 per day delay, 95% CI 1.00 to 1.09, p=0.040) and later school closure (aMRR 1.05, 95% CI 1.01 to 1.09, p=0.008) were associated with more deaths. When assessing all 50 states and setting day 1 to the day a state recorded its first death, delays in declaring an emergency (aMRR 1.05, 95% CI 1.01 to 1.09, p=0.020) or closing schools (aMRR 1.06, 95% CI 1.03 to 1.09, p<0.001) were associated with more deaths. Results were unchanged when excluding New York and New Jersey. CONCLUSIONS: Later statewide emergency declarations and school closure were associated with higher Covid-19 mortality. Each day of delay increased mortality risk 5 to 6%.", "qid": 10, "docid": "afsiuzg1", "rank": 72, "score": 0.8711480498313904}, {"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": 73, "score": 0.8710658550262451}, {"content": "Title: COVID-19 social distancing in the Kingdom of Saudi Arabia: Bold measures in the face of political, economic, social and religious challenges Content: Social distancing at its various levels has been a key measure to mitigate the transmission of COVID-19. The implementation of strict measures for social distancing is challenging, including in the Kingdom of Saudi Arabia (KSA) due to its level of urbanization, its social and religious norms and its annual hosting of high visibility international religious mass gatherings. KSA started introducing decisive social distancing measures early before the first case of COVID-19 was confirmed in the Kingdom. These ranged from suspension or cancelations of religious, entertainment and sporting mass gatherings and events such as the Umrah, temporary closure of educational establishments and mosques and postponing all non-essential gatherings, to imposing a curfew. These measures were taken in spite of their socio-economic, political and religious challenges in the interest of public and global health. The effect of these actions on the epidemic curve of the Kingdom and on the global fight against COVID-19 remains to be seen. However, given the current COVID-19 situation, further bold and probably unpopular measures are likely to be introduced in the future.", "qid": 10, "docid": "zyd0njyk", "rank": 74, "score": 0.8710349202156067}, {"content": "Title: A novel COVID-19 epidemiological model with explicit susceptible and asymptomatic isolation compartments reveals unexpected consequences of timing social distancing Content: Motivated by the current COVID-19 epidemic, this work introduces an epidemiological model in which separate compartments are used for susceptible and asymptomatic \"socially distant\" populations. Distancing directives are represented by rates of flow into these compartments, as well as by a reduction in contacts that lessens disease transmission. The dynamical behavior of this system is analyzed, under various different rate control strategies, and the sensitivity of the basic reproduction number to various parameters is studied. One of the striking features of this model is the existence of a critical implementation delay in issuing separation mandates: while a delay of about four weeks does not have an appreciable effect, issuing mandates after this critical time results in a far greater incidence of infection. In other words, there is a nontrivial but tight \"window of opportunity\" for commencing social distancing. Different relaxation strategies are also simulated, with surprising results. Periodic relaxation policies suggest a schedule which may significantly inhibit peak infective load, but that this schedule is very sensitive to parameter values and the schedule's frequency. Further, we considered the impact of steadily reducing social distancing measures over time. We find that a too-sudden reopening of society may negate the progress achieved under initial distancing guidelines, if not carefully designed.", "qid": 10, "docid": "x9d7g5kb", "rank": 75, "score": 0.8707562685012817}, {"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": 76, "score": 0.8707064390182495}, {"content": "Title: Effect of social distancing on COVID-19 incidence and mortality in the US Content: Social distancing policies were implemented in most US states as a containment strategy against severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). The effectiveness of these policy interventions on morbidity and mortality remains unknown. Our analysis examined the associations between statewide policies and objective measures of social distancing, and objective social distancing and COVID-19 incidence and mortality. We used nationwide, de-identified smartphone GPS data to estimate county-level social distancing. COVID-19 incidence and mortality data were from the Johns Hopkins Coronavirus Resource Center. Generalized linear mixed models were used to estimate incidence rate ratios (IRRs) and 95% confidence intervals (CIs) for the association between objective social distancing and COVID-19 incidence and mortality. Stay-at-home orders were associated with a 35% increase in social distancing. Higher social distancing was associated with a 29% reduction in COVID-19 incidence (adjusted IRR 0.71; 95% CI 0.57\u20130.87) and a 35% reduction in COVID-19 mortality (adjusted IRR 0.65; 95% CI 0.55\u20130.76). These findings provide evidence to inform ongoing national discussions on the effectiveness of these public health measures and the potential implications of returning to normal social activity.", "qid": 10, "docid": "z82gogvs", "rank": 77, "score": 0.8702414631843567}, {"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": 78, "score": 0.8702155351638794}, {"content": "Title: The term \"physical distancing\" is recommended rather than \"social distancing\" during the COVID-19 pandemic for reducing feelings of rejection among people with mental health problems Content: As COVID-19 has plagued our world, the term \"social distancing\" has been widely used with the aim to encourage the general population to physically distance themselves from others in order to reduce the spread of the virus. However, this term can have unintended but detrimental effects, as it evokes negative feelings of being ignored, unwelcome, left alone with one's own fears, and even excluded from society. These feelings may be stronger in people with mental illnesses and in socio-economically disadvantaged groups, such as stigmatized minorities, migrants, and homeless persons [1], many of them also having high risk for suicidal behaviors [2]. Mental health disorders are pervasive worldwide; the global burden accounting for approximately 21.2-32.4% of years lived with disability-more than any other group of illnesses [3]. So, the vulnerable group of people with mental health disorders represents a considerable share of the total global population.", "qid": 10, "docid": "ztm3m9fs", "rank": 79, "score": 0.8700233697891235}, {"content": "Title: Neighborhood income and physical distancing during the COVID-19 pandemic in the U.S. Content: Introduction: Although physical distancing has been the primary strategy to reduce the spread of COVID-19 in the U.S., people's ability to distance may vary by socioeconomic characteristics, leading to higher transmission risk in low-income neighborhoods. Methods: We used mobility data from a large, anonymized sample of smartphone users to assess the relationship between neighborhood median household income and physical distancing during the COVID-19 epidemic. We assessed changes in several behaviors including: spending the day entirely at home; working outside the home; and visits to supermarkets, parks, hospitals, and other locations. We also assessed differences in effects of state policies on physical distancing across neighborhood income levels. Results: We found a strong gradient between neighborhood income and physical distancing. Compared to January and February 2020, the proportion of individuals spending the day entirely at home in April 2020 increased by 10.9 percentage points in low-income neighborhoods and by 27.1 percentage points in high-income neighborhoods. During April 2020, people in low-income neighborhoods were more likely to work outside the home, compared to people in higher-income neighborhoods, but not more likely to visit non-work locations. State physical distancing orders were associated with a 1.5 percentage-point increase (95% CI [0.9, 2.1], p < 0.001) in staying home in low-income neighborhoods and a 2.4 percentage point increase (95% CI [1.4, 3.4], p < 0.001) in high-income neighborhoods. Discussion: People in lower-income neighborhoods have faced barriers to physical distancing, particularly the need to work outside the home. State physical distancing policies have not mitigated these disparities.", "qid": 10, "docid": "p8rpw7ff", "rank": 80, "score": 0.8698667287826538}, {"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": 10, "docid": "xcfk4efo", "rank": 81, "score": 0.8697726726531982}, {"content": "Title: Statewide Interventions and Covid-19 Mortality in the United States: An Observational Study. Content: BACKGROUND Social distancing is encouraged to mitigate viral spreading during outbreaks. However, the association between distancing and patient-centered outcomes in Covid-19 has not been demonstrated. In the United States social distancing orders are implemented at the state level with variable timing of onset. Emergency declarations and school closures were two early statewide interventions. METHODS To determine whether later distancing interventions were associated with higher mortality, we performed a state-level analysis in 55,146 Covid-19 non-survivors. We tested the association between timing of emergency declarations and school closures with 28-day mortality using multivariable negative binomial regression. Day 1 for each state was set to when they recorded \u2265 10 deaths. We performed sensitivity analyses to test model assumptions. RESULTS At time of analysis, 37 of 50 states had \u2265 10 deaths and 28 follow-up days. Both later emergency declaration (adjusted mortality rate ratio [aMRR] 1.05 per day delay, 95% CI 1.00 to 1.09, p=0.040) and later school closure (aMRR 1.05, 95% CI 1.01 to 1.09, p=0.008) were associated with more deaths. When assessing all 50 states and setting day 1 to the day a state recorded its first death, delays in declaring an emergency (aMRR 1.05, 95% CI 1.01 to 1.09, p=0.020) or closing schools (aMRR 1.06, 95% CI 1.03 to 1.09, p<0.001) were associated with more deaths. Results were unchanged when excluding New York and New Jersey. CONCLUSIONS Later statewide emergency declarations and school closure were associated with higher Covid-19 mortality. Each day of delay increased mortality risk 5 to 6%.", "qid": 10, "docid": "ztawznod", "rank": 82, "score": 0.8696101903915405}, {"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": 0.8694972395896912}, {"content": "Title: Modelling the potential impact of social distancing on the COVID-19 epidemic in South Africa Content: The novel coronavirus (COVID-19) pandemic continues to be a global health problem whose impact has been significantly felt in South Africa. Social distancing has been touted as the best form of response in managing a rapid increase in the number of infected cases. In this paper, we present a deterministic model to model the impact of social distancing on the transmission dynamics of COVID-19 in South Africa. The model is fitted to the currently available data on the cumulative number of infected cases and a scenario analysis on different levels of social distancing are presented. The results show a continued rise in the number of cases in the lock down period with the current levels of social distancing albeit at a lower rate. The model shows that the number of cases will rise to above 4000 cases by the end of the lockdown. The model also looks at the impact of relaxing the social distancing measures after the initial announcement of the lock down measures. A relaxation of the social distancing by 2% can result in a 23% rise in the number of cumulative cases while on the other hand increasing the levels of social distancing by 2% would reduce the number of cumulative cases by about 18%. These results have implications on the management and policy direction in the early phases of the epidemic.", "qid": 10, "docid": "q5xc4m3j", "rank": 84, "score": 0.868999719619751}, {"content": "Title: Proactive social distancing mitigates COVID-19 outbreaks within a month across 58 mainland China cities Content: In early 2020, cities across China enacted strict social distancing measures to contain emerging coronavirus (COVID-19) outbreaks. We estimated the speed with which these measures contained community transmission in each of 58 Chinese cities. On average, containment was achieved 7.83 days (SD 6.79 days) after the implementation of social distancing interventions, with an average reduction in the reproduction number (R(t)) of 54.3% (SD 17.6%) over that time period. A single day delay in the implementation of social distancing led to a 2.41 (95% CI: 0.97, 3.86) day delay in containment. Swift social distancing interventions may thus achieve rapid containment of newly emerging COVID-19 outbreaks.", "qid": 10, "docid": "43w659t1", "rank": 85, "score": 0.8689680695533752}, {"content": "Title: Social distancing, social justice, and risk during the COVID-19 pandemic Content: Social distancing is an important and necessary measure to help arrest the spread of SARS-CoV-2 during the COVID-19 pandemic. However, it does place persons who are socially or politically marginalized, including those who are of lower socio-economic status, at risk of further harms. In other words, marginalized or disadvantaged persons are at risk of both contracting SARS-CoV-2 and the risk of harms that may come about because of the social distancing measures themselves. Finally, a third layer of risk faced by marginalized persons would be the overuse of utility (i.e., maximize the benefit of resource x) as the primary ethics principle upon which to make allocation decisions, since oftentimes it is resource-intensive to help those in positions of social marginality. This three-fold risk of harm to which marginalized persons are subjected runs counter to the very notion of social justice that underpins public health. Social distancing in a socially just manner requires dialoguing with affected populations and providing social supports to marginalized persons, regardless of the associated costs.", "qid": 10, "docid": "vue3tg4h", "rank": 86, "score": 0.8686884045600891}, {"content": "Title: Changes in contact patterns shape the dynamics of the COVID-19 outbreak in China Content: Intense non-pharmaceutical interventions were put in place in China to stop transmission of the novel coronavirus disease (COVID-19). As transmission intensifies in other countries, the interplay between age, contact patterns, social distancing, susceptibility to infection, and COVID-19 dynamics remains unclear. To answer these questions, we analyze contact surveys data for Wuhan and Shanghai before and during the outbreak and contact tracing information from Hunan Province. Daily contacts were reduced 7-8-fold during the COVID-19 social distancing period, with most interactions restricted to the household. We find that children 0-14 years are less susceptible to SARS-CoV-2 infection than adults 15-64 years of age (odd ratio 0.34, 95%CI 0.24-0.49), while in contrast, individuals over 65 years are more susceptible to infection (odd ratio 1.47, 95%CI: 1.12-1.92). Based on these data, we build a transmission model to study the impact of social distancing and school closure on transmission. We find that social distancing alone, as implemented in China during the outbreak, is sufficient to control COVID-19. While proactive school closures cannot interrupt transmission on their own, they can reduce peak incidence by 40-60% and delay the epidemic.", "qid": 10, "docid": "f1ckv4bk", "rank": 87, "score": 0.8686662912368774}, {"content": "Title: Impact of social distancing measures for preventing coronavirus disease 2019 : A systematic review and meta-analysis protocol Content: Abstract Introduction: Social distancing measures (SDMs) protect public health from the outbreak of coronavirus disease 2019 (COVID-19). However, the impact of SDMs has been inconsistent and unclear. This study aims to assess the effects of SDMs (e.g. isolation, quarantine) for reducing the transmission of COVID-19. Methods and analysis: We will conduct a systematic review meta-analysis research of both randomised controlled trials and non-randomised controlled trials. We will search MEDLINE, EMBASE, Allied & Complementary Medicine, COVID-19 Research and WHO database on COVID-19 for primary studies assessing the enablers and barriers associated with SDMs, and will be reported in accordance with PRISMA statement. The PRISMA-P checklist will be used while preparing this protocol. We will use Joanna Briggs Institute guidelines (JBI Critical Appraisal Checklists) to assess the methodological qualities and synthesised performing thematic analysis. Two reviewers will independently screen the papers and extracted data. If sufficient data are available, the random-effects model for meta-analysis will be performed to measure the effect size of SDMs or the strengths of relationships. To assess the heterogeneity of effects, I2 together with the observed effects (Q-value, with degrees of freedom) will be used to provide the true effects in the analysis. Ethics and dissemination: Ethics approval and consent will not be required for this systematic review of the literature as it does not involve human participation. We will be able to disseminate the study findings using the following strategies: we will be publishing at least one paper in peer-reviewed journals, and an abstract will be presented at suitable national/international conferences or workshops. We will also share important information with public health authorities as well as with the World Health Organization.", "qid": 10, "docid": "3mwx9s5x", "rank": 88, "score": 0.8686046600341797}, {"content": "Title: Changes in Subway Ridership in Response to COVID-19 in Seoul, South Korea: Implications for Social Distancing Content: Introduction While numerous episodes of Coronavirus disease 2019 (COVID-19) infection and subsequent government announcements in South Korea were accompanied by widespread social distancing efforts by the people, it is unclear whether these episodes and government announcements were actually influential in improving social distancing, or whether the level of response among different demographic groups varied. Methods Data were downloaded from Seoul Data Open Plaza, and changes in the number of passengers on the Seoul Metropolitan Subway network between January 1, 2020, and March 31, 2020, were used to assess the extent to which people in Seoul practiced social distancing. Five events regarding COVID-19 that received wide public attention between January and March 2020 were identified and the changes in the number of passengers before and after each event were analyzed. Also, similar analyses were performed for 16 stations that were specific in either the age or purpose of the visit of the passengers. Results Compared to the third week of January 2020 (January 13-19), the mean daily number of passengers in all stations decreased by 2,984,857.4 or 40.6% by the first week of March (March 2-8). The percentage decrease in individual stations between this period was not significantly different between \u201cyoung\u201d and \u201cold\u201d stations (46.3% vs. 49.2%; p = 0.551) but was significantly smaller in \u201cwork\u201d stations than in \u201cleisure\u201d stations (36.2% vs. 51.6%; p = 0.021). Of the five events, the first reported death due to COVID-19 in South Korea and the identification of a mass infection cluster in Daegu on February 20 were accompanied by the greatest decrease of the mean daily number of passengers (1,352,153.3 or 20.8%), while the first mass infection in Seoul on March 10 and the announcement of aggressive social distancing campaign on March 22 were accompanied by an increase in the number of passengers. Conclusions The number of subway passengers in Seoul decreased markedly during late February but slowly increased afterward, suggesting decreasing levels of risk perception and adherence to social distancing. Understanding the differing patterns of subway use by age or purpose of the visit may guide policymakers and the general public in shaping their future response to the current pandemic.", "qid": 10, "docid": "l3rria7o", "rank": 89, "score": 0.8684705495834351}, {"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": 90, "score": 0.8684349060058594}, {"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": 91, "score": 0.8679549694061279}, {"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": 92, "score": 0.8676026463508606}, {"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": 93, "score": 0.8676025867462158}, {"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": 94, "score": 0.8675835728645325}, {"content": "Title: Modeling COVID19 mortality in the US: Community context and mobility matter Content: The United States has become an epicenter for the coronavirus disease 2019 (COVID-19) pandemic. However, communities have been unequally affected and evidence is growing that social determinants of health may be exacerbating the pandemic. Furthermore, the impact and timing of social distancing at the community level have yet to be fully explored. We investigated the relative associations between COVID-19 mortality and social distancing, sociodemographic makeup, economic vulnerabilities, and comorbidities in 24 counties surrounding 7 major metropolitan areas in the US using a flexible and robust time series modeling approach. We found that counties with poorer health and less wealth were associated with higher daily mortality rates compared to counties with fewer economic vulnerabilities and fewer pre-existing health conditions. Declines in mobility were associated with up to 15% lower mortality rates relative to pre-social distancing levels of mobility, but effects were lagged between 25-30 days. While we cannot estimate causal impact, this study provides insight into the association of social distancing on community mortality while accounting for key community factors. For full transparency and reproducibility, we provide all data and code used in this study.", "qid": 10, "docid": "li3slzw6", "rank": 95, "score": 0.8675471544265747}, {"content": "Title: COVID-19 Growth Rate Decreases with Social Capital Content: Background: Social capital has been associated with many public health variables including mortality, obesity, diabetes, and sexually-transmitted disease rates. However, the relationship of social capital to the spread of infectious disease like COVID-19 is lacking. The COVID-19 pandemic presents an unprecedented threat to global health and economy, for which control strategies have relied on aggressive social distancing. However, an understanding of how social capital is related to changes in human mobility patterns for adherence to social distancing is lacking. Objective: This study examines the association between state- and county-level social capital indices and community health indices in the United States, and the growth rate of COVID-19 cases. It also examines changes in human mobility. Methods: Using publicly available state- and county-specific time series data for COVID-19 cases from March 13 to March 31, we used exponential fits to determine growth rate. We obtained publicly available mobility change data, originally measured from GPS-enabled mobile devices. The design was then state- and county-level correlation analysis with social capital and community health indices from the Social Capital Project (United States Senate). Results: In bivariate linear correlation analyses, we find social capital and community health indices were negatively associated with COVID-19 growth rates at both the state and county levels. The correlation was strongest at the county level for the community health index: a one-unit increase in the county community health index was associated with a decrease in the COVID-19 growth rate exponent by 0.045. In further bivariate correlation analyses, we find that social capital indices were negatively associated with retail/recreation movement and positively associated with residential movement. That is, an increase in social capital is correlated with slower COVID-19 infection spread and more adherence to social distancing protocols. Conclusion: Our results indicate the potential benefit of incorporating social capital concepts in planning policies to control the spread of COVID-19, e.g. different social distancing requirements in different communities. The results also indicate a need for further research into this potentially causal relationship, including examining interventions to increase social capital, community health, and institutional health.", "qid": 10, "docid": "jcjb89wa", "rank": 96, "score": 0.8675159215927124}, {"content": "Title: A mathematical study on the spread of COVID-19 considering social distancing and rapid assessment : The case of Jakarta, Indonesia Content: The aim of this study is to investigate the effects of rapid testing and social distancing in controlling the spread of COVID-19, particularly in the city of Jakarta, Indonesia. We formulate a modified susceptible exposed infectious recovered compartmental model considering asymptomatic individuals. Rapid testing is intended to trace the existence of asymptomatic infected individuals among the population. This asymptomatic class is categorized into two subclasses: detected and undetected asymptomatic individuals. Furthermore, the model considers the limitations of medical resources to treat an infected individual in a hospital. The model shows two types of equilibrium point: COVID-19 free and COVID-19 endemic. The COVID-19-free equilibrium point is locally and asymptotically stable if the basic reproduction number [Formula: see text] is less than unity. In contrast, COVID-19-endemic equilibrium always exists when [Formula: see text]. The model can also show a backward bifurcation at [Formula: see text] whenever the treatment saturation parameter, which describes the hospital capacity, is larger than a specific threshold. To justify the model parameters, we use the incidence data from the city of Jakarta, Indonesia. The data pertain to infected individuals who self-isolate in their homes and visit the hospital for further treatment. Our numerical experiments indicate that strict social distancing has the potential to succeed in reducing and delaying the time of an outbreak. However, if the strict social distancing policy is relaxed, a massive rapid-test intervention should be conducted to avoid a large-scale outbreak in the future.", "qid": 10, "docid": "srpgcy4b", "rank": 97, "score": 0.8674784302711487}, {"content": "Title: Social Media and COVID-19: Can Social Distancing be Quantified without Measuring Human Movements? Content: The COVID-19 outbreak has posed significant threats to international health and the economy. In the absence of treatment for this virus, public health officials asked the public to practice social distancing to reduce the number of physical contacts. However, quantifying social distancing is a challenging task and current methods are based on human movements. We propose a time and cost-effective approach to measure how people practice social distancing. This study proposes a new method based on utilizing the frequency of hashtags supporting and encouraging social distancing for measuring social distancing. We have identified 18 related hashtags and tracked their trends between Jan and May 2020. Our evaluation results show that there is a strong correlation (P<0.05) between our findings and the Google social distancing report.", "qid": 10, "docid": "k574jppq", "rank": 98, "score": 0.8671966791152954}, {"content": "Title: A Statistical Model for Quantifying the Needed Duration of Social Distancing for the COVID-19 Pandemic Content: Understanding the effectiveness of strategies such as social distancing is a central question in attempts to control the COVID-19 pandemic. A key unknown in social distancing strategies is the duration of time for which such strategies are needed. Answering this question requires an accurate model of the transmission trajectory. A challenge in fitting such a model is the limited COVID-19 case data available from a given location. To overcome this challenge, we propose fitting a model of SARS-CoV-2 transmission jointly across multiple locations. We apply the model to COVID-19 case data from Spain, UK, Germany, France, Denmark, and New York to estimate the time needed for social distancing to end to be around October 2020. Our method is not specific to COVID-19, and it can also be applied to future pandemics.", "qid": 10, "docid": "v59xzlf3", "rank": 99, "score": 0.8671883344650269}, {"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": 100, "score": 0.8670738935470581}]}
{"query": "what are the guidelines for triaging patients infected with coronavirus?", "hits": [{"content": "Title: Simple, fast and affordable triaging pathway for COVID-19 Content: Coronavirus disease 2019 has caused a global pandemic. The majority of patients will experience mild disease, but others will develop a severe respiratory infection that requires hospitalisation. This is causing a significant strain on health services. Patients are presenting at emergency departments with symptoms of dyspnoea, dry cough and fever with varying severity. The appropriate triaging of patients will assist in preventing health services becoming overwhelmed during the pandemic. This is assisted through clinical assessment and various imaging and laboratory investigations, including chest X-ray, blood analysis and identification of viral infection with SARS-CoV-2. Here, a succinct triaging pathway that aims to be fast, reliable and affordable is presented. The hope is that such a pathway will assist health services in appropriately combating the pandemic.", "qid": 11, "docid": "h1z8rg9p", "rank": 1, "score": 0.8868314027786255}, {"content": "Title: Simple, fast and affordable triaging pathway for COVID-19. Content: Coronavirus disease 2019 has caused a global pandemic. The majority of patients will experience mild disease, but others will develop a severe respiratory infection that requires hospitalisation. This is causing a significant strain on health services. Patients are presenting at emergency departments with symptoms of dyspnoea, dry cough and fever with varying severity. The appropriate triaging of patients will assist in preventing health services becoming overwhelmed during the pandemic. This is assisted through clinical assessment and various imaging and laboratory investigations, including chest X-ray, blood analysis and identification of viral infection with SARS-CoV-2. Here, a succinct triaging pathway that aims to be fast, reliable and affordable is presented. The hope is that such a pathway will assist health services in appropriately combating the pandemic.", "qid": 11, "docid": "ba5x3ysq", "rank": 2, "score": 0.8868314027786255}, {"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": 3, "score": 0.8648184537887573}, {"content": "Title: Triage of Patients with Venous and Lymphatic Diseases during the COVID-19 pandemic- the Venous and Lymphatic Triage and Acuity Scale (VELTAS) Content: The coronavirus disease 2019 (COVID-19) global pandemic has resulted in diversion of healthcare resources to the management of patients infected with SARS-CoV-2 virus. Elective interventions and surgical procedures in most countries have been postponed and operating room resources have been diverted to manage the pandemic. The Venous and Lymphatic Triage and Acuity Scale (VELTAS) was developed to provide an international standard to rationalise and harmonise the management of patients with venous and lymphatic disorders or vascular anomalies. Triage urgency was determined based on clinical assessment of urgency with which a patient would require medical treatment or surgical intervention. Clinical conditions were classified into six categories of: 1) Venous thromboembolism (VTE), 2) Chronic Venous Disease (CVD), 3) Vascular anomalies, 4) Venous trauma 5) Venous compression and 6) Lymphatic disease. Triage urgency was categorised into four groups and individual conditions were allocated to each class of triage. These included 1) Medical Emergencies (requiring immediate attendance), example massive pulmonary embolism; 2) Urgent (to be seen as soon as possible), example deep vein thrombosis ; 3) Semi-urgent (to be attended to within 30-90 days), example highly symptomatic CVD, and 4) Discretionary/Non-urgent- (to be seen within 6-12 months), example chronic lymphoedema. VELTAS aims to standardise the triage of patients with venous and lymphatic disease or vascular anomalies by providing an international consensus-based classification of clinical categories and triage urgency. The scale may be used during pandemics such as the current COVID-19 crisis but may also be used as a general framework to classify urgency of the listed conditions.", "qid": 11, "docid": "bx8q2gst", "rank": 4, "score": 0.8644178509712219}, {"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": 5, "score": 0.8638067841529846}, {"content": "Title: Triage of patients with venous and lymphatic diseases during the COVID-19 pandemic - The Venous and Lymphatic Triage and Acuity Scale (VELTAS):: A consensus document of the International Union of Phlebology (UIP), Australasian College of Phlebology (ACP), American Vein and Lymphatic Society (AVLS), American Venous Forum (AVF), European College of Phlebology (ECoP), European Venous Forum (EVF), Interventional Radiology Society of Australasia (IRSA), Latin American Venous Forum, Pan-American Society of Phlebology and Lymphology and the Venous Association of India (VAI) Content: The coronavirus disease 2019 (COVID-19) global pandemic has resulted in diversion of healthcare resources to the management of patients infected with SARS-CoV-2 virus. Elective interventions and surgical procedures in most countries have been postponed and operating room resources have been diverted to manage the pandemic. The Venous and Lymphatic Triage and Acuity Scale was developed to provide an international standard to rationalise and harmonise the management of patients with venous and lymphatic disorders or vascular anomalies. Triage urgency was determined based on clinical assessment of urgency with which a patient would require medical treatment or surgical intervention. Clinical conditions were classified into six categories of: (1) venous thromboembolism (VTE), (2) chronic venous disease, (3) vascular anomalies, (4) venous trauma, (5) venous compression and (6) lymphatic disease. Triage urgency was categorised into four groups and individual conditions were allocated to each class of triage. These included (1) medical emergencies (requiring immediate attendance), example massive pulmonary embolism; (2) urgent (to be seen as soon as possible), example deep vein thrombosis; (3) semiurgent (to be attended to within 30-90 days), example highly symptomatic chronic venous disease, and (4) discretionary/nonurgent- (to be seen within 6-12 months), example chronic lymphoedema. Venous and Lymphatic Triage and Acuity Scale aims to standardise the triage of patients with venous and lymphatic disease or vascular anomalies by providing an international consensus-based classification of clinical categories and triage urgency. The scale may be used during pandemics such as the current COVID-19 crisis but may also be used as a general framework to classify urgency of the listed conditions.", "qid": 11, "docid": "5icvvvp1", "rank": 6, "score": 0.8614434003829956}, {"content": "Title: Triage of patients with venous and lymphatic diseases during the COVID-19 pandemic - The Venous and Lymphatic Triage and Acuity Scale (VELTAS): A consensus document of the International Union of Phlebology (UIP), Australasian College of Phlebology (ACP), American Vein and Lymphatic Society (AVLS), American Venous Forum (AVF), European College of Phlebology (ECoP), European Venous Forum (EVF), Interventional Radiology Society of Australasia (IRSA), Latin American Venous Forum, Pan-American Society of Phlebology and Lymphology and the Venous Association of India (VAI) This consensus document has been co-published in Phlebology [DOI: 10.1177/0268355520930884 ] and Journal of Vascular Surgery: Venous and Lymphatic Disorders [DOI: 10.1016/j.jvsv.2020.05.002 ]. The publications are identical except for minor stylistic and spelling differences in keeping with each journal's style. The contribution has been published under a Attribution-Non Commercial-No Derivatives 4.0 International (CC BY-NC-ND 4.0), ( https://creativecommons.org/licenses/by-nc-nd/4.0/ ) Content: The coronavirus disease 2019 (COVID-19) global pandemic has resulted in diversion of healthcare resources to the management of patients infected with SARS-CoV-2 virus. Elective interventions and surgical procedures in most countries have been postponed and operating room resources have been diverted to manage the pandemic. The Venous and Lymphatic Triage and Acuity Scale was developed to provide an international standard to rationalise and harmonise the management of patients with venous and lymphatic disorders or vascular anomalies. Triage urgency was determined based on clinical assessment of urgency with which a patient would require medical treatment or surgical intervention. Clinical conditions were classified into six categories of: (1) venous thromboembolism (VTE), (2) chronic venous disease, (3) vascular anomalies, (4) venous trauma, (5) venous compression and (6) lymphatic disease. Triage urgency was categorised into four groups and individual conditions were allocated to each class of triage. These included (1) medical emergencies (requiring immediate attendance), example massive pulmonary embolism; (2) urgent (to be seen as soon as possible), example deep vein thrombosis; (3) semi-urgent (to be attended to within 30-90 days), example highly symptomatic chronic venous disease, and (4) discretionary/non-urgent- (to be seen within 6-12 months), example chronic lymphoedema. Venous and Lymphatic Triage and Acuity Scale aims to standardise the triage of patients with venous and lymphatic disease or vascular anomalies by providing an international consensus-based classification of clinical categories and triage urgency. The scale may be used during pandemics such as the current COVID-19 crisis but may also be used as a general framework to classify urgency of the listed conditions.", "qid": 11, "docid": "ma9hm5gn", "rank": 7, "score": 0.8613122701644897}, {"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": 8, "score": 0.8552635908126831}, {"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": 9, "score": 0.8552180528640747}, {"content": "Title: European Resuscitation Council COVID-19 Guidelines Executive Summary Content: These coronavirus disease 2019 (COVID-19) guidelines focus specifically on patients with suspected or confirmed COVID-19. For resuscitation of those who are low risk or confirmed negative for COVID-19, the reader is directed to the standard resuscitation guidelines for adults and children.1, 2, 3 Where uncertainty exists treatment should be informed by a dynamic risk assessment which may consider current COVID-19 prevalence, the patient's presentation (e.g. history of COVID-19 contact, COVID-19 symptoms), likelihood that treatment will be effective, availability of personal protective equipment (PPE) and personal risks for those providing treatment. These guidelines will be subject to evolving knowledge and experience of COVID-19. As countries are at different stages of the pandemic, there may some international variation in practice.", "qid": 11, "docid": "hp6lf65q", "rank": 10, "score": 0.8552134037017822}, {"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": 11, "score": 0.8550312519073486}, {"content": "Title: Reorganizing Cross-Sectional Interventional Procedures Practice During the Coronavirus Disease (COVID-19) Pandemic Content: OBJECTIVE. The purpose of this article is to present strategies and guidelines that can be implemented in the performance of cross-sectional interventional procedures during the coronavirus disease (COVID-19) pandemic. CONCLUSION. Radiologists who perform cross-sectional interventional procedures can take several steps to minimize the risks to patients and radiology personnel, including screening referred patients to decide which procedures can be postponed, using appropriate personal protective equipment (PPE), minimizing the number of people involved in procedures, preserving PPE when possible, and applying proper room and equipment cleaning measures.", "qid": 11, "docid": "580r9syn", "rank": 12, "score": 0.8546064496040344}, {"content": "Title: Reorganizing Cross-Sectional Interventional Procedures Practice During the Coronavirus Disease (COVID-19) Pandemic. Content: OBJECTIVE. The purpose of this article is to present strategies and guidelines that can be implemented in the performance of cross-sectional interventional procedures during the coronavirus disease (COVID-19) pandemic. CONCLUSION. Radiologists who perform cross-sectional interventional procedures can take several steps to minimize the risks to patients and radiology personnel, including screening referred patients to decide which procedures can be postponed, using appropriate personal protective equipment (PPE), minimizing the number of people involved in procedures, preserving PPE when possible, and applying proper room and equipment cleaning measures.", "qid": 11, "docid": "85tn8v04", "rank": 13, "score": 0.8546064496040344}, {"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": 14, "score": 0.8502405285835266}, {"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": 15, "score": 0.8502405285835266}, {"content": "Title: European Resuscitation Council COVID-19 guidelines executive summary Content: Coronavirus disease 2019 (COVID-19) has had a substantial impact on the incidence of cardiac arrest and survival. The challenge is to find the correct balance between the risk to the rescuer when undertaking cardiopulmonary resuscitation (CPR) on a person with possible COVID-19 and the risk to that person if CPR is delayed. These guidelines focus specifically on patients with suspected or confirmed COVID-19. The guidelines include the delivery of basic and advanced life support in adults and children and recommendations for delivering training during the pandemic. Where uncertainty exists treatment should be informed by a dynamic risk assessment which may consider current COVID-19 prevalence, the person's presentation (e.g. history of COVID-19 contact, COVID-19 symptoms), likelihood that treatment will be effective, availability of personal protective equipment (PPE) and personal risks for those providing treatment. These guidelines will be subject to evolving knowledge and experience of COVID-19. As countries are at different stages of the pandemic, there may some international variation in practice.", "qid": 11, "docid": "m5dshyoo", "rank": 16, "score": 0.8478642106056213}, {"content": "Title: Saudi heart association, national heart center and national cardiopulmonary resuscitation committee taskforce statement on cpr and resuscitation during COVID-19 pandemic Content: Corona virus disease 2019 is a global pandemic, which affects around 2million individuals with a high death rate that exceeds 90,000 death cases across the globe. The Saudi Heart Association and the national cardiopulmonary resuscitation committee developed a taskforce to discuss the magnitude of clinical situation and CPR management on COVID-19 patients in a prehospital and in-hospital settings. Meanwhile, the taskforce aims to develop a nation-wide clinical guidance to be used by health care workers and untrained laypersons to resuscitate COVID-19 suspected and diagnosed patients.", "qid": 11, "docid": "h9yngwaw", "rank": 17, "score": 0.8472516536712646}, {"content": "Title: Urology in the Era of COVID-19: Mass Casualty Triage Content: INTRODUCTION: The COVID-19 pandemic represents an uncertain challenge that could generate large numbers of patients in a short period of time. METHODS: How best to manage this situation is evolving. There will not be an ideal solution so we must all work together to solve the challenge. RESULTS: Applying principles of mass casualty medicine in triaging urology patients in need of elective and emergent surgeries is of paramount importance. CONCLUSIONS: Accordingly, there is a crucial need to find a guide to pragmatic management of urological patients during this pandemic.", "qid": 11, "docid": "od9u6bup", "rank": 18, "score": 0.8462397456169128}, {"content": "Title: Optimizing response in surgical systems during and after COVID-19 pandemic: lessons from China and the UK \u2013 Perspective Content: Triage strategies to keep suspected and confirmed cases in isolation. Virtual consultations and limiting all out patient activity. Screening asymptomatic patients with nucleic acid test, antibody testing & CT chest. Designated staff and operating areas for COVID 19 infected patients. Careful use of laparoscopy with precautions. Limited operating on cancer patients with consideration of alternatives treatment strategies. Precaution and protocol are needed after the epidemic.", "qid": 11, "docid": "caahtt3b", "rank": 19, "score": 0.8459908366203308}, {"content": "Title: CSC Expert Consensus on Principles of Clinical Management of Patients With Severe Emergent Cardiovascular Diseases During the COVID-19 Epidemic Content: In response to the outbreak of coronavirus disease 2019 (COVID-19) in Wuhan, China, the Chinese Society of Cardiology (CSC) issued this consensus statement after consulting with 125 medical experts in the fields of cardiovascular disease and infectious disease. The over-arching principles laid out here are the following: 1) Consider the prevention and control of COVID-19 transmission as the highest priority, including self-protection of medical staff; 2) Patient risk assessment of both infection and cardiovascular issues. Where appropriate, preferential use of conservative medical therapeutic approaches to minimize disease spread; 3) At all times, medical practices and interventional procedures should be conducted in accordance with the directives of the infection control department of local hospitals and local health commissions.", "qid": 11, "docid": "uq6zf21w", "rank": 20, "score": 0.8451350331306458}, {"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": 21, "score": 0.8429234027862549}, {"content": "Title: Cardiac Surgery During the Coronavirus Disease 2019 Pandemic: Perioperative Considerations and Triage Recommendations Content: The coronavirus disease 2019 pandemic, caused by severe acute respiratory syndrome coronavirus-2, represents the third human affliction attributed to the highly pathogenic coronavirus in the current century. Because of its highly contagious nature and unprecedented global spread, its aggressive clinical presentation, and the lack of effective treatment, severe acute respiratory syndrome coronavirus-2 infection is causing the loss of thousands of lives and imparting unparalleled strain on healthcare systems around the world. In the current report, we discuss perioperative considerations for patients undergoing cardiac surgery and provide clinicians with recommendations to effectively triage and plan these procedures during the coronavirus disease 2019 outbreak. This will help reduce the risk of exposure to patients and healthcare workers and allocate resources appropriately to those in greatest need. We include an algorithm for preoperative testing for coronavirus disease 2019, personal protective equipment recommendations, and a classification system to categorize and prioritize common cardiac surgery procedures.", "qid": 11, "docid": "2n3cdspj", "rank": 22, "score": 0.8426353335380554}, {"content": "Title: Thromboembolism and anticoagulant therapy during the COVID-19 pandemic: interim clinical guidance from the anticoagulation forum Content: Coronavirus disease 2019 (COVID-19) is a viral infection that can, in severe cases, result in cytokine storm, systemic inflammatory response and coagulopathy that is prognostic of poor outcomes. While some, but not all, laboratory findings appear similar to sepsis-associated disseminated intravascular coagulopathy (DIC), COVID-19- induced coagulopathy (CIC) appears to be more prothrombotic than hemorrhagic. It has been postulated that CIC may be an uncontrolled immunothrombotic response to COVID-19, and there is growing evidence of venous and arterial thromboembolic events in these critically ill patients. Clinicians around the globe are challenged with rapidly identifying reasonable diagnostic, monitoring and anticoagulant strategies to safely and effectively manage these patients. Thoughtful use of proven, evidence-based approaches must be carefully balanced with integration of rapidly emerging evidence and growing experience. The goal of this document is to provide guidance from the Anticoagulation Forum, a North American organization of anticoagulation providers, regarding use of anticoagulant therapies in patients with COVID-19. We discuss in-hospital and post-discharge venous thromboembolism (VTE) prevention, treatment of suspected but unconfirmed VTE, laboratory monitoring of COVID-19, associated anticoagulant therapies, and essential elements for optimized transitions of care specific to patients with COVID-19.", "qid": 11, "docid": "4g6wq80m", "rank": 23, "score": 0.8417513370513916}, {"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": 11, "docid": "d5yc1rzs", "rank": 24, "score": 0.8404003381729126}, {"content": "Title: Being a front-line dentist during the Covid-19 pandemic: a literature review Content: Coronavirus is an enveloped virus with positive-sense single-stranded RNA. Coronavirus infection in humans mainly affects the upper respiratory tract and to a lesser extent the gastrointestinal tract. Clinical symptoms of coronavirus infections can range from relatively mild (similar to the common cold) to severe (bronchitis, pneumonia, and renal involvement). The disease caused by the 2019 novel coronavirus (2019-nCoV) was called Covid-19 by the World Health Organization in February 2020. Face-to-face communication and consistent exposure to body fluids such as blood and saliva predispose dental care workers at serious risk for 2019-nCoV infection. As demonstrated by the recent coronavirus outbreak, information is not enough. During dental practice, blood and saliva can be scattered. Accordingly, dental practice can be a potential risk for dental staff, and there is a high risk of cross-infection. This article addresses all information collected to date on the virus, in accordance with the guidelines of international health care institutions, and provides a comprehensive protocol for managing possible exposure to patients or those suspected of having coronavirus.", "qid": 11, "docid": "gyvvcnuf", "rank": 25, "score": 0.8402186036109924}, {"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": 11, "docid": "ls3cqvz3", "rank": 26, "score": 0.8399282693862915}, {"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": 11, "docid": "gdr1dhbd", "rank": 27, "score": 0.8399282693862915}, {"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": 28, "score": 0.8396025896072388}, {"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": 29, "score": 0.8396025896072388}, {"content": "Title: Ethical triage during the COVID-19 pandemic: a toolkit for neurosurgical resource allocation Content: BACKGROUND: The COVID-19 pandemic confronts healthcare workers, including neurosurgeons, with difficult choices regarding which patients to treat. METHODS: In order to assist ethical triage, this article gives an overview of the main considerations and ethical principles relevant when allocating resources in times of scarcity. RESULTS: We discuss a framework employing four principles: prioritizing the worst off, maximizing benefits, treating patients equally, and promoting instrumental value. We furthermore discuss the role of age and comorbidity in triage and highlight some principles that may seem intuitive but should not form a basis for triage. CONCLUSIONS: This overview is presented on behalf of the European Association of Neurosurgical Societies and can be used as a toolkit for neurosurgeons faced with ethical dilemmas when triaging patients in times of scarcity.", "qid": 11, "docid": "qdtntsc3", "rank": 30, "score": 0.8388677835464478}, {"content": "Title: COVID-19 challenge for modern medicine. Content: Coronaviruses cause disease in animals and people around the world. Human coronaviruses (HCoV) are mainly known to cause infections of the upper and lower respiratory tract but the symptoms may also involve the nervous and digestive systems. Since the beginning of December 2019, there has been an epidemic of SARS-CoV-2, which was originally referred to as 2019-nCoV. The most common symptoms are fever and cough, fatigue, sputum production, dyspnea, myalgia, arthralgia or sore throat, headache, nausea, vomiting or diarrhea (30%). The best prevention is to avoid exposure. In addition, contact persons should be subjected to mandatory quarantine. COVID-19 patients should be treated in specialist centers. A significant number of patients with pneumonia require passive oxygen therapy. Non-invasive ventilation and high-flow nasal oxygen therapy can be applied in mild and moderate non-hypercapnia cases. A lung-saving ventilation strategy must be implemented in acute respiratory distress syndrome and mechanically ventilated patients. Extracorporeal membrane oxygenation is a highly specialized method, available only in selected centers and not applicable to a significant number of cases. Specific pharmacological treatment for COVID-19 is not currently available. Modern medicine is gearing up to fight the new coronavirus pandemic. The key is a holistic approach to the patient including, primarily, the use of personal protective equipment to reduce the risk of further virus transmission, as well as patient management, which consists in both quarantine and, in the absence of specific pharmacological therapy, symptomatic treatment.", "qid": 11, "docid": "y4pyt8ke", "rank": 31, "score": 0.8380995392799377}, {"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": 32, "score": 0.8379713296890259}, {"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": 33, "score": 0.8377283215522766}, {"content": "Title: Practical considerations in prevention and treatment of venous thromboembolism in hospitalized patients with COVID-19 Content: DISCLAIMER: In an effort to expedite the publication of articles related to the COVID-19 pandemic, AJHP is posting these manuscripts online as soon as possible after acceptance. Accepted manuscripts have been peer-reviewed and copyedited, but are posted online before technical formatting and author proofing. These manuscripts are not the final version of record and will be replaced with the final article (formatted per AJHP style and proofed by the authors) at a later time. PURPOSE: There are increasing reports in the literature of high rates of coagulopathy and venous thromboembolism (VTE) among hospitalized patients with coronavirus disease 2019 (COVID-19). Understanding of these abnormalities is continually evolving, but these conditions may pose a risk to COVID-19 patients beyond the risk typically seen in critically ill patients. SUMMARY: There are currently no widely accepted evidence-based guidelines regarding specifics related to treatment and prevention of COVID-19-related coagulopathies. Areas of management requiring clinical equipoise include agent selection and dosing, continuation vs interruption of home oral anticoagulant therapy during hospital admission, and postdischarge VTE prophylaxis. Clinicians may wish to consider use of a stratified, 3-tiered approach of low-intensity anticoagulation, intermediate-intensity anticoagulation, and therapeutic-dose anticoagulation. Patients can be categorized by tier depending on their risk factors for VTE, acuity of illness, and laboratory values such as D-dimer level. CONCLUSION: Practical guidance on anticoagulation considerations and dosing suggestions are provided to assist clinicians faced with challenging anticoagulation-related situations in caring for hospitalized COVID patients until formal evidence-based guidelines become available.", "qid": 11, "docid": "f58qqihs", "rank": 34, "score": 0.8375535011291504}, {"content": "Title: Evidence-Based Practical Guidance for the Antithrombotic Management in Patients With Coronavirus Disease (COVID-19) in 2020 Content: This practical guidance, endorsed by the Brazilian Society of Thrombosis and Hemostasis and The Brazilian Society of Angiology and Vascular Surgery, the International Union of Angiology and the European Venous Forum, aims to provide physicians with clear guidance, based on current best evidence-based data, on clinical strategies to manage antithrombotic strategies in patients with coronavirus disease 2019.", "qid": 11, "docid": "f2c3dfve", "rank": 35, "score": 0.8372862935066223}, {"content": "Title: Evidence-Based Practical Guidance for the Antithrombotic Management in Patients With Coronavirus Disease (COVID-19) in 2020. Content: This practical guidance, endorsed by the Brazilian Society of Thrombosis and Hemostasis and The Brazilian Society of Angiology and Vascular Surgery, the International Union of Angiology and the European Venous Forum, aims to provide physicians with clear guidance, based on current best evidence-based data, on clinical strategies to manage antithrombotic strategies in patients with coronavirus disease 2019.", "qid": 11, "docid": "37zwfexp", "rank": 36, "score": 0.8372862935066223}, {"content": "Title: Triaging algorithm for Head & Neck oncology follow-up patients in COVID-19 climate Content: Abstract The current climate is one of uncertainty and immeasurable tragedy for people afflicted by the pandemic of SARS-CoV-2 virus infection. As professionals, we have a duty of care towards all patients especially the vulnerable and those suffering with life-threatening illnesses such as oral cancer. We present a safe & objective triaging method for afflicted with this disease in the prevailing morbid situation.", "qid": 11, "docid": "qjd31m8l", "rank": 37, "score": 0.8371866941452026}, {"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": 38, "score": 0.8370996713638306}, {"content": "Title: Triaging algorithm for head & neck oncology follow-up patients in COVID-19 climate Content: The current climate is one of uncertainty and immeasurable tragedy for people afflicted by the pandemic of SARS-CoV-2 virus infection. As professionals, we have a duty of care towards all patients especially the vulnerable and those suffering with life-threatening illnesses such as oral cancer. We present a safe & objective triaging method for afflicted with this disease in the prevailing morbid situation.", "qid": 11, "docid": "26jxvscc", "rank": 39, "score": 0.8369398713111877}, {"content": "Title: Cardiac Surgery during the COVID-19 Pandemic: Perioperative Considerations and Triage Recommendations. Content: The COVID-19 (Coronavirus disease 2019) pandemic caused by SARS-CoV-2 (Sudden Acute Respiratory Syndrome Coronavirus-2) represents the third human affliction attributed to the highly pathogenic coronavirus in the current century. Due to its highly contagious nature and unprecedented global spread, its aggressive clinical presentation and the lack of effective treatment, SARS-CoV-2 infection is causing the losses of thousands of lives and imparting unparalleled strains on healthcare systems around the world. In the current report, we discuss perioperative considerations for patients undergoing cardiac surgery and provide clinicians with recommendations to effectively triage and plan these procedures during the COVID-19 outbreak. This will help reduce the risk of exposure to patients and healthcare workers and allocate resources appropriately to those in greatest need. We include an algorithm for preoperative testing for COVID-19, personal protective equipment (PPE) recommendations, and a classification system to categorize and prioritize common cardiac surgery procedures.", "qid": 11, "docid": "0t5cvl4n", "rank": 40, "score": 0.8364019393920898}, {"content": "Title: Ethical triage during the COVID-19 pandemic: a toolkit for neurosurgical resource allocation. Content: BACKGROUND The COVID-19 pandemic confronts healthcare workers, including neurosurgeons, with difficult choices regarding which patients to treat. METHODS In order to assist ethical triage, this article gives an overview of the main considerations and ethical principles relevant when allocating resources in times of scarcity. RESULTS We discuss a framework employing four principles: prioritizing the worst off, maximizing benefits, treating patients equally, and promoting instrumental value. We furthermore discuss the role of age and comorbidity in triage and highlight some principles that may seem intuitive but should not form a basis for triage. CONCLUSIONS This overview is presented on behalf of the European Association of Neurosurgical Societies and can be used as a toolkit for neurosurgeons faced with ethical dilemmas when triaging patients in times of scarcity.", "qid": 11, "docid": "nvwn8lzy", "rank": 41, "score": 0.8361864686012268}, {"content": "Title: COVID-19 (Coronavirus) Content: This strain of coronavirus is a new one and scientists do not yet know all there is to know about it. While these common sense points will always be helpful, it is important that you keep up to date with the advice being given by the Centers for Disease Control and Prevention (CDC) and NHS England and how it might affect you personally. These suggestions have been produced using the most up-to-date advice available to us from our Scientific and Medical Advisors and are not intended to replace or supersede advice you may have been given from your health care professional.", "qid": 11, "docid": "9jons9u9", "rank": 42, "score": 0.8361469507217407}, {"content": "Title: COVID-19 (Coronavirus). Content: This strain of coronavirus is a new one and scientists do not yet know all there is to know about it. While these common sense points will always be helpful, it is important that you keep up to date with the advice being given by the Centers for Disease Control and Prevention (CDC) and NHS England and how it might affect you personally. These suggestions have been produced using the most up-to-date advice available to us from our Scientific and Medical Advisors and are not intended to replace or supersede advice you may have been given from your health care professional.", "qid": 11, "docid": "azdrlir3", "rank": 43, "score": 0.8361469507217407}, {"content": "Title: Considerations for cardiac catheterization laboratory procedures during the COVID-19 pandemic perspectives from the Society for Cardiovascular Angiography and Interventions Emerging Leader Mentorship (SCAI ELM) Members and Graduates Content: The novel coronavirus, severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), is highly infectious, carries significant morbidity and mortality, and has rapidly resulted in strained health care system and hospital resources. In addition to patient-related care concerns in infected individuals, focus must also relate to diminishing community spread, protection of staff, case selection, and concentration of resources. The current document based on available data and consensus opinion addresses appropriate catheterization laboratory preparedness for treating these patients, including procedure-room readiness to minimize external contamination, safe donning and doffing of personal protective equipment (PPE) to eliminate risk to staff, and staffing algorithms to minimize exposure and maximize team availability. Case selection and management of both emergent and urgent procedures are discussed in detail, including procedures that may be safely deferred or performed bedside.", "qid": 11, "docid": "5veg78oy", "rank": 44, "score": 0.8360499143600464}, {"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": 45, "score": 0.8360292911529541}, {"content": "Title: Neurosurgical Practice During Coronavirus Disease 2019 (COVID-19) Pandemic Content: Coronavirus disease 2019 (COVID-19), caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), is a highly contagious life-threatening condition with unprecedented impacts for worldwide societies and health care systems. Since the first detection in China, it has spread rapidly worldwide. The increased burden has substantially affected neurosurgical practice and intensive modifications have been required in surgical scheduling, inpatient and outpatient clinics, management of emergency cases, and even in academic activities. In some systems, nonoverlapping teams have been created to minimize transmission among health care workers. In cases of a massive burden, neurosurgeons may need to be reassigned to COVID-19 wards, or teams from other regions may need to be sent to severely affected areas. Recommendations are as following. In outpatient practice, if possible, appointments should be undertaken via telemedicine. All staff assigned to the non-COVID treatment unit should be clothed in level 1 personal protective equipment. If possible, postponement is recommended for operations that do not require urgent or emergent intervention. All patients indicated for surgery must receive COVID-19 screening, including a nasopharyngeal swab and thorax computed tomography. Level 2 protection measures are appropriate during COVID-19-negative patients' operations. Operations of COVID-19-positive patients and emergency operations, in which screening cannot be obtained, should be performed after level 3 protective measures. During surgery, the use of high-speed drills and electrocautery should be reduced to minimize aerosol production. Screening is crucial in all patients because the surgical outcome is highly mortal in patients with COVID-19. All educational and academic conferences can be undertaken as virtual webinars.", "qid": 11, "docid": "vif00f8y", "rank": 46, "score": 0.8359546065330505}, {"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": 47, "score": 0.8359044194221497}, {"content": "Title: COVID-19 challenge for modern medicine Content: Coronaviruses cause disease in animals and people around the world. Human coronaviruses (HCoV) are mainly known to cause infections of the upper and lower respiratory tract but the symptoms may also involve the nervous and digestive systems. Since the beginning of December 2019, there has been an epidemic of SARS-CoV-2, which was originally referred to as 2019-nCoV. The most common symptoms are fever and cough, fatigue, sputum production, dyspnea, myalgia, arthralgia or sore throat, headache, nausea, vomiting or diarrhea (30%). The best prevention is to avoid exposure. In addition, contact per-sons should be subjected to mandatory quarantine. COVID-19 patients should be treated in specialist centers. A significant number of patients with pneumonia require passive oxygen therapy. Non-invasive ventilation and high-flow nasal oxygen therapy can be applied in mild and moderate non-hypercapnia cases. A lung-saving ventilation strategy must be implemented in acute respiratory distress syndrome and mechanically ventilated patients. Extracorporeal membrane oxygenation is a highly specialized method, available only in selected centers and not applicable to a significant number of cases. Specific pharmacological treatment for COVID-19 is not currently available. Modern medicine is gearing up to fight the new coronavirus pandemic. The key is a holistic approach to the patient including, primar-ily, the use of personal protective equipment to reduce the risk of further virus transmission, as well as patient management, which consists in both quarantine and, in the absence of specific pharmacological therapy, symptomatic treatment.", "qid": 11, "docid": "ooj8n1bs", "rank": 48, "score": 0.8356828093528748}, {"content": "Title: Management of acute myocardial infarction during the COVID-19 pandemic: A Consensus Statement from the Society for Cardiovascular Angiography and Interventions (SCAI), the American College of Cardiology (ACC), and the American College of Emergency Physicians (ACEP) Content: The worldwide pandemic caused by the novel acute respiratory syndrome coronavirus 2 has resulted in a new and lethal disease termed coronavirus disease 2019 (COVID-19). Although there is an association between cardiovascular disease and COVID-19, the majority of patients who need cardiovascular care for the management of ischemic heart disease may not be infected with this novel coronavirus. The objective of this document is to provide recommendations for a systematic approach for the care of patients with an acute myocardial infarction (AMI) during the COVID-19 pandemic. There is a recognition of two major challenges in providing recommendations for AMI care in the COVID-19 era. Cardiovascular manifestations of COVID-19 are complex with patients presenting with AMI, myocarditis simulating an ST-elevation myocardial infarction (STEMI) presentation, stress cardiomyopathy, non-ischemic cardiomyopathy, coronary spasm, or nonspecific myocardial injury, and the prevalence of COVID-19 disease in the US population remains unknown with risk of asymptomatic spread. This document addresses the care of these patients focusing on (a) varied clinical presentations; (b) appropriate personal protection equipment (PPE) for health care workers; (c) the roles of the emergency department, emergency medical system, and the cardiac catheterization laboratory (CCL); and (4) regional STEMI systems of care. During the COVID-19 pandemic, primary percutaneous coronary intervention (PCI) remains the standard of care for STEMI patients at PCI-capable hospitals when it can be provided in a timely manner, with an expert team outfitted with PPE in a dedicated CCL room. A fibrinolysis-based strategy may be entertained at non-PCI-capable referral hospitals or in specific situations where primary PCI cannot be executed or is not deemed the best option.", "qid": 11, "docid": "hjyxkm4i", "rank": 49, "score": 0.8354673385620117}, {"content": "Title: Physiotherapy Care of Patients with Coronavirus Disease 2019 (COVID-19) - A Brazilian Experience Content: Some patients with coronavirus disease (COVID-19) present with severe acute respiratory syndrome, which causes multiple organ dysfunction, besides dysfunction of the respiratory system, that requires invasive procedures. On the basis of the opinions of front-line experts and a review of the relevant literature on several topics, we proposed clinical practice recommendations on the following aspects for physiotherapists facing challenges in treating patients and containing virus spread: 1. personal protective equipment, 2. conventional chest physiotherapy, 3. exercise and early mobilization, 4. oxygen therapy, 5. nebulizer treatment, 6. non-invasive ventilation and high-flow nasal oxygen, 7. endotracheal intubation, 8. protective mechanical ventilation, 9. management of mechanical ventilation in severe and refractory cases of hypoxemia, 10. prone positioning, 11. cuff pressure, 12. tube and nasotracheal suction, 13. humidifier use for ventilated patients, 14. methods of weaning ventilated patients and extubation, and 15. equipment and hand hygiene. These recommendations can serve as clinical practice guidelines for physiotherapists. This article details the development of guidelines on these aspects for physiotherapy of patients with COVID-19.", "qid": 11, "docid": "2tbowk4n", "rank": 50, "score": 0.8352667093276978}, {"content": "Title: Clinical Management of Adult Coronavirus Infection Disease 2019 (COVID-19) Positive in the Setting of Low and Medium Intensity of Care: a Short Practical Review Content: Coronavirus disease 2019 (COVID-2019) is a viral infection which is rapidly spreading on a global scale and causing a severe acute respiratory syndrome that affects today about four and a half million registered cases of people around the world. The aim of this narrative review is to provide an urgent guidance for the doctors who take care of these patients. Recommendations contained in this protocol are based on limited, non-definitive, evidence and experience-based opinions about patients with low and medium intensity of care. A short guidance on the management of COVID-19 is provided for an extensive use in different hospital settings. The evidence-based knowledge of COVID-19 is rapidly evolving, and we hope that, in the near future, a definitive and most efficacious treatment will be available including a specific vaccine for SARS-CoV-2.", "qid": 11, "docid": "5c6lwhno", "rank": 51, "score": 0.8347970247268677}, {"content": "Title: A Collaborative Multidisciplinary Approach to the Management of Coronavirus Disease-19 in the Hospital Setting Content: \u2022 Supportive care is the standard approach to the management of coronavirus disease-19, with particular attention to respiratory support, and early detection of potential complications such as cytokine storm and organ dysfunction. \u2022 Therapeutic management of coronavirus disease-19 using antivirals and immunomodulators remain investigational, and should be implemented using clinical trial protocols. \u2022 3. A multidisciplinary collaborative approach to management of coronavirus disease-19 is an essential component of providing optimal care to patients.", "qid": 11, "docid": "4snfwx8r", "rank": 52, "score": 0.8342344760894775}, {"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": 53, "score": 0.8340604305267334}, {"content": "Title: Recomendaciones de consenso respecto al soporte respiratorio no invasivo en el paciente adulto con insuficiencia respiratoria aguda secundaria a infecci\u00f3n por SARS-CoV-2() Content: Coronavirus disease 2019 (COVID-19) is a respiratory tract infection caused by a newly emergent coronavirus, that was first recognized in Wuhan, China, in December 2019. Currently, the World Health Organization (WHO) has defined the infection as a global pandemic and there is a health and social emergency for the management of this new infection. While most people with COVID-19 develop only mild or uncomplicated illness, approximately 14% develop severe disease that requires hospitalization and oxygen support, and 5% require admission to an intensive care unit. In severe cases, COVID-19 can be complicated by the acute respiratory distress syndrome (ARDS), sepsis and septic shock, and multiorgan failure. This consensus document has been prepared on evidence-informed guidelines developed by a multidisciplinary panel of health care providers from four Spanish scientific societies (Spanish Society of Intensive Care Medicine [SEMICYUC], Spanish Society of Pulmonologists [SEPAR], Spanish Society of Emergency [SEMES], Spanish Society of Anesthesiology, Reanimation, and Pain [SEDAR]) with experience in the clinical management of patients with COVID-19 and other viral infections, including SARS, as well as sepsis and ARDS. The document provides clinical recommendations for the noninvasive respiratory support (noninvasive ventilation, high flow oxygen therapy with nasal cannula) in any patient with suspected or confirmed presentation of COVID-19 with acute respiratory failure. This consensus guidance should serve as a foundation for optimized supportive care to ensure the best possible chance for survival and to allow for reliable comparison of investigational therapeutic interventions as part of randomized controlled trials.", "qid": 11, "docid": "2z82hmfh", "rank": 54, "score": 0.8338813185691833}, {"content": "Title: Recomendaciones de consenso respecto al soporte respiratorio no invasivo en el paciente adulto con insuficiencia respiratoria aguda secundaria a infecci\u00f3n por SARS-CoV-2./ Recomendaciones de consenso respecto al soporte respiratorio no invasivo en el paciente adulto con insuficiencia respiratoria aguda secundaria a infecci\u00f3n por SARS-CoV-2./ Clinical consensus recommendations regarding non-invasive respiratory support in the adult patient with acute respiratory failure secondary to SARS-CoV-2 infection Content: Coronavirus disease 2019 (COVID-19) is a respiratory tract infection caused by a newly emergent coronavirus, that was first recognized in Wuhan, China, in December 2019. Currently, the World Health Organization (WHO) has defined the infection as a global pandemic and there is a health and social emergency for the management of this new infection. While most people with COVID-19 develop only mild or uncomplicated illness, approximately 14% develop severe disease that requires hospitalization and oxygen support, and 5% require admission to an intensive care unit. In severe cases, COVID-19 can be complicated by the acute respiratory distress syndrome (ARDS), sepsis and septic shock, and multiorgan failure. This consensus document has been prepared on evidence-informed guidelines developed by a multidisciplinary panel of health care providers from four Spanish scientific societies (Spanish Society of Intensive Care Medicine [SEMICYUC], Spanish Society of Pulmonologists [SEPAR], Spanish Society of Emergency [SEMES], Spanish Society of Anesthesiology, Reanimation, and Pain [SEDAR]) with experience in the clinical management of patients with COVID-19 and other viral infections, including SARS, as well as sepsis and ARDS. The document provides clinical recommendations for the noninvasive respiratory support (noninvasive ventilation, high flow oxygen therapy with nasal cannula) in any patient with suspected or confirmed presentation of COVID-19 with acute respiratory failure. This consensus guidance should serve as a foundation for optimized supportive care to ensure the best possible chance for survival and to allow for reliable comparison of investigational therapeutic interventions as part of randomized controlled trials.", "qid": 11, "docid": "z5wgjdre", "rank": 55, "score": 0.8338813185691833}, {"content": "Title: Recomendaciones de consenso respecto al soporte respiratorio no invasivo en el paciente adulto con insuficiencia respiratoria aguda secundaria a infecci\u00f3n por SARS-CoV-2./ Recomendaciones de consenso respecto al soporte respiratorio no invasivo en el paciente adulto con insuficiencia respiratoria aguda secundaria a infecci\u00f3n por SARS-CoV-2./ Clinical Consensus Recommendations Regarding Non-Invasive Respiratory Support in the Adult Patient with Acute Respiratory Failure Secondary to SARS-CoV-2 infection Content: Coronavirus disease 2019 (COVID-19) is a respiratory tract infection caused by a newly emergent coronavirus, that was first recognized in Wuhan, China, in December 2019. Currently, the World Health Organization (WHO) has defined the infection as a global pandemic and there is a health and social emergency for the management of this new infection. While most people with COVID-19 develop only mild or uncomplicated illness, approximately 14% develop severe disease that requires hospitalization and oxygen support, and 5% require admission to an intensive care unit. In severe cases, COVID-19 can be complicated by the acute respiratory distress syndrome (ARDS), sepsis and septic shock, and multiorgan failure. This consensus document has been prepared on evidence-informed guidelines developed by a multidisciplinary panel of health care providers from four Spanish scientific societies (Spanish Society of Intensive Care Medicine [SEMICYUC], Spanish Society of Pulmonologists [SEPAR], Spanish Society of Emergency [SEMES], Spanish Society of Anesthesiology, Reanimation, and Pain [SEDAR]) with experience in the clinical management of patients with COVID-19 and other viral infections, including SARS, as well as sepsis and ARDS. The document provides clinical recommendations for the noninvasive respiratory support (noninvasive ventilation, high flow oxygen therapy with nasal cannula) in any patient with suspected or confirmed presentation of COVID-19 with acute respiratory failure. This consensus guidance should serve as a foundation for optimized supportive care to ensure the best possible chance for survival and to allow for reliable comparison of investigational therapeutic interventions as part of randomized controlled trials.", "qid": 11, "docid": "wgwfmfqv", "rank": 56, "score": 0.8338813185691833}, {"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": 57, "score": 0.8328031301498413}, {"content": "Title: Coronavirus Disease 2019: A Comprehensive Review of Etiology, Pathogenesis, Diagnosis, and Ongoing Clinical Trials Content: Coronavirus disease 2019 (COVID-19) is an acute respiratory viral infection caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). The disease outbreak started in China in late December 2019 and quickly spread to the rest of the world, resulting in a pandemic. The incidence of cases is increasing every day, affecting millions of people around the globe and resulting in a public health emergency. Furthermore, disease management has been challenging for the clinicians and other medical personnel in terms of treatment options and availability of personal protective equipment. The off-label use of drugs such as hydroxychloroquine and emergency use authorization of remdesivir can hopefully help the clinicians while treating critically ill patients. The use of convalescent serum has also shown some interim benefit until a definitive treatment and preventive options are uncovered, such as vaccines and other effective treatment regimens.", "qid": 11, "docid": "au5akuop", "rank": 58, "score": 0.8322964906692505}, {"content": "Title: Prehospital Triage of Acute Stroke Patients During the COVID-19 Pandemic Content: The coronavirus disease 2019 (COVID-19) pandemic has broad implications on stroke patient triage. Emergency medical services providers have to ensure timely transfer of patients while minimizing the risk of infectious exposure for themselves, their co-workers, and other patients. This statement paper provides a conceptual framework for acute stroke patient triage and transfer during the COVID-19 pandemic and similar healthcare emergencies in the future.", "qid": 11, "docid": "8c1s89dc", "rank": 59, "score": 0.8320255279541016}, {"content": "Title: Prehospital Triage of Acute Stroke Patients During the COVID-19 Pandemic. Content: The coronavirus disease 2019 (COVID-19) pandemic has broad implications on stroke patient triage. Emergency medical services providers have to ensure timely transfer of patients while minimizing the risk of infectious exposure for themselves, their co-workers, and other patients. This statement paper provides a conceptual framework for acute stroke patient triage and transfer during the COVID-19 pandemic and similar healthcare emergencies in the future.", "qid": 11, "docid": "yomkl4pp", "rank": 60, "score": 0.8320255279541016}, {"content": "Title: Triaging Patients Undergoing Endoscopy During COVID-19 Pandemic Content: \"Triaging for endoscopy\" is the process to determine the most deserving patients after careful scrutiny amongst a pool of patients who report for Gastrointestinal (GI) Endoscopy diagnostic or interventional procedures that include Esophago-gastro-duodenoscopy (OGD), Colonoscopy, ERCP, EUS and Enteroscopy. The purpose of triaging at endoscopy is to prevent transmission of SARS-COV2 infection from suspected patient to the health care workers involved at endoscopy. The three professional Indian Gastroenterology bodies namely Society of Gastrointestinal Endoscopy of India (SGEI), Indian Society of Gastroenterology (ISG) & Indian Association for the study of the liver (INASL) have recently provided guidance of scheduling of endoscopic procedures in the current Covid-9 pandemic. Similar suggestions have been promulgated by other international bodies.", "qid": 11, "docid": "0578tin1", "rank": 61, "score": 0.831732988357544}, {"content": "Title: A Novel Cohorting and Isolation Strategy for Suspected COVID-19 Cases during a Pandemic Content: INTRODUCTION: The COVID-19 pandemic presents a significant infection prevention and control challenge. The admission of large numbers of patients with suspected COVID-19 disease risks overwhelming the capacity to protect other patients from exposure. The delay between clinical suspicion and confirmatory testing adds to the complexity of the problem. METHODS: We implemented a triage tool aimed at minimising hospital acquired COVID-19 particularly to patients at risk of severe disease. Patients were allocated to triage categories defined by likelihood of COVID-19 and risk of a poor outcome. Category A (low-likelihood; high-risk), B (high-likelihood; high-risk), C (high-likelihood; low-risk) and D (low-likelihood; low-risk). This determined the order of priority for isolation in single-occupancy rooms with Category A the highest. Patients in other groups were cohorted when isolation capacity was limited with additional interventions to reduce transmission. RESULTS: 93 patients were evaluated with 79 (85%) receiving a COVID-19 diagnosis during their admission. Of those without a COVID-19 diagnosis: 10 were initially triaged to Category A; 0 to B; 1 to C and 4 to D. All high risk patients requiring isolation were, therefore, admitted to single-occupancy rooms and protected from exposure. 28 (30%) suspected COVID-19 patients were evaluated to be low risk (groups C & D) and eligible for cohorting. No symptomatic hospital acquired infections were detected in the cohorted patients. DISCUSSION: Application of a clinical triage tool to guide isolation and cohorting decisions may reduce the risk of hospital acquired transmission of COVID-19 especially to individuals at the greatest of risk of severe disease.", "qid": 11, "docid": "sglgo6hy", "rank": 62, "score": 0.8316612243652344}, {"content": "Title: Practical considerations in prevention and treatment of venous thromboembolism in hospitalized patients with COVID-19. Content: DISCLAIMER In an effort to expedite the publication of articles related to the COVID-19 pandemic, AJHP is posting these manuscripts online as soon as possible after acceptance. Accepted manuscripts have been peer-reviewed and copyedited, but are posted online before technical formatting and author proofing. These manuscripts are not the final version of record and will be replaced with the final article (formatted per AJHP style and proofed by the authors) at a later time. PURPOSE There are increasing reports in the literature of high rates of coagulopathy and venous thromboembolism (VTE) among hospitalized patients with coronavirus disease 2019 (COVID-19). Understanding of these abnormalities is continually evolving, but these conditions may pose a risk to COVID-19 patients beyond the risk typically seen in critically ill patients. SUMMARY There are currently no widely accepted evidence-based guidelines regarding specifics related to treatment and prevention of COVID-19-related coagulopathies. Areas of management requiring clinical equipoise include agent selection and dosing, continuation vs interruption of home oral anticoagulant therapy during hospital admission, and postdischarge VTE prophylaxis. Clinicians may wish to consider use of a stratified, 3-tiered approach of low-intensity anticoagulation, intermediate-intensity anticoagulation, and therapeutic-dose anticoagulation. Patients can be categorized by tier depending on their risk factors for VTE, acuity of illness, and laboratory values such as D-dimer level. CONCLUSION Practical guidance on anticoagulation considerations and dosing suggestions are provided to assist clinicians faced with challenging anticoagulation-related situations in caring for hospitalized COVID patients until formal evidence-based guidelines become available.", "qid": 11, "docid": "toeq4xq0", "rank": 63, "score": 0.8316603899002075}, {"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": 11, "docid": "6bdzut3d", "rank": 64, "score": 0.8316056728363037}, {"content": "Title: Management of Acute Myocardial Infarction During the COVID-19 Pandemic. Content: The worldwide pandemic caused by the novel acute respiratory syndrome coronavirus 2 (SARS-CoV2) has resulted in a new and lethal disease termed coronavirus disease 2019 (COVID-19). Although there is an association between cardiovascular disease and COVID-19, the majority of patients who need cardiovascular care for the management of ischemic heart disease may not be infected with COVID-19. The objective of this document is to provide recommendations for a systematic approach for the care of patients with an acute myocardial infarction (AMI) during the COVID-19 pandemic. There is a recognition of two major challenges in providing recommendations for AMI care in the COVID-19 era. Cardiovascular manifestations of COVID-19 are complex with patients presenting with AMI, myocarditis simulating a ST-elevation MI presentation, stress cardiomyopathy, non-ischemic cardiomyopathy, coronary spasm, or nonspecific myocardial injury and the prevalence of COVID-19 disease in the US population remains unknown with risk of asymptomatic spread. This document addresses the care of these patients focusing on 1) the varied clinical presentations; 2) appropriate personal protection equipment (PPE) for health care workers; 3) role of the Emergency Department, Emergency Medical System and the Cardiac Catheterization Laboratory; and 4) Regional STEMI systems of care. During the COVID-19 pandemic, primary PCI remains the standard of care for STEMI patients at PCI capable hospitals when it can be provided in a timely fashion, with an expert team outfitted with PPE in a dedicated CCL room. A fibrinolysis-based strategy may be entertained at non-PCI capable referral hospitals or in specific situations where primary PCI cannot be executed or is not deemed the best option. This article is protected by copyright. All rights reserved.", "qid": 11, "docid": "odxbz23x", "rank": 65, "score": 0.8313997387886047}, {"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": 66, "score": 0.8312788009643555}, {"content": "Title: Consensus guidelines for interventional cardiology services delivery during covid-19 pandemic in Australia and new Zealand Content: The global coronavirus disease (COVID-19) pandemic poses an unprecedented stress on healthcare systems internationally. These Health system-wide demands call for efficient utilisation of resources at this time in a fair, consistent, ethical and efficient manner would improve our ability to treat patients. Excellent co-operation between hospital units (especially intensive care unit [ICU], emergency department [ED] and cardiology) is critical in ensuring optimal patient outcomes. The purpose of this document is to provide practical guidelines for the effective use of interventional cardiology services in Australia and New Zealand. The document will be updated regularly as new evidence and knowledge is gained with time. Goals Considerations.", "qid": 11, "docid": "txoc927o", "rank": 67, "score": 0.8310996294021606}, {"content": "Title: COVID-19 Guidance for Triage of Operations for Thoracic Malignancies: A Consensus Statement from Thoracic Surgery Outcomes Research Network Content: Abstract The extraordinary demands of managing the COVID-19 pandemic has disrupted the world\u2019s ability to care for patients with thoracic malignancies. As a hospital\u2019s COVID-19 population increases and hospital resources are depleted, the ability to provide surgical care is progressively restricted - forcing surgeons to prioritize among their cancer populations. Representatives from multiple cancer, surgical and research organizations have come together to provide a guide for triaging patients with thoracic malignancies, as the impact of COVID-19 evolves as each hospital.", "qid": 11, "docid": "qyh1vkgi", "rank": 68, "score": 0.8304229974746704}, {"content": "Title: Recommendations on trichological treatments during COVID-19 pandemic. Content: COVID-19 is an infectious disease caused by the novel coronavirus SARS-CoV-2, which rapidly spreads via respiratory droplets and is the cause of the current pandemic. In this alarming situation, it is a delicate matter how to visit patients safely and how to manage their chronic treatments.The aim of this paper is to examine in detail the potential impact on SARS-CoV-2 infection of treatments routinely used in trichology and to provide a useful guide for the therapeutic management of thricological patients in this new COVID-19 era.", "qid": 11, "docid": "64sox1ud", "rank": 69, "score": 0.8300412893295288}, {"content": "Title: COVID-19 pandemic: Effects and evidence-based recommendations for otolaryngology and head and neck surgery practice Content: The 2019 novel coronavirus disease (COVID-19) is a highly contagious zoonosis produced by SARS-CoV-2 that is spread human-to-human by respiratory secretions. It was declared by the WHO as a public health emergency. The most susceptible populations, needing mechanical ventilation, are the elderly and people with associated comorbidities. There is an important risk of contagion for anesthetists, dentists, head and neck surgeons, maxillofacial surgeons, ophthalmologists, and otolaryngologists. Health workers represent between 3.8% and 20% of the infected population; some 15% will develop severe complaints and among them, many will lose their lives. A large number of patients do not have overt signs and symptoms (fever/respiratory), yet pose a real risk to surgeons (who should know this fact and must therefore apply respiratory protective strategies for all patients they encounter). All interventions that have the potential to aerosolize aerodigestive secretions should be avoided or used only when mandatory. Health workers who are: pregnant, over 55 to 65 years of age, with a history of chronic diseases (uncontrolled hypertension, diabetes mellitus, chronic obstructive pulmonary diseases, and all clinical scenarios where immunosuppression is feasible, including that induced to treat chronic inflammatory conditions and organ transplants) should avoid the clinical attention of a potentially infected patient. Health care facilities should prioritize urgent and emergency visits and procedures until the present condition stabilizes; truly elective care should cease and discussed on a case-by-case basis for patients with cancer. For those who are working with COVID-19 infected patients' isolation is compulsory in the following settings: (a) unprotected close contact with COVID-19 pneumonia patients; (b) onset of fever, cough, shortness of breath, and other symptoms (gastrointestinal complaints, anosmia, and dysgeusia have been reported in a minority of cases). For any care or intervention in the upper aerodigestive tract region, irrespective of the setting and a confirmed diagnosis (eg, rhinoscopy or flexible laryngoscopy in the outpatient setting and tracheostomy or rigid endoscopy under anesthesia), it is strongly recommended that all health care personnel wear personal protective equipment such as N95, gown, cap, eye protection, and gloves. The procedures described are essential in trying to maintain safety of health care workers during COVID-19 pandemic. In particular, otolaryngologists, head and neck, and maxillofacial surgeons are per se exposed to the greatest risk of infection while caring for COVID-19 positive subjects, and their protection should be considered a priority in the present circumstances.", "qid": 11, "docid": "lclpuqvw", "rank": 70, "score": 0.8298946619033813}, {"content": "Title: Considerations for Management of Acute Coronary Syndromes During the SARS-CoV-2 (COVID-19) Pandemic Content: Accumulating evidence suggests that influenza and influenza-like illnesses can act as a trigger for acute myocardial infarction (AMI). Despite these unprecedented times providers should not overlook ACS guidelines, but may choose to modify the recommended approach in situations with confirmed or suspected COVID-19 disease. In this document, we suggest recommendations as to how to triage patients diagnosed with acute coronary syndromes (ACS) and provide with algorithms of how to manage the patients and decide the appropriate treatment options in the era of COVID-19 pandemic. We also address the inpatient logistics and discharge to follow-up considerations for the function of already established ACS network during the pandemic.", "qid": 11, "docid": "ro20ibaq", "rank": 71, "score": 0.8297950029373169}, {"content": "Title: The cutting edge of thoracic anesthesia during the 2019 coronavirus disease (COVID-19) outbreak Content: Coronavirus disease 2019 (COVID-19) has quickly spread globally, causing a real pandemic. In this critical scenario, lung cancer patients scheduled for surgical treatment need to continue to receive optimal care while protecting them from an eventual severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection. Adequate use of personal protective equipment (PPE) during aerosol-generating procedures (AGPs) and a COVID-19 specific intraoperative management are paramount in order to prevent cross infections. New suggestions or improvement of existing contagion control guidance are needed, even in case of non-symptomatic patients, possibly responsible for virus spread.", "qid": 11, "docid": "ti7g7b42", "rank": 72, "score": 0.8297522664070129}, {"content": "Title: The Cutting Edge of Thoracic Anesthesia During the Coronavirus Disease 2019 (COVID-19) Outbreak Content: Coronavirus disease 2019 (COVID-19) has quickly spread globally, causing a real pandemic. In this critical scenario, lung cancer patients scheduled for surgical treatment need to continue to receive optimal care while protecting them from an eventual severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection. Adequate use of personal protective equipment (PPE) during aerosol-generating procedures (AGPs) and a COVID-19 specific intraoperative management are paramount in order to prevent cross infections. New suggestions or improvement of existing contagion control guidance are needed, even in case of non-symptomatic patients, possibly responsible for virus spread.", "qid": 11, "docid": "r0dppfhl", "rank": 73, "score": 0.8297522664070129}, {"content": "Title: Peri-operative and critical care concerns in coronavirus pandemic Content: World Health Organization (WHO) declared novel coronavirus outbreak a \u201cpandemic\u201d on March 11(th), 2020. India has already reached Stage 2 (local transmission) and the Indian Government, in collaboration with the Indian Council of Medical Research (ICMR), is taking all necessary steps to halt the community transmission(Stage 3). Anaesthesiologists and intensivists around the globe are making untiring efforts akin to soldiers at the final frontier during war. All efforts pertaining to adequate staffing, Personal Protective Equipment (PPE) and strict adherence to hand hygiene measures are being stressed upon to prevent in-hospital transmission. In this article, all outbreak response measures including triaging, preparation of isolation rooms, decontamination and disinfection protocols as well as fundamental principles of critical care and anaesthetic management in Covid-19 cases is being discussed. All the recommendations have been derived from the past experiences of SARS (Severe Acute Respiratory Syndrome) and MERS (Middle East Respiratory Syndrome) outbreak as well as upcoming guidelines from the international health fraternity and Indian Health Services.", "qid": 11, "docid": "909chgl0", "rank": 74, "score": 0.8297044634819031}, {"content": "Title: Biophotonic telemedicine for disease diagnosis and monitoring during pandemics: overcoming COVID-19 and shaping the future of healthcare Content: \u2022 Infection prevention and control (IPC) strategies against coronavirus disease 2019 (COVID-19) include social distancing and isolating infected patients. \u2022 Telemedicine has become a common clinical practice for early disease diagnostics and monitoring. \u2022 Optical and biophotonic technologies have potential to improve treatment outcome and increase survival rates by advancing telemedicine.", "qid": 11, "docid": "n1e1m3fv", "rank": 75, "score": 0.8296606540679932}, {"content": "Title: Palliativ farmakologisk behandling vid sv\u00e5r covid-19./ [Palliation in patients with severe COVID-19] Content: Coronavirus Disease 2019 (COVID-19) can cause severe respiratory failure and distressing symptoms including fever, cough, breathlessness and anxiety. Symptomatic (palliative) treatment is of fundamental importance both in conjuncture with life-sustaining interventions and in end of life care. Based on the evidence to date, there are several treatment options to consider for the relief of fever (acetaminophen, NSAID, oral glucocorticoids), cough (morphine), breathlessness (morphine, oxygen, fan), anxiety (benzodiazepines) and pain (NSAID, morphine). Top priorities include precautions to protect staff and people at-risk from infection and planning how to provide adequate treatment for each individual depending on setting, including palliative care.", "qid": 11, "docid": "3qspd4hl", "rank": 76, "score": 0.8293633460998535}, {"content": "Title: [Palliation in patients with severe COVID-19]. Content: Coronavirus Disease 2019 (COVID-19) can cause severe respiratory failure and distressing symptoms including fever, cough, breathlessness and anxiety. Symptomatic (palliative) treatment is of fundamental importance both in conjuncture with life-sustaining interventions and in end of life care. Based on the evidence to date, there are several treatment options to consider for the relief of fever (acetaminophen, NSAID, oral glucocorticoids), cough (morphine), breathlessness (morphine, oxygen, fan), anxiety (benzodiazepines) and pain (NSAID, morphine). Top priorities include precautions to protect staff and people at-risk from infection and planning how to provide adequate treatment for each individual depending on setting, including palliative care.", "qid": 11, "docid": "38x16h44", "rank": 77, "score": 0.8293633460998535}, {"content": "Title: Managing the supportive care needs of those affected by COVID-19 Content: Globally, the number of people affected by coronavirus disease 2019 (COVID-19) is rapidly increasing. In most (>80%), the illness is relatively mild and can be self-managed out of hospital. However, in about 20% the illness causes respiratory compromise severe enough to require hospital admission [1]. Patients with severe and critical disease need full active treatment. This may include oxygen for hypoxaemia and ventilatory support, along with optimal management of complications, e.g. super-imposed bacterial infection, and any underlying co-morbidities, e.g. chronic obstructive pulmonary disease, congestive heart failure. To date, no antiviral agent has shown to be effective in treating the disease [2].", "qid": 11, "docid": "9mo6h3l3", "rank": 78, "score": 0.8291826248168945}, {"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": 11, "docid": "lpy7mh95", "rank": 79, "score": 0.8291019201278687}, {"content": "Title: [Ethical guides, criteria for admission in intensive care, palliative care. Multi-society recommendations for allocation of resources during the COVID-19 pandemic]. Content: Guidelines on resource allocation, ethics, triage processes with admission and discharge criteria from critical care and palliative care units during the pandemia are here presented. The interdisciplinary and multi-society panel that prepared these guidelines represented by bioethicists and specialists linked to the end of life: clinicians, geriatricians, emergentologists, intensivists, and experts in palliative care and cardiopulmonary resuscitation. The available information indicates that approximately 80% of people with COVID-19 will develop mild symptoms and will not require hospital care, while 15% will require intermediate or general room care, and the remaining 5% will require assistance in intensive care units. The need to think about justice and establish ethical criteria for allocation patients arise in conditions of exceeding available resources, such as outbreaks of diseases and pandemics, with transparency being the main criterion for allocation. These guides recommend general criteria for the allocation of resources relies on bioethical considerations, rooted in Human Rights and based on the value of the dignity of the human person and substantial principles such as solidarity, justice and equity. The guides are recommendations of general scope and their usefulness is to accompany and sustain the technical and scientific decisions made by the different specialists in the care of critically ill patients, but given the dynamic nature of the pandemic, a process of permanent revision and adaptation of recommendations must be ensured.", "qid": 11, "docid": "x06ujgin", "rank": 80, "score": 0.8289903402328491}, {"content": "Title: Recommendations for the management of critically ill adult patients with COVID-19. Content: Except for pregnant women, the management of critically ill patients with COVID-19 during the pandemic includes the standard procedures that are used for any patient that requires to be attended to at the intensive care unit, as well as limited administration of crystalloid solutions, orotracheal intubation, invasive mechanical ventilation in the event of patient clinical deterioration, and muscle relaxants continuous infusion only if necessary. Non-invasive mechanical ventilation and high-flow oxygen therapy are not recommended due to the generation of aerosol (associated with risk of viral spread among health personnel), and neither is extracorporeal membrane oxygenation or the use of steroids. So far, there is no specific antiviral treatment for patients with COVID-19, and neither are there results of controlled trials supporting the use of any.", "qid": 11, "docid": "bvlw56d9", "rank": 81, "score": 0.8289495706558228}, {"content": "Title: Recommendations for the management of critically ill adult patients with COVID-19 Content: Except for pregnant women, the management of critically ill patients with COVID-19 during the pandemic includes the standard procedures that are used for any patient that requires to be attended to at the intensive care unit, as well as limited administration of crystalloid solutions, orotracheal intubation, invasive mechanical ventilation in the event of patient clinical deterioration, and muscle relaxants continuous infusion only if necessary. Non-invasive mechanical ventilation and high-flow oxygen therapy are not recommended due to the generation of aerosol (associated with risk of viral spread among health personnel), and neither is extracorporeal membrane oxygenation or the use of steroids. So far, there is no specific antiviral treatment for patients with COVID-19, and neither are there results of controlled trials supporting the use of any.", "qid": 11, "docid": "pru9a40f", "rank": 82, "score": 0.828949511051178}, {"content": "Title: Recomendaciones de tratamiento para pacientes adultos graves con COVID-19./ Recommendations for the management of critically ill adult patients with COVID-19 Content: Except for pregnant women, the management of critically ill patients with COVID-19 during the pandemic includes the standard procedures that are used for any patient that requires to be attended to at the intensive care unit, as well as limited administration of crystalloid solutions, orotracheal intubation, invasive mechanical ventilation in the event of patient clinical deterioration, and muscle relaxants continuous infusion only if necessary. Non-invasive mechanical ventilation and high-flow oxygen therapy are not recommended due to the generation of aerosol (associated with risk of viral spread among health personnel), and neither is extracorporeal membrane oxygenation or the use of steroids. So far, there is no specific antiviral treatment for patients with COVID-19, and neither are there results of controlled trials supporting the use of any.", "qid": 11, "docid": "ziqor1sm", "rank": 83, "score": 0.828949511051178}, {"content": "Title: Management of Acute Myocardial Infarction During the COVID-19 Pandemic Content: Abstract The worldwide pandemic caused by the novel acute respiratory syndrome coronavirus 2 (SARS-CoV2) has resulted in a new and lethal disease termed coronavirus disease 2019 (COVID-19). Although there is an association between cardiovascular disease and COVID-19, the majority of patients who need cardiovascular care for the management of ischemic heart disease may not be infected with COVID-19. The objective of this document is to provide recommendations for a systematic approach for the care of patients with an acute myocardial infarction (AMI) during the COVID-19 pandemic. There is a recognition of two major challenges in providing recommendations for AMI care in the COVID-19 era. Cardiovascular manifestations of COVID-19 are complex with patients presenting with AMI, myocarditis simulating a ST-elevation MI presentation, stress cardiomyopathy, non-ischemic cardiomyopathy, coronary spasm, or nonspecific myocardial injury and the prevalence of COVID-19 disease in the US population remains unknown with risk of asymptomatic spread. This document addresses the care of these patients focusing on 1) the varied clinical presentations; 2) appropriate personal protection equipment (PPE) for health care workers; 3) role of the Emergency Department, Emergency Medical System and the Cardiac Catheterization Laboratory; and 4) Regional STEMI systems of care. During the COVID-19 pandemic, primary PCI remains the standard of care for STEMI patients at PCI capable hospitals when it can be provided in a timely fashion, with an expert team outfitted with PPE in a dedicated CCL room. A fibrinolysis-based strategy may be entertained at non-PCI capable referral hospitals or in specific situations where primary PCI cannot be executed or is not deemed the best option.", "qid": 11, "docid": "ipo5zgus", "rank": 84, "score": 0.8289238214492798}, {"content": "Title: Clinical consensus recommendations regarding non-invasive respiratory support in the adult patient with acute respiratory failure secondary to SARS-CoV-2 infection Content: Abstract Coronavirus disease 2019 (COVID-19) is a respiratory tract infection caused by a newly emergent coronavirus, that was first recognized in Wuhan, China, in December 2019. Currently, the World Health Organization (WHO) has defined the infection as a global pandemic and there is a health and social emergency for the management of this new infection. While most people with COVID-19 develop only mild or uncomplicated illness, approximately 14% develop severe disease that requires hospitalization and oxygen support, and 5% require admission to an intensive care unit. In severe cases, COVID-19 can be complicated by the acute respiratory distress syndrome (ARDS), sepsis and septic shock, and multiorgan failure. This consensus document has been prepared on evidence-informed guidelines developed by a multidisciplinary panel of health care providers from four Spanish scientific societies (Spanish Society of Intensive Care Medicine [SEMICYUC], Spanish Society of Pulmonologists [SEPAR], Spanish Society of Emergency [SEMES], Spanish Society of Anesthesiology, Reanimation, and Pain [SEDAR]) with experience in the clinical management of patients with COVID-19 and other viral infections, including SARS, as well as sepsis and ARDS. The document provides clinical recommendations for the noninvasive respiratory support (noninvasive ventilation, high flow oxygen therapy with nasal cannula) in any patient with suspected or confirmed presentation of COVID-19 with acute respiratory failure. This consensus guidance should serve as a foundation for optimized supportive care to ensure the best possible chance for survival and to allow for reliable comparison of investigational therapeutic interventions as part of randomized controlled trials.", "qid": 11, "docid": "oc2glu4a", "rank": 85, "score": 0.828821063041687}, {"content": "Title: Clinical Consensus Recommendations Regarding Non-Invasive Respiratory Support in the Adult Patient with Acute Respiratory Failure Secondary to SARS-CoV-2 infection Content: Abstract Coronavirus disease 2019 (COVID-19) is a respiratory tract infection caused by a newly emergent coronavirus, that was first recognized in Wuhan, China, in December 2019. Currently, the World Health Organization (WHO) has defined the infection as a global pandemic and there is a health and social emergency for the management of this new infection. While most people with COVID-19 develop only mild or uncomplicated illness, approximately 14% develop severe disease that requires hospitalization and oxygen support, and 5% require admission to an intensive care unit. In severe cases, COVID-19 can be complicated by the acute respiratory distress syndrome (ARDS), sepsis and septic shock, and multiorgan failure. This consensus document has been prepared on evidence-informed guidelines developed by a multidisciplinary panel of health care providers from four Spanish scientific societies (Spanish Society of Intensive Care Medicine [SEMICYUC], Spanish Society of Pulmonologists [SEPAR], Spanish Society of Emergency [SEMES], Spanish Society of Anesthesiology, Reanimation, and Pain [SEDAR]) with experience in the clinical management of patients with COVID-19 and other viral infections, including SARS, as well as sepsis and ARDS. The document provides clinical recommendations for the noninvasive respiratory support (noninvasive ventilation, high flow oxygen therapy with nasal cannula) in any patient with suspected or confirmed presentation of COVID-19 with acute respiratory failure. This consensus guidance should serve as a foundation for optimized supportive care to ensure the best possible chance for survival and to allow for reliable comparison of investigational therapeutic interventions as part of randomized controlled trials.", "qid": 11, "docid": "7d8x7fjp", "rank": 86, "score": 0.828821063041687}, {"content": "Title: Clinical pathways for urology patients during the COVID-19 pandemic Content: The public health emergency caused by the Coronavirus Disease 2019 (COVID-19) pandemic has resulted in a significant reallocation of health resources with a consequent reorganization of the clinical activities also in several urological centers. A panel of Italian urologists has agreed on a set of recommendations on pathways of pre-, intra- and post-operative care for urological patients undergoing urgent procedures or non-deferrable oncological interventions during the COVID-19 pandemic. Simplification of the diagnostic and staging pathway has to be prioritized in order to reduce hospital visits and consequently the risk of contagion. In absence of strict uniform regulations that impose the implementation of nasopharyngeal swabs, we recommend that an accurate triage for COVID-19 symptoms be performed both by telephone at home before hospitalization and at the time of hospitalization. We recommend that during hospital stay patients should be provided with as many instructions as possible to facilitate their return to, and stay at, home. Patients should be discharged under stable good conditions in order to minimize the risk of readmission. It is advisable to reduce or reschedule post-discharge controls and implement an adequate system of communication for telemonitoring discharged patients.", "qid": 11, "docid": "j7s6504d", "rank": 87, "score": 0.8288030624389648}, {"content": "Title: Atenci\u00f3n al ictus agudo durante la pandemia por COVID-19. Recomendaciones Plan Ictus Madrid./ Atenci\u00f3n al ictus agudo durante la pandemia por COVID-19. Recomendaciones Plan Ictus Madrid./ Acute stroke care during the COVID-19 pandemic. Ictus Madrid Program recommendations Content: INTRODUCTION: The COVID-19 pandemic has resulted in complete saturation of healthcare capacities, making it necessary to reorganise healthcare systems. In this context, we must guarantee the provision of acute stroke care and optimise code stroke protocols to reduce the risk of SARS-CoV-2 infection and rationalise the use of hospital resources. The Madrid Stroke multidisciplinary group presents a series of recommendations to achieve these goals. METHODS: We conducted a non-systematic literature search using the keywords \"stroke\" and \"COVID-19\" or \"coronavirus\" or \"SARS-CoV-2.\" Our literature review also included other relevant studies known to the authors. Based on this literature review, a series of consensus recommendations were established by the Madrid Stroke multidisciplinary group and its neurology committee. RESULTS: These recommendations address 5 main objectives: 1) coordination of action protocols to ensure access to hospital care for stroke patients; 2) recognition of potentially COVID-19-positive stroke patients; 3) organisation of patient management to prevent SARS-CoV-2 infection among healthcare professionals; 4) avoidance of unnecessary neuroimaging studies and other procedures that may increase the risk of infection; and 5) safe, early discharge and follow-up to ensure bed availability. This management protocol has been called CORONA (Coordinate, Recognise, Organise, Neuroimaging, At home). CONCLUSIONS: The recommendations presented here may assist in the organisation of acute stroke care and the optimisation of healthcare resources, while ensuring the safety of healthcare professionals.", "qid": 11, "docid": "ylgozb4t", "rank": 88, "score": 0.8287563323974609}, {"content": "Title: Korean clinical practice guidelines for preventing transmission of coronavirus disease 2019 (COVID-19) in hemodialysis facilities Content: Coronavirus disease 2019 (COVID-19) is a highly contagious viral disease that is caused by the novel virus Severe Acute Respiratory Syndrome Coronavirus-2 (SARS-CoV-2). COVID-19 has become pandemic since December 2019, when the first case developed in Wuhan, China. Patients receiving hemodialysis are more vulnerable to viral transmission because their immune functions are impaired and they receive treatment within a narrow space. Calling on previous experience with Middle East Respiratory Syndrome during the 2015 outbreak, the joint committee of the Korean Society of Nephrology and the Korean Society of Dialysis Therapy quickly formed a COVID-19 task force team to develop a manual before the first index case was diagnosed in the hemodialysis unit. This special article introduces clinical practice guidelines to prevent secondary transmission of COVID-19 within hemodialysis facilities, which were developed to protect patients, healthcare workers, and caregivers from this highly transmissible virus. The areas of infection control covered by these guidelines include standard precautions, performing dialysis therapy for confirmed or suspected cases, performing cohort isolation for contact patients, and disease monitoring and contact surveillance. We hope these guidelines help healthcare workers and hemodialysis patients around the world cope with the COVID-19 pandemic.", "qid": 11, "docid": "7wx4zh5p", "rank": 89, "score": 0.8286667466163635}, {"content": "Title: Clinical trials during COVID\u201019 Content: As this ever\u2010evolving pandemic lays itself, more of its impact is being understood. Until recently, most guidelines were reported to aid in managing and treating suspected or confirmed cases. Research institutions around the world are responding with a sense of confusion. Some are continuing routinely, especially those who are overseeing clinical trials that could offer life\u2010saving therapies, particularly against the novel coronavirus. Since research must continue even in the face of a shutdown, we aim to collate the currently available recommendations from various organizations and provide guidance to head and neck researchers across the world during these trying times.", "qid": 11, "docid": "nesvd10a", "rank": 90, "score": 0.8286272287368774}, {"content": "Title: Interventional radiology workflow during the COVID-19 pandemic: recommendations of the Swiss Society of Vascular and Interventional Radiology Content: Given the importance of continuum in providing services and exigence of protecting health care professionals during this period, the Swiss Society of Vascular and Interventional Radiology (SSVIR) is releasing guidance for interventional radiologists as preparedness to manage COVID-19 patients, the workflow of non-COVID-19 patients and optimize interactions with other healthcare professionals.", "qid": 11, "docid": "87pqhnei", "rank": 91, "score": 0.8285237550735474}, {"content": "Title: Interventional radiology workflow during the COVID-19 pandemic: recommendations of the Swiss Society of Vascular and Interventional Radiology. Content: Given the importance of continuum in providing services and exigence of protecting health care professionals during this period, the Swiss Society of Vascular and Interventional Radiology (SSVIR) is releasing guidance for interventional radiologists as preparedness to manage COVID-19 patients, the workflow of non-COVID-19 patients and optimize interactions with other healthcare professionals.", "qid": 11, "docid": "cfsr5vf5", "rank": 92, "score": 0.8285237550735474}, {"content": "Title: Prevention, Diagnosis, and Treatment of VTE in Patients With COVID-19: CHEST Guideline and Expert Panel Report Content: BACKGROUND: Emerging evidence shows that severe coronavirus disease 2019 (COVID-19) can be complicated by a significant coagulopathy, that likely manifests in the form of both microthrombosis and VTE. This recognition has led to the urgent need for practical guidance regarding prevention, diagnosis, and treatment of VTE. METHODS: A group of approved panelists developed key clinical questions by using the PICO (Population, Intervention, Comparator, Outcome) format that addressed urgent clinical questions regarding the prevention, diagnosis, and treatment of VTE in patients with COVID-19. MEDLINE (via PubMed or Ovid), Embase, and Cochrane Controlled Register of Trials were systematically searched for relevant literature, and references were screened for inclusion. Validated evaluation tools were used to grade the level of evidence to support each recommendation. When evidence did not exist, guidance was developed based on consensus using the modified Delphi process. RESULTS: The systematic review and critical analysis of the literature based on 13 Population, Intervention, Comparator, Outcome questions resulted in 22 statements. Very little evidence exists in the COVID-19 population. The panel thus used expert consensus and existing evidence-based guidelines to craft the guidance statements. CONCLUSIONS: The evidence on the optimal strategies to prevent, diagnose, and treat VTE in patients with COVID-19 is sparse but rapidly evolving.", "qid": 11, "docid": "t5kbtvz8", "rank": 93, "score": 0.8284263610839844}, {"content": "Title: The role of initial chest X-ray in triaging patients with suspected COVID-19 during the pandemic Content: PURPOSE: The purpose of our research is to evaluate the usefulness of chest X-ray for triaging patients with suspected COVID-19 infection. METHODS: IRB approval was obtained to allow a retrospective review of adult patients who presented to the Emergency Department with a complaint of fever, cough, dyspnea or hypoxia and had a chest X-ray between 12 March 2020 and 26 March 2020. The initial chest X-ray was graded on a scale of 0-3 with grade 0 representing no alveolar opacities, grade 1: < 1/3 alveolar opacities of the lung, Grade 2: 1/3 to 2/3 lung with alveolar opacities and grade 3: > 2/3 alveolar opacities of the lung. Past medical history of diabetes and hypertension, initial oxygen saturation, COVID-19 testing results, intubation, and outcome were also collected. RESULTS: Four hundred ten patient chest X-rays were reviewed. Oxygen saturation and X-ray grade were both significantly associated with the length of stay in hospital, the hazard ratio (HR) of discharge was 1.05 (95% CI [1.01, 1.09], p = 0.017) and 0.61 (95% CI [0.51, 0.73], p < 0.001), respectively. In addition, oxygen saturation and X-ray grade were significant predictors of intubation (odds ratio (OR) of intubation is 0.88 (95% CI [0.81, 0.96], p = 0.004) and 3.69 (95% CI [2.25, 6.07], p < 0.001). CONCLUSIONS: Initial chest X-ray is a useful tool for triaging those subjects who might have poor outcomes with suspected COVID-19 infection and benefit most from hospitalization.", "qid": 11, "docid": "v2pjvppf", "rank": 94, "score": 0.8284053802490234}, {"content": "Title: Recommendations on trichological treatments during COVID-19 pandemic Content: COVID-19 is an infectious disease caused by the novel coronavirus SARS-CoV-2, which rapidly spreads via respiratory droplets and is the cause of the current pandemic. In this alarming situation, it is a delicate matter how to visit patients safely and how to manage their chronic treatments. The aim of this paper is to examine in detail the potential impact on SARS-CoV-2 infection of treatments routinely used in trichology and to provide a useful guide for the therapeutic management of trichological patients in this new COVID-19 era.", "qid": 11, "docid": "me4z2n86", "rank": 95, "score": 0.8283892869949341}, {"content": "Title: COVID-19: Precautionary Guidelines for Ophthalmologists Content: Several coronaviruses can infect humans, and the globally endemic human coronaviruses, HCoV-229E (human coronavirus 229E), HCoV-NL63 (human coronavirus NL63), and others, tend to cause mild respiratory diseases. The zoonotic Middle East respiratory syndrome coronavirus (MERS-CoV) and severe acute respiratory syndrome coronavirus type1 (SARS-CoV-1) have high fatality rates. In December 2019, the World Health Organization (WHO) was notified by Chinese authorities about an outbreak of pneumonia before the causative organism was identified in January 2020 as a novel coronavirus family. The WHO refers to the virus as coronavirus disease 2019 (COVID-19). Within several weeks, the outbreak has become an emergency, and many countries have since been affected. The method of transmission is not yet fully known but is thought to be mainly respiratory. Healthcare providers, particularly ophthalmologists, are at high risk of a COVID-19 infection through unprotected contact with eye secretions during routine ophthalmic examinations that involve the use of direct ophthalmoscopy and slit-lamp examinations, which are usually performed in a setting that allows for close doctor-patient contact. In light of these, specific measures are needed from an ophthalmic point of view to control the COVID-19 outbreak and to protect health care providers.", "qid": 11, "docid": "ffgd2ets", "rank": 96, "score": 0.828157901763916}, {"content": "Title: Managing haematology and oncology patients during the COVID\u201019 pandemic: interim consensus guidance Content: INTRODUCTION: A pandemic coronavirus, SARS\u2010CoV\u20102, causes COVID\u201019, a potentially life\u2010threatening respiratory disease. Patients with cancer may have compromised immunity due to their malignancy and/or treatment, and may be at elevated risk of severe COVID\u201019. Community transmission of COVID\u201019 could overwhelm health care services, compromising delivery of cancer care. This interim consensus guidance provides advice for clinicians managing patients with cancer during the pandemic. MAIN RECOMMENDATIONS: During the COVID\u201019 pandemic: In patients with cancer with fever and/or respiratory symptoms, consider causes in addition to COVID\u201019, including other infections and therapy\u2010related pneumonitis. For suspected or confirmed COVID\u201019, discuss temporary cessation of cancer therapy with a relevant specialist. Provide information on COVID\u201019 for patients and carers. Adopt measures within cancer centres to reduce risk of nosocomial SARS\u2010CoV\u20102 acquisition; support population\u2010wide social distancing; reduce demand on acute services; ensure adequate staffing; and provide culturally safe care. Measures should be equitable, transparent and proportionate to the COVID\u201019 threat. Consider the risks and benefits of modifying cancer therapies due to COVID\u201019. Communicate treatment modifications, and review once health service capacity allows. Consider potential impacts of COVID\u201019 on the blood supply and availability of stem cell donors. Discuss and document goals of care, and involve palliative care services in contingency planning. CHANGES IN MANAGEMENT AS A RESULT OF THIS STATEMENT: This interim consensus guidance provides a framework for clinicians managing patients with cancer during the COVID\u201019 pandemic. In view of the rapidly changing situation, clinicians must also monitor national, state, local and institutional policies, which will take precedence. ENDORSED BY: Australasian Leukaemia and Lymphoma Group; Australasian Lung Cancer Trials Group; Australian and New Zealand Children's Haematology/Oncology Group; Australia and New Zealand Society of Palliative Medicine; Australasian Society for Infectious Diseases; Bone Marrow Transplantation Society of Australia and New Zealand; Cancer Council Australia; Cancer Nurses Society of Australia; Cancer Society of New Zealand; Clinical Oncology Society of Australia; Haematology Society of Australia and New Zealand; National Centre for Infections in Cancer; New Zealand Cancer Control Agency; New Zealand Society for Oncology; and Palliative Care Australia.", "qid": 11, "docid": "xaj2623u", "rank": 97, "score": 0.8281214833259583}, {"content": "Title: [The keypoints in treatment of the critical coronavirus disease 2019 patient] Content: The treatment of critically ill patients with coronavirus disease 2019(COVID-19) faces compelling challenges. In this issue, we'd like to share our first-line treatment experience in treating COVID-19. Hemodynamics need be closely monitored and different types of shock should be distinguished. Vasoconstrictor drugs should be used rationally and alerting of complications is of the same importance. The risk of venous thromboembolism (VTE) needs to be assessed, and effective prevention should be carried out for high-risk patients. It is necessary to consider the possibility of pulmonary thromboembolism (PTE) in patients with sudden onset of oxygenation deterioration, respiratory distress, reduced blood pressure. However, comprehensive analysis of disease state should be taken into the interpretation of abnormally elevated D-Dimer. Nutritional support is the basis of treatment. It's important to establish individual therapy regimens and to evaluate, monitor and adjust dynamically. Under the current epidemic situation, convalescent plasma can only be used empirically, indications need to be strictly screened, the blood transfusion process should be closely monitored and the curative effect should be dynamically evaluated.", "qid": 11, "docid": "yzmrxpr8", "rank": 98, "score": 0.8281022310256958}, {"content": "Title: [The keypoints in treatment of the critical coronavirus disease 2019 patient(2)] Content: The treatment of critically ill patients with coronavirus disease 2019(COVID-19) faces compelling challenges. In this issue, we'd like to share our first-line treatment experience in treating COVID-19. Hemodynamics need be closely monitored and different types of shock should be distinguished. Vasoconstrictor drugs should be used rationally and alerting of complications is of the same importance. The risk of venous thromboembolism (VTE) needs to be assessed, and effective prevention should be carried out for high-risk patients. It is necessary to consider the possibility of pulmonary thromboembolism (PTE) in patients with sudden onset of oxygenation deterioration, respiratory distress, reduced blood pressure. However, comprehensive analysis of disease state should be taken into the interpretation of abnormally elevated D-Dimer. Nutritional support is the basis of treatment. It's important to establish individual therapy regimens and to evaluate, monitor and adjust dynamically. Under the current epidemic situation, convalescent plasma can only be used empirically, indications need to be strictly screened, the blood transfusion process should be closely monitored and the curative effect should be dynamically evaluated.", "qid": 11, "docid": "y9mfi63m", "rank": 99, "score": 0.8281022310256958}, {"content": "Title: [The keypoints in treatment of the critical coronavirus disease 2019 patient]. Content: The treatment of critically ill patients with coronavirus disease 2019(COVID-19) faces compelling challenges. In this issue, we'd like to share our first-line treatment experience in treating COVID-19. Hemodynamics need be closely monitored and different types of shock should be distinguished. Vasoconstrictor drugs should be used rationally and alerting of complications is of the same importance. The risk of venous thromboembolism (VTE) needs to be assessed, and effective prevention should be carried out for high-risk patients. It is necessary to consider the possibility of pulmonary thromboembolism (PTE) in patients with sudden onset of oxygenation deterioration, respiratory distress, reduced blood pressure. However, comprehensive analysis of disease state should be taken into the interpretation of abnormally elevated D-Dimer. Nutritional support is the basis of treatment. It's important to establish individual therapy regimens and to evaluate, monitor and adjust dynamically. Under the current epidemic situation, convalescent plasma can only be used empirically, indications need to be strictly screened, the blood transfusion process should be closely monitored and the curative effect should be dynamically evaluated.", "qid": 11, "docid": "bj142e9b", "rank": 100, "score": 0.8281022310256958}]}
{"query": "what are best practices in hospitals and at home in maintaining quarantine?", "hits": [{"content": "Title: Barrier precautions, isolation protocols, and personal hygiene in veterinary hospitals Content: Because nosocomial and zoonotic diseases are inherent and ever-present risks in veterinary hospitals, proactive policies should be in place to reduce the risk of sporadic cases and outbreaks. Policies should ideally be put in place before disease issues arise, and policies should be effectively conveyed to all relevant personnel. Written policies are required for practical and liability reasons and should be reviewed regularly. Although no infection control program can eliminate disease concerns, proper implementation of barrier precautions and isolation can reduce the exposure of hospitalized animals and hospital personnel to infectious agents. Appropriate personal hygiene, particularly hand hygiene, can assist in the prevention of disease transmission when pathogens bypass barriers and are able to contact personnel. Veterinary hospitals have moral, professional, and legal requirements to provide a safe workplace and to reduce the risks to hospitalized patients. Based on experience in the human medical field and on the continual emergence of new infectious diseases, infection control challenges can only be expected to increase in the future. Regular reassessment of protocols based on ongoing research and clinical experiences is required.", "qid": 12, "docid": "2el9tx9v", "rank": 1, "score": 0.8488592505455017}, {"content": "Title: Hospital-Associated Infections in Small Animal Practice Content: Hospital-associated infections (HAIs) occur in veterinary hospitals of all types and sizes, and their frequency is likely to increase. Urinary tract infections, pneumonia, bloodstream infections, surgical site infections, and infectious diarrhea are the HAIs most frequently identified in veterinary medicine. A hospital infection control program, consisting of an infectious disease control officer, written protocols, and staff training, is critical to reducing HAIs and promoting patient, staff, and client health. Infection control protocols (plans) should include discussion of hand hygiene and use of personal protective equipment, cleaning and disinfection, patient management, with-in hospital surveillance, and antimicrobial stewardship.", "qid": 12, "docid": "36gyix12", "rank": 2, "score": 0.8420467972755432}, {"content": "Title: Do established infection prevention and control measures prevent spread of SARS-CoV-2 to the hospital environment beyond the patient room? Content: The role of the hospital environment in the transmission of infection is well described. With an emerging infection whose mode of transmission is under investigation, strict infection prevention and control measures, including patient isolation, hand hygiene, personal protective equipment that is doffed on exiting the patient room, and environmental cleaning should be implemented to prevent spread. Environmental testing demonstrated that COVID-19 patients contaminated the patient area (11/26, 42.3% of tests) but contamination of general ward areas was minimal (1/30, 3%) and the virus was detected after cleaning on one item only (1/25, 4%) which was noted to be in disrepair.", "qid": 12, "docid": "xgs92uwo", "rank": 3, "score": 0.8403903245925903}, {"content": "Title: Implementing Basic Infection Control Practices in Disaster Situations Content: Infections, troublesome in even optimal health care environments, can be a source of serious and persistent concern for local populations and health care workers during a disaster, and in austere environments such as those found in Iraq and Afghanistan. For these scenarios, it is vital to have standard infection control practices in place and to have them used consistently. Only then will healthcare workers be able to contain the potential spread of disease and improve conditions for those affected.", "qid": 12, "docid": "ys0ndxun", "rank": 4, "score": 0.8391396999359131}, {"content": "Title: Management-supportive measures for managers of healthcare organizations during the COVID-19 epidemic Content: Contagious or infectious diseases are one of the major causes of death.(1) Epidemics are a serious threat to public health and a global challenge (2)and management the of these epidemics is very difficult. In these conditions, economic, social and health factors of the country are of great worry, therefore, healthcare managers must properly manage and support health care centers (3)and use management-supportive measures for the organization and staff to provide best healthcare services. Presenting a scientific framework for managing health centers can be very helpful.The most important management-supportive practices at healthcare centers during outbreaks are listed below:1.Engage Leadership: Leadership affects the performance of physicians and nurses. Maintain effective communication with employees, pay attention to them, and listen to them effectively.2.Choose Wise Motivations: Talk about the importance of staff work, appreciate their work, and provide encouragement.3.Note to Work-life Balance: Note that you define a proper and balanced workload for employees. Say that optimal performance depends on enough rest and emphasize the need to re-energize.4.Encourage Peer Support: Protect your staff from external pressures, illogical or uncertain demands from patients and individuals, and promote support among colleagues.5.Provide Resources to Protect Employees and Their Mental Health: Minimize risky conditions in the organization and minimize workplace stress to ensure that staff are not exposed to additional stressors.6.Build A Good Community: Build the right teamwork and improve working relationships.7.Increase Employee Control Over Their Work: Clarify your expectations of employees and create an environment for team members to perform important tasks without interruption.8.Review Your Achievements Regularly: Talk to staff about your progress and successes.9.Cancel Unnecessary Meetings: Try to avoid unnecessary gatherings at work. Use video conferencing if a meeting needs to be held.", "qid": 12, "docid": "jtn9d0d6", "rank": 5, "score": 0.8357847929000854}, {"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": 6, "score": 0.8341176509857178}, {"content": "Title: ASID (HICSIG) position statement: infection control guidelines for patients with influenza-like illnesses, including pandemic (H1N1) influenza 2009, in Australian health care facilities. Content: Standard and Droplet Precautions are considered adequate to control the transmission of influenza in most health care situations. Vaccination of health care staff, carers and vulnerable patients against seasonal and, eventually, pandemic influenza strains is an essential protective strategy. Management principles include: performance of hand hygiene before and after every patient contact or contact with the patient environment, in accord with the national 5 Moments for Hand Hygiene Standard; disinfection of the patient environment; early identification and isolation of patients with suspected or proven influenza; adoption of a greater minimum distance of patient separation (2 metres) than previously recommended; use of a surgical mask and eye protection for personal protection on entry to infectious areas or within 2 metres of an infectious patient; contact tracing for patient and health care staff and restriction of prophylactic antivirals mainly to those at high risk of severe disease; in high aerosol-risk settings, use of particulate mask, eye protection, impervious long-sleeved gown, and gloves donned in that sequence and removed in reverse sequence, avoiding self-contamination; exclusion of symptomatic staff from the workplace until criteria for non-infectious status are met; reserving negative-pressure ventilation rooms (if available) for intensive care patients, especially those receiving non-invasive ventilation; ensuring that infectious postpartum women wear surgical masks when caring for their newborn infants and practise strict hand hygiene; and implementation of special arrangements for potentially infected newborns who require nursery or intensive care.", "qid": 12, "docid": "i6ygg9yh", "rank": 7, "score": 0.8334850072860718}, {"content": "Title: Guidelines for environmental infection control in health-care facilities. Recommendations of CDC and the Healthcare Infection Control Practices Advisory Committee (HICPAC). Content: The health-care facility environment is rarely implicated in disease transmission, except among patients who are immunocompromised. Nonetheless, inadvertent exposures to environmental pathogens (e.g., Aspergillus spp. and Legionella spp.) or airborne pathogens (e.g., Mycobacterium tuberculosis and varicella-zoster virus) can result in adverse patient outcomes and cause illness among health-care workers. Environmental infection-control strategies and engineering controls can effectively prevent these infections. The incidence of health-care--associated infections and pseudo-outbreaks can be minimized by 1) appropriate use of cleaners and disinfectants; 2) appropriate maintenance of medical equipment (e.g., automated endoscope reprocessors or hydrotherapy equipment); 3) adherence to water-quality standards for hemodialysis, and to ventilation standards for specialized care environments (e.g., airborne infection isolation rooms, protective environments, or operating rooms); and 4) prompt management of water intrusion into the facility. Routine environmental sampling is not usually advised, except for water quality determinations in hemodialysis settings and other situations where sampling is directed by epidemiologic principles, and results can be applied directly to infection-control decisions. This report reviews previous guidelines and strategies for preventing environment-associated infections in health-care facilities and offers recommendations. These include 1) evidence-based recommendations supported by studies; 2) requirements of federal agencies (e.g., Food and Drug Administration, U.S. Environmental Protection Agency, U.S. Department of Labor, Occupational Safety and Health Administration, and U.S. Department of Justice); 3) guidelines and standards from building and equipment professional organizations (e.g., American Institute of Architects, Association for the Advancement of Medical Instrumentation, and American Society of Heating, Refrigeration, and Air-Conditioning Engineers); 4) recommendations derived from scientific theory or rationale; and 5) experienced opinions based upon infection-control and engineering practices. The report also suggests a series of performance measurements as a means to evaluate infection-control efforts.", "qid": 12, "docid": "s9c9utbq", "rank": 8, "score": 0.8324055075645447}, {"content": "Title: Perioperative COVID-19 Defense: An Evidence-Based Approach for Optimization of Infection Control and Operating Room Management Content: We describe an evidence-based approach for optimization of infection control and operating room management during the coronavirus disease 2019 (COVID-19) pandemic. Confirmed modes of viral transmission are primarily, but not exclusively, contact with contaminated environmental surfaces and aerosolization. Evidence-based improvement strategies for attenuation of residual environmental contamination involve a combination of deep cleaning with surface disinfectants and ultraviolet light (UV-C). (1) Place alcohol-based hand rubs on the intravenous (IV) pole to the left of the provider. Double glove during induction. (2) Place a wire basket lined with a zip closure plastic bag on the IV pole to the right of the provider. Place all contaminated instruments in the bag (eg, laryngoscope blades and handles) and close. Designate and maintain clean and dirty areas. After induction of anesthesia, wipe down all equipment and surfaces with disinfection wipes that contain a quaternary ammonium compound and alcohol. Use a top-down cleaning sequence adequate to reduce bioburden. Treat operating rooms using UV-C. (3) Decolonize patients using preprocedural chlorhexidine wipes, 2 doses of nasal povidone-iodine within 1 hour of incision, and chlorhexidine mouth rinse. (4) Create a closed lumen IV system and use hub disinfection. (5) Provide data feedback by surveillance of Enterococcus, Staphylococcus aureus, Klebsiella, Acinetobacter, Pseudomonas, and Enterobacter spp. (ESKAPE) transmission. (6) To reduce the use of surgical masks and to reduce potential COVID-19 exposure, use relatively long (eg, 12 hours) staff shifts. If there are 8 essential cases to be done (each lasting 1-2 hours), the ideal solution is to have 2 teams complete the 8 cases, not 8 first case starts. (7) Do 1 case in each operating room daily, with terminal cleaning after each case including UV-C or equivalent. (8) Do not have patients go into a large, pooled phase I postanesthesia care unit because of the risk of contaminating facility at large along with many staff. Instead, have most patients recover in the room where they had surgery as is done routinely in Japan. These 8 programmatic recommendations stand on a substantial body of empirical evidence characterizing the epidemiology of perioperative transmission and infection development made possible by support from the Anesthesia Patient Safety Foundation (APSF).", "qid": 12, "docid": "wcqxqkqw", "rank": 9, "score": 0.832366943359375}, {"content": "Title: Perioperative COVID-19 Defense: An Evidence-Based Approach for Optimization of Infection Control and Operating Room Management Content: We describe an evidence-based approach for optimization of infection control and operating room management during the Coronavirus Disease 2019 (COVID-19) pandemic. Confirmed modes of viral transmission are primarily, but not exclusively, contact with contaminated environmental surfaces and aerosolization. Evidence-based improvement strategies for attenuation of residual environmental contamination involve a combination of deep cleaning with surface disinfectants and ultraviolet light (UV-C). (1) Place alcohol-based hand rubs on the intravenous (IV) pole to the left of the provider. Double glove during induction. (2) Place a wire basket lined with a zip closure plastic bag on the IV pole to the right of the provider. Place all contaminated instruments in the bag (eg, laryngoscope blades and handles) and close. Designate and maintain clean and dirty areas. After induction of anesthesia, wipe down all equipment and surfaces with disinfection wipes that contain a quaternary ammonium compound and alcohol. Use a top-down cleaning sequence adequate to reduce bioburden. Treat operating rooms using UV-C. (3) Decolonize patients using preprocedural chlorhexidine wipes, 2 doses of nasal povidone-iodine within 1 hour of incision, and chlorhexidine mouth rinse. (4) Create a closed lumen IV system and use hub disinfection. (5) Provide data feedback by surveillance of Enterococcus, Staphylococcusaureus, Klebsiella, Acinetobacter, Pseudomonas, and Enterobacter spp. (ESKAPE)transmission. (6) To reduce the use of surgical masks and to reduce potential COVID-19 exposure, use relatively long (eg, 12hours) staff shifts. If there are 8 essential cases to be done (each lasting 1\u20132 hours), the ideal solution is to have 2 teams complete the 8 cases, not 8 first case starts. (7) Do 1 case in each operating room daily, with terminal cleaning after each case including UV-C or equivalent. (8) Do not have patients go into a large, pooled phase I postanesthesia care unit because of the risk of contaminating facility at large along with many staff. Instead, have most patients recover in the room where they had surgery as is done routinely in Japan. These 8 programmatic recommendations stand on a substantial body of empirical evidence characterizing the epidemiology of perioperative transmission and infection development made possible by support from the Anesthesia Patient Safety Foundation (APSF).", "qid": 12, "docid": "7km43hig", "rank": 10, "score": 0.8320868611335754}, {"content": "Title: Transport and Management of Patients With Confirmed or Suspected Ebola Virus Disease Content: The foundation of safe care for patients with confirmed or suspected Ebola virus disease is effective infection control practice, which requires implementation of appropriate administrative policies, work practices, and environmental controls, accompanied by focused education, training, and supervision. In 2002, Emory University partnered with the Centers for Disease Control and Prevention to develop a capability for the evaluation and management of individuals with serious communicable disease. In 2005, the University of Nebraska developed a similar isolation capability. In each case, the hospitals partnered with emergency medical services (EMS) professionals to ensure safe out-of-hospital transport and management of their patients. The objectives of these hospital and out-of-hospital collaborations were to close education, training, and practice gaps to best facilitate the care for patients with serious communicable disease while ensuring the safety of the medics and the general public through meticulous implementation of infection control practices as recommended by Centers for Disease Control and Prevention. The description of practices implemented by EMS teams in these communities for the transport of patients with confirmed Ebola virus disease is shared so that others might more readily implement these practices, policies, and procedures as applicable to their mission requirements and system design. Transport of patients with relevant travel history and development of illness (persons under investigation) is also included.", "qid": 12, "docid": "4b3i30hi", "rank": 11, "score": 0.8295987844467163}, {"content": "Title: Prevention of infectious diseases in cat shelters: ABCD guidelines. Content: OVERVIEW Recommendations are given in relation to infectious diseases in rescue shelters. The ABCD recognises that there is a wide variation in the design and management of shelters, and that these largely reflect local pressures. These guidelines are written with this diverse audience in mind; they point to the ideal, and also provide for some level of compromise where this ideal cannot immediately be attained. In addition consideration should be given to general requirements in order to optimise overall health and wellbeing of cats within the shelter. HOUSING: Compartmentalisation of the shelter into at least three individual sections (quarantine area for incoming cats, isolation facilities for sick or potentially infectious cats, and accommodation for clinically healthy, retrovirus-negative cats) can facilitate containment of a disease outbreak, should it occur. STANDARD OF CARE: Incoming cats should receive a full health check by a veterinary surgeon, should be dewormed and tested for retrovirus infections (feline leukaemia virus [FeLV] and/or feline immunodeficiency virus [FIV]) in regions with high prevalence and in shelters that allow contact between cats. Cats which are not rehomed should receive a regular veterinary check-up at intervals recommended by their veterinarian. VACCINATION Each cat should be vaccinated as soon as possible against feline panleukopenia virus (FPV), feline herpesvirus (FHV-1) and feline calicivirus (FCV) infections. HYGIENE: Adequate hygiene conditions should ensure that contact between shedders of infectious agents and susceptible animals is reduced as efficiently as possible by movement control, hygiene procedures of care workers, barrier nursing, cleaning and disinfection. STRESS REDUCTION: Stress reduction is important for overall health and for minimising the risk of recrudescence and exacerbation of infectious diseases. In general, a special effort should be made to rehome cats as soon as possible.", "qid": 12, "docid": "n0h6syqo", "rank": 12, "score": 0.8286040425300598}, {"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": 0.8280665874481201}, {"content": "Title: Transportation of Patients in a Bioemergency Content: Serious recurrent and emerging communicable diseases, such as novel influenza strains, highly pathogenic viral hemorrhagic fevers, and novel coronaviruses in an era of increased globalization and travel, necessitate heightened vigilance and preparedness. Last year over four billion persons traveled by air. Systems and processes need to be in place to not just recognize and treat individuals, who harbor a serious pathogen, but also to manage and transport them safely while minimizing the risk of transmission to healthcare workers and others in the community. In this chapter, environmental and administrative controls, work practices, and personal protective equipment necessary to prevent transmission are described for the management and transportation of patients in both the out-of-hospital and hospital settings.", "qid": 12, "docid": "qnpagtt1", "rank": 14, "score": 0.8278920650482178}, {"content": "Title: Viral Haemorrhagic Fever (VHF) and Other Serious Viral Infections: First contact - how to act and protect Content: Viral haemorrhagic fever\u2014VHF\u2014virus and a number of other special viruses are considered to cause the world\u2019s most dangerous infections with very high mortality, lack of therapeutic possibilities and often absence of effective vaccines. Such viruses are identified as \u201cbiohazard-level 4\u201d agents and are treated at the highest level of infection protection with strict isolation measures. At least 14 patients with Ebola disease were transported to Europe and the United States (11 patients) for hospital treatment during the African epidemic in 2014. There were no secondary spread of VHF import cases in Europe and the United States from 1999 until the Ebola outbreak in 2014. Then there were three cases of nosocomial spread to personnel in hospitals, two in the United States and one in Spain, despite alleged use of strict containment routines. This indicates a high risk of spread of infection through intensive treatment and handling of very sick persons with VHF like Ebola. In most cases vaccines are not available or specific antiviral drugs. Therefore, infection control must be based on a proper infection protection. This chapter is focused on practical means to handle and treat patients with suspect VHF or other dangerous agents to avoid spread to personnel and environment", "qid": 12, "docid": "8smcftey", "rank": 15, "score": 0.8278194665908813}, {"content": "Title: Raising the Yellow Flag: State Variation in Quarantine Laws. Content: Quarantine is an important but often misused tool of public health. An effective quarantine requires a process that inspires trust in government, only punishes noncompliance, and promotes a culture of social responsibility. Accomplishing successful quarantine requires incentives and enabling factors, payments, job security, and a tiered enforcement plan. In this article, we examine the variation in state-level quarantine laws and assess the effectiveness of these laws and regulations. We find that most states allow for an individual to have a hearing (63%) and to have a voice in burial and cremation procedures (71%), yet are weak on all other individual rights measures. Only 20% of states have provisions to protect employment when an individual is under quarantine, and less than half have plans for safe and humane quarantines. Decision makers at the state and local levels must make a concerted effort to revise and update quarantine laws and regulations. Ideally, these laws and regulations should be harmonized so as to avoid confusion and disruption between states, and public health officials should work with populations to identify and address the factors that will support successful quarantines if they are ever required.", "qid": 12, "docid": "ivznlkhp", "rank": 16, "score": 0.8269374370574951}, {"content": "Title: Review of Hygiene and Disinfection Recommendations for Outpatient Glaucoma Care: A COVID Era Update Content: This review focuses on best practices and recommendations for hygiene and disinfection to limit exposure and transmission of infection in outpatient glaucoma clinics during the current COVID-19 pandemic.", "qid": 12, "docid": "welen5fl", "rank": 17, "score": 0.826566219329834}, {"content": "Title: High-Containment Pathogen Preparation in the Intensive Care Unit Content: The recent Ebola virus disease outbreak highlighted the need to build national and worldwide capacity to provide care for patients with highly infectious diseases. Specialized biocontainment units were successful in treating a number of critically ill patients with Ebola virus disease both in the United States and Europe. Several key principles underlie the care of critically ill patients in a high containment environment. Environmental factors, staffing, equipment, training, laboratory testing, procedures and waste management each present unique challenges. A multidisciplinary approach is key to developing effective systems and protocols to maintain the safety of patients, staff and communities.", "qid": 12, "docid": "yw2rn54u", "rank": 18, "score": 0.8262544870376587}, {"content": "Title: What does isolation mean in home healthcare? Content: In the event of an infectious disease outbreak, home health nurses are called upon to care for patients who have been placed on isolation precautions. To protect themselves, patients, and caregivers, nurses must be knowledgeable about infectious diseases and infection control procedures. A checklist is provided to assist the nurse and caregiver with guidance in performing the patient's care.", "qid": 12, "docid": "bdvcwaau", "rank": 19, "score": 0.8250306844711304}, {"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": 20, "score": 0.8231952786445618}, {"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": 21, "score": 0.8222566843032837}, {"content": "Title: Isolation: Serious, Infectious Diseases Content: All persons staying in hospitals should be protected against exposure to infectious agents, and especially to high-risk, dangerous agents - that pose a risk to health and life. It is not acceptable to place a patient with a known high-risk, serious infection in the same hospital room as other patients (WHO). In this chapter, the preparedness of isolation capacity and escalation of hospital beds for patients with dangerous infections are described.", "qid": 12, "docid": "rp10euqb", "rank": 22, "score": 0.8218646049499512}, {"content": "Title: Urgent and Emergent Eye Care Strategies to Protect Against COVID-19. Content: Objective This article presents additional strategies to the medical professional and support tactics to keep both the health care provider and patient as safe as possible during the COVID-19 pandemic. Observations Follicular conjunctivitis has been reported as an early sign of infection or during hospitalization for severe COVID-19 disease. It has been confirmed that COVID-19 is transmitted through both respiratory droplets and direct contact. Another possible route of viral transmission is entry through aerosolized droplets into the tears, which then pass through the nasolacrimal ducts and into the respiratory tract. For nonemergent care, eye care providers should use telehealth. Eye care providers should prioritize patient care in order of absolute necessity, such as sudden vision loss, sudden onset flashes and floaters, and eye trauma. In those cases, exposure should be minimized. The close proximity between eye care providers and their patients during slit-lamp examination may require further precautions, such as shields, barriers, and mask use to lower the risk of transmission via droplets or through hand to eye contact. Conclusions All nonemergent eye care appointments should be delayed or conducted remotely. For emergent in-person appointments, careful and appropriate adherence to Centers for Disease Control and Prevention recommendations may minimize exposure for both the health care provider and patient.", "qid": 12, "docid": "kf0jtqwl", "rank": 23, "score": 0.8218384981155396}, {"content": "Title: Challenge and strategies of infection control in psychiatric hospitals during biological disasters\u2014From SARS to COVID-19 in Taiwan Content: Psychiatric hospitals play an important role in supporting patients with mental illness to relieve symptoms and improve functioning in a physically and psychologically safe environment. However, these hospitals are also vulnerable to emerging infectious diseases. In early 2020, a psychiatric hospital and a psychiatric unit were reported to have nosocomial coronavirus disease 2019 (COVID-19) infection. A large number of patients and staff were severely impacted. This type of nosocomial infection threatens patient safety and quality of care. By learning from previous experiences of severe acute respiratory syndrome (SARS) and previous studies, psychiatric hospitals can provide safeguards to prevent nosocomial infection among patients and staff during an epidemic or biological disaster. These strategies include a series of actions such as following national guidelines for infection control, reserving adequate support for disinfection equipment, providing relevant and sufficient pro-service and in-service education and training, establishing regular surveillance of hand hygiene habits, proper communication and health education, and providing opportunities for vaccination if possible. Based on the harm reduction concept, staff division of office breaks and ward classification and shunting are recommended and should be further implemented.", "qid": 12, "docid": "vyun75bu", "rank": 24, "score": 0.8214412927627563}, {"content": "Title: Challenge and strategies of infection control in psychiatric hospitals during biological disasters-From SARS to COVID-19 in Taiwan Content: Psychiatric hospitals play an important role in supporting patients with mental illness to relieve symptoms and improve functioning in a physically and psychologically safe environment. However, these hospitals are also vulnerable to emerging infectious diseases. In early 2020, a psychiatric hospital and a psychiatric unit were reported to have nosocomial coronavirus disease 2019 (COVID-19) infection. A large number of patients and staff were severely impacted. This type of nosocomial infection threatens patient safety and quality of care. By learning from previous experiences of severe acute respiratory syndrome (SARS) and previous studies, psychiatric hospitals can provide safeguards to prevent nosocomial infection among patients and staff during an epidemic or biological disaster. These strategies include a series of actions such as following national guidelines for infection control, reserving adequate support for disinfection equipment, providing relevant and sufficient pro-service and in-service education and training, establishing regular surveillance of hand hygiene habits, proper communication and health education, and providing opportunities for vaccination if possible. Based on the harm reduction concept, staff division of office breaks and ward classification and shunting are recommended and should be further implemented.", "qid": 12, "docid": "6jivoj9l", "rank": 25, "score": 0.8214412927627563}, {"content": "Title: COVID-19 and endoscopy services in intermediately affected countries: a position statement from the saudi gastroenterology association Content: With the global pandemic due to coronavirus disease 2019 (COVID-19), there has been a significant strain on healthcare facilities. The infectivity rate, as well as the rate of healthcare workers who have fallen ill to the disease, has raised concerns globally on the proper management of patients as well as the role of safe healthcare provision utilizing personal protective equipment (PPE). Furthermore, the limited supply of PPEs has mandated rationing their use to achieve maximum utility and preservation. Multiple gastroenterology associations have issued guidance and statements that would help healthcare providers in navigating these unprecedented and difficult times, and the Saudi Gastroenterology Association has provided this statement in an effort to bring the most up to date information for the management of endoscopy units in terms of resources, manpower planning, scheduling, as well as infection control policies and leadership.", "qid": 12, "docid": "ltapj9xm", "rank": 26, "score": 0.8212428092956543}, {"content": "Title: COVID-19 and endoscopy services in intermediately affected countries: a position statement from the saudi gastroenterology association. Content: With the global pandemic due to coronavirus disease 2019 (COVID-19), there has been a significant strain on healthcare facilities. The infectivity rate, as well as the rate of healthcare workers who have fallen ill to the disease, has raised concerns globally on the proper management of patients as well as the role of safe healthcare provision utilizing personal protective equipment (PPE). Furthermore, the limited supply of PPEs has mandated rationing their use to achieve maximum utility and preservation. Multiple gastroenterology associations have issued guidance and statements that would help healthcare providers in navigating these unprecedented and difficult times, and the Saudi Gastroenterology Association has provided this statement in an effort to bring the most up to date information for the management of endoscopy units in terms of resources, manpower planning, scheduling, as well as infection control policies and leadership.", "qid": 12, "docid": "ytd9hpt1", "rank": 27, "score": 0.8212428092956543}, {"content": "Title: Application of the Updated CDC Isolation Guidelines for Health Care Facilities Content: THE CENTERS FOR DISEASE CONTROL and Prevention has published updated guidelines for isolation precautions that outline how health care workers can prevent the transmission of infectious agents to their patients and to themselves. THE GUIDELINES RE-EMPHASIZE standard precautions, which guide clinicians in the use of appropriate personal protective equipment (PPE), depending on the expected type of exposure. Respiratory hygiene/cough etiquette is incorporated into infection control practices as a new component of standard precautions. THE ARTICLE PROVIDES information on the new guidelines as well as information on newly emerging patho gens and methods to prevent disease transmission in health care settings.", "qid": 12, "docid": "q1rby2to", "rank": 28, "score": 0.8210077285766602}, {"content": "Title: Practical Steps to Improve Air Flow in Long-Term Care Resident Rooms to Reduce COVID-19 Infection Risk Content: The potential for spread of COVID-19 infections in skilled nursing facilities and other long-term care sites poses new challenges for nursing home administrators to protect patients and staff. It is anticipated that as acute care hospitals reach capacity, nursing homes may retain COVID-19 infected residents longer prior to transferring to an acute care hospital. This article outlines 5 pragmatic steps that long-term care facilities can take to manage airflow within resident rooms to reduce the potential for spread of infectious airborne droplets into surrounding areas, including hallways and adjacent rooms, using strategies adapted from negative-pressure isolation rooms in acute care facilities.", "qid": 12, "docid": "5gtasqn4", "rank": 29, "score": 0.8202601671218872}, {"content": "Title: Horses and the risk of zoonotic infections Content: Infectious agents are insidious, often changing to adapt to host defenses or treatment advances. Because these challenges will continue, the need to apply standard and transmission-based precautions is important not only in the human hospital setting but in the veterinary clinic setting. In addition, to prevent human infection and potential liability, clinics need to establish program algorithms to prevent disease spread for specific agents or planned procedures to respond to potential nosocomial and zoonotic disease events. These need to be done proactively. Furthermore, more money needs to be dedicated to establish infection control programs and to improve the science of infection control in the veterinary setting.", "qid": 12, "docid": "icwzey8o", "rank": 30, "score": 0.8202481865882874}, {"content": "Title: Inpatient Care of Patients with COVID-19: A Guide for Hospitalists Content: Since its emergence in December 2019, the virus known as severe acute respiratory syndrome coronavirus 2 has quickly caused a pandemic. This virus causes a disease now known as coronavirus disease 2019, or COVID-19. As an increasing proportion of the at-risk population becomes infected, and patients with severe illness are hospitalized, it is essential for hospitalists to remain current on how to best care for people with suspected or confirmed disease. Establishing a system for logistical planning, and accurate information sharing is strongly recommended. Infection control remains the ultimate goal. As such, health care workers should be educated on universal and isolation precautions, and the appropriate use of personal protective equipment. Social distancing should be encouraged to prevent the spread of infection, and creative and innovative ways to reduce contact may need to be considered. Moreover, it is imperative to prepare for contingencies as medical staff will inevitably get sick or become unavailable. Hospitalists have the difficult task of caring for patients while also adapting to the many logistical and social elements of a pandemic.", "qid": 12, "docid": "6a3u4gt0", "rank": 31, "score": 0.8194682598114014}, {"content": "Title: The Role of the Home Environment in the Transmission of Infectious Diseases Content: The purpose of this paper is to examine current health care literature (1980\u20132000) regarding the microbiology of the home environment, to summarize evidence of transmission within the home, and to assess effectiveness of cleaning practices and products. The home environment, particularly the kitchen and bathroom, serves as a reservoir of large numbers of microorganisms, particularly Enterobacteriacae,and infectious disease transmission has been demonstrated to occur in 6\u201360% of households in which one member is ill. Current food preparation and cleaning practices provide multiple opportunities for intra-household member spread. Routine cleaning is often sufficient, but in cases of household infection, may not adequately reduce environmental contamination. The effectiveness of disinfectants varies considerably and depends on how they are used as well as their intrinsic efficacy. The behavioral aspects of infection prevention in the home (e.g., foodhandling and cleaning practices) warrant increased public attention and education.", "qid": 12, "docid": "jwpb7862", "rank": 32, "score": 0.8189901113510132}, {"content": "Title: Current Practices for Infection Prevention in the Hospital Settings Content: The principles and practices aimed at prevention and control of hospital-acquired infections are directed at various links in the chain of transmission. They include the following: (1) to contain or eliminate the reservoirs of agents and/or to curtail the persistence of agents in a specific setting, (2) to protect the host against disease caused by microorganisms, and (3) to interrupt the transmission of infection. Interventions to modify environmental reservoirs are aimed at interrupting the transmission for these inanimate environmental sources. The barriers, e.g., masks, were used to keep the smells and \u201ccontagion\u201d away even before the germ theory of disease was conceived. The appropriate barriers now include gloves, gowns, and eye protection for blood/body fluid\u2013borne infections and high-filtration masks for infections transmitted by droplet nuclei. The most important and effective nosocomial infection control intervention remains the routine washing of hands before, between, and after patient contact in healthcare settings. This chapter focuses on the interruption of transmission of infectious agents in the hospital setting by Standard Precautions recommended for all patients and \u201cisolation\u201d of patients using precautions based on known methods of transmission.", "qid": 12, "docid": "mtpbzgr9", "rank": 33, "score": 0.8188503980636597}, {"content": "Title: Ethics and public health emergencies: restrictions on liberty. Content: Responses to public health emergencies can entail difficult decisions about restricting individual liberties to prevent the spread of disease. The quintessential example is quarantine. While isolating sick patients tends not to provoke much concern, quarantine of healthy people who only might be infected often is controversial. In fact, as the experience with severe acute respiratory syndrome (SARS) shows, the vast majority of those placed under quarantine typically don't become ill. Efforts to enforce involuntary quarantine through military or police powers also can backfire, stoking both panic and disease spread. Yet quarantine is part of a limited arsenal of options when effective treatment or prophylaxis is not available, and some evidence suggests it can be effective, especially when it is voluntary, home-based and accompanied by extensive outreach, communication and education efforts. Even assuming that quarantine is medically effective, however, it still must be ethically justified because it creates harms for many of those affected. Moreover, ethical principles of reciprocity, transparency, non-discrimination and accountability should guide any implementation of quarantine.", "qid": 12, "docid": "3rtx6fo3", "rank": 34, "score": 0.8187803030014038}, {"content": "Title: Protecting Chinese healthcare workers while combating the 2019 novel coronavirus Content: Hospital-associated transmission is an important route of spreading the 2019 novel coronavirus (2019-nCoV) infection and pneumonia (Corona Virus Disease 2019, COVID-19) [1]. Healthcare workers (HCWs) are at high risk while combating COVID-19 at the very frontline, and nosocomial outbreaks among HCWs are not unusual in similar settings; the 2003 severe acute respiratory syndrome (SARS) outbreak led to over 966 HCW infections with 1.4% deaths in mainland China [2]. As of 11 February 2020, 3019 HCWs might have been infected with 2019-nCov in China, 1716 HCW cases were confirmed by nucleic acid testing[3], and at least 6 HCWs died, including the famous whistleblower Dr Li Wenliang. In view of this severe situation, we are recommending urgent interventions to help to protect HCWs.", "qid": 12, "docid": "07ljynpv", "rank": 35, "score": 0.8185984492301941}, {"content": "Title: Inpatient Care of Patients with COVID-19: A Guide for Hospitalists Content: Abstract Since its emergence in December 2019, the virus known as severe acute respiratory syndrome coronavirus 2 has quickly caused a pandemic. This virus causes a disease now known as coronavirus disease 2019, or COVID-19. As an increasing proportion of the at-risk population becomes infected, and patients with severe illness are hospitalized, it is essential for hospitalists to remain current on how to best care for people with suspected or confirmed disease. Establishing a system for logistical planning, and accurate information sharing is strongly recommended. Infection control remains the ultimate goal. As such, healthcare workers should be educated on universal and isolation precautions, and the appropriate use of personal protective equipment. Social distancing should be encouraged to prevent the spread of infection, and creative and innovative ways to reduce contact may need to be considered. Moreover, it is imperative to prepare for contingencies as medical staff will inevitably get sick or become unavailable. Hospitalists have the difficult task of caring for patients, while also adapting to the many logistical and social elements of a pandemic.", "qid": 12, "docid": "kugr54if", "rank": 36, "score": 0.8182628154754639}, {"content": "Title: Hospital care in Departments defined as COVID-free: A proposal for a safe hospitalization protecting healthcare professionals and patients not affected by COVID-19 Content: The COVID-19 pandemic influenced the normal course of clinical practice leading to significant delays in the delivery of healthcare services for patients non affected by COVID-19. In the near future, it will be crucial to identify facilities capable of providing health care in compliance with the safety of healthcare professionals, administrative staff and patients. All the staff involved in the project of a Covid-free hospital should be subjected to a diagnostic swab for COVID-19 before the beginning of healthcare activity and then periodically in order to avoid the risk of contamination of patients during the process of care. The modifications of various activities involved in the process of care are described: outpatient care, reception of inpatients, inpatient ward and operating room. For outpatient care, modality of appointment procedure, characteristics of waiting room and personal protective equipment (PPE) for healthcare professionals and administrative staff are presented. Reception of inpatients shall be conditional on a negative swab for COVID-19 obtained with a drive-in procedure. The management of the operating room represents the most crucial step of the patient's care process. The surgical team should be restricted and monitored with periodic swabs; surgical procedures should be performed by experienced surgeons according to standard procedures; surgical training experimental treatments and research protocols should be suspended. Adequate personal protective equipment and measures to reduce aerosolization in the operating room (closed circuits, continuous cycle insufflators, fume extraction) should be adopted. Prevention of possible transmission of the virus during procedures in open, laparoscopic and endoscopic surgery is to use a multi-tactic approach, which includes correct filtration and ventilation of the operating room, the use of appropriate PPE (FFP3 plus surgical mask and protective visor for all the staff working in the operating room) and smoke evacuation devices with a suction and filter system. on behalf of the UrOP Executive Committee Giuseppe Ludovico, Angelo Cafarelli, Ottavio De Cobelli, Ferdinando De Marco, Giovanni Ferrari, Stefano Pecoraro, Angelo Porreca, Domenico Tuzzolo.", "qid": 12, "docid": "fpxfqss4", "rank": 37, "score": 0.8181256055831909}, {"content": "Title: Hospital care in Departments defined as COVID-free: A proposal for a safe hospitalization protecting healthcare professionals and patients not affected by COVID-19. Content: The COVID-19 pandemic influenced the normal course of clinical practice leading to significant delays in the delivery of healthcare services for patients non affected by COVID-19. In the near future, it will be crucial to identify facilities capable of providing health care in compliance with the safety of healthcare professionals, administrative staff and patients. All the staff involved in the project of a Covid-free hospital should be subjected to a diagnostic swab for COVID-19 before the beginning of healthcare activity and then periodically in order to avoid the risk of contamination of patients during the process of care. The modifications of various activities involved in the process of care are described: outpatient care, reception of inpatients, inpatient ward and operating room. For outpatient care, modality of appointment procedure, characteristics of waiting room and personal protective equipment (PPE) for healthcare professionals and administrative staff are presented. Reception of inpatients shall be conditional on a negative swab for COVID-19 obtained with a drive-in procedure. The management of the operating room represents the most crucial step of the patient's care process. The surgical team should be restricted and monitored with periodic swabs; surgical procedures should be performed by experienced surgeons according to standard procedures; surgical training experimental treatments and research protocols should be suspended. Adequate personal protective equipment and measures to reduce aerosolization in the operating room (closed circuits, continuous cycle insufflators, fume extraction) should be adopted. Prevention of possible transmission of the virus during procedures in open, laparoscopic and endoscopic surgery is to use a multi-tactic approach, which includes correct filtration and ventilation of the operating room, the use of appropriate PPE (FFP3 plus surgical mask and protective visor for all the staff working in the operating room) and smoke evacuation devices with a suction and filter system. on behalf of the UrOP Executive Committee Giuseppe Ludovico, Angelo Cafarelli, Ottavio De Cobelli, Ferdinando De Marco, Giovanni Ferrari, Stefano Pecoraro, Angelo Porreca, Domenico Tuzzolo.", "qid": 12, "docid": "dbt8h1u8", "rank": 38, "score": 0.8181256055831909}, {"content": "Title: Effective infection prevention and control strategies in a large, accredited, psychiatric facility in Singapore Content: The Institute of Mental Health in Singapore continues to attempt to prevent the introduction of COVID-19, despite community transmission. Essential services are maintained and quarantine measures are currently unnecessary. To help similar organizations, strategies are listed along three themes: sustaining essential services, preventing infection, and managing human and consumable resources.", "qid": 12, "docid": "8rs3oep3", "rank": 39, "score": 0.8179057836532593}, {"content": "Title: A home toolkit for primary prevention of influenza by individuals and families. Content: An influenza pandemic can overwhelm the capacities of hospitals, clinics, nursing facilities, and emergency services. The likelihood is that most of the individuals who are stricken will be cared for at home, and there is strong evidence that in-home caregivers bear a disproportionate risk of becoming infected. We reviewed the scientific literature after 2000 to identify steps that in-home caregivers can take to reduce the chances that they and other household members will become infected in the home. Personal hygiene, common masks, and technologies including air filters and UV light each offer incremental benefits, and in combination are expected to reduce a portion of the risk that household members face when caring for a member who has become infected. In pandemics and even seasonal epidemics, seemingly small steps can literally mean the difference between life and death, especially for in-home caregivers.", "qid": 12, "docid": "s4ahnmo8", "rank": 40, "score": 0.8178305625915527}, {"content": "Title: Medical Isolation and Solitary Confinement: Balancing Health and Humanity in US Jails and Prisons During COVID-19 Content: In the face of the continually worsening COVID-19 pandemic, jails and prisons have become the greatest vectors of community transmission and are a point of heightened crisis and fear within the global crisis. Critical public health tools to mitigate the spread of COVID-19 are medical isolation and quarantine, but use of these tools is complicated in prisons and jails where decades of overuse of punitive solitary confinement is the norm. This has resulted in advocates denouncing the use of any form of isolation and attorneys litigating to end its use. It is essential to clarify the critical differences between punitive solitary confinement and the ethical use of medical isolation and quarantine during a pandemic. By doing so, then all those invested in stopping the spread of COVID-19 in prisons can work together to integrate medically sound, humane forms of medical isolation and quarantine that follow community standards of care rather than punitive forms of solitary confinement to manage COVID-19.", "qid": 12, "docid": "mujpekyu", "rank": 41, "score": 0.8176953196525574}, {"content": "Title: Policies and practices of SHEA Research Network hospitals during the COVID-19 pandemic Content: To understand hospital policies and practices as the COVID-19 pandemic accelerated, the Society for Healthcare Epidemiology of America (SHEA) conducted a survey through the SHEA Research Network (SRN). The survey assessed policies and practices around the optimization of personal protection equipment (PPE), testing, healthcare personnel policies, visitors of COVID-19 patients in relation to procedures, and types of patients. Overall, 69 individual healthcare facilities responded in the United States and internationally, for a 73% response rate.", "qid": 12, "docid": "f8j89otm", "rank": 42, "score": 0.8167702555656433}, {"content": "Title: Management of Tracheostomy during COVID-19 Outbreak: Heat and Moisture Exchanger Filter and Closed Suctioning System Content: \u2022 Precautions for safer management of tracheostomy should be taken for all patients. \u2022 HMEFs and closed endotracheal suctioning systems protect patients and healthcare professionals. \u2022 Precaution for reduce the COVID-19 diffusion should be taken until the epidemic is controlled.", "qid": 12, "docid": "77kedzec", "rank": 43, "score": 0.8165547847747803}, {"content": "Title: COVID-19 in Correctional and Detention Facilities - United States, February-April 2020 Content: An estimated 2.1 million U.S. adults are housed within approximately 5,000 correctional and detention facilities\u0086 on any given day (1). Many facilities face significant challenges in controlling the spread of highly infectious pathogens such as SARS-CoV-2, the virus that causes coronavirus disease 2019 (COVID-19). Such challenges include crowded dormitories, shared lavatories, limited medical and isolation resources, daily entry and exit of staff members and visitors, continual introduction of newly incarcerated or detained persons, and transport of incarcerated or detained persons in multiperson vehicles for court-related, medical, or security reasons (2,3). During April 22-28, 2020, aggregate data on COVID-19 cases were reported to CDC by 37 of 54 state and territorial health department jurisdictions. Thirty-two (86%) jurisdictions reported at least one laboratory-confirmed case from a total of 420 correctional and detention facilities. Among these facilities, COVID-19 was diagnosed in 4,893 incarcerated or detained persons and 2,778 facility staff members, resulting in 88 deaths in incarcerated or detained persons and 15 deaths among staff members. Prompt identification of COVID-19 cases and consistent application of prevention measures, such as symptom screening and quarantine, are critical to protecting incarcerated and detained persons and staff members.", "qid": 12, "docid": "aghf4p8h", "rank": 44, "score": 0.8165338039398193}, {"content": "Title: COVID-19 in Correctional and Detention Facilities - United States, February-April 2020. Content: An estimated 2.1 million U.S. adults are housed within approximately 5,000 correctional and detention facilities\u2020 on any given day (1). Many facilities face significant challenges in controlling the spread of highly infectious pathogens such as SARS-CoV-2, the virus that causes coronavirus disease 2019 (COVID-19). Such challenges include crowded dormitories, shared lavatories, limited medical and isolation resources, daily entry and exit of staff members and visitors, continual introduction of newly incarcerated or detained persons, and transport of incarcerated or detained persons in multiperson vehicles for court-related, medical, or security reasons (2,3). During April 22-28, 2020, aggregate data on COVID-19 cases were reported to CDC by 37 of 54 state and territorial health department jurisdictions. Thirty-two (86%) jurisdictions reported at least one laboratory-confirmed case from a total of 420 correctional and detention facilities. Among these facilities, COVID-19 was diagnosed in 4,893 incarcerated or detained persons and 2,778 facility staff members, resulting in 88 deaths in incarcerated or detained persons and 15 deaths among staff members. Prompt identification of COVID-19 cases and consistent application of prevention measures, such as symptom screening and quarantine, are critical to protecting incarcerated and detained persons and staff members.", "qid": 12, "docid": "jlxkr8p6", "rank": 45, "score": 0.8161985874176025}, {"content": "Title: Open visiting in the NHS Content: Sam Foster, Chief Nurse, Oxford University Hospitals, considers the balance of the benefits of enabling visiting with infection prevention and control practice during this pandemic.", "qid": 12, "docid": "h9kfn3nn", "rank": 46, "score": 0.8158231377601624}, {"content": "Title: Open visiting in the NHS. Content: Sam Foster, Chief Nurse, Oxford University Hospitals, considers the balance of the benefits of enabling visiting with infection prevention and control practice during this pandemic.", "qid": 12, "docid": "2oh90qjr", "rank": 47, "score": 0.8158231377601624}, {"content": "Title: Airway management considerations in patients with COVID-19 Content: Approximately 12% to 15% of hospitalized patients with COVID-19 infection require invasive ventilation via endotracheal intubation. The key to minimizing risk of disease transmission during this aerosol-generating procedure is careful preparation, which includes having necessary equipment and medications on hand as well as an experienced intubation team who can troubleshoot any unforeseen complications. Personal protective equipment should be donned and doffed in the presence of an assistant (ie, \"buddy\" system).", "qid": 12, "docid": "67y4nm2i", "rank": 48, "score": 0.8150290846824646}, {"content": "Title: Airway management considerations in patients with COVID-19. Content: Approximately 12% to 15% of hospitalized patients with COVID-19 infection require invasive ventilation via endotracheal intubation. The key to minimizing risk of disease transmission during this aerosol-generating procedure is careful preparation, which includes having necessary equipment and medications on hand as well as an experienced intubation team who can troubleshoot any unforeseen complications. Personal protective equipment should be donned and doffed in the presence of an assistant (ie, \"buddy\" system).", "qid": 12, "docid": "ed609mjn", "rank": 49, "score": 0.8150290846824646}, {"content": "Title: Optimizing response in surgical systems during and after COVID-19 pandemic: lessons from China and the UK \u2013 Perspective Content: Triage strategies to keep suspected and confirmed cases in isolation. Virtual consultations and limiting all out patient activity. Screening asymptomatic patients with nucleic acid test, antibody testing & CT chest. Designated staff and operating areas for COVID 19 infected patients. Careful use of laparoscopy with precautions. Limited operating on cancer patients with consideration of alternatives treatment strategies. Precaution and protocol are needed after the epidemic.", "qid": 12, "docid": "caahtt3b", "rank": 50, "score": 0.814994215965271}, {"content": "Title: Nonpharmaceutical Interventions for Pandemic Influenza, National and Community Measures Content: The World Health Organization's recommended pandemic influenza interventions, based on limited data, vary by transmission pattern, pandemic phase, and illness severity and extent. In the pandemic alert period, recommendations include isolation of patients and quarantine of contacts, accompanied by antiviral therapy. During the pandemic period, the focus shifts to delaying spread and reducing effects through population-based measures. Ill persons should remain home when they first become symptomatic, but forced isolation and quarantine are ineffective and impractical. If the pandemic is severe, social distancing measures such as school closures should be considered. Nonessential domestic travel to affected areas should be deferred. Hand and respiratory hygiene should be routine; mask use should be based on setting and risk, and contaminated household surfaces should be disinfected. Additional research and field assessments during pandemics are essential to update recommendations. Legal authority and procedures for implementing interventions should be understood in advance and should respect cultural differences and human rights.", "qid": 12, "docid": "bb6lv6yg", "rank": 51, "score": 0.814761757850647}, {"content": "Title: Control of Viral Contamination of Food and Environment Content: Viruses are often transmitted via food and the environment. Contamination may be controlled either by preventing its occurrence or by inactivating the contaminating virus. The majority of agents transmitted in this way are human enteric viruses, produced either in the intestines or the liver. They are shed in human feces (noroviruses also in vomitus) in a broad range of circumstances, and they are relatively stable outside the host. Non-enteric viruses are less often transmitted via foods and are generally less environmentally stable. Insofar as vaccines are available, they are able to prevent fecal shedding. Viruses shed in feces via the water-carriage toilet may be eliminated by proper treatment and disinfection of the wastewater. In the foods context, the most effective antiviral measures are cooking and hand washing. Detection methods are most useful after the fact, in investigating outbreaks and devising preventive measures.", "qid": 12, "docid": "wvfrwnft", "rank": 52, "score": 0.8147448301315308}, {"content": "Title: Infections in Confined Spaces: Cruise Ships, Military Barracks, and College Dormitories Content: The presence of a vast cohort of individuals in semi-confined settings such as cruise ships, military barracks, and college dormitories is often accompanied by an increase in the risk of particular infections. These are often gastrointestinal infections on cruise ships and respiratory pathogens that are easily transmitted in the barrack and dormitory setting. The control of these infections involves attention to good personal hygiene, safe food and water handling, and use of vaccines to prevent vaccine-preventable diseases.", "qid": 12, "docid": "u0v2zfze", "rank": 53, "score": 0.8147270679473877}, {"content": "Title: Will your ED have staff quarantined for SARS? Brace yourself for the worst. Content: One Albuquerque, NM, ED's staff were quarantined after exposure to a suspected severe acute respiratory syndrome (SARS) patient, which underscores the importance of reducing risks of transmission. Reduce the number of contacts by isolating patients immediately. Triage nurses should have quick access to N-95 respirators. Ask security to screen all patients arriving by car before they enter the ED.", "qid": 12, "docid": "8z1tko13", "rank": 54, "score": 0.814477801322937}, {"content": "Title: Healthcare personnel and nosocomial transmission of pandemic 2009 influenza. Content: Knowledge regarding the modes of transmission of pandemic 2009 H1N1 influenza continues to develop, as do recommendations for the prevention of spread within healthcare facilities. The adoption of the most prudent, multifaceted approaches is recommended until there is significant evidence to reduce protective measures. The greatest threat to healthcare personnel and patients appears to be exposure to patients, healthcare personnel, or visitors who have not been recognized as contagious. The processes used within healthcare facilities must hold this concept central to any infection control plan and act in a preventive manner. This article focuses on the development of an algorithm for intensive care unit intake precautions, based on the early identification of potential source patients, as well as appropriate selection and adequate use of personal protective equipment. Visitor management, hand and respiratory hygiene, and cough etiquette have been used as measures to decrease the spread of infection. Vaccination of healthcare personnel, combined with work furlough for ill workers, is also explored. Recommendations include the elimination of potential exposures, engineering and administrative controls, and utilization of personal protective equipment.", "qid": 12, "docid": "d2axm29e", "rank": 55, "score": 0.8142248392105103}, {"content": "Title: 15 Cleaning and decontamination of the healthcare environment Content: Abstract: Evidence is accumulating for the role of cleaning in controlling hospital infections. Hospital pathogens such as meticillin-resistant Staphylococcus aureus (MRSA), vancomycin-resistant enterococci (VRE), norovirus, multi-resistant Gram-negative bacilli and Clostridium difficile persist in the healthcare environment for considerable lengths of time. Cleaning with both detergent and disinfectant-based regimens help control these pathogens in both routine and outbreak situations. The most important transmission risk comes from organisms on frequently handled items because hand contact with a contaminated site could deliver a pathogen to a patient. Cleaning practices should be tailored to clinical risk, near-patient areas and hand-touch-sites and scientifically evaluated for all surfaces and equipment in today\u2019s hospitals.", "qid": 12, "docid": "9rn8kzst", "rank": 56, "score": 0.8142098188400269}, {"content": "Title: Urgent and Emergent Eye Care Strategies to Protect Against COVID-19 Content: Objective: This article presents additional strategies to the medical professional and support tactics to keep both the health care provider and patient as safe as possible during the COVID-19 pandemic Observations: Follicular conjunctivitis has been reported as an early sign of infection or during hospitalization for severe COVID-19 disease It has been confirmed that COVID-19 is transmitted through both respiratory droplets and direct contact Another possible route of viral transmission is entry through aerosolized droplets into the tears, which then pass through the nasolacrimal ducts and into the respiratory tract For nonemergent care, eye care providers should use telehealth Eye care providers should prioritize patient care in order of absolute necessity, such as sudden vision loss, sudden onset flashes and floaters, and eye trauma In those cases, exposure should be minimized The close proximity between eye care providers and their patients during slit-lamp examination may require further precautions, such as shields, barriers, and mask use to lower the risk of transmission via droplets or through hand to eye contact Conclusions: All nonemergent eye care appointments should be delayed or conducted remotely For emergent in-person appointments, careful and appropriate adherence to Centers for Disease Control and Prevention recommendations may minimize exposure for both the health care provider and patient", "qid": 12, "docid": "v4e771kj", "rank": 57, "score": 0.8138337135314941}, {"content": "Title: Strategie einer universit\u00e4ren Notaufnahme f\u00fcr das COVID-19-Management im Rahmen einer beginnenden Epidemie Content: Due to the increasing number of COVID-19 infections worldwide, all hospitals are faced with the challenge associated with the pandemic. In particular, emergency rooms must prepare and implement completely new workflows. This applies in particular to patient screening and selection (triage). Close cooperation with other specialist areas such as hygiene, infectiology or virology is also necessary in order to implement appropriate treatment concepts before, during and after the diagnosis is completed. In addition, communication and quality and risk management are highly relevant in addition to the clinical aspects. This article uses COVID-19 as an example to describe how emergency rooms can prepare for a pandemic.", "qid": 12, "docid": "vf0k6doq", "rank": 58, "score": 0.8135652542114258}, {"content": "Title: Tuberculosis control: lessons for outbreak preparedness in correctional facilities. Content: Correctional facilities typically house large numbers of persons in close and crowded conditions for long periods. Clusters of communicable diseases ranging from simple viral upper respiratory infections to more serious threats, such as tuberculosis (TB), infections with methicillin-resistant Staphylococcus aureus, and influenza, often emerge in these surroundings. The recent H1N1 influenza pandemic highlights the importance of outbreak prevention and containment preparedness, particularly in congregate settings. In this commentary, the authors propose that the TB control model can provide valuable lessons for infection control practitioners to prepare for, identify, investigate, and control outbreaks of communicable diseases to prevent transmission in correctional facilities and to the surrounding community.", "qid": 12, "docid": "nfdnoee2", "rank": 59, "score": 0.8134047985076904}, {"content": "Title: Rewarding and Recognizing Frontline Staff for Success in Infection Prevention Content: Management practices help support efforts to prevent healthcare-associated infections (HAIs). Providing rewards and recognition to frontline staff is one management practice found to be in use by hospitals that are higher-performers in HAI prevention. Using data from interviews with hospital managers and frontline staff at 18 US hospitals, our study identifies how managers can use reward and recognition programs as motivational tools to sustain frontline HAI prevention efforts.", "qid": 12, "docid": "d19gp1st", "rank": 60, "score": 0.8133587837219238}, {"content": "Title: Infection control and pandemic influenza. Content: If an influenza pandemic occurs, the spread of the virus should be reduced for as long as possible while an effective vaccine is produced. Influenza spreads mainly by large respiratory droplets (> 5 microm) depositing onto the mucosal surfaces of the eye, mouth or respiratory tract. Hands are another major means for spread, and are frequently contaminated by droplets. The most effective way to reduce the spread of the virus is with good infection control practices and social distancing. Infection control practices include the use of personal protective equipment (PPE), hand hygiene, and respiratory hygiene and cough etiquette. Infected people should be isolated and spatial separation observed in common areas where infected people may be present. Any practices that create aerosols (eg, nebulisation) should be avoided, unless performed with appropriate precautions, especially with all people in the room wearing appropriate PPE. Now is the time to re-examine all our current practices so that we are better prepared, well practised and have good infection control practices in place for all transmissible respiratory infections.", "qid": 12, "docid": "z6upi7y2", "rank": 61, "score": 0.8132839798927307}, {"content": "Title: Quarantine Stressing Voluntary Compliance Content: A 1-day table-top exercise in San Diego, California, in December 2004 emphasized voluntary compliance with home quarantine to control an emerging infectious disease outbreak. The exercise heightened local civilian-military collaboration in public health emergency management. Addressing concerns about lost income by residents in quarantine was particularly challenging.", "qid": 12, "docid": "bu617h9z", "rank": 62, "score": 0.8129804134368896}, {"content": "Title: Infection control and its application to the administration of intravenous medications during gastrointestinal endoscopy Content: Several infection control practices and procedures crucial to the prevention of disease transmission in the health care setting are reviewed and discussed. Emphasis is placed on the importance of infection control to gastrointestinal endoscopy. Recommendations that minimize the risk of nosocomial infection during the preparation, handling, and administration of intravenous medications, particularly propofol, are provided. These recommendations include the labeling of predrawn syringes; use of sterile single-use syringes, needles, and administration sets for each patient; and, whenever feasible, administration of intravenous medications promptly after opening their prefilled syringes or after opening their ampoules or vials and filling the sterile syringes.", "qid": 12, "docid": "4ks6i3gi", "rank": 63, "score": 0.8122369050979614}, {"content": "Title: Communicable Diseases and Emerging Pathogens: The Past, Present, and Future of High-Level Containment Care Content: High-level containment care involves the management of patients with highly hazardous communicable diseases in specialized biocontainment units possessing a unique collection of engineering, administrative, and personnel controls. These controls are more stringent than those found in conventional airborne infection isolation rooms and provide additional safeguards against nosocomial disease transmission. Borne amidst a convergence of events in 1969, the employment of HLCC units was validated during the 2014\u20132016 Ebola virus disease outbreak, and the United States (as well as many other nations) is in the process of expanding its HLCC capacity. Beyond Ebola, however, the specific diseases that might warrant care in a HLCC unit remain unclear. We review here the fascinating history of HLCC and of biocontainment units and make recommendations regarding those highly hazardous communicable diseases that might optimally be managed in these units.", "qid": 12, "docid": "92hnaiyc", "rank": 64, "score": 0.8120582103729248}, {"content": "Title: Tracing and Preventing Infections Content: A total of 10\u201320% of somatic patients experience hospital infections during/after hospitalization. Pneumonia, sepsis, surgical site infections and urinary tract infections are most often associated with patient-related use of medical devices for approximately 65% of cases, while nontechnical equipment may be linked to 35% of cases. It is resource-intensive to detect the cause of infection outbreaks and even more expensive not to take action. Unexplained causes of outbreaks may lead to uncertainty and reduced activity at the hospital. To trace and prevent hospital outbreaks, joint efforts from hospital management, microbiology and infection control are needed. This chapter is focused on practical measures to trace and prevent hospital outbreaks.", "qid": 12, "docid": "e5m4lerm", "rank": 65, "score": 0.8118903636932373}, {"content": "Title: Saudi Society for Cardiac Surgeons consensus document on COVID-19, April 1, 2020 Content: The COVID-19 pandemic represents an international health crisis that is challenging to all governments. Health practitioners in different fields have a duty to guide people and governments to achieve safe health practices. The Saudi Society for Cardiac Surgeons recognizes that it is difficult to establish evidence-based guidelines for safe cardiac surgery practices in such a crisis because this is an unprecedented health pandemic. So we decided to work with our colleagues in other societies by reviewing different recommendations and safe practices issued by different health organizations and scientific societies. The aim was to come up with recommendations that could guide hospitals, physicians, and other members of the healthcare team on the best available practices that are applicable to our community and that will not only ensure optimum patient care delivery but also protect healthcare workers from the risk of infection and aid the national effort in containing and managing this worldwide pandemic.", "qid": 12, "docid": "ww4jwn6q", "rank": 66, "score": 0.8117698431015015}, {"content": "Title: Saudi Society for Cardiac Surgeons consensus document on COVID-19, April 1, 2020. Content: The COVID-19 pandemic represents an international health crisis that is challenging to all governments. Health practitioners in different fields have a duty to guide people and governments to achieve safe health practices. The Saudi Society for Cardiac Surgeons recognizes that it is difficult to establish evidence-based guidelines for safe cardiac surgery practices in such a crisis because this is an unprecedented health pandemic. So we decided to work with our colleagues in other societies by reviewing different recommendations and safe practices issued by different health organizations and scientific societies. The aim was to come up with recommendations that could guide hospitals, physicians, and other members of the healthcare team on the best available practices that are applicable to our community and that will not only ensure optimum patient care delivery but also protect healthcare workers from the risk of infection and aid the national effort in containing and managing this worldwide pandemic.", "qid": 12, "docid": "cgbphd7l", "rank": 67, "score": 0.8117698431015015}, {"content": "Title: Preventing needlestick injuries among healthcare workers: a WHO-ICN collaboration. Content: Effective measures to prevent infections from occupaonal exposure of healthcare workers to blood include mmunization against HBV, eliminating unnecessary injections, implementing Universal Precautions, eliminating needle recapping and disposing of the sharp into a sharps container immediately after use, use of safer devices such as needles that sheath or retract after use, provision and use of personal protective equipment, and training workers in the risks and prevention of transmission. Post-exposure prophylaxis with antiretroviral medications can reduce the risk of HIV transmission by 80%. In 2003, the World Health Organization and the International Council of Nurses launched a pilot project in three countries to protect healthcare workers from needlestick injuries. The results of the pilot will be disseminated worldwide, along with best policies and practices for prevention.", "qid": 12, "docid": "bfxfgfke", "rank": 68, "score": 0.811441957950592}, {"content": "Title: Outbreaks in Health Care Settings Content: Outbreaks and pseudo-outbreaks in health care settings can be complex and should be evaluated systematically using epidemiologic tools. Laboratory testing is an important part of an outbreak evaluation. Health care personnel, equipment, supplies, water, ventilation systems, and the hospital environment have been associated with health care outbreaks. Settings including the neonatal intensive care unit, endoscopy, oncology, and transplant units are areas that have specific issues which impact the approach to outbreak investigation and control. Certain organisms have a predilection for health care settings because of the illnesses of patients, the procedures performed, and the care provided.", "qid": 12, "docid": "6fk6r2n2", "rank": 69, "score": 0.8112735152244568}, {"content": "Title: U.S. High-Level Isolation Unit Clinical Laboratory Capabilities Update. Content: In late 2014, 56 hospitals in the United States were designated by state and federal public health authorities as specially designed high-level isolation units (HLIUs) equipped with advanced infrastructure, laboratory capabilities, and trained staff to care for patients with highly hazardous communicable diseases (HHCDs), such as Ebola virus disease. This survey describes the clinical laboratory support capabilities of U.S. HLIUs, including the specific test menus that HLIUs have identified to safely manage HHCD patients and the locations where such testing would be performed. In spring 2016, a survey was electronically distributed, as a fillable pdf file, to the 56 U.S. HLIUs. Site representatives completed the surveys, and data were coded and analyzed in an electronic spreadsheet, using descriptive statistics. Thirty-six HLIUs (64%) responded, and 33 completed the laboratory capabilities section. Thirty-one HLIUs (94%) had performed risk analyses for all laboratory procedures and equipment. Twenty-nine (88%) had decontamination procedures specified for all laboratory equipment used for patients with suspected or confirmed HHCDs. On-site laboratories in 27 HLIUs (81%) had the capacity to inventory and to securely store HHCD patient specimens. Ten HLIUs (31%) had at least one test they would conduct within the patient isolation room. The high-risk nature of HHCDs and the occupational exposures that may occur in clinical laboratories demand advanced preparation and risk assessment of work practices, laboratory equipment, and instrumentation by HLIU laboratories. Although risk analyses of clinical laboratory testing and equipment that HLIUs have conducted have likely focused on those for Ebola virus, HLIUs must be prepared to revise their current procedures for other HHCDs.", "qid": 12, "docid": "1a9c2grr", "rank": 70, "score": 0.8106811046600342}, {"content": "Title: COVID-19, Quarantines, Sheltering-in-Place, and Human Rights: The Developing Crisis Content: As COVID-19 has spread across the globe, quarantines and sheltering-in-place orders have become important public health tools but, as currently implemented, have eroded human rights, particularly for the marginalized, including essential workers, detainees, women, and children. Quarantines and sheltering-in-place orders must include explicit guarantees of human rights protections. We outline protections for the quarantined that communities and governments should strive to guarantee.", "qid": 12, "docid": "r8vug98w", "rank": 71, "score": 0.8105714321136475}, {"content": "Title: COVID-19, Quarantines, Sheltering-in-Place, and Human Rights: The Developing Crisis. Content: As COVID-19 has spread across the globe, quarantines and sheltering-in-place orders have become important public health tools but, as currently implemented, have eroded human rights, particularly for the marginalized, including essential workers, detainees, women, and children. Quarantines and sheltering-in-place orders must include explicit guarantees of human rights protections. We outline protections for the quarantined that communities and governments should strive to guarantee.", "qid": 12, "docid": "uys4etn0", "rank": 72, "score": 0.8105714321136475}, {"content": "Title: Rapid responses in the emergency department of Linkou Chang Gung Memorial Hospital, Taiwan effectively prevents spread of COVID-19 among healthcare workers of emergency department during outbreak: Lessons learnt from SARS Content: Linkou Chang Gung Memorial Hospital, Taiwan has been on the forefront of efforts to manage and mitigate the Coronavirus Disease 2019 (COVID-19) pandemic since 20th January 2020. Despite having one of the largest and busiest emergency departments (EDs) in the world, we have managed to maintain a \u201czero-infection\u201d rate among our ED healthcare workers through various systematic approaches. The measures implemented include establishing a clear flowchart with route planning, strict infection control policies and regulation of medical equipment, and team-based segregation in the workplace. These strategies, borne of our experience during the severe acute respiratory syndrome (SARS) outbreak, can complement a network of well-trained personnel to enable EDs around the world in successfully mounting an effective defense against new airborne illness while minimizing healthcare personnel casualties.", "qid": 12, "docid": "ye63gmm0", "rank": 73, "score": 0.8105214834213257}, {"content": "Title: Measuring voluntary social distancing behavior during the COVID-19 pandemic Content: Staying home is an important part of the effort to contain COVID-19 and limit deaths. Every state in the United States has enacted policies to encourage distancing and staying home. An important question is how these policies interact with individuals voluntary responses to COVID-19 cases and deaths. We find evidence of a non-trivial voluntary response to local and nationally reported COVID-19 cases and deaths.", "qid": 12, "docid": "38hw71ax", "rank": 74, "score": 0.8102879524230957}, {"content": "Title: Protective measures for COVID-19 for healthcare providers and laboratory personnel Content: In the COVID-19 pandemic, which affects the whole world, healthcare professionals (HCP) are at high risk of transmission due to their direct contact with patients with COVID-19. Therefore, how to ensure the triage of the patient with acute respiratory symptoms should be determined in advance, the contact distance should be arranged to be at least 2 m, COVID-19 suspect or diagnosed patient should be instructed to wear a surgical mask. During the care of these patients, HCP should wear their personal protective equipment (PPE) in accordance with the procedure and should not neglect hand hygiene. The samples of the patient with known or suspected COVID-19, patient should also be known to be risky in terms of contamination, and a risk assessment should be performed for the procedures to be performed in laboratories. The PPE should be used in accordance with the procedure to be performed. The protection of the HCP, who sacrifice at the risk of life, is possible only by complying with infection control and precautions.", "qid": 12, "docid": "5ozpmq39", "rank": 75, "score": 0.810239315032959}, {"content": "Title: The Role of the Environment and Colonization in Healthcare-Associated Infections Content: Healthcare-associated infections (HAIs) can be caused by endogenous host microbial flora or by exogenous microbes, including those found in the hospital environment. Efforts to decrease endogenous pathogens via decolonization and skin antisepsis may decrease the risk of infection in some settings. Controlling the spread of potential pathogens from the environment requires meticulous attention to cleaning and disinfection practices. In addition to selection of the appropriate cleaning agent, use of tools that assess the adequacy of cleaning and addition of no-touch cleaning technology may decrease environmental contamination. Hand hygiene is also a critical component of preventing transmission of pathogens from the environment to patients via healthcare worker hands.", "qid": 12, "docid": "aw3wirmb", "rank": 76, "score": 0.810081422328949}, {"content": "Title: Dietary habits in adults during quarantine in the context of COVID-19 pandemic Content: \u2022 Quarantine leads to stress condition that can change in dietary habits. \u2022 Better dietary habits are critical to enhance the body\u2019s immune system against COVID-19.", "qid": 12, "docid": "so658wa8", "rank": 77, "score": 0.8099527955055237}, {"content": "Title: Isolation rooms for highly infectious diseases: an inventory of capabilities in European countries Content: Summary Isolation of patients with highly infectious diseases (HIDs) in hospital rooms with adequate technical facilities is essential to reduce the risk of spreading disease. The European Network for Infectious Diseases (EUNID), a project co-funded by European Commission and involving 16 European Union member states, performed an inventory of high level isolation rooms (HIRs, hospital rooms with negative pressure and anteroom). In participating countries, HIRs are available in at least 211 hospitals, with at least 1789 hospital beds. The adequacy of this number is not known and will depend on prevailing circumstances. Sporadic HID cases can be managed in the available HIRs. HIRs could also have a role in the initial phases of an influenza pandemic. However, large outbreaks due to natural or to bioterrorist events will need management strategies involving healthcare facilities other than HIRs.", "qid": 12, "docid": "hxpo3wwf", "rank": 78, "score": 0.8098816871643066}, {"content": "Title: Practical Steps to Improve Air Flow in Long-Term Care Resident Rooms to Reduce COVID-19 Infection Risk Content: Abstract The potential for spread of COVID-19 infections in Skilled Nursing Facilities and other Long-Term Care sites poses new challenges for Nursing Home Administrators to protect patients and staff. It is anticipated that as Acute Care Hospitals reach capacity, Nursing Homes may retain COVID-19 infected residents longer prior to transferring to an Acute Care Hospital. This article outlines 5 pragmatic steps that Long-Term Care facilities can take to manage airflow within resident rooms to reduce the potential for spread of infectious airborne droplets into surrounding areas including hallways and adjacent rooms, using strategies adapted from negative pressure isolation rooms in acute care facilities.", "qid": 12, "docid": "djjarc0f", "rank": 79, "score": 0.8096607327461243}, {"content": "Title: Intubation of the patient with a suspected or confirmed COVID-19 infection Content: Abstract We propose a set of recommendations from our clinical practice for intubation of the patient with a suspected or confirmed COVID-19 infection, with a goal to safely securing the airway while optimizing infection prevention practices to reduce the risk to healthcare personnel.", "qid": 12, "docid": "uov0hvrc", "rank": 80, "score": 0.8095099925994873}, {"content": "Title: Are Contact Precautions ethically justifiable in contemporary hospital care? Content: Hospital infection control practices known as Contact Precautions are recommended for the management of people with pathogens such as methicillin-resistant Staphylococcus aureus or vancomycin-resistant Enterococci. Background: The patient is isolated, and staff are required to wear gloves, and a gown or apron when providing care. A notice is displayed to remind staff of these requirements and an 'alert' message is placed in the patient's medical record. Objective: The aim of this article is to discuss and explore whether practices used in hospitals to reduce the transmission of endemic antibiotic-resistant organisms are ethically justified in today's healthcare environment in the developed world. In order to do this, the history of the development of these practices is summarised, and the evidence base for their effectiveness is reviewed. Key bioethics principles are then discussed and contextualised from the perspective of hospital infection prevention and control, and an ethically superior model for the prevention and control of healthcare associated infection is proposed.", "qid": 12, "docid": "ky79aheq", "rank": 81, "score": 0.8094289302825928}, {"content": "Title: Management of patients infected with airborne-spread diseases: An algorithm for infection control professionals Content: BACKGROUND: Many US hospitals lack the capacity to house safely a surge of potentially infectious patients, increasing the risk of secondary transmission. Respiratory protection and negative-pressure rooms are needed to prevent transmission of airborne-spread diseases, but US hospitals lack available and/or properly functioning negative-pressure rooms. Creating new rooms or retrofitting existing facilities is time-consuming and expensive. METHODS: Safe methods of managing patients with airborne-spread diseases and establishing temporary negative-pressure and/or protective environments were determined by a literature review. Relevant data were analyzed and synthesized to generate a response algorithm. RESULTS: Ideal patient management and placement guidelines, including instructions for choosing respiratory protection and creating temporary negative-pressure or other protective environments, were delineated. Findings were summarized in a treatment algorithm. CONCLUSION: The threat of bioterrorism and emerging infections increases health care's need for negative-pressure and/or protective environments. The algorithm outlines appropriate response steps to decrease transmission risk until an ideal protective environment can be utilized. Using this algorithm will prepare infection control professionals to respond more effectively during a surge of potentially infectious patients following a bioterrorism attack or emerging infectious disease outbreak.", "qid": 12, "docid": "d4qany6k", "rank": 82, "score": 0.8093621730804443}, {"content": "Title: Prevention by Design Construction and Renovation of Health Care Facilities for Patient Safety and Infection Prevention Content: The built environment supports the safe care of patients in health care facilities. Infection preventionists and health care epidemiologists have expertise in prevention and control of health care\u2013associated infections (HAIs) and assist with designing and constructing facilities to prevent HAIs. However, design elements are often missing from initial concepts. In addition, there is a large body of evidence that implicates construction and renovation as being associated with clusters of HAIs, many of which are life threatening for select patient populations. This article summarizes known risks and prevention strategies within a framework for patient safety.", "qid": 12, "docid": "f3bpwm5j", "rank": 83, "score": 0.809346079826355}, {"content": "Title: Can the human coronavirus epidemic also spread through solid waste? Content: Wastes generated in healthcare facilities have been discussed and the World Health Organization has proposed a guideline for controlling the spread of the virus that causes Coronavirus Disease 2019 (COVID-19). However, waste management outside the generating facility should be discussed in more detail, taking into account factors such as virus resistance, differences in waste management systems and the climatic conditions in each affected region. Patients infected by human coronavirus being treated at home are generating infected waste possibly discarded as domestic waste, which can pose risks to workers and the environment, depending on the conditions of transport and disposal. In particular, the spread of the coronavirus may be increased by inadequate waste management, highlighting poor handling conditions associated with inappropriate use of personal protective equipment and other unfavourable conditions presented mainly in developing countries.", "qid": 12, "docid": "jkutm5ha", "rank": 84, "score": 0.8092248439788818}, {"content": "Title: Designing Medical Facilities to Care for Patients with Highly Hazardous Communicable Diseases Content: Certain highly hazardous communicable diseases (HHCD), including viral hemorrhagic fevers, the Middle East respiratory syndrome coronavirus (MERS-CoV), and severe acute respiratory syndrome virus (SARS), have caused nosocomial outbreaks in unprepared facilities. Consequently, biocontainment units have been constructed to protect caregivers, patients, and family members, in addition to providing optimal care of the infected patient. Biocontainment units have adopted many of the design features originally found in biocontainment laboratories and can serve as national referral facilities for the most severe and highly hazardous infections. Although a patient with a HHCD can show up at any healthcare facility unannounced, not every hospital can or should attempt to establish a biocontainment unit. Nevertheless, there are design features or management principles found in biocontainment units that can be adopted in most facilities. Awareness of the potential risk, in addition to adopting structural and policy control measures, can do a lot to prepare a facility for the next unexpected infectious disease outbreak.", "qid": 12, "docid": "2jhxnape", "rank": 85, "score": 0.8092234134674072}, {"content": "Title: COVID-19 Among Workers in Meat and Poultry Processing Facilities - 19 States, April 2020 Content: Congregate work and residential locations are at increased risk for infectious disease transmission including respiratory illness outbreaks. SARS-CoV-2, the virus that causes coronavirus disease 2019 (COVID-19), is primarily spread person to person through respiratory droplets. Nationwide, the meat and poultry processing industry, an essential component of the U.S. food infrastructure, employs approximately 500,000 persons, many of whom work in proximity to other workers (1). Because of reports of initial cases of COVID-19, in some meat processing facilities, states were asked to provide aggregated data concerning the number of meat and poultry processing facilities affected by COVID-19 and the number of workers with COVID-19 in these facilities, including COVID-19-related deaths. Qualitative data gathered by CDC during on-site and remote assessments were analyzed and summarized. During April 9-27, aggregate data on COVID-19 cases among 115 meat or poultry processing facilities in 19 states were reported to CDC. Among these facilities, COVID-19 was diagnosed in 4,913 (approximately 3%) workers, and 20 COVID-19-related deaths were reported. Facility barriers to effective prevention and control of COVID-19 included difficulty distancing workers at least 6 feet (2 meters) from one another (2) and in implementing COVID-19-specific disinfection guidelines.* Among workers, socioeconomic challenges might contribute to working while feeling ill, particularly if there are management practices such as bonuses that incentivize attendance. Methods to decrease transmission within the facility include worker symptom screening programs, policies to discourage working while experiencing symptoms compatible with COVID-19, and social distancing by workers. Source control measures (e.g., the use of cloth face covers) as well as increased disinfection of high-touch surfaces are also important means of preventing SARS-CoV-2 exposure. Mitigation efforts to reduce transmission in the community should also be considered. Many of these measures might also reduce asymptomatic and presymptomatic transmission (3). Implementation of these public health strategies will help protect workers from COVID-19 in this industry and assist in preserving the critical meat and poultry production infrastructure (4).", "qid": 12, "docid": "3145se46", "rank": 86, "score": 0.8087999820709229}, {"content": "Title: COVID-19 Among Workers in Meat and Poultry Processing Facilities - 19 States, April 2020. Content: Congregate work and residential locations are at increased risk for infectious disease transmission including respiratory illness outbreaks. SARS-CoV-2, the virus that causes coronavirus disease 2019 (COVID-19), is primarily spread person to person through respiratory droplets. Nationwide, the meat and poultry processing industry, an essential component of the U.S. food infrastructure, employs approximately 500,000 persons, many of whom work in proximity to other workers (1). Because of reports of initial cases of COVID-19, in some meat processing facilities, states were asked to provide aggregated data concerning the number of meat and poultry processing facilities affected by COVID-19 and the number of workers with COVID-19 in these facilities, including COVID-19-related deaths. Qualitative data gathered by CDC during on-site and remote assessments were analyzed and summarized. During April 9-27, aggregate data on COVID-19 cases among 115 meat or poultry processing facilities in 19 states were reported to CDC. Among these facilities, COVID-19 was diagnosed in 4,913 (approximately 3%) workers, and 20 COVID-19-related deaths were reported. Facility barriers to effective prevention and control of COVID-19 included difficulty distancing workers at least 6 feet (2 meters) from one another (2) and in implementing COVID-19-specific disinfection guidelines.* Among workers, socioeconomic challenges might contribute to working while feeling ill, particularly if there are management practices such as bonuses that incentivize attendance. Methods to decrease transmission within the facility include worker symptom screening programs, policies to discourage working while experiencing symptoms compatible with COVID-19, and social distancing by workers. Source control measures (e.g., the use of cloth face covers) as well as increased disinfection of high-touch surfaces are also important means of preventing SARS-CoV-2 exposure. Mitigation efforts to reduce transmission in the community should also be considered. Many of these measures might also reduce asymptomatic and presymptomatic transmission (3). Implementation of these public health strategies will help protect workers from COVID-19 in this industry and assist in preserving the critical meat and poultry production infrastructure (4).", "qid": 12, "docid": "oshnjs1v", "rank": 87, "score": 0.8087999820709229}, {"content": "Title: Guidelines for prevention of hospital acquired infections Content: These guidelines, written for clinicians, contains evidence-based recommendations for the prevention of hospital acquired infections Hospital acquired infections are a major cause of mortality and morbidity and provide challenge to clinicians. Measures of infection control include identifying patients at risk of nosocomial infections, observing hand hygiene, following standard precautions to reduce transmission and strategies to reduce VAP, CR-BSI, CAUTI. Environmental factors and architectural lay out also need to be emphasized upon. Infection prevention in special subsets of patients - burns patients, include identifying sources of organism, identification of organisms, isolation if required, antibiotic prophylaxis to be used selectively, early removal of necrotic tissue, prevention of tetanus, early nutrition and surveillance. Immunodeficient and Transplant recipients are at a higher risk of opportunistic infections. The post tranplant timetable is divided into three time periods for determining risk of infections. Room ventilation, cleaning and decontamination, protective clothing with care regarding food requires special consideration. Monitoring and Surveillance are prioritized depending upon the needs. Designated infection control teams should supervise the process and help in collection and compilation of data. Antibiotic Stewardship Recommendations include constituting a team, close coordination between teams, audit, formulary restriction, de-escalation, optimizing dosing, active use of information technology among other measure. The recommendations in these guidelines are intended to support, and not replace, good clinical judgment. The recommendations are rated by a letter that indicates the strength of the recommendation and a Roman numeral that indicates the quality of evidence supporting the recommendation, so that readers can ascertain how best to apply the recommendations in their practice environments.", "qid": 12, "docid": "4g9u7obr", "rank": 88, "score": 0.808624804019928}, {"content": "Title: Anesthesia Management and Perioperative Infection Control in Patients With the Novel Coronavirus Content: Anesthesiologists have a high risk of infection with COVID-19 during perioperative care and as first responders to airway emergencies. The potential of becoming infected can be reduced by a systematic and integrated approach that assesses infection risk. The latter leads to an acceptable choice of materials and techniques for personal protection and prevention of cross-contamination to other patients and staff. The authors have presented a protocolized approach that uses diagnostic criteria to clearly define benchmarks from the medical history along with clinical symptoms and laboratory tests. Patients can then be rapidly assigned into 1 of 3 risk categories that direct the choice of protective materials and/or techniques. Each hospital can adapt this approach to develop a system that fits its individual resources. Educating medical staff about the proper use of high-risk areas for containment serves to protect staff and patients.", "qid": 12, "docid": "0artqu2m", "rank": 89, "score": 0.8085403442382812}, {"content": "Title: Environmental Cleaning and Disinfection Content: The guidelines in this article provide veterinarians, veterinary technicians, and veterinary health care workers with an overview of evidence-based recommendations for the best practices associated with environmental cleaning and disinfection of a veterinary clinic that deals with small animals. Hospital-associated infections and the control and prevention programs necessary to alleviate them are addressed from an environmental perspective. Measures of hospital cleaning and disinfection include understanding mechanisms and types of contamination in veterinary settings, recognizing areas of potential concern, addressing appropriate decontamination techniques and selection of disinfectants, the management of potentially contaminated equipment, laundry, and waste management, and environmental surveillance strategies.", "qid": 12, "docid": "kjjis7hu", "rank": 90, "score": 0.8082346320152283}, {"content": "Title: Coronavirus Disease 2019 (COVID-19): Protecting Hospitals From the Invisible Content: Coronavirus disease 2019 (COVID-19) is optimized to spread widely: Its signs and symptoms are largely indistinguishable from those of other respiratory viruses. This commentary specifically addresses best ways to protect our hospitals against COVID-19.", "qid": 12, "docid": "e8073l9p", "rank": 91, "score": 0.8082082271575928}, {"content": "Title: Travel/Tropical Medicine and Pandemic Considerations for the Global Surgeon Content: International travel goes hand-in-hand with medical delivery to underserved communities. The global health care worker (HCW) can be exposed to a wide range of infectious diseases during their global experiences. A pre-travel risk assessment visit and all appropriate vaccinations and education are performed. Universal practices of water safety, food safety, and insect avoidance will prevent a majority of travel related infections and complications. Region specific vaccinations will further reduce illness risk.. An understanding of common travel related illness signs and symptoms is helpful. Lastly, emerging pathogens that can cause a pandemic, such as SARS-CoV-2, should be understood to avoid healthcare worker infection and spread in the workplace and when returning home.", "qid": 12, "docid": "nysj3d5q", "rank": 92, "score": 0.8081753253936768}, {"content": "Title: Staff Uniforms and Uniform Policy Content: Personnel in contact with patients or equipment and textiles should always use the hospital\u2019s work attire. It includes anyone handling food, medicines, textile, waste or cleaning tools. By caring, treating, examining and transporting patients, there will be direct contact between own work clothes and the patient\u2019s cloths/bedding or skin. The same is true when working with used patient equipment such as bedpans, toilet chairs, beds and other aids and working in patient rooms, toilets and bathrooms or when handling bedding and bandages, giving physiotherapy, etc. The work uniform is particularly exposed to organic matter and microbes, for example, in ambulances, in emergency services, in restless and anxious patients and children, during sampling and examination/treatment, etc. In acute wards, the staff is often exposed to splashes from patients, especially blood but also vomit, sputum, pus, faeces and urine. This chapter is focused on practical measures to prevent transmission of infections via contaminated staff uniforms.", "qid": 12, "docid": "j1fcatmb", "rank": 93, "score": 0.8079777359962463}, {"content": "Title: Nurses and the control of infectious disease. Understanding epidemiology and disease transmission is vital to nursing care. Content: Epidemiology examines the distribution and source of a disease in a population. Understanding epidemiology and disease transmission is vital to nursing care. Infectious disease transmission requires three components: an agent (virus, bacterium, parasite or other microbe), a vulnerable host and a conducive environment. Disease spread can occur through direct contact or via indirect methods (airborne droplets, vectors, fomites, water or food). Intervention can occur by attacking the agent (e.g., using microbicides), changing the environment (e.g., providing negative pressure rooms) or strengthening the host (e.g., vaccination). Three epidemiologically relevant microbes are the SARS (severe acute respiratory syndrome)-associated coronavirus, methicillin-resistant Staphylococcus aureus (MRSA) and Clostridium difficile (C. difficile). The first is an emerging pathogen, and the latter two are existing agents that have mutated such that they are resistant to their standard treatments. For SARS, control measures include screening for possible cases and appropriate triage, respiratory and barrier precautions within the healthcare facility, and voluntary isolation in the community for contacts or healthcare workers who exhibit symptoms. Control measures for MRSA include the screening of patient lesions, isolating or cohorting patients who are already infected, covering wounds with impermeable dressings, treating staff and patient carriers with antibiotics, and improved hygiene. Control measures for C. difficile Control measures include paying close attention to the hygiene of the clinical setting, disinfecting using bleach and the isolation of infected patients.", "qid": 12, "docid": "zuu1etgn", "rank": 94, "score": 0.8078991174697876}, {"content": "Title: Application of Biosafety Principles in Laboratory Analysis of Clinical Samples from Patients with COVID-19 Content: COVID-19 poses a great challenge to clinical and diagnostic services around the world. The need of biosafety practices can never be emphasised more than under current circumstances. The four pillars of biosafety namely, leadership, standard operating procedures, personal protective equipment (PPE) and engineering controls must be employed for effective and safe practices in the clinical setting in general and laboratory settings in particular. Risk assessment must be carried out before meeting up the diagnostic challenge for COVID-19 and essential biorisk management measures are required to be taken. In our resource-poor settings, we need to adapt safe but cost-effective and improvised solutions to ensure safe handling of clinical samples from COVID-19 patients in the laboratories. The correct use of PPE and their suitable alternatives are available for selection and use. Disinfection of the lab areas and safe disposal of the clinical samples from such patients is also of paramount importance.", "qid": 12, "docid": "8h4adfqi", "rank": 95, "score": 0.8077765107154846}, {"content": "Title: Application of Biosafety Principles in Laboratory Analysis of Clinical Samples from Patients with COVID-19. Content: COVID-19 poses a great challenge to clinical and diagnostic services around the world. The need of biosafety practices can never be emphasised more than under current circumstances. The four pillars of biosafety namely, leadership, standard operating procedures, personal protective equipment (PPE) and engineering controls must be employed for effective and safe practices in the clinical setting in general and laboratory settings in particular. Risk assessment must be carried out before meeting up the diagnostic challenge for COVID-19 and essential biorisk management measures are required to be taken. In our resource-poor settings, we need to adapt safe but cost-effective and improvised solutions to ensure safe handling of clinical samples from COVID-19 patients in the laboratories. The correct use of PPE and their suitable alternatives are available for selection and use. Disinfection of the lab areas and safe disposal of the clinical samples from such patients is also of paramount importance.", "qid": 12, "docid": "7z2cq8gq", "rank": 96, "score": 0.8077765107154846}, {"content": "Title: Blue Ribbon Abstract Award: Assessment of Education and Communication Resources for Public Health Emergencies in U.S. Hospitals Content: Abstract BACKGROUND: Established systems for education and rapid dissemination of information are essential to a healthcare facility's ability to respond to emerging public health threats. We assessed the education activities and communication resources available for this purpose in a representative sample of U.S. hospitals. METHODS: We selected a 20% (n=1236) random sample of hospitals from the 2000 American Hospital Association database, stratified by bed size, service, metropolitan statistical sampling area (MSSA), and region to ensure representativeness. Infection control professionals (ICPs) at the hospitals were asked to complete a Web-based questionnaire during October 21\u2013December 22, 2003. RESULTS: ICPs at 556 (45%) hospitals completed the survey, including 518 (93%) general medical-surgical, 20 (4%) other specialty (including oncology), and 18 (3%) children's hospitals; 352 (63%) were in urban (<100,000 population) areas and 224 (40%) had <100 beds. Most hospitals had provided educational programs about infection control issues related to smallpox (87%), smallpox vaccine-related adverse events (76%), severe acute respiratory syndrome (SARS) (75%); and anthrax (73%). Fewer offered programs on monkeypox (27%). Hospitals reported that the best ways to disseminate information to them were via e-mail (97%), Web sites or group e-mail lists (72%), videoconference (40%), or teleconference (35%). Urban hospitals were more likely than rural to identify Web sites (p=0.001) and videoconference (p=0.03) as the best ways to receive information. Hospitals used e-mail (94%), teleconferencing (72%), Web-based training (61%), computer-based tools (50%), and videoconferencing (46%) to reach hospital-based clinical personnel. Urban hospitals were more likely than rural to use e-mail (p=0.01) to reach personnel. Hospitals identified model preparedness plans (61%), educational materials for personnel (54%) or patients/public (40%), and tabletop exercises/drills (46%) as being most helpful to preparedness efforts. CONCLUSIONS: Hospitals may differ substantially in preparedness and response readiness. These findings will assist in determining the best strategies for communicating with hospitals and providing information to assist them in preparedness efforts.", "qid": 12, "docid": "y7808p91", "rank": 97, "score": 0.8077689409255981}, {"content": "Title: Safe Hospital Preparedness in the Era of COVID-19: The Swiss Cheese Model Content: Since the first emergence in December 2019, COVID-19 rapidly spread out worldwide. During the pandemic of an emerging infectious disease, it is very important to prevent nosocomial outbreak and operate hospitals safely to maintain their functions. In this article, we presented the strategies for safe hospital operation based on the experiences of the Republic of Korea during early COVID-19 pandemic. Each hospital should keep multiple layered defenses to prevent even small cracks in the hospital's quarantine system.", "qid": 12, "docid": "n1z68cyg", "rank": 98, "score": 0.8077643513679504}, {"content": "Title: Screening for SARS-CoV-2 Infection Within a Psychiatric Hospital and Considerations for Limiting Transmission Within Residential Psychiatric Facilities \u2014 Wyoming, 2020 Content: In the United States, approximately 180,000 patients receive mental health services each day at approximately 4,000 inpatient and residential psychiatric facilities (1). SARS-CoV-2, the virus that causes coronavirus disease 2019 (COVID-19), can spread rapidly within congregate residential settings (2-4), including psychiatric facilities. On April 13, 2020, two patients were transferred to Wyoming's state psychiatric hospital from a private psychiatric hospital that had confirmed COVID-19 cases among its residents and staff members (5). Although both patients were asymptomatic at the time of transfer and one had a negative test result for SARS-CoV-2 at the originating facility, they were both isolated and received testing upon arrival at the state facility. On April 16, 2020, the test results indicated that both patients had SARS-CoV-2 infection. In response, the state hospital implemented expanded COVID-19 infection prevention and control (IPC) procedures (e.g., enhanced screening, testing, and management of new patient admissions) and adapted some standard IPC measures to facilitate implementation within the psychiatric patient population (e.g., use of modified face coverings). To assess the likely effectiveness of these procedures and determine SARS-CoV-2 infection prevalence among patients and health care personnel (HCP) (6) at the state hospital, a point prevalence survey was conducted. On May 1, 2020, 18 days after the patients' arrival, 46 (61%) of 76 patients and 171 (61%) of 282 HCP had nasopharyngeal swabs collected and tested for SARS-CoV-2 RNA by reverse transcription-polymerase chain reaction. All patients and HCP who received testing had negative test results, suggesting that the hospital's expanded IPC strategies might have been effective in preventing the introduction and spread of SARS-CoV-2 infection within the facility. In congregate residential settings, prompt identification of COVID-19 cases and application of strong IPC procedures are critical to ensuring the protection of other patients and staff members. Although standard guidance exists for other congregate facilities (7) and for HCP in general (8), modifications and nonstandard solutions might be needed to account for the specific needs of psychiatric facilities, their patients, and staff members.", "qid": 12, "docid": "qrypdgpa", "rank": 99, "score": 0.8077043890953064}, {"content": "Title: Screening for SARS-CoV-2 Infection Within a Psychiatric Hospital and Considerations for Limiting Transmission Within Residential Psychiatric Facilities - Wyoming, 2020 Content: In the United States, approximately 180,000 patients receive mental health services each day at approximately 4,000 inpatient and residential psychiatric facilities (1). SARS-CoV-2, the virus that causes coronavirus disease 2019 (COVID-19), can spread rapidly within congregate residential settings (2-4), including psychiatric facilities. On April 13, 2020, two patients were transferred to Wyoming's state psychiatric hospital from a private psychiatric hospital that had confirmed COVID-19 cases among its residents and staff members (5). Although both patients were asymptomatic at the time of transfer and one had a negative test result for SARS-CoV-2 at the originating facility, they were both isolated and received testing upon arrival at the state facility. On April 16, 2020, the test results indicated that both patients had SARS-CoV-2 infection. In response, the state hospital implemented expanded COVID-19 infection prevention and control (IPC) procedures (e.g., enhanced screening, testing, and management of new patient admissions) and adapted some standard IPC measures to facilitate implementation within the psychiatric patient population (e.g., use of modified face coverings). To assess the likely effectiveness of these procedures and determine SARS-CoV-2 infection prevalence among patients and health care personnel (HCP) (6) at the state hospital, a point prevalence survey was conducted. On May 1, 2020, 18 days after the patients' arrival, 46 (61%) of 76 patients and 171 (61%) of 282 HCP had nasopharyngeal swabs collected and tested for SARS-CoV-2 RNA by reverse transcription-polymerase chain reaction. All patients and HCP who received testing had negative test results, suggesting that the hospital's expanded IPC strategies might have been effective in preventing the introduction and spread of SARS-CoV-2 infection within the facility. In congregate residential settings, prompt identification of COVID-19 cases and application of strong IPC procedures are critical to ensuring the protection of other patients and staff members. Although standard guidance exists for other congregate facilities (7) and for HCP in general (8), modifications and nonstandard solutions might be needed to account for the specific needs of psychiatric facilities, their patients, and staff members.", "qid": 12, "docid": "afzz3flg", "rank": 100, "score": 0.8077043890953064}]}
{"query": "what are the transmission routes of coronavirus?", "hits": [{"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": 1, "score": 0.8798270225524902}, {"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": 2, "score": 0.8798270225524902}, {"content": "Title: Indirect Virus Transmission in Cluster of COVID-19 Cases, Wenzhou, China, 2020 Content: To determine possible modes of virus transmission, we investigated a cluster of coronavirus disease cases associated with a shopping mall in Wenzhou, China. Data indicated that indirect transmission of the causative virus occurred, perhaps resulting from virus contamination of common objects, virus aerosolization in a confined space, or spread from asymptomatic infected persons.", "qid": 13, "docid": "yp7bniwt", "rank": 3, "score": 0.8672301769256592}, {"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": 4, "score": 0.8593230843544006}, {"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": 13, "docid": "3q3sktuq", "rank": 5, "score": 0.8555478453636169}, {"content": "Title: Transference of COVID-19 patient in hospitals \u2013 A crucial phase Content: \u2022 COVID-19 virus is primarily transmitted between humans through respiratory droplets and contact routes. \u2022 Transportation of COVID-19 patient carries very high transmission risk to personals involved. \u2022 Worldwide, clinicians are using many measures that can be executed easily to prevent aerosol exposure.", "qid": 13, "docid": "y7v8tcnb", "rank": 6, "score": 0.8553718328475952}, {"content": "Title: Effect of Nonpharmaceutical Interventions on Transmission of Severe Acute Respiratory Syndrome Coronavirus 2, South Korea, 2020 Content: We analyzed transmission of coronavirus disease outside of the Daegu-Gyeongsangbuk provincial region in South Korea. We estimated that nonpharmaceutical measures reduced transmissibility by a maximum of 34% without resorting to a strict lockdown strategy. To optimize epidemic control, continuous efforts to monitor the transmissibility are needed.", "qid": 13, "docid": "12uca8kw", "rank": 7, "score": 0.852536678314209}, {"content": "Title: Effect of Nonpharmaceutical Interventions on Transmission of Severe Acute Respiratory Syndrome Coronavirus 2, South Korea, 2020. Content: We analyzed transmission of coronavirus disease outside of the Daegu-Gyeongsangbuk provincial region in South Korea. We estimated that nonpharmaceutical measures reduced transmissibility by a maximum of 34% without resorting to a strict lockdown strategy. To optimize epidemic control, continuous efforts to monitor the transmissibility are needed.", "qid": 13, "docid": "odmx6ng8", "rank": 8, "score": 0.852536678314209}, {"content": "Title: Cross host transmission in the emergence of MERS coronavirus Content: Coronaviruses (CoVs) able to infect humans emerge through cross-host transmission from animals. There is substantial evidence that the recent Middle East respiratory syndrome (MERS)-CoV outbreak is fueled by zoonotic transmission from dromedary camels. This is largely based on the fact that closely related viruses have been isolated from this but not any other animal species. Given the widespread geographical distribution of dromedaries found seropositive for MERS-CoV, continued transmission may likely occur in the future. Therefore, a further understanding of the cross host transmission of MERS-CoV is needed to limit the risks this virus poses to man.", "qid": 13, "docid": "xehv2atz", "rank": 9, "score": 0.8515568971633911}, {"content": "Title: Animal-to-Human Viral Transitions: Is SARS-CoV-2 an Evolutionary Successful One? Content: Transmission of viruses from one species to another is not unusual in nature. Despite this, evolutionarily successful transmissions are rare. Such events can cause pandemics and are followed by host\u2013virus coevolution procedures that can increase the fitness potential of viruses. In this perspective article, I recognize eight main types of trans-species viral transmission. I consider two of them as evolutionarily successful, explaining why coronavirus SARS-CoV-2 could be one of them.", "qid": 13, "docid": "ke51zzhl", "rank": 10, "score": 0.8514389395713806}, {"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": 13, "docid": "rqw9jir0", "rank": 11, "score": 0.85118168592453}, {"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": 12, "score": 0.8505505919456482}, {"content": "Title: COVID 19 in neonates Content: Corona virus disease 2019 started in December 2019 as an outbreak of unexplained pneumonias in Wuhan, a city in Hubei province of China. This illness emerged as an epidemic in China and later spread to almost all countries over the globe except Antarctica. This is caused by a beta Corona virus, which is genetically similar to SARS virus. The predominant mode of transmission is via droplet spread, when the infected person coughs, sneezes or talks the virus is released in the respiratory secretions. As there are only a few cases of COVID 19 in neonates, there is no convincing evidence to support the possibility of vertical transmission. Clinical presentation in neonates is nonspecific, commonly observed are temperature instability, respiratory distress, poor feeding, lethargy, vomiting and diarrhea. Laboratory examinations may be nonspecific. Definitive test for 2019-nCoV is the detection of viral nucleic acid by real-time fluorescence polymerase chain reaction (RT-PCR). Suspected and confirmed COVID positive mothers should be delivered in separate delivery rooms and operation theaters. Since there is no approved treatment or drug for this disease, prevention of infection and breaking the chain of transmission plays a crucial role.", "qid": 13, "docid": "usee3zt5", "rank": 13, "score": 0.8500008583068848}, {"content": "Title: COVID 19 in neonates. Content: Corona virus disease 2019 started in December 2019 as an outbreak of unexplained pneumonias in Wuhan, a city in Hubei province of China. This illness emerged as an epidemic in China and later spread to almost all countries over the globe except Antarctica. This is caused by a beta Corona virus, which is genetically similar to SARS virus. The predominant mode of transmission is via droplet spread, when the infected person coughs, sneezes or talks the virus is released in the respiratory secretions. As there are only a few cases of COVID 19 in neonates, there is no convincing evidence to support the possibility of vertical transmission. Clinical presentation in neonates is nonspecific, commonly observed are temperature instability, respiratory distress, poor feeding, lethargy, vomiting and diarrhea. Laboratory examinations may be nonspecific. Definitive test for 2019-nCoV is the detection of viral nucleic acid by real-time fluorescence polymerase chain reaction (RT-PCR). Suspected and confirmed COVID positive mothers should be delivered in separate delivery rooms and operation theaters. Since there is no approved treatment or drug for this disease, prevention of infection and breaking the chain of transmission plays a crucial role.", "qid": 13, "docid": "356vat73", "rank": 14, "score": 0.8500008583068848}, {"content": "Title: History is repeating itself: Probable zoonotic spillover as the cause of the 2019 novel Coronavirus Epidemic Content: Pathogen transmission from a vertebrate animal to a human, also known as zoonotic spillover, represents a global public health burden, which while associated with multiple outbreaks, still remains a poorly understood phenomenon. Coronaviruses, like influenza viruses, circulate in nature in various animal species. Alpha-coronaviruses and beta-coronaviruses can infect mammals and gamma-coronaviruses and delta-coronaviruses tend to infect birds, but some of them can also be transmitted to mammals. Although still preliminary, current data suggest that bats are the most probable initial source of the current 2019 novel CoV (2019nCoV) outbreak, that begun on December 2019 in Wuhan, China, apparently spreading from a \"wet market\" to multiple cities and provinces in China. This epidemic of 2019nCoV, already reaching more than 6,000 cases to-day (end of January 2020) (>90% in China), will not be the last one linked to zoonotic spillover events.", "qid": 13, "docid": "cjwy2bcx", "rank": 15, "score": 0.849880576133728}, {"content": "Title: History is repeating itself, a probable zoonotic spillover as a cause of an epidemic: the case of 2019 novel Coronavirus. Content: Pathogen transmission from a vertebrate animal to a human, also known as zoonotic spillover, represents a global public health burden, which while associated with multiple outbreaks, still remains a poorly understood phenomenon. Coronaviruses, like influenza viruses, circulate in nature in various animal species. Alpha-coronaviruses and beta-coronaviruses can infect mammals and gamma-coronaviruses and delta-coronaviruses tend to infect birds, but some of them can also be transmitted to mammals. Although still preliminary, current data suggest that bats are the most probable initial source of the current 2019 novel CoV (2019nCoV) outbreak, that begun on December 2019 in Wuhan, China, apparently spreading from a \"wet market\" to multiple cities and provinces in China. This epidemic of 2019nCoV, already reaching more than 6,000 cases to-day (end of January 2020) (>90% in China), will not be the last one linked to zoonotic spillover events.", "qid": 13, "docid": "q8im1agz", "rank": 16, "score": 0.849880576133728}, {"content": "Title: Animal-to-Human Viral Transitions: Is SARS-CoV-2 an Evolutionarily Successful One? Content: Transmission of viruses from one species to another is not unusual in nature. Despite this, evolutionarily successful transmissions are rare. Such events can cause pandemics and are followed by host-virus coevolution procedures that can increase the fitness potential of viruses. In this perspective article, I recognize eight main types of trans-species viral transmission. I consider two of them as evolutionarily successful, explaining why coronavirus SARS-CoV-2 could be one of them.", "qid": 13, "docid": "t01raxcv", "rank": 17, "score": 0.8493987321853638}, {"content": "Title: Coronavirus: An emergency for healthcare professionals Content: Coronavirus infection is a transmissible disease. It was first described in China in December, 2019. It has been said to have a person-to-person transmission after prolonged and unprotected exposure. Patients with a potential SARS-CoV-2 exposure present with symptoms of low-grade pyrexia, dry cough, or shortness of breath. People with these symptoms should contact health-care providers before seeking medical intervention so that appropriate preventive actions may be implemented. Health-care facilities should rapidly isolate suspected individuals and notify local health departments for support involved in performing laboratory tests and efforts in containment. The present article describes the nature of virus, method of detection, and its mode of transmission.", "qid": 13, "docid": "yxmkaqo8", "rank": 18, "score": 0.8492512702941895}, {"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": 19, "score": 0.8485186100006104}, {"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": 13, "docid": "xkzvzonj", "rank": 20, "score": 0.8483614921569824}, {"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": 21, "score": 0.8478807806968689}, {"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": 22, "score": 0.8475160598754883}, {"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": 23, "score": 0.8474278450012207}, {"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": 24, "score": 0.8473685383796692}, {"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": 25, "score": 0.8466365933418274}, {"content": "Title: Hand disinfection in the combat against Covid-19 Content: The World Health Organization (WHO) has declared a global health emergency over a new coronavirus. The new corona virus (SARS-CoV-2) has raised global attention with raising concerns of rapid spread from human-to-human. Like severe acute respiratory syndrome (SARS)-nCoV, 2019-nCoV can be passed directly from person to person by respiratory droplets, and may also be transmitted through contact and fomites.", "qid": 13, "docid": "0macgbcn", "rank": 26, "score": 0.8458648920059204}, {"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": 27, "score": 0.845255434513092}, {"content": "Title: COVID-19 and animals: What do we know? Content: Coronaviruses, which were generally considered harmless to humans before 2003, have appeared again with a pandemic threatening the world since December 2019 after the epidemics of SARS and MERS. It is known that transmission from person to person is the most important way to spread. However, due to the widespread host diversity, a detailed examination of the role of animals in this pandemic is essential to effectively fight against the outbreak. Although coronavirus infections in pets are known to be predominantly related to the gastrointestinal tract, it has been observed that there are human-to-animal transmissions in this outbreak and some animals have similar symptoms to humans. Although animal-to-animal transmission has been shown to be possible, there is no evidence of animal-to-human transmission.", "qid": 13, "docid": "hbs9inah", "rank": 28, "score": 0.8451423645019531}, {"content": "Title: Making waves: Coronavirus detection, presence and persistence in the water environment: State of the art and knowledge needs for public health Content: The main route of transmission of the human coronaviruses (HCoVs), and presumably also of the new pandemic SARS-CoV-2, is via droplets and close contacts, however their fecal elimination also suggests the possible spread via water. A scientific literature search was thus carried out to highlight the current state of the art and knowledge gaps regarding coronavirus in water. Since 1978 only 22 studies have met the inclusion criteria, and considered heterogeneous purposes, detection methods and types of water. In vitro experiments have addressed the recovery efficiency of analytical methods, survival in different types of water and the removal efficiency of water treatments. Field studies have monitored coronaviruses in surface waters, sewage, slurry, and biosolids. Overall, at the lab scale, HCoVs or surrogates can survive for several days at 4 \u00b0C, however their persistence is lower compared with non-enveloped viruses and is strongly influenced by temperature and organic or microbial pollution. HCoVs have rarely been detected in field investigations, however may be due to the low recovery efficiency of the analytical methods. The scarcity of information on HCoV in the environment suggests that research is needed to understand the fate of these viruses in the water cycle.", "qid": 13, "docid": "vuzf3dnr", "rank": 29, "score": 0.8441446423530579}, {"content": "Title: Making Waves: Coronavirus detection, presence and persistence in the water environment: State of the art and knowledge needs for public health Content: The main route of transmission of the human coronaviruses (HCoVs), and presumably also of the new pandemic SARS-CoV-2, is via droplets and close contacts, however their fecal elimination also suggests the possible spread via water. A scientific literature search was thus carried out to highlight the current state of the art and knowledge gaps regarding coronavirus in water. Since 1978 only 22 studies have met the inclusion criteria, and considered heterogeneous purposes, detection methods and types of water. In vitro experiments have addressed the recovery efficiency of analytical methods, survival in different types of water and the removal efficiency of water treatments. Field studies have monitored coronaviruses in surface waters, sewage, slurry, and biosolids. Overall, at the lab scale, HCoVs or surrogates can survive for several days at 4 \u00b0C, however their persistence is lower compared with non-enveloped viruses and is strongly influenced by temperature and organic or microbial pollution. HCoVs have rarely been detected in field investigations, however may be due to the low recovery efficiency of the analytical methods. The scarcity of information on HCoV in the environment suggests that research is needed to understand the fate of these viruses in the water cycle.", "qid": 13, "docid": "c17eijdt", "rank": 30, "score": 0.8441446423530579}, {"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": 31, "score": 0.8440637588500977}, {"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": 32, "score": 0.8433793783187866}, {"content": "Title: Transmission dynamics of coronavirus disease 2019 outside of Daegu-Gyeongsangbuk provincial region in South Korea Content: We analyzed transmission of coronavirus disease 2019 in South Korea. We estimated that non-pharamaceutical measures reduced the immediate transmissibility by maximum of 34% for coronavirus disease 2019. Continuous efforts are needed for monitoring the transmissibility to optimize epidemic control.", "qid": 13, "docid": "5vda46uh", "rank": 33, "score": 0.8433284759521484}, {"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": 34, "score": 0.8431154489517212}, {"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": 35, "score": 0.8422266840934753}, {"content": "Title: Mechano-genomic regulation of coronaviruses and its interplay with ageing Content: Coronaviruses employ various nuclear signalling mechanisms for their propagation. Here we link replication of coronaviruses, including SARS-CoV-2, the coronavirus disease 2019 (COVID-19)-causing virus, with cytoskeleton-dependent signalling and 3D genome organization. This link could provide novel insights into the high coronavirus pathogenicity in certain cellular states, particularly those associated with ageing.", "qid": 13, "docid": "20zs4unc", "rank": 36, "score": 0.8409929275512695}, {"content": "Title: Differential diagnosis of illness in patients under investigation for the novel coronavirus (SARS-CoV-2), Italy, February 2020 Content: A novel coronavirus (SARS-CoV-2) has been identified as the causative pathogen of an ongoing outbreak of respiratory disease, now named COVID-19. Most cases and sustained transmission occurred in China, but travel-associated cases have been reported in other countries, including Europe and Italy. Since the symptoms are similar to other respiratory infections, differential diagnosis in travellers arriving from countries with wide-spread COVID-19 must include other more common infections such as influenza and other respiratory tract diseases.", "qid": 13, "docid": "err1npxf", "rank": 37, "score": 0.8409691452980042}, {"content": "Title: Coronavirus Host Range Expansion and Middle East Respiratory Syndrome Coronavirus Emergence: Biochemical Mechanisms and Evolutionary Perspectives. Content: Coronaviruses have frequently expanded their host range in recent history, with two events resulting in severe disease outbreaks in human populations. Severe acute respiratory syndrome coronavirus (SARS-CoV) emerged in 2003 in Southeast Asia and rapidly spread around the world before it was controlled by public health intervention strategies. The 2012 Middle East respiratory syndrome coronavirus (MERS-CoV) outbreak represents another prime example of virus emergence from a zoonotic reservoir. Here, we review the current knowledge of coronavirus cross-species transmission, with particular focus on MERS-CoV. MERS-CoV is still circulating in the human population, and the mechanisms governing its cross-species transmission have been only partially elucidated, highlighting a need for further investigation. We discuss biochemical determinants mediating MERS-CoV host cell permissivity, including virus spike interactions with the MERS-CoV cell surface receptor dipeptidyl peptidase 4 (DPP4), and evolutionary mechanisms that may facilitate host range expansion, including recombination, mutator alleles, and mutational robustness. Understanding these mechanisms can help us better recognize the threat of emergence for currently circulating zoonotic strains.", "qid": 13, "docid": "yoyofprr", "rank": 38, "score": 0.8406233787536621}, {"content": "Title: Emerging novel coronavirus (2019-nCoV)-current scenario, evolutionary perspective based on genome analysis and recent developments Content: Coronaviruses are the well-known cause of severe respiratory, enteric and systemic infections in a wide range of hosts including man, mammals, fish, and avian. The scientific interest on coronaviruses increased after the emergence of Severe Acute Respiratory Syndrome coronavirus (SARS-CoV) outbreaks in 2002-2003 followed by Middle East Respiratory Syndrome CoV (MERS-CoV). This decade's first CoV, named 2019-nCoV, emerged from Wuhan, China, and declared as 'Public Health Emergency of International Concern' on January 30th, 2020 by the World Health Organization (WHO). As on February 4, 2020, 425 deaths reported in China only and one death outside China (Philippines). In a short span of time, the virus spread has been noted in 24 countries. The zoonotic transmission (animal-to-human) is suspected as the route of disease origin. The genetic analyses predict bats as the most probable source of 2019-nCoV though further investigations needed to confirm the origin of the novel virus. The ongoing nCoV outbreak highlights the hidden wild animal reservoir of the deadly viruses and possible threat of spillover zoonoses as well. The successful virus isolation attempts have made doors open for developing better diagnostics and effective vaccines helping in combating the spread of the virus to newer areas.", "qid": 13, "docid": "22fc1qly", "rank": 39, "score": 0.8405795097351074}, {"content": "Title: Limbic encephalitis after inhalation of a murine coronavirus. Content: The spread of a neurotropic coronavirus, mouse hepatitis virus strain A59, in the mouse central nervous system was studied after intranasal inoculation. Mouse hepatitis virus strain A59 spread during the 3- to 5-day postinoculation period, through the olfactory pathway into the limbic system. Coronavirus particles were detected in the limbic system by electron microscopy. The combination of temporal propagation through an anatomical-physiological central nervous system pathway and anatomical restriction of viral infection suggests that specific interneuronal transport is important in spread of the virus. This experimental system may represent a model for diseases associated with human coronaviruses (common cold viruses) and/or the human limbic system.", "qid": 13, "docid": "om35s8u9", "rank": 40, "score": 0.8402975797653198}, {"content": "Title: The impact of the SARS\u2010CoV\u20102 outbreak on the safety and availability of blood transfusions in Italy Content: Coronaviruses are enveloped single-stranded RNA viruses belonging to the family of Coronaviridae. While initial research focused on their ability to cause enzootic infections, infections which have emerged in the past two decades demonstrate their ability to cross the species barrier and infect humans [1,2]. The ensuing epidemics have included Severe Acute Respiratory Syndrome (SARS) in 2002 and the more recent Middle East Respiratory Syndrome (MERS) in 2012, and have resulted in severe disease burden, mortality and economic disruption [3]. A novel flu-like coronavirus, emerging towards the end of 2019 and subsequently named SARS-CoV-2, has been associated with an epidemic initially focused in Wuhan, China.", "qid": 13, "docid": "7imgvale", "rank": 41, "score": 0.839545488357544}, {"content": "Title: Progress in cross-species transmission of human coronaviruses (HCoVs)/ \u4eba\u51a0\u72b6\u75c5\u6bd2\u8de8\u79cd\u4f20\u64ad\u7684\u7814\u7a76\u8fdb\u5c55 Content: Coronaviruses (CoVs) are a group of ancient and common viruses, posing a severe threat to the health of humans and other animals. Currently, seven human CoVs (HCoVs) have been identified. They are all animal-derived zoonotic pathogens that jump the species barrier from their natural host animals to humans in a direct or indirect manner and lead to interpersonal transmission. The receptor binding domain (RBD) on the S1 subunit of CoV spike (S) protein is one of the key factors determining the cross-species transmission and the invasion potential. This review summarized and analyzed the transmission modes of seven HCoVs and the available structures of HCoV-RBD that mediated the cross-species transmission in order to better understanding the mechanism of CoV cross-species transmission and providing valuable knowledge in response to the potential cross-species transmission of novel CoVs in the future.", "qid": 13, "docid": "4ct9d311", "rank": 42, "score": 0.8394370079040527}, {"content": "Title: Chapter 7 Coronaviridae: 100,000 Years of Emergence and Reemergence Content: Abstract The coronavirus family (Coronaviridae) is a positive-sense single-stranded RNA, with a size of 27kb. These viruses have a potential species specificity and interspecies transmission. The interspecies transmission of viruses from one host species to another is a major factor responsible for the majority of emerging and reemerging infections. The Coronaviridae is one of the most popular emerging viral families that threaten to the public health.", "qid": 13, "docid": "ytk5s6m8", "rank": 43, "score": 0.8394209146499634}, {"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": 44, "score": 0.8389700651168823}, {"content": "Title: Coronaviruses: General Features Content: Coronaviruses have the largest known RNA genomes (\u223c30kb), which are of positive sense. Together with toroviruses, they are classified in the family Coronaviridae, order Nidovirales. All coronaviruses have four common proteins, three in the envelope and one associated with the genome. Assembly of virus particles occurs at internal membranes. The genes for the structural proteins are at the 3\u2032 end of the genome. Most of the genome (\u223c20kb) is gene 1, which encodes 15\u201316 proteins associated with RNA replication and transcription. Translation of gene 1 involves ribosomal frameshifting. Transcription is by a discontinuous process which results in a 3\u2032 co-terminal nested set of mRNAs, each of which has a common leader sequence transcribed from the 5\u2032 terminus of the genome. Only the most 5\u2032-proximal gene of each mRNA is translated. Recombination is a feature of coronavirus evolution. The outbreak of severe acute respiratory syndrome (SARS) has resulted in the discovery of more coronaviruses in humans, other mammals, and avian species, and the realization that the host range of coronaviruses is wider than previously acknowledged. Coronaviruses are associated with a wide range of diseases, including the respiratory and enteric systems, though not necessarily restricted to these, for example, some coronaviruses affect the central nervous system, kidneys, and gonads. The most widely used coronavirus vaccine (billions of doses annually) is against infectious bronchitis virus, which affects chickens.", "qid": 13, "docid": "sneqefec", "rank": 45, "score": 0.8389660120010376}, {"content": "Title: Coping With COVID-19: Learning From Past Pandemics to Avoid Pitfalls and Panic Content: It is imperative to concur on the main transmission routes of COVID-19 to explain risk and determine the most effective means to reduce illness and mortality. We must avoid generating irrational fear and maintain a broader perspective in the pandemic response, including assessing the possibility for substantial unintended consequences.", "qid": 13, "docid": "n7w1psr4", "rank": 46, "score": 0.8387650847434998}, {"content": "Title: Passengers' destinations from China: low risk of Novel Coronavirus (2019-nCoV) transmission into Africa and South America Content: Novel Coronavirus (2019-nCoV [SARS-COV-2]) was detected in humans during the last week of December 2019 at Wuhan city in China, and caused 24 554 cases in 27 countries and territories as of 5 February 2020. The objective of this study was to estimate the risk of transmission of 2019-nCoV through human passenger air flight from four major cities of China (Wuhan, Beijing, Shanghai and Guangzhou) to the passengers' destination countries. We extracted the weekly simulated passengers' end destination data for the period of 1-31 January 2020 from FLIRT, an online air travel dataset that uses information from 800 airlines to show the direct flight and passengers' end destination. We estimated a risk index of 2019-nCoV transmission based on the number of travellers to destination countries, weighted by the number of confirmed cases of the departed city reported by the World Health Organization (WHO). We ranked each country based on the risk index in four quantiles (4th quantile being the highest risk and 1st quantile being the lowest risk). During the period, 388 287 passengers were destined for 1297 airports in 168 countries or territories across the world. The risk index of 2019-nCoV among the countries had a very high correlation with the WHO-reported confirmed cases (0.97). According to our risk score classification, of the countries that reported at least one Coronavirus-infected pneumonia (COVID-19) case as of 5 February 2020, 24 countries were in the 4th quantile of the risk index, two in the 3rd quantile, one in the 2nd quantile and none in the 1st quantile. Outside China, countries with a higher risk of 2019-nCoV transmission are Thailand, Cambodia, Malaysia, Canada and the USA, all of which reported at least one case. In pan-Europe, UK, France, Russia, Germany and Italy; in North America, USA and Canada; in Oceania, Australia had high risk, all of them reported at least one case. In Africa and South America, the risk of transmission is very low with Ethiopia, South Africa, Egypt, Mauritius and Brazil showing a similar risk of transmission compared to the risk of any of the countries where at least one case is detected. The risk of transmission on 31 January 2020 was very high in neighbouring Asian countries, followed by Europe (UK, France, Russia and Germany), Oceania (Australia) and North America (USA and Canada). Increased public health response including early case recognition, isolation of identified case, contract tracing and targeted airport screening, public awareness and vigilance of health workers will help mitigate the force of further spread to na\u00efve countries.", "qid": 13, "docid": "0mytklmf", "rank": 47, "score": 0.8387547731399536}, {"content": "Title: Passengers' destinations from China: low risk of Novel Coronavirus (2019-nCoV) transmission into Africa and South America Content: Novel Coronavirus (2019-nCoV [SARS-COV-2]) was detected in humans during the last week of December 2019 at Wuhan city in China, and caused 24 554 cases in 27 countries and territories as of 5 February 2020. The objective of this study was to estimate the risk of transmission of 2019-nCoV through human passenger air flight from four major cities of China (Wuhan, Beijing, Shanghai and Guangzhou) to the passengers' destination countries. We extracted the weekly simulated passengers' end destination data for the period of 1\u201331 January 2020 from FLIRT, an online air travel dataset that uses information from 800 airlines to show the direct flight and passengers' end destination. We estimated a risk index of 2019-nCoV transmission based on the number of travellers to destination countries, weighted by the number of confirmed cases of the departed city reported by the World Health Organization (WHO). We ranked each country based on the risk index in four quantiles (4(th) quantile being the highest risk and 1(st) quantile being the lowest risk). During the period, 388 287 passengers were destined for 1297 airports in 168 countries or territories across the world. The risk index of 2019-nCoV among the countries had a very high correlation with the WHO-reported confirmed cases (0.97). According to our risk score classification, of the countries that reported at least one Coronavirus-infected pneumonia (COVID-19) case as of 5 February 2020, 24 countries were in the 4(th) quantile of the risk index, two in the 3(rd) quantile, one in the 2(nd) quantile and none in the 1(st) quantile. Outside China, countries with a higher risk of 2019-nCoV transmission are Thailand, Cambodia, Malaysia, Canada and the USA, all of which reported at least one case. In pan-Europe, UK, France, Russia, Germany and Italy; in North America, USA and Canada; in Oceania, Australia had high risk, all of them reported at least one case. In Africa and South America, the risk of transmission is very low with Ethiopia, South Africa, Egypt, Mauritius and Brazil showing a similar risk of transmission compared to the risk of any of the countries where at least one case is detected. The risk of transmission on 31 January 2020 was very high in neighbouring Asian countries, followed by Europe (UK, France, Russia and Germany), Oceania (Australia) and North America (USA and Canada). Increased public health response including early case recognition, isolation of identified case, contract tracing and targeted airport screening, public awareness and vigilance of health workers will help mitigate the force of further spread to na\u00efve countries.", "qid": 13, "docid": "32gw2ug3", "rank": 48, "score": 0.838188886642456}, {"content": "Title: Tracing the SARS-coronavirus. Content: Four coronaviruses (HCoV-229E, HCoV-OC43, HCoV-NL63, HCoV-HKU1) are endemic in humans and mainly associated with mild respiratory illnesses; whereas the other two coronaviruses [Severe Acute Respiratory Syndrome Coronavirus (SARS-CoV) and Middle East Respiratory Syndrome Coronavirus (MERS-CoV)] present as emerging infections causing severe respiratory syndrome. Coronaviruses evolve by accumulation of point mutations and recombination of genomes among different strains or species. Mammalian coronaviruses including those infect humans are evolved from bat coronaviruses. While SARS-CoV and MERS-CoV are genetically closely related to bat coronaviruses, intermediate host(s) is (are) likely to be involved in the emergence and cross-species transmission of these novel human viruses. High prevalence of SARS-like coronaviruses have been found from masked palm civet cats and raccoon dogs collected from markets around the time of outbreaks in humans, but these animals are likely to be a transient accidental host rather than a persisting reservoir. More research is needed to elucidate the ecology of coronaviruses. Vigilance and surveillance should be maintained to promptly identify newly emerged coronaviruses.", "qid": 13, "docid": "81knkem4", "rank": 49, "score": 0.8381185531616211}, {"content": "Title: Severe Acute Respiratory Syndrome Coronavirus-2 (SARS-CoV-2): An Update Content: Coronaviruses (CoVs) belong to the family of Coronaviridae, the order Nidovirales, and the genus Coronavirus. They are the largest group of viruses causing respiratory and gastrointestinal infections. Morphologically, CoVs are enveloped viruses containing a non-segmented positive-sense, single-stranded ribonucleic acid (RNA) viruses. CoVs are categorized into four important genera that include Alphacoronavirus, Betacoronavirus, Gammacoronavirus, and Deltacoronavirus. A novel member of human CoV that has recently emerged in Wuhan, China, is now formally named as SARS-CoV-2 (severe acute respiratory syndrome coronavirus 2). This is a unique strain of RNA viruses that have not been previously observed in humans. The virus has wide host adaptability and is capable of causing severe diseases in humans, masked palm civets, mice, dogs, cats, camels, pigs, chickens, and bats. The SARS-CoV-2 typically causes respiratory and gastrointestinal sickness in both humans and animals. It can be transmitted through aerosols and direct/indirect contact, as well as during medical cases and laboratory sample handling. Specific structural proteins, which might be found on the surface of the virus, play an important role in the pathogenesis and development of the complications. The disease is characterized by distinct medical signs and symptoms that include high fever, chills, cough, and shortness of breath or difficulty in breathing. The infected people may also present with other symptoms such as diarrhea, myalgia, fatigue, expectoration, and hemoptysis. It is important from the public health and economic point of view as it affects the growth of the country, which is majorly attributed to the restriction in the movement of the people and the cost associated with the control and prevention of the disease. Since there is no specific therapeutic intervention nor a vaccine available against the virus, supportive management and treatment with non-specific therapeutic agents (repurposed drugs) may provide relief to the patients. Some preventive strategies of the disease include blocking the routes of transmission of the infections, disinfection of instruments used during medical case handling, using personal protective equipment, proper and early diagnosis of the disease, avoiding contact with the sick patients, and quarantine of the infected/exposed people.", "qid": 13, "docid": "oq16de67", "rank": 50, "score": 0.8376922607421875}, {"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": 51, "score": 0.8376801609992981}, {"content": "Title: Severe Acute Respiratory Syndrome Historical, Epidemiologic, and Clinical Features Content: Severe acute respiratory syndrome coronavirus (SARS-CoV), emerged from China and rapidly spread worldwide. Over 8098 people fell ill and 774 died before the epidemic ended in July 2003. Bats are likely an important reservoir for SARS-CoV. SARS-like CoVs have been detected in horseshoe bats and civet cats. The main mode of transmission of SARS-CoV is through inhalation of respiratory droplets. Faeco-oral transmission has been recorded. Strict infection control procedures with respiratory and contact precautions are essential. Fever and respiratory symptoms predominate, and diarrhea is common. Treatment involves supportive care. There are no specific antiviral treatments or vaccines available.", "qid": 13, "docid": "qrnycol5", "rank": 52, "score": 0.8375964760780334}, {"content": "Title: Hand disinfection in the combat against Covid\u201019 Content: The World Health Organization (WHO) has declared a global health emergency over a new coronavirus. The new corona virus (SARS\u2010CoV\u20102) has raised global attention with raising concerns of rapid spread from human\u2010to\u2010human. Like severe acute respiratory syndrome (SARS)\u2010nCoV, 2019\u2010nCoV can be passed directly from person to person by respiratory droplets, and may also be transmitted through contact and fomites.", "qid": 13, "docid": "t9ir627s", "rank": 53, "score": 0.8375129103660583}, {"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": 54, "score": 0.8374477624893188}, {"content": "Title: Public Health Response to the Initiation and Spread of Pandemic COVID-19 in the United States, February 24-April 21, 2020 Content: From January 21 through February 23, 2020, a total of 14 cases of coronavirus disease 2019 (COVID-19) were diagnosed in six U.S. states, including 12 cases in travelers arriving from China and two in household contacts of persons with confirmed infections. An additional 39 cases were identified in persons repatriated from affected areas outside the United States (1). Starting in late February, reports of cases with no recent travel to affected areas or links to known cases signaled the initiation of pandemic spread in the United States (2). By mid-March, transmission of SARS-CoV-2, the virus that causes COVID-19, had accelerated, with rapidly increasing case counts indicating established transmission in the United States. Ongoing traveler importation of SARS-CoV-2, attendance at professional and social events, introduction into facilities or settings prone to amplification, and challenges in virus detection all contributed to rapid acceleration of transmission during March. Public health responses included intensive efforts to detect cases and trace contacts, and implementation of multiple community mitigation strategies. Because most of the population remains susceptible to infection, recognition of factors associated with amplified spread during the early acceleration period will help inform future decisions as locations in the United States scale back some components of mitigation and strengthen systems to detect a potential transmission resurgence. U.S. circulation of SARS-CoV-2 continues, and sustained efforts will be needed to prevent future spread within the United States.", "qid": 13, "docid": "qdkhr8ch", "rank": 55, "score": 0.8369324207305908}, {"content": "Title: Public Health Response to the Initiation and Spread of Pandemic COVID-19 in the United States, February 24-April 21, 2020. Content: From January 21 through February 23, 2020, a total of 14 cases of coronavirus disease 2019 (COVID-19) were diagnosed in six U.S. states, including 12 cases in travelers arriving from China and two in household contacts of persons with confirmed infections. An additional 39 cases were identified in persons repatriated from affected areas outside the United States (1). Starting in late February, reports of cases with no recent travel to affected areas or links to known cases signaled the initiation of pandemic spread in the United States (2). By mid-March, transmission of SARS-CoV-2, the virus that causes COVID-19, had accelerated, with rapidly increasing case counts indicating established transmission in the United States. Ongoing traveler importation of SARS-CoV-2, attendance at professional and social events, introduction into facilities or settings prone to amplification, and challenges in virus detection all contributed to rapid acceleration of transmission during March. Public health responses included intensive efforts to detect cases and trace contacts, and implementation of multiple community mitigation strategies. Because most of the population remains susceptible to infection, recognition of factors associated with amplified spread during the early acceleration period will help inform future decisions as locations in the United States scale back some components of mitigation and strengthen systems to detect a potential transmission resurgence. U.S. circulation of SARS-CoV-2 continues, and sustained efforts will be needed to prevent future spread within the United States.", "qid": 13, "docid": "us0nk3om", "rank": 56, "score": 0.8369324207305908}, {"content": "Title: Active tuberculosis, sequelae and COVID-19 co-infection: first cohort of 49 cases Content: The severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) disease (COVID-19) pandemic has attracted interest because of its global rapid spread, clinical severity, high mortality rate, and capacity to overwhelm healthcare systems [1, 2]. SARS-CoV-2 transmission occurs mainly through droplets, although surface contamination contributes and debate continues on aerosol transmission [3\u20135].", "qid": 13, "docid": "onn8n9bl", "rank": 57, "score": 0.8366362452507019}, {"content": "Title: Is 0.5% Hydrogen Peroxide Effective against SARS\u2010CoV\u20102? Content: SARS\u2010CoV\u20102 is mostly transmitted through respiratory droplets and contact routes, but the WHO also states that \u201cairborne transmission may be possible in specific circumstances and settings in which procedures or support treatments that generate aerosols are performed\u201d (WHO, 2020).", "qid": 13, "docid": "w939rrhm", "rank": 58, "score": 0.8362196683883667}, {"content": "Title: Avoiding COVID-19: Aerosol Guidelines Content: The COVID-19 pandemic has brought into sharp focus the need to understand respiratory virus transmission mechanisms. In preparation for an anticipated influenza pandemic, a substantial body of literature has developed over the last few decades showing that the short-range aerosol route is an important, though often neglected transmission path. We develop a simple mathematical model for COVID-19 transmission via aerosols, apply it to known outbreaks, and present quantitative guidelines for ventilation and occupancy in the workplace.", "qid": 13, "docid": "n5bqf6rj", "rank": 59, "score": 0.8357075452804565}, {"content": "Title: COVID-19: Structural Predictions of Viral Success Content: Since the beginning of the 21st century, three coronaviruses have crossed the species barrier and caused serious human disease: severe acute respiratory syndrome coronavirus (SARS-CoV) in November 2002 [1, 2], Middle-East respiratory syndrome coronavirus (MERS-CoV) in 2012 [3, 4], and SARS-CoV-2 in 2019 [5, 6]. SARS-CoV-2 [7], initially called 2019-nCoV, is the etiological agent of COVID-19, a highly contagious infectious illness that was first reported in December 2019 in Wuhan, China and subsequently spread globally [8]. As of May 24, 2020, COVID-19 has caused >5,370,000 infections and >343,000 deaths worldwide [9].", "qid": 13, "docid": "p6r7d0sh", "rank": 60, "score": 0.8356467485427856}, {"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": 13, "docid": "30j0auua", "rank": 61, "score": 0.8355497121810913}, {"content": "Title: CHAPTER 28 Coronaviridae Content: Publisher Summary Coronaviruses are ssRNA viruses that infect a wide range of mammalian and avian species; they are important causes of respiratory and enteric disease, encephalomyelitis, hepatitis, serositis, and vasculitis in domestic animals. In humans, coronaviruses are one of several groups of viruses that cause the common cold. The prototype of the family, avian infectious brochitis virus, is one of the most infectious of all viruses and causes an acute respiratory disease, which in young chicks can cause very high mortality. Outbreaks can be explosive, involving nearly every bird in the flock at about the same time, because of respiratory transmission and a very short incubation period. In many ways, transmissible gastroenteritis virus of swine and mouse hepatitis virus behave similarly, affecting young animals most severely, spreading very quickly to all animals at risk, and causing major economic losses before control strategies can be put into place. The strategy of expression of the coronavirus genome is unique. The input virion RNA molecule is translated directly, one of the products being an RNA polymerase that then transcribes a full-length (\u2014) sense copy RNA, from which in turn is transcribed a 3\u2032-coterminal nested set of subgenomic mRNAs. The nested set comprises six overlapping species of mRNAs that extend for different lengths from a common 3\u2032 terminus. Only the unique sequence toward the 5\u2032 end, which is not shared with the next smallest mRNA in the nested set, is translated, each product, therefore, being a unique protein.", "qid": 13, "docid": "smmrl5i6", "rank": 62, "score": 0.8353123664855957}, {"content": "Title: Coronaviruses fusion with the membrane and entry to the host cell Content: Coronaviruses (CoVs) are positive-strand RNA viruses with the largest genome among all RNA viruses. They are able to infect many host, such as mammals or birds. Whereas CoVs were identified 1930s, they became known again in 2003 as the agents of the Severe Acute Respiratory Syndrome (SARS). The spike protein is thought to be essential in the process of CoVs entry, because it is associated with the binding to the receptor on the host cell. It is also involved in cell tropism and pathogenesis. Receptor recognition is the crucial step in the infection. CoVs are able to bind a variety of receptors, although the selection of receptor remains unclear. Coronaviruses were initially believed to enter cells by fusion with the plasma membrane. Further studies demonstrated that many of them involve endocytosis through clathrin-dependent, caveolae-dependent, clathrin-independent, as well as caveolae-independent mechanisms. The aim of this review is to summarise current knowledge about coronaviruses, focussing especially on CoVs entry into the host cell. Advances in understanding coronaviruses replication strategy and the functioning of the replicative structures are also highlighted. The development of host-directed antiviral therapy seems to be a promising way to treat infections with SARS-CoV or other pathogenic coronaviruses. There is still much to be discovered in the inventory of pro- and anti-viral host factors relevant for CoVs replication. The latest pandemic danger, originating from China, has given our previously prepared work even more of topicality.", "qid": 13, "docid": "e2agtvvu", "rank": 63, "score": 0.8351684808731079}, {"content": "Title: Coronaviruses fusion with the membrane and entry to the host cell. Content: Coronaviruses (CoVs) are positive-strand RNA viruses with the largest genome among all RNA viruses. They are able to infect many host, such as mammals or birds. Whereas CoVs were identified 1930s, they became known again in 2003 as the agents of the Severe Acute Respiratory Syndrome (SARS). The spike protein is thought to be essential in the process of CoVs entry, because it is associated with the binding to the receptor on the host cell. It is also involved in cell tropism and pathogenesis. Receptor recognition is the crucial step in the infection. CoVs are able to bind a variety of receptors, although the selection of receptor remains unclear. Coronaviruses were initially believed to enter cells by fusion with the plasma membrane. Further studies demonstrated that many of them involve endocytosis through clathrin-dependent, caveolae-dependent, clathrin-independent, as well as caveolae-independent mechanisms. The aim of this review is to summarise current knowledge about coronaviruses, focussing especially on CoVs entry into the host cell. Advances in understanding coronaviruses replication strategy and the functioning of the replicative structures are also highlighted. The development of host-directed antiviral therapy seems to be a promising way to treat infections with SARS-CoV or other pathogenic coronaviruses. There is still much to be discovered in the inventory of pro- and anti-viral host factors relevant for CoVs replication. The latest pandemic danger, originating from China, has given our previously prepared work even more of topicality.", "qid": 13, "docid": "16ofs0pu", "rank": 64, "score": 0.8351684808731079}, {"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": 13, "docid": "bm0ldeue", "rank": 65, "score": 0.8351445198059082}, {"content": "Title: Coronaviruses: An Overview of Their Replication and Pathogenesis Content: Coronaviruses (CoVs), enveloped positive-sense RNA viruses, are characterized by club-like spikes that project from their surface, an unusually large RNA genome, and a unique replication strategy. Coronaviruses cause a variety of diseases in mammals and birds ranging from enteritis in cows and pigs and upper respiratory disease chickens to potentially lethal human respiratory infections. Here we provide a brief introduction to coronaviruses discussing their replication and pathogenicity, and current prevention and treatment strategies. We will also discuss the outbreaks of the highly pathogenic Severe Acute Respiratory Syndrome Coronavirus (SARS-CoV) and the recently identified Middle Eastern Respiratory Syndrome Coronavirus (MERS-CoV).", "qid": 13, "docid": "kdnfnpla", "rank": 66, "score": 0.8351297378540039}, {"content": "Title: Coronaviruses Content: The members of coronavirus family are facultative pathogens of birds and mammals, including men. From their first isolation 60 years ago, they caused smaller or larger epidemics mainly originating from China. The most recent pandemic quickly spreading worldwide has affected over 2,000,000 people. Keywords: coronavirus; epidemic; single strand vRNA.", "qid": 13, "docid": "5ebutfr2", "rank": 67, "score": 0.8350493311882019}, {"content": "Title: Coronaviruses. Content: The members of coronavirus family are facultative pathogens of birds and mammals, including men. From their first isolation 60 years ago, they caused smaller or larger epidemics mainly originating from China. The most recent pandemic quickly spreading worldwide has affected over 2,000,000 people. Keywords: coronavirus; epidemic; single strand vRNA.", "qid": 13, "docid": "7nkpfm17", "rank": 68, "score": 0.8350493311882019}, {"content": "Title: 10 \u201cC\u201d in COVID19 Content: World war \u201cC\u201d(1) has set in against an invisible virus. The routes of transmission include *Contact of contaminated objects,*Circulating droplets in the air called aerosols disseminated through *Cough, sneeze, ocular secretions(2) from an infected individual.", "qid": 13, "docid": "6pwqa8zk", "rank": 69, "score": 0.8350180983543396}, {"content": "Title: The Rheumatologist's Role in Covid-19. Content: The novel coronavirus (SARS-CoV-2) pandemic has spread rapidly throughout the planet. It is believed to have originated in the Wuhan province of China, but this highly contagious respiratory virus has spread to over 140 countries on 6 continents as of mid-March 2020 according to the World Health Organization (WHO). Worldwide, there have been over 164,000 cases identified and over 6,500 deaths attributed to the viral infection. As of March 15, 2020, there are over 3,700 confirmed cases and 68 deaths ascribed to Covid-19 (the disease caused by SARS-CoV-2) in the United States [https://www.livescience.com/coronavirus-updates-unitedstates.html].", "qid": 13, "docid": "8m7l0uid", "rank": 70, "score": 0.8346319794654846}, {"content": "Title: Pandemic Human Coronavirus \u2013 Characterization and Comparison of Selected Properties of Hcov-sars and Hcov-mers Content: It: Two Coronaviruses, HCoV-229E and HCoV-OC43, causing generally mild respiratory tract infections in humans, were described in the XX c Pandemic Coronaviruses were first discovered as late as in the XXI c : SARS-HCoV in 2002 \u2013 causing severe respiratory tract infections (SARS) in China;MERS-HCoV in 2012 \u2013 circulating mostly on the Arabian Peninsula The SARS epidemic ended in 2004 resulting in morbidity of &gt;8000 and &gt;770 deaths, while the MERS epidemic is still ongoing (&gt;2000 ill, &gt;700 deaths) although its intensity decreased Both viruses are zoonotic and require at least two \u201chost jumps\u201d for the transmission of the infection to humans: for HCoV-SARS \u2013 from bat to palm civet and then to human;for HCoV-MERS \u2013 from bats to camels and subsequently to humans Primary mode of transmission is droplet in close contact (&lt;1 m), but both viruses remain active in aerosol (up to 24 h), so infection can be also spread by air (ventilation) The ability for human-to-human transmission is higher for HCoV-SARS than for HCoV-MERS (8 generations vs 4, respectively) Moreover, there are differences in genome structure and pathogenic mechanisms: different receptor, cell entry mechanism, different way of host response modulation (e g inhibition of IFN\u03b2 cascade), etc Probably, these differences influence the overall manifestation of the disease in humans Infection caused by HCoV-MERS might manifest itself as ARDS, a mild-mannered and asymptomatic disease HCoV-SARS infections seem to be associated with severe disease only In this paper, a comparison of the structure of these viruses, the mechanisms underlying their ability to cross the interspecies barrier and to multiply in the human body, including modulation of IFN\u03b2 cascade, as well as routes of infection transmission and symptoms caused, were presented", "qid": 13, "docid": "9eso10is", "rank": 71, "score": 0.8345938920974731}, {"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": 72, "score": 0.8344520330429077}, {"content": "Title: Tackling Corona Virus Disease 2019 (COVID 19) in Workplaces Content: Coronaviruses are zoonotic viruses and six species of Coronaviruses are known to cause human disease such as cause common cold, severe acute respiratory syndrome and the Middle East Respiratory Syndrome. In January 2020, scientists in Wuhan, China isolated a novel coronavirus (SARS-CoV-2), responsible for an outbreak of unknown pneumonia that had not been previously reported among humans. This virus spreads from person to person, through respiratory droplets, close contact, and by touching surfaces or objects contaminated by the virus. The incubation period varies between 2 days and 14 days. Symptoms usually include fever, cough, difficulty in breathing, pneumonia, severe acute respiratory syndrome. Older age and co-morbid conditions increase the fatality. Any person with a history of travel to and from COVID-19 affected countries in the past 14 days or any person who has had close contact with a laboratory confirmed COVID-19 are suspect cases and needs evaluation. Currently no vaccine is available and treatment is mainly supportive. Measures at workplace should include- avoiding non-essential travel, identifying and isolating sick employees at the earliest, hand hygiene, respiratory hygiene, environmental hygiene and social distancing.", "qid": 13, "docid": "rzr8qjw8", "rank": 73, "score": 0.8344123959541321}, {"content": "Title: A Mathematical Model of the Evolution and Spread of Pathogenic Coronaviruses from Natural Host to Human Host Content: Coronaviruses are highly transmissible and are pathogenic viruses of the 21(st) century worldwide. In general, these viruses are originated in bats or rodents. At the same time, the transmission of the infection to the human host is caused by domestic animals that represent in the habitat the intermediate host. In this study, we review the currently collected information about coronaviruses and establish a model of differential equations with piecewise constant arguments to discuss the spread of the infection from the natural host to the intermediate, and from them to the human host, while we focus on the potential spillover of bat-borne coronaviruses. The local stability of the positive equilibrium point of the model is considered via the Linearized Stability Theorem. Besides, we discuss global stability by employing an appropriate Lyapunov function. To analyze the outbreak in early detection, we incorporate the Allee effect at time t and obtain stability conditions for the dynamical behavior. Furthermore, it is shown that the model demonstrates the Neimark-Sacker Bifurcation. Finally, we conduct numerical simulations to support the theoretical findings.", "qid": 13, "docid": "afx977mr", "rank": 74, "score": 0.8342323303222656}, {"content": "Title: [Editorial] Possibility of transmission through dogs being a contributing factor to the extreme Covid\u00ad19 outbreak in North Italy Content: Covid\u00ad19 origin and transmission to humans. Covid\u00ad19 infection began in Wuhan (Hubei, China) in December, 2019. Although to date it is considered that Covid\u00ad19 originates from bats (96.2% overall genome sequence identity) (1), the type of intermediate animals that caused the transmission to humans remains unknown (2-4). Zhou et al (1) mentioned that 'Direct contact with intermediate host animals or consumption of wild animals was suspected to be the main route of SARS\u00adCoV\u00ad2 transmission. However, the source(s) and transmission routine(s) of SARS\u00adCoV\u00ad2 remain elusive' (1).", "qid": 13, "docid": "jwxt4ygt", "rank": 75, "score": 0.8337419629096985}, {"content": "Title: Post-donation COVID-19 identification in blood donors. Content: The coronavirus disease 19 (COVID-19) outbreak, which was characterized as a pandemic on 11 March 2020 by the WHO, started in December 2019 with the emergence of pneumonia cases of unknown cause in Wuhan, Hubei, China [1]. SARS-CoV-2, the causative agent of COVID-19, are enveloped, non-segmented, single stranded positive sense RNA viruses and are classified as a sister clade to the prototype human and bat severe acute respiratory syndrome coronaviruses (SARS-CoVs) of the species Severe acute respiratory syndrome-related coronavirus [2]. So far, no respiratory virus, including SARS-CoV and the Middle East Respiratory Syndrome (MERS)-CoV, has been confirmed as transfusion-transmissible [3,4].", "qid": 13, "docid": "82sc928x", "rank": 76, "score": 0.8335374593734741}, {"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": 13, "docid": "713ey27b", "rank": 77, "score": 0.8332509994506836}, {"content": "Title: Coronavirus Disease 2019: Coronaviruses and Blood Safety Content: With the outbreak of unknown pneumonia in Wuhan, China, in December 2019, a new coronavirus, Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2), aroused the attention of the entire world. The current outbreak of infections with SARS-CoV-2 is termed Coronavirus Disease 2019 (COVID-19). The World Health Organization declared COVID-19 in China as a Public Health Emergency of International Concern. Two other coronavirus infections-SARS in 2002-2003 and Middle East Respiratory Syndrome (MERS) in 2012-both caused severe respiratory syndrome in humans. All 3 of these emerging infectious diseases leading to a global spread are caused by \u00df-coronaviruses. Although coronaviruses usually infect the upper or lower respiratory tract, viral shedding in plasma or serum is common. Therefore, there is still a theoretical risk of transmission of coronaviruses through the transfusion of labile blood products. Because more and more asymptomatic infections are being found among COVID-19 cases, considerations of blood safety and coronaviruses have arisen especially in endemic areas. In this review, we detail current evidence and understanding of the transmission of SARS-CoV, MERS-CoV, and SARS-CoV-2 through blood products as of February 10, 2020, and also discuss pathogen inactivation methods on coronaviruses.", "qid": 13, "docid": "wpy3tt1x", "rank": 78, "score": 0.8331621885299683}, {"content": "Title: Perioperative airway management in patients infected with COVID-19/ Manejo de la v\u00eda a\u00e9rea en el perioperatorio de los pacientes infectados con COVID-19 Content: Coronavirus disease 2019 (COVID-19) is highly contagious. Transmission is predominantly by droplet spread. Procedures during the initial handling of the airway and critical areas can generate drops and aerosols that increase the risk of transmission. The aim of this paper is to review the recommendations and guidelines related to airway management in patient infected by SARS-Cov-2.", "qid": 13, "docid": "1i9z1agk", "rank": 79, "score": 0.8328765630722046}, {"content": "Title: Coronaviruses: Molecular Biology Content: Coronaviruses (CoVs) are enveloped, positive-strand RNA viruses with characteristic spike glycoproteins that project outward like the rays of the sun (corona \u2013 Latin for \u2018crown\u2019), when visualized by electron microscopy. CoV are classified, together with the toroviruses, in the family Coronaviridae and the order Nidovirales. All nidoviruses have a common genome organization and generate a nested set (nido \u2013 Latin for \u2018nest\u2019) of 3\u2032 co-terminal mRNAs. CoVs have been isolated from a variety of species, including birds, livestock, domestic animals, and humans. CoV infections can cause respiratory, gastrointestinal, and neurologic disease, depending on the strain of the virus and the site of infection. Importantly, CoVs have been shown to cross species barriers and have emerged from animal reservoirs to infect humans and cause severe disease. The CoV responsible for an outbreak of severe acute respiratory disease (SARS-CoV) in 2002\u201303 likely originated as a bat coronavirus which, during replication in an intermediate host (such as the palm civet), evolved to be able to infect humans efficiently. SARS-CoV infected over 8000 people with approximately 10% mortality rate. The SARS-CoV outbreak was controlled by public health measures alone. However, emergence or re-emergence of CoV from animal reservoirs is a potential concern for public health.", "qid": 13, "docid": "tktqlfgd", "rank": 80, "score": 0.8324175477027893}, {"content": "Title: Being a front-line dentist during the Covid-19 pandemic: a literature review Content: Coronavirus is an enveloped virus with positive-sense single-stranded RNA. Coronavirus infection in humans mainly affects the upper respiratory tract and to a lesser extent the gastrointestinal tract. Clinical symptoms of coronavirus infections can range from relatively mild (similar to the common cold) to severe (bronchitis, pneumonia, and renal involvement). The disease caused by the 2019 novel coronavirus (2019-nCoV) was called Covid-19 by the World Health Organization in February 2020. Face-to-face communication and consistent exposure to body fluids such as blood and saliva predispose dental care workers at serious risk for 2019-nCoV infection. As demonstrated by the recent coronavirus outbreak, information is not enough. During dental practice, blood and saliva can be scattered. Accordingly, dental practice can be a potential risk for dental staff, and there is a high risk of cross-infection. This article addresses all information collected to date on the virus, in accordance with the guidelines of international health care institutions, and provides a comprehensive protocol for managing possible exposure to patients or those suspected of having coronavirus.", "qid": 13, "docid": "gyvvcnuf", "rank": 81, "score": 0.8323830366134644}, {"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": 82, "score": 0.8322786092758179}, {"content": "Title: Axonal Transport Enables Neuron-to-Neuron Propagation of Human Coronavirus OC43. Content: Human coronaviruses (HCoVs) are recognized respiratory pathogens for which accumulating evidence indicates that in vulnerable patients the infection can cause more severe pathologies. HCoVs are not always confined to the upper respiratory tract and can invade the central nervous system (CNS) under still unclear circumstances. HCoV-induced neuropathologies in humans are difficult to diagnose early enough to allow therapeutic interventions. Making use of our already described animal model of HCoV neuropathogenesis, we describe the route of neuropropagation from the nasal cavity to the olfactory bulb and piriform cortex and then the brain stem. We identified neuron-to-neuron propagation as one underlying mode of virus spreading in cell culture. Our data demonstrate that both passive diffusion of released viral particles and axonal transport are valid propagation strategies used by the virus. We describe for the first time the presence along axons of viral platforms whose static dynamism is reminiscent of viral assembly sites. We further reveal that HCoV OC43 modes of propagation can be modulated by selected HCoV OC43 proteins and axonal transport. Our work, therefore, identifies processes that may govern the severity and nature of HCoV OC43 neuropathogenesis and will make possible the development of therapeutic strategies to prevent occurrences.IMPORTANCE Coronaviruses may invade the CNS, disseminate, and participate in the induction of neurological diseases. Their neuropathogenicity is being increasingly recognized in humans, and the presence and persistence of human coronaviruses (HCoV) in human brains have been proposed to cause long-term sequelae. Using our mouse model relying on natural susceptibility to HCoV OC43 and neuronal cell cultures, we have defined the most relevant path taken by HCoV OC43 to access and spread to and within the CNS toward the brain stem and spinal cord and studied in cell culture the underlying modes of intercellular propagation to better understand its neuropathogenesis. Our data suggest that axonal transport governs HCoV OC43 egress in the CNS, leading to the exacerbation of neuropathogenesis. Exploiting knowledge on neuroinvasion and dissemination will enhance our ability to control viral infection within the CNS, as it will shed light on underlying mechanisms of neuropathogenesis and uncover potential druggable molecular virus-host interfaces.", "qid": 13, "docid": "xptxoc3t", "rank": 83, "score": 0.8321510553359985}, {"content": "Title: Coronavirus nCOVID-19: A Pandemic Disease and the Saudi precautions Content: Now nCOVID-19 has a foothold in many countries, and the threat of a pandemic situation has risen. Recently a novel coronavirus (nCOVID-19) has first emerged in China, causing multiple symptoms in humans and closely related to those caused by SARS (Severe Acute Respiratory Syndrome) and MERS (Middle East Respiratory Syndrome). The nCOVID-19 has reported in Wuhan city of China has recently infected over six million people and at least 0.4 million confirmed deaths all over the world, while 2.8 million people has recovered from this deadly virus. Many instances of this respiratory syndrome coronavirus infection have already reported in more than 216 countries and territories. In contrast, the majority of cases reported in the USA, Brazil, Russia, Spain, UK, Italy, France and many more countries. In today's context, the coronavirus is one of the significant issues faced by the world with plenty of cases. In these circumstances, rapid reviews which recommended by WHO (World Health Organization), and these recommendations are very significant, helpful and cover current data with different preventive measures developed by the Saudi CDC (Saudi Centre for Disease Prevention and Control). This review article describes the possible modes of transmission so that proper preventive actions should be taking. Importantly, this work mentioned the animal reservoir through which may infect humans, and it must be identified to break the transmission chain. In additions, this review paper briefly discussed the spread of the coronavirus in the Arabian Peninsula and what precaution measures are in place by each country to limit the spreading of this virus. Taking into consideration the preventive measures by pharmacists as part of health care professions, however, the number of infected people, especially those with close contact with nCOVID-19 patients, are rise day by day and currently seems unstoppable.", "qid": 13, "docid": "0twnkv93", "rank": 84, "score": 0.831989049911499}, {"content": "Title: Better Safe than Sorry: Interventional Radiology Should Be Prepared for the Coronavirus Disease 2019 Pandemic Content: Coronavirus disease 2019 (COVID-19) is a viral pneumonia that has plagued the world for much of the first quarter of 2020 and was recently declared a global pandemic. The caregivers must be aware of the disease and take steps to curb its transmission within the premises of our care settings (hospitals/clinics). In this article, we suggest a few proactive steps that can be taken at the institutional and departmental levels to break the transmission chain.", "qid": 13, "docid": "h76joy68", "rank": 85, "score": 0.8319050073623657}, {"content": "Title: A Computer Simulation Study on novel Corona Virus Transmission among the People in a Queue Content: The World Health Organization (WHO) on March 11, 2020, has declared the novel Corona virus (COVID-19) outbreak a global pandemic. It is essential to understand how coronavirus transmits from one person to another and this knowledge will help protect the vulnerable and limit the spread of the Corona virus. The mode of respiratory transmission of Corona virus is not completely understood as of date. Using a computer simulation, this paper analyses the probability of spreading of Corona virus through air among the people who are standing in a queue. The parameters such as the diameter of the virus particle, room temperature, relative humidity, height of the person, distance between the people and the waiting time in the queue are considered in the computer model to determine the distribution of Corona virus and hence identify the risk factor of spreading the Covid-19. This paper describes the possibilities of getting infectious when a Covid-19 infected person present in a queue and the impact on the waiting time and the position in the queue on the transmission of Corona virus.", "qid": 13, "docid": "9x4d6skf", "rank": 86, "score": 0.8318578004837036}, {"content": "Title: Transmission and risk factors of OF COVID-19 Content: SARS-CoV-2, the virus that causes COVID-19, is transmitted through respiratory secretions and saliva. The virus can also live for short periods of time (1 to several hours) on fomites such as doorknobs, handrails, and tables. Aerosolization of the virus can occur during procedures including bronchoscopy, endotracheal intubation, and administration of nebulized treatments. Asymptomatic shedding of the virus does occur and may account for up to 60% of cases. Risk factors for a more severe course of COVID-19 include age 65 and older, living in a nursing home or long term care facility, chronic lung disease, and others.", "qid": 13, "docid": "eimqd5b9", "rank": 87, "score": 0.8317247629165649}, {"content": "Title: Transmission and risk factors of OF COVID-19. Content: SARS-CoV-2, the virus that causes COVID-19, is transmitted through respiratory secretions and saliva. The virus can also live for short periods of time (1 to several hours) on fomites such as doorknobs, handrails, and tables. Aerosolization of the virus can occur during procedures including bronchoscopy, endotracheal intubation, and administration of nebulized treatments. Asymptomatic shedding of the virus does occur and may account for up to 60% of cases. Risk factors for a more severe course of COVID-19 include age 65 and older, living in a nursing home or long term care facility, chronic lung disease, and others.", "qid": 13, "docid": "l1nvnvkg", "rank": 88, "score": 0.8317247629165649}, {"content": "Title: Airborne transmission of severe acute respiratory syndrome coronavirus-2 to healthcare workers: a narrative review Content: Healthcare workers are at risk of infection during the severe acute respiratory syndrome coronavirus-2 pandemic. International guidance suggests direct droplet transmission is likely and airborne transmission occurs only with aerosol-generating procedures. Recommendations determining infection control measures to ensure healthcare worker safety follow these presumptions. Three mechanisms have been described for the production of smaller sized respiratory particles ('aerosols') that, if inhaled, can deposit in the distal airways. These include: laryngeal activity such as talking and coughing; high velocity gas flow; and cyclical opening and closure of terminal airways. Sneezing and coughing are effective aerosol generators, but all forms of expiration produce particles across a range of sizes. The 5-\u00b5m diameter threshold used to differentiate droplet from airborne is an over-simplification of multiple complex, poorly understood biological and physical variables. The evidence defining aerosol-generating procedures comes largely from low-quality case and cohort studies where the exact mode of transmission is unknown as aerosol production was never quantified. We propose that transmission is associated with time in proximity to severe acute respiratory syndrome coronavirus-1 patients with respiratory symptoms, rather than the procedures per se. There is no proven relation between any aerosol-generating procedure with airborne viral content with the exception of bronchoscopy and suctioning. The mechanism for severe acute respiratory syndrome coronavirus-2 transmission is unknown but the evidence suggestive of airborne spread is growing. We speculate that infected patients who cough, have high work of breathing, increased closing capacity and altered respiratory tract lining fluid will be significant producers of pathogenic aerosols. We suggest several aerosol-generating procedures may in fact result in less pathogen aerosolisation than a dyspnoeic and coughing patient. Healthcare workers should appraise the current evidence regarding transmission and apply this to the local infection prevalence. Measures to mitigate airborne transmission should be employed at times of risk. However, the mechanisms and risk factors for transmission are largely unconfirmed. Whilst awaiting robust evidence, a precautionary approach should be considered to assure healthcare worker safety.", "qid": 13, "docid": "j4abgq88", "rank": 89, "score": 0.8317073583602905}, {"content": "Title: COVID-19: Emergence, Spread, Possible Treatments, and Global Burden Content: The Coronavirus (CoV) is a large family of viruses known to cause illnesses ranging from the common cold to acute respiratory tract infection. The severity of the infection may be visible as pneumonia, acute respiratory syndrome, and even death. Until the outbreak of SARS, this group of viruses was greatly overlooked. However, since the SARS and MERS outbreaks, these viruses have been studied in greater detail, propelling the vaccine research. On December 31, 2019, mysterious cases of pneumonia were detected in the city of Wuhan in China's Hubei Province. On January 7, 2020, the causative agent was identified as a new coronavirus (2019-nCoV), and the disease was later named as COVID-19 by the WHO. The virus spread extensively in the Wuhan region of China and has gained entry to over 210 countries and territories. Though experts suspected that the virus is transmitted from animals to humans, there are mixed reports on the origin of the virus. There are no treatment options available for the virus as such, limited to the use of anti-HIV drugs and/or other antivirals such as Remdesivir and Galidesivir. For the containment of the virus, it is recommended to quarantine the infected and to follow good hygiene practices. The virus has had a significant socio-economic impact globally. Economically, China is likely to experience a greater setback than other countries from the pandemic due to added trade war pressure, which have been discussed in this paper.", "qid": 13, "docid": "vx7ebtbp", "rank": 90, "score": 0.8316479325294495}, {"content": "Title: Coronavirus Disease (COVID-19): Implications for Cardiovascular and Socially At-risk Populations Content: Dennison Himmelfarb and Baptiste discuss the implications of coronavirus disease (COVID-19) for cardiovascular and socially at-risk populations COVID-19 is an infectious respiratory disease caused by the newly discovered pathogen, SARS-CoV-2, a novel RNA-dependent RNA polymerase betacoronavirus that is thought to derive from bats At this time, there are no specific vaccines or treatments for COVID-19 The best way to prevent and slow transmission is to be well informed about the COVID-19 virus, the disease it causes, and how it spreads", "qid": 13, "docid": "cw37jrt2", "rank": 91, "score": 0.8314656019210815}, {"content": "Title: Coronaviruses: Molecular Biology\u2606 Content: Abstract Coronaviruses (CoVs) are enveloped, positive-strand RNA viruses with characteristic spike glycoproteins that project outward like the rays of the sun (corona \u2013 Latin for \u2018crown\u2019), when visualized by electron microscopy. CoV are classified, together with the toroviruses, in the family Coronaviridae and the order Nidovirales. All nidoviruses have a common genome organization and generate a nested set (nido \u2013 Latin for \u2018nest\u2019) of 3\u2032 co-terminal mRNAs. CoVs have been isolated from a variety of species, including birds, livestock, domestic animals, and humans. CoV infections can cause respiratory, gastrointestinal, and neurologic disease, depending on the strain of the virus and the site of infection. Importantly, CoVs have been shown to cross species barriers and have emerged from animal reservoirs to infect humans and cause severe disease. The CoV responsible for an outbreak of severe acute respiratory disease (SARS-CoV) in 2002\u201303 likely originated as a bat coronavirus which, during replication in an intermediate host (such as the palm civet), evolved to be able to infect humans efficiently. SARS-CoV infected over 8000 people with approximately 10% mortality rate before it was controlled by public health measures of isolation of infected individuals and contacts. Middle East Respiratory Syndrome CoV (MERS-CoV), first reported in 2012, is likely transmitted from camels to humans with potentially fatal consequences. To date, there are no approved vaccines or direct acting antiviral drugs to combat coronavirus infections in humans. The emergence or re-emergence of CoVs from animal reservoirs is a potential concern for public health.", "qid": 13, "docid": "eqfz0wpm", "rank": 92, "score": 0.8313886523246765}, {"content": "Title: Recombination, reservoirs, and the modular spike: mechanisms of coronavirus cross-species transmission. Content: Over the past 30 years, several cross-species transmission events, as well as changes in virus tropism, have mediated significant animal and human diseases. Most notable is severe acute respiratory syndrome (SARS), a lower respiratory tract disease of humans that was first reported in late 2002 in Guangdong Province, China. The disease, which quickly spread worldwide over a period of 4 months spanning late 2002 and early 2003, infected over 8,000 individuals and killed nearly 800 before it was successfully contained by aggressive public health intervention strategies. A coronavirus (SARS-CoV) was identified as the etiological agent of SARS, and initial assessments determined that the virus crossed to human hosts from zoonotic reservoirs, including bats, Himalayan palm civets (Paguma larvata), and raccoon dogs (Nyctereutes procyonoides), sold in exotic animal markets in Guangdong Province. In this review, we discuss the molecular mechanisms that govern coronavirus cross-species transmission both in vitro and in vivo, using the emergence of SARS-CoV as a model. We pay particular attention to how changes in the Spike attachment protein, both within and outside of the receptor binding domain, mediate the emergence of coronaviruses in new host populations.", "qid": 13, "docid": "dfyshke7", "rank": 93, "score": 0.8313682079315186}, {"content": "Title: The role of environmental factors to transmission of SARS-CoV-2 (COVID-19) Content: The current outbreak of the novel coronavirus disease 2019 (COVID-19) in more than 250 countries has become a serious threat to the health of people around the world. Human-to-human transmission of the Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) occurs most often when people are in the incubation stage of the disease or are carriers and have no symptoms. Therefore, in this study, was discussed the role of environmental factors and conditions such as temperature, humidity, wind speed as well as food, water and sewage, air, insects, inanimate surfaces, and hands in COVID-19 transmission. The results of studies on the stability of the SARS-CoV-2 on different levels showed that the resistance of this virus on smooth surfaces was higher than others. Temperature increase and sunlight can facilitate the destruction of SARS-COV-2 and the stability of it on surfaces. When the minimum ambient air temperature increases by 1 \u00b0C, the cumulative number of cases decreases by 0.86%. According to the latest evidence, the presence of coronavirus in the sewer has been confirmed, but there is no evidence that it is transmitted through sewage or contaminated drinking water. Also, SARS-COV-2 transmission through food, food packages, and food handlers has not been identified as a risk factor for the disease. According to the latest studies, the possibility of transmitting SARS-COV-2 bioaerosol through the air has been reported in the internal environment of ophthalmology. The results additionally show that infectious bio-aerosols can move up to 6 feet. There have been no reports of SARS-COV-2 transmission by blood-feeding arthropods such as mosquitoes.", "qid": 13, "docid": "t01njoxo", "rank": 94, "score": 0.831123948097229}, {"content": "Title: Active Monitoring of Persons Exposed to Patients with Confirmed COVID-19 - United States, January-February 2020 Content: In December 2019, an outbreak of coronavirus disease 2019 (COVID-19), caused by the virus SARS-CoV-2, began in Wuhan, China (1). The disease spread widely in China, and, as of February 26, 2020, COVID-19 cases had been identified in 36 other countries and territories, including the United States. Person-to-person transmission has been widely documented, and a limited number of countries have reported sustained person-to-person spread.* On January 20, state and local health departments in the United States, in collaboration with teams deployed from CDC, began identifying and monitoring all persons considered to have had close contact\u0086 with patients with confirmed COVID-19 (2). The aims of these efforts were to ensure rapid evaluation and care of patients, limit further transmission, and better understand risk factors for transmission.", "qid": 13, "docid": "npyo0597", "rank": 95, "score": 0.8309745788574219}, {"content": "Title: Comparison of transmissibility of coronavirus between symptomatic and asymptomatic patients: Reanalysis of the Ningbo Covid-19 data Content: We investigate the transmissibility of coronavirus for symptomatic and asymptomatic patients using the Ningbo Covid-19 data1. Through more in-depth and comprehensive statistical analysis, we conclude that there is no difference in the transmission rates of coronavirus between the symptomatic and asymptomatic patients, which is consistent with the original findings in Chen et al.1", "qid": 13, "docid": "nlzdto1h", "rank": 96, "score": 0.8309731483459473}, {"content": "Title: COVID\u201019: Structural Predictions of Viral Success Content: Since the beginning of the 21(st) century, three coronaviruses have crossed the species barrier and caused serious human disease: severe acute respiratory syndrome coronavirus (SARS\u2010CoV) in November 2002 [1, 2], Middle\u2010East respiratory syndrome coronavirus (MERS\u2010CoV) in 2012 [3, 4], and SARS\u2010CoV\u20102 in 2019 [5, 6]. SARS\u2010CoV\u20102 [7], initially called 2019\u2010nCoV, is the etiological agent of COVID\u201019, a highly contagious infectious illness that was first reported in December 2019 in Wuhan, China and subsequently spread globally [8]. As of May 24, 2020, COVID\u201019 has caused >5,370,000 infections and >343,000 deaths worldwide [9].", "qid": 13, "docid": "4tq0ujal", "rank": 97, "score": 0.8308961391448975}, {"content": "Title: Active Monitoring of Persons Exposed to Patients with Confirmed COVID-19 - United States, January-February 2020. Content: In December 2019, an outbreak of coronavirus disease 2019 (COVID-19), caused by the virus SARS-CoV-2, began in Wuhan, China (1). The disease spread widely in China, and, as of February 26, 2020, COVID-19 cases had been identified in 36 other countries and territories, including the United States. Person-to-person transmission has been widely documented, and a limited number of countries have reported sustained person-to-person spread.* On January 20, state and local health departments in the United States, in collaboration with teams deployed from CDC, began identifying and monitoring all persons considered to have had close contact\u2020 with patients with confirmed COVID-19 (2). The aims of these efforts were to ensure rapid evaluation and care of patients, limit further transmission, and better understand risk factors for transmission.", "qid": 13, "docid": "mvm1t0y7", "rank": 98, "score": 0.8308334946632385}, {"content": "Title: Household transmission of COVID-19, Shenzhen, January-February 2020 Content: Coronavirus disease 2019 has led to more than three million cases globally. Since the first family cluster of COVID-19 cases identified in Shenzhen in early January, most of the local transmission occurred within household contacts. Identifying the factors associated with household transmission is of great importance to guide preventive measures.", "qid": 13, "docid": "uuay24nq", "rank": 99, "score": 0.8306001424789429}, {"content": "Title: Middle East Respiratory Syndrome Virus Pathogenesis Content: Coronaviruses (CoVs) are enveloped RNA viruses that infect birds, mammals, and humans. Infections caused by human coronaviruses (hCoVs) are mostly associated with the respiratory, enteric, and nervous systems. The hCoVs only occasionally induce lower respiratory tract disease, including bronchitis, bronchiolitis, and pneumonia. In 2002 to 2003, a global outbreak of severe acute respiratory syndrome (SARS) was the seminal detection of a novel CoV (SARS-CoV). A decade later (June 2012), another novel CoV was implicated as the cause of Middle East respiratory syndrome (MERS) in Saudi Arabia. Although bats might serve as a reservoir of MERS-CoV, it is unlikely that they are the direct source for most human cases. Severe lines of evidence suggest that dromedary camels have been the major cause of transmission to humans. The emergence of MERS-CoV has triggered serious concerns about the potential for a widespread outbreak. All MERS cases were linked directly or indirectly to the Middle East region including Saudi Arabia, Jordan, Qatar, Oman, Kuwait, and UAE. MERS cases have also been reported in the later phases in the United Kingdom, France, Germany, Italy, Spain, and Tunisia. Most of these MERS cases were linked with the Middle East. The high mortality rates in family-based and hospital-based outbreaks were reported among patients with comorbidities such as diabetes and renal failure. MERS-CoV causes an acute, highly lethal pneumonia and renal dysfunction. The major complications reported in fatal cases are hyperkalemia with associated ventricular tachycardia, disseminated intravascular coagulation, pericarditis, and multiorgan failure. The case-fatality rate seems to be higher for MERS-CoV (around 30%) than for SARS-CoV (9.6%). The combination regimen of type 1 interferon + lopinavir/ritonavir is considered as the first-line therapy for MERS. Antiviral treatment is generally recommended for 10 to 14 days in patients with MERS-CoV infection. Convalescent plasma therapy has shown some efficacy among patients refractory to antiviral drugs if administered within 2 weeks of the onset of the disease.", "qid": 13, "docid": "9zd88mba", "rank": 100, "score": 0.8304764032363892}]}
{"query": "what evidence is there related to COVID-19 super spreaders", "hits": [{"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": 1, "score": 0.8764585256576538}, {"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": 0.8764585256576538}, {"content": "Title: Do superspreaders generate new superspreaders? a hypothesis to explain the propagation pattern of COVID-19 Content: Abstract The current global propagation of COVID-19 is heterogeneous, with slow transmission continuing in many countries, and exponential propagation in others, in which the time that took to begin this explosive spread varies greatly. It is proposed that this could be explained by cascading superspreading events, in which new infections caused by a superspreader are more likely to be highly infectious. The mechanism suggested for this is related to viral loads. Exposure to high viral loads may result in infections of high intensity, which exposes new cases to high viral loads, and so on. This notion is supported by experimental veterinary research.", "qid": 14, "docid": "5906wju4", "rank": 3, "score": 0.8718783855438232}, {"content": "Title: Do superspreaders generate new superspreaders? A hypothesis to explain the propagation pattern of COVID-19 Content: The current global propagation of COVID-19 is heterogeneous, with slow transmission continuing in many countries and exponential propagation in others, where the time that it took for the explosive spread to begin varied greatly. It is proposed that this could be explained by cascading superspreading events, in which new infections caused by a superspreader are more likely to be highly infectious. The mechanism suggested for this is related to viral loads. Exposure to high viral loads may result in high-intensity infection, which exposes new cases to high viral loads. This notion is supported by experimental veterinary research.", "qid": 14, "docid": "oocco483", "rank": 4, "score": 0.8714169263839722}, {"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": 5, "score": 0.8699464797973633}, {"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": 6, "score": 0.8675966262817383}, {"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 (R(0)) 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": "w4l2vpiy", "rank": 7, "score": 0.8670204877853394}, {"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": 8, "score": 0.8647511601448059}, {"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": 9, "score": 0.8642557859420776}, {"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": 10, "score": 0.8598041534423828}, {"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": 11, "score": 0.8545008301734924}, {"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": 12, "score": 0.850156307220459}, {"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": 13, "score": 0.8492196798324585}, {"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": 14, "score": 0.8428019285202026}, {"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": 15, "score": 0.8428019285202026}, {"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": 16, "score": 0.8404993414878845}, {"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": 17, "score": 0.8390637040138245}, {"content": "Title: Closed environments facilitate secondary transmission of coronavirus disease 2019 (COVID-19) Content: Objective: To identify common features of cases with novel coronavirus disease (COVID-19) so as to better understand what factors promote secondary transmission including superspreading events. Methods: A total of 110 cases were examined among eleven clusters and sporadic cases, and investigated who acquired infection from whom. The clusters included four in Tokyo and one each in Aichi, Fukuoka, Hokkaido, Ishikawa, Kanagawa and Wakayama prefectures. The number of secondary cases generated by each primary case was calculated using contact tracing data. Results: Of the 110 cases examined, 27 (24.6%) were primary cases who generated secondary cases. The odds that a primary case transmitted COVID-19 in a closed environment was 18.7 times greater compared to an open-air environment (95% confidence interval [CI]: 6.0, 57.9). Conclusions: It is plausible that closed environments contribute to secondary transmission of COVID-19 and promote superspreading events. Our findings are also consistent with the declining incidence of COVID-19 cases in China, as gathering in closed environments was prohibited in the wake of the rapid spread of the disease.", "qid": 14, "docid": "p3dex2to", "rank": 18, "score": 0.8390473127365112}, {"content": "Title: Superspreading in Early Transmissions of COVID-19 in Indonesia Content: We estimate the basic reproduction number R0 and the overdispersion parameter K at two COVID-19 clusters in Indonesia: Jakarta-Depok and Batam. Based on the first 397 confirmed cases in both clusters, we find a high degree of individual-level variation in the transmission. The basic reproduction number R0 is estimated at 6.79 and 2.47, while the overdispersion parameter K of a negative-binomial distribution is estimated at 0.08 and 0.2 for Jakarta-Depok and Batam, respectively. This suggests that superspreading events played a key role in the early stage of the outbreak, i.e., a small number of infected individuals are responsible for large amounts of COVID-19 transmission.", "qid": 14, "docid": "ogrlidrs", "rank": 19, "score": 0.8386400938034058}, {"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": 20, "score": 0.8383361101150513}, {"content": "Title: Stochasticity and heterogeneity in the transmission dynamics of SARS-CoV-2 Content: SARS-CoV-2 causing COVID-19 disease has moved rapidly around the globe, infecting millions and killing hundreds of thousands. The basic reproduction number, which has been widely used and misused to characterize the transmissibility of the virus, hides the fact that transmission is stochastic, is dominated by a small number of individuals, and is driven by super-spreading events (SSEs). The distinct transmission features, such as high stochasticity under low prevalence, and the central role played by SSEs on transmission dynamics, should not be overlooked. Many explosive SSEs have occurred in indoor settings stoking the pandemic and shaping its spread, such as long-term care facilities, prisons, meat-packing plants, fish factories, cruise ships, family gatherings, parties and night clubs. These SSEs demonstrate the urgent need to understand routes of transmission, while posing an opportunity that outbreak can be effectively contained with targeted interventions to eliminate SSEs. Here, we describe the potential types of SSEs, how they influence transmission, and give recommendations for control of SARS-CoV-2.", "qid": 14, "docid": "en6fgilb", "rank": 21, "score": 0.8359639644622803}, {"content": "Title: Post-donation COVID-19 identification in blood donors. Content: The coronavirus disease 19 (COVID-19) outbreak, which was characterized as a pandemic on 11 March 2020 by the WHO, started in December 2019 with the emergence of pneumonia cases of unknown cause in Wuhan, Hubei, China [1]. SARS-CoV-2, the causative agent of COVID-19, are enveloped, non-segmented, single stranded positive sense RNA viruses and are classified as a sister clade to the prototype human and bat severe acute respiratory syndrome coronaviruses (SARS-CoVs) of the species Severe acute respiratory syndrome-related coronavirus [2]. So far, no respiratory virus, including SARS-CoV and the Middle East Respiratory Syndrome (MERS)-CoV, has been confirmed as transfusion-transmissible [3,4].", "qid": 14, "docid": "82sc928x", "rank": 22, "score": 0.8355278372764587}, {"content": "Title: Characterizing super-spreading events and age-specific infectivity of COVID-19 transmission in Georgia, USA Content: As the current COVID-19 pandemic continues to impact countries around the globe, refining our understanding of its transmission dynamics and the effectiveness of interventions is imperative. In particular, it is essential to obtain a firmer grasp on the effect of social distancing, potential individual-level heterogeneities in transmission such as age-specific infectivity, and impact of super-spreading. To this end, it is important to exploit multiple data streams that are becoming abundantly available during the pandemic. In this paper, we formulate an individual-level spatio-temporal mechanistic framework to statistically integrate case data with geo-location data and aggregate mobility data, enabling a more granular understanding of the transmission dynamics of COVID-19. We analyze reported cases from surveillance data, between March and early May 2020, in five (urban and rural) counties in the State of Georgia USA. We estimate natural history parameters of COVID-19 and infer unobserved quantities including infection times and transmission paths using Bayesian data-augmentation techniques. First, our results show that the overall median reproductive number was 2.88 (with 95% C.I. [1.85, 4.9]) before the state-wide shelter-in-place order issued in early April, and the effective reproductive number was reduced to below 1 about two weeks by the order. Super-spreading appears to be widespread across space and time, and it may have a particularly important role in driving the outbreak in the rural area and increasing importance towards later stages of outbreaks in both urban and rural settings. Overall, about 2% of cases may have directly infected 20% of all infections. We estimate that the infected children and younger adults (<60 years old) may be 2.38 [1.30, 3.51] times more transmissible than infected elderly (>=60), and the former may be the main driver of super-spreading. Through the synthesis of multiple data streams using our transmission modelling framework, our results enforce and improve our understanding of the natural history and transmission dynamics of COVID-19. More importantly, we reveal the roles of age-specific infectivity and characterize systematic variations and associated risk factors of super-spreading. These have important implications for the planning of relaxing social distancing and, more generally, designing optimal control measures.", "qid": 14, "docid": "2jy2hjwy", "rank": 23, "score": 0.833625853061676}, {"content": "Title: Evaluating new evidence in the early dynamics of the novel coronavirus COVID-19 outbreak in Wuhan, China with real time domestic traffic and potential asymptomatic transmissions Content: The novel coronavirus (COVID-19), first detected in Wuhan, China in December 2019, has spread to 28 countries/regions with over 43,000 confirmed cases. Much about this outbreak is still unknown. At this early stage of the epidemic, it is important to investigate alternative sources of information to understand its dynamics and spread. With updated real time domestic traffic, this study aims to integrate recent evidence of international evacuees extracted from Wuhan between Jan. 29 and Feb. 2, 2020 to infer the dynamics of the COVD-19 outbreak in Wuhan. In addition, a modified SEIR model was used to evaluate the empirical support for the presence of asymptomatic transmissions. Based on the data examined, this study found little evidence for the presence of asymptomatic transmissions. However, it is still too early to rule out its presence conclusively due to sample size and other limitations. The updated basic reproductive number was found to be 2.12 on average with a 95% credible interval of [2.04, 2.18]. It is smaller than previous estimates probably because the new estimate factors in the social and non-pharmaceutical mitigation implemented in Wuhan through the evacuee dataset. Detailed predictions of infected individuals exported both domestically and internationally were produced. The estimated case confirmation rate has been low but has increased steadily to 23.37% on average. The findings of this study depend on the validity of the underlying assumptions, and continuing work is needed, especially in monitoring the current infection status of Wuhan residents.", "qid": 14, "docid": "ehm4fgos", "rank": 24, "score": 0.8333817720413208}, {"content": "Title: SUPERSPREADING AS A REGULAR FACTOR OF THE COVID-19 PANDEMIC Content: An impact of superspreading on the course of the COVID-19 epidemic is considered. A two-component model of the epidemic has been developed, in which all infected are divided in two groups. They are asymptomatic superspreaders spreading the infection and sensitive persons which can only get infection. Once infected the sensitive exhibit clear symptoms and become isolated. Taking into account both factors allows find the numbers of superspreaders and sensitive persons. It is shown, that the ratio of increment of the number of daily cases in the beginning of the epidemic and decrement at the end of the epidemic is equal to the ratio of numbers of the superspreaders and sensitive persons. In this way, on the base of data from 12 countries and territories, the share of asymptomatic among all infected persons is found to be (17 {+/-} 3)%. Specific measures to limit the epidemical incidence are proposed. The possibility of an allergic component in the disease is discussed.", "qid": 14, "docid": "c8byhwsj", "rank": 25, "score": 0.8322845101356506}, {"content": "Title: No evidence for distinct types in the evolution of SARS-CoV-2 Content: A recent study by Tang et al. (2020) claimed that two major types of SARS-CoV-2 had evolved in the ongoing COVID-19 pandemic and that one of these types was more \u201caggressive\u201d than the other. Given the repercussions of these claims and the intense media coverage of these types of articles, we have examined in detail the data presented by Tang et al, and show that the major conclusions of that paper cannot be substantiated. Using examples from other viral outbreaks we discuss the difficulty in demonstrating the existence or nature of a functional effect of a viral mutation, and we advise against overinterpretation of genomic data during the pandemic.", "qid": 14, "docid": "m61qihyq", "rank": 26, "score": 0.8316249847412109}, {"content": "Title: Scientometric Trends for Coronaviruses and Other Emerging Viral Infections Content: COVID-19 is the most rapidly expanding coronavirus outbreak in the past two decades. To provide a swift response to a novel outbreak, prior knowledge from similar outbreaks is essential. Here, we study the volume of research conducted on previous coronavirus outbreaks, specifically SARS and MERS, relative to other infectious diseases by analyzing over 35 million papers from the last 20 years. Our results demonstrate that previous coronavirus outbreaks have been understudied compared to other viruses. We also show that the research volume of emerging infectious diseases is very high after an outbreak and drops drastically upon the containment of the disease. This can yield inadequate research and limited investment in gaining a full understanding of novel coronavirus management and prevention. Independent of the outcome of the current COVID-19 outbreak, we believe that measures should be taken to encourage sustained research in the field.", "qid": 14, "docid": "kh9whqzd", "rank": 27, "score": 0.8308628797531128}, {"content": "Title: Severe acute respiratory syndrome-coronavirus 2 and novel coronavirus disease 2019: An extraordinary pandemic Content: COVID-19 has emerged as one of the most significant illnesses of the current century. It is caused by severe acute respiratory syndrome coronavirus 2. The world was initially viewing it as a localized outbreak in Wuhan city of China; however, it started spreading quickly to other parts of the world. Globally, half-hearted containment measures and a false sense of safety against this novel coronavirus led to the dissemination of disease. Currently, no effective therapy or vaccine is available to manage this illness. After learning a huge lesson, global efforts would hopefully lead to effective control of this pandemic.", "qid": 14, "docid": "i8opdley", "rank": 28, "score": 0.8287997245788574}, {"content": "Title: Projection of COVID-19 Pandemic in Uganda Content: COVID-19 (Corona Virus) is caused by Severe Acute Respiratory Syndrome Corona Virus 2 (SARS-COV-2). The virus that was first discovered in China Wuhan Province about 3 months ago (first cases were reported in Wuhan on December 31st, 2019) has spread world wide. The six (6) top countries (excluding China) most affected so far include; USA, Italy, Spain, Germany, France, and Iran. With Italy showing the highest death toll. In Uganda where it was discovered on 19/3/2020 with one (01) case has just in nine (9) days, increased to thirty (30) infected individuals. This model is a wake-up call over the rate at which COVID-19 is likely to spread throughout the country. Thus it is a guide for policymakers and planners to benchmark on for solutions to this deadly virus.", "qid": 14, "docid": "co4ckyp9", "rank": 29, "score": 0.8279018402099609}, {"content": "Title: Early detection of superspreaders by mass group pool testing can mitigate COVID-19 pandemic Content: Background Most of epidemiological models applied for COVID-19 do not consider heterogeneity in infectiousness and impact of superspreaders, despite the broad viral loading distributions amongst COVID-19 positive people (1-1 000 000 per mL). Also, mass group testing is not used regardless to existing shortage of tests. I propose new strategy for early detection of superspreaders with reasonable number of RT-PCR tests, which can dramatically mitigate development COVID-19 pandemic and even turn it endemic. Methods I used stochastic social-epidemiological SEIAR model, where S-suspected, E-exposed, I-infectious, A-admitted (confirmed COVID-19 positive, who are admitted to hospital or completely isolated), R-recovered. The model was applied to real COVID-19 dynamics in London, Moscow and New York City. Findings Viral loading data measured by RT-PCR were fitted by broad log-normal distribution, which governed high importance of superspreaders. The proposed full scale model of a metropolis shows that top 10% spreaders (100+ higher viral loading than median infector) transmit 45% of new cases. Rapid isolation of superspreaders leads to 4-8 fold mitigation of pandemic depending on applied quarantine strength and amount of currently infected people. High viral loading allows efficient group matrix pool testing of population focused on detection of the superspreaders requiring remarkably small amount of tests. Interpretation The model and new testing strategy may prevent thousand or millions COVID-19 deaths requiring just about 5000 daily RT-PCR test for big 12 million city such as Moscow. Though applied to COVID-19 pandemic the results are universal and can be used for other infectious heterogenous epidemics. Funding No funding", "qid": 14, "docid": "h7vqmlq9", "rank": 30, "score": 0.8278748989105225}, {"content": "Title: Aktu\u00e1ln\u00ed problematika COVID-19 z pohledu imunologa./ COVID-19 from the perspective of an immunologist Content: COVID-19 is an infectious disease caused by a coronavirus SARS-CoV-2. COVID-19 has a number of similarities to SARS and MERS diseases. Its highly contagious nature is particularly due to the rapid spread of the disease through asymptomatic individuals; however, the worlds most contagious infectious disease is still considered measles. Scientific data have revealed the interactions between COVID-19 and the immune system. These findings may contribute to the development of novel preventive and therapeutic approaches. Just as coronavirus itself the reports about the disease have massively spread through media and public contributing to overall public fear and stress. This promotion of non-scientific evidence and misinformation through social media might have also a devastating impact on the individuals immune system. Data regarding the mortality rates of COVID-19 have achieved unprecedented media and public engagements, however, the true facts about the disease prevention, immunomodulation and novel treatments are often left unsaid. We present the most recent facts about COVID-19 disease and its interactions with the immune system.", "qid": 14, "docid": "pfyqjrwk", "rank": 31, "score": 0.8275001049041748}, {"content": "Title: COVID-19 from the perspective of an immunologist. Content: COVID-19 is an infectious disease caused by a coronavirus SARS-CoV-2. COVID-19 has a number of similarities to SARS and MERS diseases. Its highly contagious nature is particularly due to the rapid spread of the disease through asymptomatic individuals; however, the worlds most contagious infectious disease is still considered measles. Scientific data have revealed the interactions between COVID-19 and the immune system. These findings may contribute to the development of novel preventive and therapeutic approaches. Just as coronavirus itself the reports about the disease have massively spread through media and public contributing to overall public fear and stress. This promotion of non-scientific evidence and misinformation through social media might have also a devastating impact on the individuals immune system. Data regarding the mortality rates of COVID-19 have achieved unprecedented media and public engagements, however, the true facts about the disease prevention, immunomodulation and novel treatments are often left unsaid. We present the most recent facts about COVID-19 disease and its interactions with the immune system.", "qid": 14, "docid": "mwpbrbqu", "rank": 32, "score": 0.8275001049041748}, {"content": "Title: Climate&BCG: Effects on COVID-19 Death Growth Rates Content: Multiple studies have suggested the spread of COVID-19 is affected by factors such as climate, BCG vaccinations, pollution and blood type. We perform a joint study of these factors using the death growth rates of 40 regions worldwide with both machine learning and Bayesian methods. We find weak, non-significant (<3$\\sigma$) evidence for temperature and relative humidity as factors in the spread of COVID-19 but little or no evidence for BCG vaccination prevalence or $\\text{PM}_{2.5}$ pollution. The only variable detected at a statistically significant level (>3$\\sigma$) is the rate of positive COVID-19 tests, with higher positive rates correlating with higher daily growth of deaths.", "qid": 14, "docid": "d70yn81e", "rank": 33, "score": 0.8242788314819336}, {"content": "Title: Transmission of SARS-CoV-2 by inhalation of respiratory aerosol in the Skagit Valley Chorale superspreading event Content: During the 2020 COVID-19 pandemic, an outbreak occurred following attendance of a symptomatic index case at a regular weekly rehearsal on 10 March of the Skagit Valley Chorale (SVC). After that rehearsal, 53 members of the SVC among 61 in attendance were confirmed or strongly suspected to have contracted COVID-19 and two died. Transmission by the airborne route is likely. It is vital to identify features of cases such as this so as to better understand the factors that promote superspreading events. Based on a conditional assumption that transmission during this outbreak was by inhalation of respiratory aerosol, we use the available evidence to infer the emission rate of airborne infectious quanta from the primary source. We also explore how the risk of infection would vary with several influential factors: the rates of removal of respiratory aerosol by ventilation; deposition onto surfaces; and viral decay. The results indicate an emission rate of the order of a thousand quanta per hour (mean [interquartile range] for this event = 970 [680-1190] quanta per hour) and demonstrate that the risk of infection is modulated by ventilation conditions, occupant density, and duration of shared presence with an infectious individual.", "qid": 14, "docid": "mazqe344", "rank": 34, "score": 0.8240854144096375}, {"content": "Title: Is it super-spreading? Content: If the covid-19 virus is transmitted largely by superspreaders, it might not go pandemic, reports Debora MacKenzie", "qid": 14, "docid": "kb8dz8hd", "rank": 35, "score": 0.8234272599220276}, {"content": "Title: Climate & BCG: Effects on COVID-19 DeathGrowth Rates Content: Multiple studies have suggested the spread of COVID-19 is affected by factors such as climate, BCG vaccinations, pollution and blood type. We perform a joint study of these factors using the death growth rates of 40 regions worldwide with both machine learning and Bayesian methods. We find weak, non-significant (< 3 sigma) evidence for temperature and relative humidity as factors in the spread of COVID-19 but little or no evidence for BCG vaccination prevalence or PM2.5 pollution. The only variable detected at a statistically significant level (> 3 sigma) is the rate of positive COVID-19 tests, with higher positive rates correlating with higher daily growth of deaths.", "qid": 14, "docid": "3hm0ulno", "rank": 36, "score": 0.82337886095047}, {"content": "Title: Active Monitoring of Persons Exposed to Patients with Confirmed COVID-19 - United States, January-February 2020. Content: In December 2019, an outbreak of coronavirus disease 2019 (COVID-19), caused by the virus SARS-CoV-2, began in Wuhan, China (1). The disease spread widely in China, and, as of February 26, 2020, COVID-19 cases had been identified in 36 other countries and territories, including the United States. Person-to-person transmission has been widely documented, and a limited number of countries have reported sustained person-to-person spread.* On January 20, state and local health departments in the United States, in collaboration with teams deployed from CDC, began identifying and monitoring all persons considered to have had close contact\u2020 with patients with confirmed COVID-19 (2). The aims of these efforts were to ensure rapid evaluation and care of patients, limit further transmission, and better understand risk factors for transmission.", "qid": 14, "docid": "mvm1t0y7", "rank": 37, "score": 0.8229534029960632}, {"content": "Title: Active Monitoring of Persons Exposed to Patients with Confirmed COVID-19 - United States, January-February 2020 Content: In December 2019, an outbreak of coronavirus disease 2019 (COVID-19), caused by the virus SARS-CoV-2, began in Wuhan, China (1). The disease spread widely in China, and, as of February 26, 2020, COVID-19 cases had been identified in 36 other countries and territories, including the United States. Person-to-person transmission has been widely documented, and a limited number of countries have reported sustained person-to-person spread.* On January 20, state and local health departments in the United States, in collaboration with teams deployed from CDC, began identifying and monitoring all persons considered to have had close contact\u0086 with patients with confirmed COVID-19 (2). The aims of these efforts were to ensure rapid evaluation and care of patients, limit further transmission, and better understand risk factors for transmission.", "qid": 14, "docid": "npyo0597", "rank": 38, "score": 0.8225299119949341}, {"content": "Title: Review of published systematic reviews and meta-analyses on COVID-19 Content: Purpose: The rapid spread of the COVID-19 pandemic has prompted researchers from all over the world to share their experience. The results were numerous reports with variable quality. The latter has provided an impetus to examine all published meta-analyses and systematic reviews on COVID-19 to date to examine available evidence. Methods: Using predefined selection criteria, a literature search identified 43 eligible meta-analyses and/or systematic reviews. Results: Most (N=17) studies addressed clinical manifestations and associated comorbidity, 6 studies addressed clinical manifestations in pregnant women and younger individuals, 8 studies addressed diagnostic data, 9 studies addressed various interventions, and 9 studies addressed prevention and control. The number of studies included in the various systemic reviews and meta-analyses ranged from 2 to 89. While there were some similarities and consistency for some findings, e.g. the relation between comorbidities and disease severity, we also noted occasionally conflicting data. Conclusion: As more data are collected from patients infected with COVID-19 all over the world, more studies will undoubtedly be published and attention to scientific accuracy in the performance of trials must be exercised to inform clinical decision-making and treatment guidelines.", "qid": 14, "docid": "w170rm6q", "rank": 39, "score": 0.8224539756774902}, {"content": "Title: Genetic drift and environmental spreading dynamics of COVID-19 Content: Objective To delineate the genetic and environmental determinants of COVID-19 spreading. Design Retrospective case series. Setting Spain, Italy, Sweden, Finland, Norway. Participants All laboratory-confirmed infection cases (n=168,089) collected from February 21st to April 14th 2020. Main outcome measures Infection spreading velocity according to viral mutation load and to climate region. Results The mean doubling time of COVID-19 was 6.63 days in northern Italy, 5.87 days in central areas, and 5.38 days in southern Italy, with shorter COVID-19 doubling time in warmer regions. Spain extended this trend, with a mean COVID-19 doubling time of 4.2 days. At the other end of the spectrum, slower diffusion across progressively colder regions was observed in Scandinavia, with 9.4 days COVID-19 doubling time in Sweden, 10.8 days in Finland and 12.95 days in Norway. Mutations and mutation rates of SARS-CoV-2 versus COVID-19 spreading were analyzed worldwide. Models of increased aggressiveness of SARS-CoV-2 upon progressive acquisition of genetic changes were not supported by regional mutation data. Conclusion Current propagation models suggest dependence of COVID-19 pandemic spreading on wintertime conditions, with expected waning over the summer. Our findings indicate association of COVID-19 to a sharp North/South climate gradient, with faster spreading in southern regions. Thus, warmer climate conditions may not limit SARS-CoV-2 diffusion. Very cold regions may be better spared by recurrent courses of infection.", "qid": 14, "docid": "iuf95x84", "rank": 40, "score": 0.8223866820335388}, {"content": "Title: Modelling spatial variations of coronavirus disease (COVID-19) in Africa Content: Clinical and epidemiological evidence has been advanced for human-to-human transmission of the novel coronavirus rampaging the world since late 2019. Outliers in the human-to-human transmission are yet to be explored. In this study, we examined the spatial density and leaned statistical credence to the global debate. We constructed spatial variations of clusters that examined the nexus between COVID-19 attributable deaths and confirmed cases. We rely on publicly available data on confirmed cases and death across Africa to unravel the unobserved factors, that could be responsible for the spread of COVID-19. We relied on the dynamic system generalised method of moment estimation procedure and found a ~0.045 Covid19 deaths as a result of confirmed cases in Africa. We accounted for cross-sectional dependence and found a basis for the strict orthogonal relationship. Policy measures were discussed.", "qid": 14, "docid": "1bepz2rj", "rank": 41, "score": 0.8220983147621155}, {"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": 42, "score": 0.8220741748809814}, {"content": "Title: Identification of super-transmitters of SARS-CoV-2 Content: A newly emerged coronavirus, SARS-CoV-2, caused severe outbreaks of pneumonia in China in December 2019 and has since spread to various countries around the world. To probe the origin and transmission dynamics of this virus, we performed phylodynamic analysis of 247 high quality genomic sequences of viruses available in the GISAID platform as of March 05, 2020. A substantial number of earliest sequences reported in Wuhan in December 2019, including those of viruses recovered from the Huanan Seafood Market (HNSM), the site of the initial outbreak, were genetically diverse, suggesting that viruses of multiple sources were involved in the original outbreak. The viruses were subsequently disseminated to different parts of China and other countries, with diverse mutational profiles being recorded in strains recovered subsequently. Interestingly, four genetic clusters defined as Super-transmitters (STs) were found to become dominant and were responsible for the major outbreaks in various countries. Among the four clusters, ST1 is widely disseminated in Asia and the US and mainly responsible for outbreaks in the states of Washington and California in the US as well as those in South Korea at the end of February and early March, whereas ST4 contributed to the pandemic in Europe. Each ST cluster carried a signature mutation profile which allowed us to trace the origin and transmission patterns of specific viruses in different parts of the world. Using the signature mutations as markers of STs, we further analysed 1539 genome sequences reported after February 29, 2020. We found that around 90% of these genomes belonged to STs with ST4 being the dominant one and their contribution to pandemic in different continents were also depicted. The identification of these super-transmitters provides insight into the control of further transmission of SARS-CoV-2.", "qid": 14, "docid": "tnfgbl05", "rank": 43, "score": 0.821835458278656}, {"content": "Title: Pandemic dynamics of COVID-19 using epidemic stage, instantaneous reproductive number and pathogen genome identity (GENI) score: modeling molecular epidemiology Content: Background: Global spread of COVID-19 created an unprecedented infectious disease crisis that progressed to a pandemic with >180,000 cases in >100 countries. Reproductive number (R) is an outbreak metric estimating the transmission of a pathogen. Initial R values were published based on the early outbreak in China with limited number of cases with whole genome sequencing. Initial comparisons failed to show a direct relationship viral genomic diversity and epidemic severity was not established for SARS-Cov-2. Methods: Each country's COVID-19 outbreak status was classified according to epicurve stage (index, takeoff, exponential, decline). Instantaneous R estimates (Wallinga and Teunis method) with a short and standard serial interval examined asymptomatic spread. Whole genome sequences were used to quantify the pathogen genome identity score that were used to estimate transmission time and epicurve stage. Transmission time was estimated based on evolutionary rate of 2 mutations/month. Findings: The country-specific R revealed variable infection dynamics between and within outbreak stages. Outside China, R estimates revealed propagating epidemics poised to move into the takeoff and exponential stages. Population density and local temperatures had variable relationship to the outbreaks. GENI scores differentiated countries in index stage with cryptic transmission. Integration of incidence data with genome variation directly increases in cases with increased genome variation. Interpretation: R was dynamic for each country and during the outbreak stage. Integrating the outbreak dynamic, dynamic R, and genome variation found a direct association between cases and genome variation. Synergistically, GENI provides an evidence-based transmission metric that can be determined by sequencing the virus from each case. We calculated an instantaneous country-specific R at different stages of outbreaks and formulated a novel metric for infection dynamics using viral genome sequences to capture gaps in untraceable transmission. Integrating epidemiology with genome sequencing allows evidence-based dynamic disease outbreak tracking with predictive evidence.", "qid": 14, "docid": "sz26gchn", "rank": 44, "score": 0.821792483329773}, {"content": "Title: Predictive Analysis of COVID-19 Time-series Data from Johns Hopkins University Content: We provide a predictive analysis of the spread of COVID-19, also known as SARS-CoV-2, using the dataset made publicly available online by the Johns Hopkins University. Our main objective is to provide predictions of the number of infected people for different countries in the next 14 days. The predictive analysis is done using time-series data transformed on a logarithmic scale. We use two well-known methods for prediction: polynomial regression and neural network. As the number of training data for each country is limited, we use a single-layer neural network called the extreme learning machine (ELM) to avoid over-fitting. Due to the non-stationary nature of the time-series, a sliding window approach is used to provide a more accurate prediction.", "qid": 14, "docid": "c8xit4tf", "rank": 45, "score": 0.8216995000839233}, {"content": "Title: Serial interval in determining the estimation of reproduction number of the novel coronavirus disease (COVID-19) during the early outbreak ;Journal of Travel Medicine ;Oxford Academic Content: Coronavirus disease 2019 (COVID-19), caused by the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), emerged in Wuhan, China in the end of 2019, and soon spread oversea A comprehensive and timely review summarized the scientific research in estimating the basic reproduction number (R0) released from 1 January to 7 February 2020 [1] During the early outbreak, when the key epidemiological features of COVID-19 were uncovered, the R0 estimation largely relied on the growth rate of the epidemic curve and the estimation of the serial interval (SI) Here, we demonstrated that an overlarge SI would lead to overestimation of R0 We adopted the growing process proposed in [2] deterministically with a population of 11 million in Wuhan, 1 case initially onset on 5 December 2019 and a fixed step at 1 day We consider two values of the mean serial interval (SI) that are \uf0b7 SI at 4 6 days estimated based on 28 records of transmission chains [3], which was largely consistent with the SI estimate at 4 4 days based on 71 records [4];and \uf0b7 SI at 8 days, which was closer to the SI of the severe acute respiratory syndrome (SARS, 8 4 days), SI of the Middle East respiratory syndrome (MERS, 7 6 days) As for demonstration that a larger SI could lead to overestimation in R0, we conducted the simulation with two schemes that are \uf0b7 Scheme (I): R0 = 2, and SI = 4 6 days;and \uf0b7 Scheme (II): R0 = 2, 3, 4 and 3 3 as summarized in [1], and SI = 8 days We also compared the simulation results with the previous estimates of the cumulative number of COVID-19 infection in Wuhan In Fig 1, the simulation results of the scheme (I) had almost the same growing trends as those of scheme (II) with R0 = 3 3 Although a higher R0 could force the epidemic curve increasing rapidly, a shorter SI could increase iteration of transmission generation, i e , transmission may occur shortly post infection According to the simple approximated formula that R0 = exp(\u03b3\u2219SI), where \u03b3 was the exponential growth rate calculated from the incidence data directly, a longer SI would lead to a higher R0 estimate theoretically With a shorter SI at 4 6 days, which was supported by richer datasets in [3, 4], the R0 of COVID-19 could be lower than previous estimates based on longer SI By using the growth rate (\u03b3) at 0 15 per day, the R0 was found at 2 0 with SI at 4 6 days, whereas 3 3 with SI at 8 days Although the effects of public health control were ignored in this analysis, our model could be Downloaded from https://academic oup com/jtm/advance-article-abstract/doi/10 1093/jtm/taaa033/5803291 by guest on 13 March 2020 4 extended by introducing an effective reproduction number accounting for the effectiveness of the control measures, and we remarked this modification would not affect the main conclusion Furthermore, as pointed out in [3], provided that the SI of COVID-19 might be shorter than its incubation period, pre-symptomatic transmission may occur shortly after being infected [5] This implies that a fraction of transmissions cannot be prevented solely through isolating the symptomatic cases, since the time when contact tracing is conducted, they may have already been infectious and generated secondary cases Therefore, the effectively quarantine of suspected (and probable) cases, as well as close contacts, and timely contact tracing were crucial in successful outbreak mitigation", "qid": 14, "docid": "0xqhpqm4", "rank": 46, "score": 0.8208272457122803}, {"content": "Title: Rich at risk: socio-economic drivers of COVID-19 pandemic spread Content: COVID-19, the novel coronavirus affecting the most part of worldwide countries since early 2020, is fast increasing its prevalence around the world, representing a significant emergency for the population and the health systems at large. While proper treatments are being developed, in-depth studies concerning its way of diffusion are necessary, in order to understand how the virus is actually spreading, through the investigation on some socio-economic indicators for the various countries in the world, retrieved through open-access data publicly available. The correlation analysis displayed significant relationships between COVID-19 incidence with several of such indicators, including the Gross Domestic Product per capita and the number of flights per capita, whereas mortality is mainly related to the main age of the population. All such data displayed an interesting mean to understand the way the virus has diffused worldwide, possibly representing the basis for future preventive measures to effectively challenge a new COVID-19 pandemic wave, but also other, similar pandemics.", "qid": 14, "docid": "arhpqgl6", "rank": 47, "score": 0.8206565976142883}, {"content": "Title: The misleading illusion of COVID-19 confirmed case data: alternative estimates and a monitoring tool Content: Confirmed Case Data have been widely cited during the current COVID-19 pandemic as an estimate of the spread of the SARS-CoV-2 virus. However, their central role in media, official reports and decision-making may be undeserved and misleading. Previously published Infection Fatality Rates were weighted by age structure in the 50 countries with more reported deaths to obtain country-specific rates. For each country, the number of infections up to the Infection Date (23 days ago = Incubation Period + Onset to Death period) and the present percentage of immune population were estimated using Infection Fatality Rate, the number of reported deaths (which is less prone to undersampling), and projecting back to Infection Date. We then estimated a Detection Index for each country as the percentage of estimated infections that confirmed cases represent. Assuming that detection remains constant after Infection Date, we estimated the number of deaths and the estimated percentage of the population of each country expected to be immune up to 23 days into the future. Estimated Infection Fatality Rates are higher in Europe. In most countries, confirmed cases currently represent less than 30% of estimated infections on Infection Date, and this value decreases with time. Countries with flat curves throughout the pandemic show the lowest immunity percentages and these values seem unlikely to change in the near future, suggesting that they remain vulnerable to new outbreaks. Estimates for some countries with low Infection Fatality Rates suggest a still steep increase in the number of casualties in the next three weeks. Countries that did not control initial outbreaks seem to have reached higher immunity percentages, although mostly still under 5%. We provide the code to monitor the trajectories of these estimates in 178 countries throughout the COVID-19 pandemic.", "qid": 14, "docid": "z9r5i0ky", "rank": 48, "score": 0.8205114603042603}, {"content": "Title: Public health measures to slow community spread of COVID-19 ;The Journal of Infectious Diseases ;Oxford Academic Content: COVID-19 was initially identified in an outbreak of viral pneumonia in Wuhan in December 2019, and has now been recognized in 77 countries with over 90,000 laboratory-confirmed cases and over 3,000 deaths as of 3 March 2020 [1] The epidemiology of COVID-19 has recently become clearer as incident cases continue to rise and researchers refine estimates of the severity, transmissibility, and populations affected Based on available data, COVID-19 is efficiently transmitted in the community, and the proportion of infections leading to severe illness is particularly high among adults \u226550 years of age and among individuals with comorbid health conditions Although rare, severe cases have also been reported among younger individuals Thus far, the estimated basic reproductive number (R0) of COVID-19 is higher than that of influenza [2], as is the case fatality risk for adults and older individuals An estimated 80% of COVID-19 cases are mild [1] This is not a glass half full statistic, as 20% of infections result in clinically severe cases that have the potential to overwhelm already overburdened health facilities Given the lack of vaccines and effective antivirals, nonpharmaceutical interventions (NPIs) are the most effective available interventions for local and global control and mitigation of COVID-19 To date, measures aimed at slowing introduction of infection globally have included travel restrictions, isolation of confirmed cases, and quarantine of exposed persons In the United States, NPIs have reduced the number of infected persons entering the country, but recent outbreaks in multiple US states make it clear that these measures have delayed but not prevented community transmission In 2009, NPIs were able to delay large epidemic waves of pandemic influenza A(H1N1)pdm09 in some locations until after the summer, since influenza transmission tends to be reduced by higher temperatures and humidity It is unclear whether COVID-19 transmission will be heavily affected by seasonal weather variation, given that transmission is now occurring in multiple tropical and sub-tropical locations", "qid": 14, "docid": "lu9mum1d", "rank": 49, "score": 0.8201813697814941}, {"content": "Title: Differential diagnosis of illness in patients under investigation for the novel coronavirus (SARS-CoV-2), Italy, February 2020 Content: A novel coronavirus (SARS-CoV-2) has been identified as the causative pathogen of an ongoing outbreak of respiratory disease, now named COVID-19. Most cases and sustained transmission occurred in China, but travel-associated cases have been reported in other countries, including Europe and Italy. Since the symptoms are similar to other respiratory infections, differential diagnosis in travellers arriving from countries with wide-spread COVID-19 must include other more common infections such as influenza and other respiratory tract diseases.", "qid": 14, "docid": "err1npxf", "rank": 50, "score": 0.8199775218963623}, {"content": "Title: Modelling spatial variations of coronavirus disease (COVID-19) in Africa Content: Abstract Clinical and epidemiological evidence has been advanced for human-to-human transmission of the novel coronavirus rampaging the world since late 2019. Outliers in the human-to-human transmission are yet to be explored. In this study, we examined the spatial density and leaned statistical credence to the global debate. We constructed spatial variations of clusters that examined the nexus between COVID-19 attributable deaths and confirmed cases. We rely on publicly available data on confirmed cases and death across Africa to unravel the unobserved factors, that could be responsible for the spread of COVID-19. We relied on the dynamic system generalised method of moment estimation procedure and found a ~0.045 Covid19 deaths as a result of confirmed cases in Africa. We accounted for cross-sectional dependence and found a basis for the strict orthogonal relationship. Policy measures were discussed.", "qid": 14, "docid": "f6qh4fva", "rank": 51, "score": 0.8199774026870728}, {"content": "Title: COVID-19 and the 5G Conspiracy Theory: Social Network Analysis of Twitter Data Content: BACKGROUND: Since the beginning of December 2019, the coronavirus disease (COVID-19) has spread rapidly around the world, which has led to increased discussions across online platforms. These conversations have also included various conspiracies shared by social media users. Amongst them, a popular theory has linked 5G to the spread of COVID-19, leading to misinformation and the burning of 5G towers in the United Kingdom. The understanding of the drivers of fake news and quick policies oriented to isolate and rebate misinformation are keys to combating it. OBJECTIVE: The aim of this study is to develop an understanding of the drivers of the 5G COVID-19 conspiracy theory and strategies to deal with such misinformation. METHODS: This paper performs a social network analysis and content analysis of Twitter data from a 7-day period (Friday, March 27, 2020, to Saturday, April 4, 2020) in which the #5GCoronavirus hashtag was trending on Twitter in the United Kingdom. Influential users were analyzed through social network graph clusters. The size of the nodes were ranked by their betweenness centrality score, and the graph's vertices were grouped by cluster using the Clauset-Newman-Moore algorithm. The topics and web sources used were also examined. RESULTS: Social network analysis identified that the two largest network structures consisted of an isolates group and a broadcast group. The analysis also revealed that there was a lack of an authority figure who was actively combating such misinformation. Content analysis revealed that, of 233 sample tweets, 34.8% (n=81) contained views that 5G and COVID-19 were linked, 32.2% (n=75) denounced the conspiracy theory, and 33.0% (n=77) were general tweets not expressing any personal views or opinions. Thus, 65.2% (n=152) of tweets derived from nonconspiracy theory supporters, which suggests that, although the topic attracted high volume, only a handful of users genuinely believed the conspiracy. This paper also shows that fake news websites were the most popular web source shared by users; although, YouTube videos were also shared. The study also identified an account whose sole aim was to spread the conspiracy theory on Twitter. CONCLUSIONS: The combination of quick and targeted interventions oriented to delegitimize the sources of fake information is key to reducing their impact. Those users voicing their views against the conspiracy theory, link baiting, or sharing humorous tweets inadvertently raised the profile of the topic, suggesting that policymakers should insist in the efforts of isolating opinions that are based on fake news. Many social media platforms provide users with the ability to report inappropriate content, which should be used. This study is the first to analyze the 5G conspiracy theory in the context of COVID-19 on Twitter offering practical guidance to health authorities in how, in the context of a pandemic, rumors may be combated in the future.", "qid": 14, "docid": "ypfg37yd", "rank": 52, "score": 0.8198244571685791}, {"content": "Title: Coronavirus Disease 2019 and Transplantation: a view from the inside. Content: Since December 2019, world healthcare community faced with Coronavirus Disease 2019 (COVID-19) outbreak caused by SARS-CoV-2. Due to the high viral contagiousness and the possible transmission during the pre-symptomatic phase, COVID-19 progressively spread to several countries. Currently, Italy is the third Country for number of confirmed cases after mainland China and South Chorea, and the first western nation with a well-established deceased transplant program to tackle a COVID-19 outbreak1 .", "qid": 14, "docid": "bn8qf8cv", "rank": 53, "score": 0.8196129202842712}, {"content": "Title: Statistically-based methodology for revealing real contagion trends and correcting delay-induced errors in the assessment of COVID-19 pandemic Content: COVID-19 pandemic has reshaped our world in a timescale much shorter than what we can understand. Particularities of SARS-CoV-2, such as its persistence in surfaces and the lack of a curative treatment or vaccine against COVID-19, have pushed authorities to apply restrictive policies to control its spreading. As data drove most of the decisions made in this global contingency, their quality is a critical variable for decision-making actors, and therefore should be carefully curated. In this work, we analyze the sources of error in typically reported epidemiological variables and usual tests used for diagnosis, and their impact on our understanding of COVID-19 spreading dynamics. We address the existence of different delays in the report of new cases, induced by the incubation time of the virus and testing-diagnosis time gaps, and other error sources related to the sensitivity/specificity of the tests used to diagnose COVID-19. Using a statistically-based algorithm, we perform a temporal reclassification of cases to avoid delay-induced errors, building up new epidemiologic curves centered in the day where the contagion effectively occurred. We also statistically enhance the robustness behind the discharge/recovery clinical criteria in the absence of a direct test, which is typically the case of non-first world countries, where the limited testing capabilities are fully dedicated to the evaluation of new cases. Finally, we applied our methodology to assess the evolution of the pandemic in Chile through the Effective Reproduction Number R(t), identifying different moments in which data was misleading governmental actions. In doing so, we aim to raise public awareness of the need for proper data reporting and processing protocols for epidemiological modelling and predictions.", "qid": 14, "docid": "iydjrmhh", "rank": 54, "score": 0.8195061683654785}, {"content": "Title: Proteome Organization of COVID-19: Illustrating Targets for Vaccine Development Content: 'COVID-19' the recent virulent viral infection had influenced the lives of millions globally leading to both loss of life, economic and financial crisis Coronavirus belongs to family coronaviridae with four genus viz alpha/beta and gamma-coronavirus, infecting both aves and mammals The SARS-Cov-2 emerged in Wuhan, China in Dec, 2019 and since then had spread to 213 countries Its origin is debatable with both natural origin and conspiracy theory providing no conclusive evidences Coronavirus have '+'ive RNA and encodes for 29 proteins, which carries out its life cycle including infection and disease progression The study of its proteome organization could illustrate the proteins which act as the key molecular players in the infection cycle of the virus These proteins can also act as important drug targets in combating COVID-19 infection Majority of the drugs have been formulated in order to act as agonist to spike proteins inhibiting infection by binding to ACE2 receptors Proteome analysis has also revealed the critical mutated proteins that are responsible for COVID-19 pathogenesis and virulence mRNA based vaccines (mRNA-1273, BNT162) also targets these spike proteins Although DNA vaccine has also been attempted using RDT, but the high rate of mutation associated with COVID-19 have made such vaccines ineffective even before use Thus evolutionarily conserved proteins have been the best candidature for vaccine development Similarly phylogenetic analysis of its proteins could help us to understand the evolutionary pattern of COVID-19 It could be used to develop a predictable model for such pathogenic infections, preparing ourselves to take preventive action against its reoccurrence", "qid": 14, "docid": "69ldtdik", "rank": 55, "score": 0.81940758228302}, {"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": 56, "score": 0.8191445469856262}, {"content": "Title: The challenges of covid-19 testing: Time for pathologists to rise to the occasion Content: An outbreak of novel coronavirus (Covid-19) was first reported in Wuhan, China in the late December 1 Since then, the positive cases have increased exponentially to 1 4 million (as of 8 April 2020) 2 The ability of a country to cope with increasing number of Covid-19 testing is the ultimate test Teaching/university hospitals should pull their resources and man-power to provide the muchneeded assistance to the demand of Covid-19 testing Inadequate testing could result in unrecognised Covid-19 infected individuals, roaming freely in the population The other issue is the sensitivity of test if samples were obtained from different sites Classically, the confirmation of diagnosis of Covid-19 depends on real time polymerase chain reaction (RT-PCR) analysis to detect viral genetic material in either a nasal swab or bronchioalveolar lavage sample Wang et al (2020) reported that bronchioalveolar lavage sample has the highest sensitivity in identifying Covid-19, followed by sputum and nasal swab with positive rates of 93%, 72% and 63%, respectively 3 Furthermore, they found that nasal swab contained the highest concentration of viral load as it required less number of cycles to achieve higher copy numbers In some patients, viral genetic material was also identified in faeces and blood 3 While the reliability of testing is a concern, the safety of the laboratory staff also has to be kept in mind In this issue, there are three review articles on Covid-19, first article described the general properties of coronavirus, second article described the diagnostic performance of Covid-19 serology assay and third article described the importance of the site of sampling for Covid-19 4-6", "qid": 14, "docid": "2buj9xrh", "rank": 57, "score": 0.819098949432373}, {"content": "Title: Analytical Review of COVID-19 Outbreak in India During the Global Pandemic Content: COVID-19 is one of the very contagious diseases from the family Coronaviridae and spreading at a faster rate in the community In December 2019, the first case of COVID-19 was reported in Wuhan, China An epidemic outbreak of COVID-19 was seen in India from March 2020 Epidemiological data of COVID-19 cases of the world and India have been analyzed in our study We have utilized publicly available two databases from data repository by Johns Hopkins CSSE and covid19india org COVID-19 cases and case fatality rate (CFR) of the world have been summarized and compared with India from January 22, 2020 to April 15, 2020 Indian cases were analyzed among states of India and also compared with age and gender by performing statistical approaches such as central tendency, standard deviation and interquartile range By April 15, 2020, Indian has reported 12,322 confirmed cases, 1,498 recovered cases and 405 death cases of COVID-19 In spite of India being a diverse country with the second-highest population, the deadly side of COVID-19 was comparatively far less as compared to the other countries India has taken preemptive measures at an early stage to prevent transmission of COVID-19 outbreak and it is reviewed from our study by comparing India with other countries Our study also summarizes that age also plays a vital role in the intervention of COVID-19 cases", "qid": 14, "docid": "xtta3yrp", "rank": 58, "score": 0.8189355731010437}, {"content": "Title: COVID-19 and the 5G Conspiracy Theory: Social Network Analysis of Twitter Data Content: BACKGROUND: Since the beginning of December 2019, the coronavirus disease (COVID-19) has spread rapidly around the world, which has led to increased discussions across online platforms. These conversations have also included various conspiracies shared by social media users. Amongst them, a popular theory has linked 5G to the spread of COVID-19, leading to misinformation and the burning of 5G towers in the United Kingdom. The understanding of the drivers of fake news and quick policies oriented to isolate and rebate misinformation are keys to combating it. OBJECTIVE: The aim of this study is to develop an understanding of the drivers of the 5G COVID-19 conspiracy theory and strategies to deal with such misinformation. METHODS: This paper performs a social network analysis and content analysis of Twitter data from a 7-day period (Friday, March 27, 2020, to Saturday, April 4, 2020) in which the #5GCoronavirus hashtag was trending on Twitter in the United Kingdom. Influential users were analyzed through social network graph clusters. The size of the nodes were ranked by their betweenness centrality score, and the graph\u2019s vertices were grouped by cluster using the Clauset-Newman-Moore algorithm. The topics and web sources used were also examined. RESULTS: Social network analysis identified that the two largest network structures consisted of an isolates group and a broadcast group. The analysis also revealed that there was a lack of an authority figure who was actively combating such misinformation. Content analysis revealed that, of 233 sample tweets, 34.8% (n=81) contained views that 5G and COVID-19 were linked, 32.2% (n=75) denounced the conspiracy theory, and 33.0% (n=77) were general tweets not expressing any personal views or opinions. Thus, 65.2% (n=152) of tweets derived from nonconspiracy theory supporters, which suggests that, although the topic attracted high volume, only a handful of users genuinely believed the conspiracy. This paper also shows that fake news websites were the most popular web source shared by users; although, YouTube videos were also shared. The study also identified an account whose sole aim was to spread the conspiracy theory on Twitter. CONCLUSIONS: The combination of quick and targeted interventions oriented to delegitimize the sources of fake information is key to reducing their impact. Those users voicing their views against the conspiracy theory, link baiting, or sharing humorous tweets inadvertently raised the profile of the topic, suggesting that policymakers should insist in the efforts of isolating opinions that are based on fake news. Many social media platforms provide users with the ability to report inappropriate content, which should be used. This study is the first to analyze the 5G conspiracy theory in the context of COVID-19 on Twitter offering practical guidance to health authorities in how, in the context of a pandemic, rumors may be combated in the future.", "qid": 14, "docid": "4i0c6474", "rank": 59, "score": 0.8188879489898682}, {"content": "Title: A pilot study to investigate the fecal dissemination of SARS-CoV-2 virus genome in COVID-19 patients in Odisha, India Content: In infectious diseases, the routes of transmission play major roles in determining the rate and extent of disease spread. Though fomites and aerosol droplets are major sources of SARS-CoV-2 human to human transmission, studies have also reported possible involvement of other routes of transmission like fecal-oral. Multiple studies around the world have reported shedding of the SARS-CoV-2 viral genome in certain COVID-19 patient fecal samples. Hence, the major objective of this study was to get the experimental evidence whether in Indian COVID-19 patients fecal dissemination of the SARS-CoV-2 genome occurs or not. Information obtained from twelve number of patients from a COVID-19 hospital of Odisha has demonstrated that both symptomatic and asymptomatic Indian patients could be positive for the SARS-CoV-2 genome in their fecal component. The findings have also established a protocol to collect and extract viral RNA for SARS-CoV-2 detection in fecal samples. Together, the study supports the hypothesis of possible fecal-oral transmission of SARS-CoV-2 virus and provides a rationale to extend this study in a larger cohort of patient samples and correlate the significance of the SARS-CoV-2 virus genome detection in fecal samples with disease severity and transmission.", "qid": 14, "docid": "plnukt32", "rank": 60, "score": 0.8186730742454529}, {"content": "Title: New measures for COVID-19 response: a lesson from the Wenzhou experience Content: As the outbreak of COVID-19 has spread globally, determining how to prevent the spread is of paramount importance. We reported the effectiveness of different responses of four affected cities in preventing the COVID-19 spread. We expect Wenzhou anti-COVID-19 measures may provide experience for cities around the world that are experiencing this epidemic.", "qid": 14, "docid": "t0c658sb", "rank": 61, "score": 0.8185681104660034}, {"content": "Title: First, second and potential third generation spreads of the COVID-19 epidemic in mainland China: an early exploratory study incorporating location-based service data of mobile devices Content: OBJECTIVES: The outbreak of atypical pneumonia caused by the novel coronavirus (COVID-19) has currently become a global concern. The generations of the epidemic spread are not well known, yet these are critical parameters to facilitate an understanding of the epidemic. A seafood wholesale market and Wuhan city, China, were recognized as the primary and secondary epidemic sources. Human movements nationwide from the two epidemic sources revealed the characteristics of the first-generation and second-generation spreads of the COVID-19 epidemic, as well as the potential third-generation spread. METHODS: We used spatiotemporal data of COVID-19 cases in mainland China and two categories of location-based service (LBS) data of mobile devices from the primary and secondary epidemic sources to calculate Pearson correlation coefficient,r, and spatial stratified heterogeneity, q, statistics. RESULTS: Two categories of device trajectories had generally significant correlations and determinant powers of the epidemic spread. Bothr and q statistics decreased with distance from the epidemic sources and their associations changed with time. At the beginning of the epidemic, the mixed first-generation and second-generation spreads appeared in most cities with confirmed cases. They strongly interacted to enhance the epidemic in Hubei province and the trend was also significant in the provinces adjacent to Hubei. The third-generation spread started in Wuhan from January 17-20, 2020, and in Hubei from January 23-24. No obvious third-generation spread was detected outside Hubei. CONCLUSIONS: The findings provide important foundations to quantify the effect of human movement on epidemic spread and inform ongoing control strategies. The spatiotemporal association between the epidemic spread and human movements from the primary and secondary epidemic sources indicates a transfer from second to third generations of the infection. Urgent control measures include preventing the potential third-generation spread in mainland China, eliminating it in Hubei, and reducing the interaction influence of first-generation and second-generation spreads.", "qid": 14, "docid": "enpeynm7", "rank": 62, "score": 0.818245530128479}, {"content": "Title: Coronavirus research before 2020 is more relevant than ever, especially when interpreted for COVID-19 Content: The speed with which biomedical researchers were able to identify and characterise COVID-19 was clearly due to prior research with other coronaviruses. Early epidemiological comparisons with two previous coronaviruses, Severe Acute Respiratory Syndrome (SARS) and Middle East Respiratory Syndrome (MERS), also made it easier to predict COVID-19's likely spread and lethality. This article assesses whether academic interest in prior coronavirus research has translated into interest in the primary source material, using Mendeley reader counts for early academic impact evidence. The results confirm that SARS and MERS research 2008-2017 experienced anomalously high increases in Mendeley readers in April-May 2020. Nevertheless, studies learning COVID-19 lessons from SARS and MERS or using them as a benchmark for COVID-19 have generated much more academic interest than primary studies of SARS or MERS. Thus, research that interprets prior relevant research for new diseases when they are discovered seems to be particularly important to help researchers to understand its implications in the new context.", "qid": 14, "docid": "n0wm7ttq", "rank": 63, "score": 0.8181928992271423}, {"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": 64, "score": 0.8181536197662354}, {"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": 65, "score": 0.8180365562438965}, {"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": 66, "score": 0.817916750907898}, {"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": 67, "score": 0.817785918712616}, {"content": "Title: Pregnant women's knowledge and practice of preventive measures against COVID-19 in a low-resource African setting. Content: Since the emergence of coronavirus disease 2019 (COVID-19) in Wuhan, China in December 2019, the virus that causes it (SARS-Cov-2) has spread to over 110 countries, including Nigeria [1-3]. Although the impact of COVID-19 on pregnant women is not yet clear, there are concerns over its potential effect on maternal and perinatal outcomes due to unique immunological suppression during pregnancy [4,5].", "qid": 14, "docid": "x97acuv6", "rank": 68, "score": 0.8176134824752808}, {"content": "Title: Virus strain of a mild COVID-19 patient in Hangzhou representing a new trend in SARS-CoV-2 evolution related to Furin cleavage site Content: We found, in our 788 confirmed COVID-19 patients, the decreased rate of severe/critical type, increased liver/kidney damage and prolonged period of nuclear acid positivity during virus dissemination, when compared with Wuhan. To investigate the underlining mechanism, we isolated one strain of SARS- CoV-2 (ZJ01) in mild COVID-19 patient and found the existence of 35 specific gene mutation by gene alignment. Further phylogenetic analysis and RSCU heat map results suggested that ZJ01 may be a potential evolutionary branch of SARS-CoV-2. We classified 54 strains of viruses worldwide (C/T type) based on the base (C or T) at positions 8824 and 28247. ZJ01 were both T at these two sites, becoming the only TT type currently identified in the world. The prediction of Furin cleavage site (FCS) and the sequence alignment of virus family indicated that FCS may be an important site of coronavirus evolution. ZJ01 had mutations near FCS (F1-2), which caused changes in the structure and the electrostatic distribution of the S protein surface, further affecting the binding capacity of Furin. Single cell sequencing and ACE2-Furin co-expression results confirmed that Furin level was higher in the whole body, especially in glands, liver, kidney and colon while FCS may help SARS-CoV-2 infect these organs. The evolutionary pattern of SARS-CoV-2 towards FCS formation may result in its clinical symptom becoming closer to HKU-1 and OC43 (the source of FCS sequence-PRRA) caused influenza, further showing potential in differentiating into mild COVID-19 subtypes.", "qid": 14, "docid": "suhqgmlo", "rank": 69, "score": 0.817560076713562}, {"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": 14, "docid": "2r0a357c", "rank": 70, "score": 0.817277729511261}, {"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": 71, "score": 0.8172686100006104}, {"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": 72, "score": 0.8172686100006104}, {"content": "Title: The recent challenges of highly contagious COVID-19; causing respiratory infections: symptoms, diagnosis, transmission, possible vaccines, animal models and immunotherapy Content: COVID-19 is highly contagious pathogenic viral infection initiated from Wuhan seafood wholesale market of China on December 2019 and spread rapidly around the whole world due to onward transmission. This recent outbreak of novel coronavirus (CoV) was believed to be originated from bats and causing respiratory infections such as common cold, dry cough, fever, headache, dyspnea, pneumonia and finally Severe Acute Respiratory Syndrome (SARS) in humans. For this widespread zoonotic virus, human-to-human transmission has resulted in nearly 83 lakh cases in 213 countries and territories with 4,50,686 deaths as on 19th June 2020. This review presents a report on the origin, transmission, symptoms, diagnosis, possible vaccines, animal models and immunotherapy for this novel virus and will provide ample references for the researchers towards the ongoing development of therapeutic agents and vaccines and also preventing the spread of this disease.", "qid": 14, "docid": "jxbk30gh", "rank": 73, "score": 0.8172672986984253}, {"content": "Title: The recent challenges of highly contagious COVID-19; causing respiratory infections: symptoms, diagnosis, transmission, possible vaccines, animal models and immunotherapy. Content: COVID-19 is highly contagious pathogenic viral infection initiated from Wuhan seafood wholesale market of China on December 2019 and spread rapidly around the whole world due to onward transmission. This recent outbreak of novel coronavirus (CoV) was believed to be originated from bats and causing respiratory infections such as common cold, dry cough, fever, headache, dyspnea, pneumonia and finally Severe Acute Respiratory Syndrome (SARS) in humans. For this widespread zoonotic virus, human-to-human transmission has resulted in nearly 83 lakh cases in 213 countries and territories with 4,50,686 deaths as on 19th June 2020. This review presents a report on the origin, transmission, symptoms, diagnosis, possible vaccines, animal models and immunotherapy for this novel virus and will provide ample references for the researchers towards the ongoing development of therapeutic agents and vaccines and also preventing the spread of this disease.", "qid": 14, "docid": "r2ynbnxx", "rank": 74, "score": 0.8172672986984253}, {"content": "Title: Genomic epidemiology put to the test against COVID-19 Content: In early April, a paper published in the journal Proceedings of the National Academy of Sciences of the United States of America (PNAS) raised the eyebrows of a number of genomic epidemiologists It suggested that there were three distinct variants of the novel coronavirus, SARS-CoV-2, spreading in different regions of the world\u2014one predominantly in Australia and North America, one in China, and one in Europe It also suggested that the variant circulating in North America and Australia was older than the one that appeared in Wuhan, China, at the end of December (Proc Natl Acad Sci U S A 2020, DOI: 10 1073/pnas 2004999117) If this were true, the outbreak of COVID-19, the disease caused by the virus, would have started outside Wuhan, which contradicts scientific consensus Some genomic epidemiologists, who track the genomes of pathogens to understand how diseases spread, thought that although the data the PNAS paper used were sound, the paper\u2019s analytical View: PDF ;Full Text HTML", "qid": 14, "docid": "cccqcfgq", "rank": 75, "score": 0.8166412711143494}, {"content": "Title: Research on COVID-19 virus spreading statistics based on the examples of the cases from different counties Content: The novel coronavirus COVID-19 originally identified in December 2019, based on the data issued by March 30, 2020 daily report, the epidemic of SARS-CoV-2 so far has caused 693224 cases and resulted in 33106 deaths in more than 200 countries. Referring to the data reported, World Health Organization declared the outbreak a pandemic. We considered the chain-binomial type of the model which involves short stages of high infectivity and approximately constant incubation periods. This research paper is to study and analyze the COVID-19 Virus spreading statistics on the examples of the cases from the different counties. High correlation coefficients (91.64%) and determinants (83.98%) between the total volumes of virus spread and recovery are considered to be high and indicate the correctness of the Bailey model. Thus, as of March 30, with the results of statistical and mathematical data processing, it is difficult to predict the future spread-reduction variables of the pandemic.", "qid": 14, "docid": "xepq1v7x", "rank": 76, "score": 0.8164879679679871}, {"content": "Title: Liver transplantation in an ICU dominated by COVID-19 Content: The Letter from D'Antiga L about concerns of transplanting patients in the context of COVID19 pandemic is very interesting [1]. COVID-19 designates the infection caused by the SARS-Cov2 virus. This illness originated in December, 2019, in Wuhan, China. Since then, it has been identified in more than 150 countries. The first case of COVID-19 in Portugal was notified in March 02, 2020.", "qid": 14, "docid": "8a6flxl6", "rank": 77, "score": 0.8164682388305664}, {"content": "Title: Liver transplantation in an ICU dominated by COVID-19. Content: The Letter from D'Antiga L about concerns of transplanting patients in the context of COVID19 pandemic is very interesting [1]. COVID-19 designates the infection caused by the SARS-Cov2 virus. This illness originated in December, 2019, in Wuhan, China. Since then, it has been identified in more than 150 countries. The first case of COVID-19 in Portugal was notified in March 02, 2020.", "qid": 14, "docid": "6ck2ntid", "rank": 78, "score": 0.8164682388305664}, {"content": "Title: Coinfection with COVID\u201019 and Coronavirus HKU1 \u2013 the critical need for repeat testing if clinically indicated Content: COVID\u201019 is the latest global pandemic caused by severe acute respiratory syndrome coronavirus \u20102 (SARS\u2010CoV\u20102). There have been seven pathogenic Human Coronaviruses (HCoVs) which cause respiratory infections. Common cold coronaviruses HCoV\u2010229E, HCoV\u2010OC43, HCoV\u2010NL63, HCoV\u2010HKU1 are the four endemic HCoVs. SARS\u2010CoV\u20101, MERS\u2010CoV, SARS\u2010CoV\u20102 are zoonotic emerging epidemic pathogens with significant morbidity, mortality and economic impact. The endemic HCoVs have been known to cause co\u2010infections or can be co\u2010detected with each other or with other respiratory viruses. In general, respiratory viral co\u2010infections are recognized more commonly today with the use of respiratory multiplex molecular diagnostic panels. Clinicians need to be aware of co\u2010infections among HCoVs. A high degree of suspicion in this rapidly evolving outbreak is required in order to make the diagnosis. This is vital if we are to try and contain and control the spread of the COVID\u201019. This article is protected by copyright. All rights reserved.", "qid": 14, "docid": "u5bj1sod", "rank": 79, "score": 0.8164178133010864}, {"content": "Title: The Rheumatologist's Role in Covid-19. Content: The novel coronavirus (SARS-CoV-2) pandemic has spread rapidly throughout the planet. It is believed to have originated in the Wuhan province of China, but this highly contagious respiratory virus has spread to over 140 countries on 6 continents as of mid-March 2020 according to the World Health Organization (WHO). Worldwide, there have been over 164,000 cases identified and over 6,500 deaths attributed to the viral infection. As of March 15, 2020, there are over 3,700 confirmed cases and 68 deaths ascribed to Covid-19 (the disease caused by SARS-CoV-2) in the United States [https://www.livescience.com/coronavirus-updates-unitedstates.html].", "qid": 14, "docid": "8m7l0uid", "rank": 80, "score": 0.8163845539093018}, {"content": "Title: COVID-19: A Risk Assessment Perspective Content: [Image: see text] COVID-19 is a newly emerging viral respiratory disease first identified in Wuhan, China, in December 2019. The disease is caused by the coronavirus SARS-CoV-2, which is related to the viruses that cause SARS and MERS. While the case fatality ratio for COVID-19 (5%) is far lower than that for SARS (11%) and MERS (34%), COVID-19 is spreading relatively uncontrolled at this time across the globe. In contrast, SARS appears to be contained, and MERS is controlled. This paper will explore why COVID-19 is able to progress to a global pandemic that affects our daily lives to an extent not known in recent history. The COVID-19 outbreak and spread will be examined based on the current literature, using a researcher\u2019s perspective of risk assessment and risk mitigation; this approach will be related to public health.", "qid": 14, "docid": "ip16lh2a", "rank": 81, "score": 0.8162176012992859}, {"content": "Title: Characteristics of a family cluster of Severe Acute Respiratory Syndrome Coronavirus 2 in Henan, China Content: \u2022 The worldwide outbreak of SARS-CoV-2 called for more close investigations of the family transmission routes of infectious diseases. \u2022 We hypothesize that the likelihood to develop COVID-19 is probably associated with the duration of being exposed to SARS-CoV-2. \u2022 In a family cluster, asymptomatic infection carriers can be persons of all ages, from nine to sixty years old.", "qid": 14, "docid": "ojjzetc8", "rank": 82, "score": 0.8160250186920166}, {"content": "Title: Data-driven Analytical Models of COVID-2019 for Epidemic Prediction, Clinical Diagnosis, Policy Effectiveness and Contact Tracing: A Survey Content: The widely spread CoronaVirus Disease (COVID)-19 is one of the worst infectious disease outbreaks in history and has become an emergency of primary international concern. As the pandemic evolves, academic communities have been actively involved in various capacities, including accurate epidemic estimation, fast clinical diagnosis, policy effectiveness evaluation and development of contract tracing technologies. There are more than 23,000 academic papers on the COVID-19 outbreak, and this number is doubling every 20 days while the pandemic is still on-going [1]. The literature, however, at its early stage, lacks a comprehensive survey from a data analytics perspective. In this paper, we review the latest models for analyzing COVID19 related data, conduct post-publication model evaluations and cross-model comparisons, and collect data sources from different projects.", "qid": 14, "docid": "xe0dhx4o", "rank": 83, "score": 0.8159515857696533}, {"content": "Title: Modeling COVID-19 Growing Trends to Reveal the Differences in the Effectiveness of Non-Pharmaceutical Interventions among Countries in the World Content: Objective: We hypothesize that COVID-19 case growth data reveals the efficacy of NPIs. In this study, we conduct a secondary analysis of COVID-19 case growth data to compare the differences in the effectiveness of NPIs among 16 representative countries in the world. Methods: This study leverages publicly available data to learn patterns of dynamic changes in the reproduction rate for sixteen countries covering Asia, Europe, North America, South America, Australia, and Africa. Furthermore, we model the relationships between the cumulative number of cases and the dynamic reproduction rate to characterize the effectiveness of the NPIs. We learn four levels of NPIs according to their effects in the control of COVID-19 growth and categorize the 16 countries into the corresponding groups. Results: The dynamic changes of the reproduction rate are learned via linear regression models for all of the studied countries, with the average adjusted R-squared at 0.96 and the 95% confidence interval as [0.94 0.98]. China, South Korea, Argentina, and Australia are at the first level of NPIs, which are the most effective. Japan and Egypt are at the second level of NPIs, and Italy, Germany, France, Netherlands, and Spain, are at the third level. The US and UK have the most inefficient NPIs, and they are at the fourth level of NPIs. Conclusions: COVID-19 case growth data provides evidence to demonstrate the effectiveness of the NPIs. Understanding the differences in the efficacy of the NPIs among countries in the world can give guidance for emergent public health events.", "qid": 14, "docid": "31vwsjvv", "rank": 84, "score": 0.8158721923828125}, {"content": "Title: Time Course of COVID-19 Cases in Austria Content: COVID-19 is an infectious disease caused by a novel coronavirus, which first appeared in China in late 2019, and reached pandemic distribution in early 2020. The first major outbreak in Europe occurred in Northern Italy where it spread to neighboring countries, notably to Austria, where skiing resorts served as a main transmission hub. Soon, the Austrian government introduced strict measures to curb the spread of the virus. Using publicly available data, we assessed the efficiency of the governmental measures. We assumed an average incubation period of one week and an average duration of infectivity of 10 days. One week after the introduction of strict measures, the increase in daily new cases was reversed, and the reproduction number dropped. The crude estimates tended to overestimate the reproduction rate in the early phase. Publicly available data provide a first estimate about the effectiveness of public health measures. However, more data are needed for an unbiased assessment.", "qid": 14, "docid": "cfk25vpu", "rank": 85, "score": 0.8155577182769775}, {"content": "Title: Psychological, Political, and Situational Factors Combine to Boost COVID-19 Conspiracy Theory Beliefs Content: Conspiracy theories (CTs) are not solely the domain of extremists and paranoids. They cut across demographic and political differences (Uscinski and Parent, 2014) and can have negative social/political consequences. For example, Imhoff and Lamberty (2020) find that belief that the seriousness of COVID-19 is being exaggerated is negatively correlated with self-reported preventative behaviours such as hand washing and social distancing, and belief that the virus was intentionally created by humans is positively correlated with self-reported hoarding of food, sanitary products, and gasoline/oil, as well as stocking up on weapons.", "qid": 14, "docid": "0n4j6wkx", "rank": 86, "score": 0.8151850700378418}, {"content": "Title: [Epidemiological analysis on 1 052 cases of COVID-19 in epidemic clusters] Content: Objective: To understand the epidemiological characteristics of the cases of COVID-19 epidemic clusters, and explore the influence of family factors and social factors such as group activities on the spread of the disease. Methods: The data of cases of COVID-19 epidemic clusters from 19 January, 2020 to 25 February, 2020 were collected from the official platforms of 36 cities in 6 provinces in China. Descriptive statistical methods, &#967;(2) test and curve fitting were used to analyze the epidemiological characteristics of the clustered cases. Results: By 25 February, 2020, the data of 1 052 cases in 366 epidemic clusters were collected. In these clustered cases, 86.9%(914/1 050) occurred in families. Among the 1 046 cases with gender information, 513 were males (49.0%) and 533 were females (51.0%). The cases were mainly young adults between 18 and 59 years old, accounting for 68.5% (711/1 038). In the 366 epidemic clusters , the clusters in which the first confirmed cases with the history of sojourn in Wuhan or Hubei accounted for 47.0%(172/366). From 19 January to 3 February, 2020, the first confirmed cases with Wuhan or Hubei sojourn history accounted for 66.5%. From 4 to 25 February, the first confirmed cases who had Wuhan or Hubei sojourn history accounted for only 18.2%. The median of interval between the first generation case onset and the second generation case onset was 5 (2-8) days. The median of onset- diagnosis interval of the initial cases was 6 (3-9) days, and the median of onset-diagnosis interval of the secondary cases was 5 (3-8) days. Conclusions: Epidemic clusters of COVID-19 were common in many cities outside Wuhan and Hubei. Close contact in family was one of the main causes for the spread of household transmission of the virus. After 4 February, the epidemic clusters were mainly caused by the first generation or second generation cases in local areas, and the time for diagnosis became shorter.", "qid": 14, "docid": "w2h67qw6", "rank": 87, "score": 0.8150879144668579}, {"content": "Title: Active tuberculosis, sequelae and COVID-19 co-infection: first cohort of 49 cases Content: The severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) disease (COVID-19) pandemic has attracted interest because of its global rapid spread, clinical severity, high mortality rate, and capacity to overwhelm healthcare systems [1, 2]. SARS-CoV-2 transmission occurs mainly through droplets, although surface contamination contributes and debate continues on aerosol transmission [3\u20135].", "qid": 14, "docid": "onn8n9bl", "rank": 88, "score": 0.8149269819259644}, {"content": "Title: Temporal data series of COVID-19 epidemics in the USA, Asia and Europe suggests a selective sweep of SARS-CoV-2 Spike D614G variant Content: The COVID-19 pandemic started in Wuhan, China, and caused the worldwide spread of the RNA virus SARS-CoV-2, the causative agent of COVID-19. Because of its mutational rate, wide geographical distribution, and host response variance this coronavirus is currently evolving into an array of strains with increasing genetic diversity. Most variants apparently have neutral effects for disease spread and symptoms severity. However, in the viral Spike protein, which is responsible for host cell attachment and invasion, an emergent variant, containing the amino acid substitution D to G in position 614 (D614G), was suggested to increase viral infection capability. To test whether this variant has epidemiological impact, the temporal distributions of the SARS-CoV-2 samples bearing D or G at position 614 were compared in the USA, Asia and Europe. The epidemiological curves were compared at early and late epidemic stages. At early stages, where containment measures were still not fully implemented, the viral variants are supposed to be unconstrained and its growth curves might approximate the free viral dynamics. Our analysis shows that the D614G prevalence and the growth rates of COVID-19 epidemic curves are correlated in the USA, Asia and Europe. Our results suggest a selective sweep that can be explained, at least in part, by a propagation advantage of this variant, in other words, that the molecular level effects of D614G have sufficient impact on population transmission dynamics as to be detected by differences in rate coefficients of epidemic growth curves.", "qid": 14, "docid": "8iyynbup", "rank": 89, "score": 0.8149088621139526}, {"content": "Title: Is visiting Qom spread CoVID-19 epidemic in the Middle East? Content: The CoVID-19 epidemic started in Wuhan, China and spread to 217 other countries around the world through direct contact with patients, goods transfer, animal transport, and touching unclean surfaces. In the Middle East, the first confirmed case in both Iran and UAE originated from China. A series of infections since those confirmed cases started in the Middle East originated from Qom, Iran, and other Shi'ite holy places. Thereafter, CoVID-19 has been transmitted to other countries in the Middle East. This report aims to trace all of the confirmed cases in the Middle East until March 6, 2020 and their further spread. This report proves that further transmission of CoVID-19 to the Middle East was because of human mobility, besides engaging in different Jewish and Shi'ite religious rites. This report suggests avoiding several religious rites, closing the borders of infected countries, and supporting the infected countries to prevent further transmission.", "qid": 14, "docid": "7h9yjkt3", "rank": 90, "score": 0.8148373365402222}, {"content": "Title: Estimating the extent of true asymptomatic COVID-19 and its potential for community transmission: systematic review and meta-analysis Content: Background: The prevalence of true asymptomatic COVID-19 cases is critical to policy makers considering the effectiveness of mitigation measures against the SARS-CoV-2 pandemic. We aimed to synthesize all available research on the asymptomatic rates and transmission rates where possible. Methods: We searched PubMed, Embase, Cochrane COVID-19 trials, and European PMC for pre-print platforms such as MedRxiv. We included primary studies reporting on asymptomatic prevalence where: (a) the sample frame includes at-risk population, and (b) there was sufficiently long follow up to identify pre-symptomatic cases. Meta-analysis used fixed effect and random effects models. Results: We screened 571 articles and included five low risk-of-bias studies from three countries (China (2), USA (2), Italy (1)) that tested 9,242 at-risk people, of which 413 were positive and 65 were asymptomatic. Diagnosis in all studies was confirmed using a RT-qPCR test. The proportion of asymptomatic cases ranged from 6% to 41%. Meta-analysis (fixed effect) found that the proportion of asymptomatic cases was 16% (95% CI: 12% - 20%) overall; higher in non-aged care 19% (15% - 24%), and lower in long-term aged care 8% (4% - 14%). Two studies provided direct evidence of forward transmission of the infection by asymptomatic cases but suggested lower rates than symptomatic cases. Conclusion: Our estimates of the prevalence of asymptomatic COVID-19 cases are lower than many highly publicized studies, but still substantial. Further robust epidemiological evidence is urgently needed, including in sub-populations such as children, to better understand the importance of asymptomatic cases for driving spread of the pandemic.", "qid": 14, "docid": "li8kvzdh", "rank": 91, "score": 0.8147779703140259}, {"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": 92, "score": 0.81472247838974}, {"content": "Title: [Advances on presymptomatic or asymptomatic carrier transmission of COVID-19] Content: COVID-19 is rapidly spreading. Patients in incubation period and healthy carriers are possible sources for transmission. However, such sources of infection cannot be effectively identified due to the symptoms absent. The research evidence is very lacking so far, although there are a few studies suggesting that presymptomatic or asymptomatic carrier may cause COVID-19 transmission. Nearly half of the literature is in the state of preprint without peer review. The question of \"the degree to which presymptomatic or asymptomatic infections can transmit\" is not fully understood. There is an urgent need to screen infected carriers in larger close contacts or in the general population, and assess their risk for transmission.", "qid": 14, "docid": "3fd81ovn", "rank": 93, "score": 0.8146979808807373}, {"content": "Title: [Advances on presymptomatic or asymptomatic carrier transmission of COVID-19]. Content: COVID-19 is rapidly spreading. Patients in incubation period and healthy carriers are possible sources for transmission. However, such sources of infection cannot be effectively identified due to the symptoms absent. The research evidence is very lacking so far, although there are a few studies suggesting that presymptomatic or asymptomatic carrier may cause COVID-19 transmission. Nearly half of the literature is in the state of preprint without peer review. The question of \"the degree to which presymptomatic or asymptomatic infections can transmit\" is not fully understood. There is an urgent need to screen infected carriers in larger close contacts or in the general population, and assess their risk for transmission.", "qid": 14, "docid": "xbv0b96w", "rank": 94, "score": 0.8146979808807373}, {"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": 95, "score": 0.8146852850914001}, {"content": "Title: Estimating the generation interval for coronavirus disease (COVID-19) based on symptom onset data, March 2020 Content: BACKGROUND: Estimating key infectious disease parameters from the coronavirus disease (COVID-19) outbreak is essential for modelling studies and guiding intervention strategies. AIM: We estimate the generation interval, serial interval, proportion of pre-symptomatic transmission and effective reproduction number of COVID-19. We illustrate that reproduction numbers calculated based on serial interval estimates can be biased. METHODS: We used outbreak data from clusters in Singapore and Tianjin, China to estimate the generation interval from symptom onset data while acknowledging uncertainty about the incubation period distribution and the underlying transmission network. From those estimates, we obtained the serial interval, proportions of pre-symptomatic transmission and reproduction numbers. RESULTS: The mean generation interval was 5.20 days (95% credible interval (CrI): 3.78\u20136.78) for Singapore and 3.95 days (95% CrI: 3.01\u20134.91) for Tianjin. The proportion of pre-symptomatic transmission was 48% (95% CrI: 32\u201367) for Singapore and 62% (95% CrI: 50\u201376) for Tianjin. Reproduction number estimates based on the generation interval distribution were slightly higher than those based on the serial interval distribution. Sensitivity analyses showed that estimating these quantities from outbreak data requires detailed contact tracing information. CONCLUSION: High estimates of the proportion of pre-symptomatic transmission imply that case finding and contact tracing need to be supplemented by physical distancing measures in order to control the COVID-19 outbreak. Notably, quarantine and other containment measures were already in place at the time of data collection, which may inflate the proportion of infections from pre-symptomatic individuals.", "qid": 14, "docid": "4ciz99oy", "rank": 96, "score": 0.814647912979126}, {"content": "Title: COVID-19: A New Virus as a Potential Rapidly Spreading in the Worldwide Content: Covid-19 is a novel virus with high affinity to spread in the community In December 2019, it was first identified in Wuhan, China The symptoms are non-specific, so fever, cough, dyspnea, are prominent features Respiratory failure and mortality have also been reported The most common lung CT scan findings are bilateral ground glass opacities", "qid": 14, "docid": "0em5sf3g", "rank": 97, "score": 0.8145945072174072}, {"content": "Title: On the COVID-19 Pandemic in Indian State of Maharashtra: Forecasting & Effect of different parameters Content: This work details the outbreak and factors affecting the spread of novel coronavirus (COVID-19) in the Indian state of Maharashtra, which is considered as one of the most massive and deadly pandemic outbreaks. Observational data collected between 14 March 2020 and 4 May 2020 is statistically analyzed to determine the nonlinear behaviour of the epidemic. It is followed by validating predicted results with real-time data. Proposed model is further used to obtain statistical summaries in which Grubbs tests for outlier detection have justified high values of evaluation metrics. Outliers are found to be pilot elements in an outbreak under considered region. Statistically, a significant correlation has been observed between dependent and explanatory variables. Transmission pattern of this virus is very much different from the SARS-CoV-1 virus. Key findings of this work will be predominant in maintaining environment conditions at healthcare facilities to reduce transmission rates at these most vulnerable places. KEY WORDS-: SARS-CoV-1; COVID-19, Humidity, Polynomial, Temperature, Confirmed cases; Tests; Maharashtra.", "qid": 14, "docid": "77yjvrkr", "rank": 98, "score": 0.8145877718925476}, {"content": "Title: A Machine Learning Explanation of Incidence Inequalities of SARS-CoV-2 Across 88 Days in 157 Countries Content: Because the SARS-CoV-2 (COVID-19) pandemic viral outbreaks will likely continue until effective vaccines are widely administered, (1) new capabilities to accurately predict incidence rates by location and time to know in advance the disease burden and specific needs for any given population are valuable to minimize morbidity and mortality. In this study, a random forest of 9,250 regression trees was applied to 6,941 observations of 13 statistically significant predictor variables targeting SARS-CoV-2 incidence rates per 100,000 across 88 days in 157 countries. One key finding is an algorithm that can predict the incidence rate per day of a SARS-CoV-2 epidemic cycle with a pseudo-R2 accuracy of 98.5% and explain 97.4% of the variances. Another key finding is the relative importance of 13 demographic, economic, environmental, and public health modulators to the SARS-CoV-2 incidence rate. Four factors proposed in earlier research as potential modulators have no statistically significant relationship with incidence rates (2)(3). These findings give leaders new capabilities for improved capacity planning and targeting stay-at-home interventions and prioritizing programming by knowing the atypical social determinants that are the root causes of SARS-CoV-2 incidence variance. This work also proves that machine learning can accurately and quickly explain disease dynamics for zoonoses with pandemic potential.", "qid": 14, "docid": "wbrnhpgs", "rank": 99, "score": 0.8145711421966553}, {"content": "Title: Covid-19 outbreak and perspective in morocco Content: Coronavirus disease 2019 (COVID-19) is a respiratory illness that can spread from person to person. The virus that causes COVID-19 is a novel coronavirus that was first identified during an investigation into an outbreak in Wuhan, China and rapidly spread across the world to become the first pandemic caused by a coronavirus. As of 26 March 2020, there are 275 cases affected by COVID-19 announced by the Moroccan government, and it possible to limit the spread of this serious disease, with the cooperation of all the citizens in respect of the measures of containment and individual protection. Also, with the announce yesterday by the Moroccan government of the authorization of use of chloroquine in treatment of COVID-19 pneumonia, COVID-19 will be soon eradicated from Morocco and hopefully from all over the world.", "qid": 14, "docid": "8yr41aa8", "rank": 100, "score": 0.8144552707672119}]}
{"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": 0.900225818157196}, {"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": 2, "score": 0.8634325265884399}, {"content": "Title: Tackling Corona Virus Disease 2019 (COVID 19) in Workplaces Content: Coronaviruses are zoonotic viruses and six species of Coronaviruses are known to cause human disease such as cause common cold, severe acute respiratory syndrome and the Middle East Respiratory Syndrome. In January 2020, scientists in Wuhan, China isolated a novel coronavirus (SARS-CoV-2), responsible for an outbreak of unknown pneumonia that had not been previously reported among humans. This virus spreads from person to person, through respiratory droplets, close contact, and by touching surfaces or objects contaminated by the virus. The incubation period varies between 2 days and 14 days. Symptoms usually include fever, cough, difficulty in breathing, pneumonia, severe acute respiratory syndrome. Older age and co-morbid conditions increase the fatality. Any person with a history of travel to and from COVID-19 affected countries in the past 14 days or any person who has had close contact with a laboratory confirmed COVID-19 are suspect cases and needs evaluation. Currently no vaccine is available and treatment is mainly supportive. Measures at workplace should include- avoiding non-essential travel, identifying and isolating sick employees at the earliest, hand hygiene, respiratory hygiene, environmental hygiene and social distancing.", "qid": 15, "docid": "rzr8qjw8", "rank": 3, "score": 0.8434791564941406}, {"content": "Title: Environmental concern regarding the effect of humidity and temperature on 2019-nCoV survival: fact or fiction Content: The new coronavirus, called 2019-nCoV, is a new type of virus that was first identified in Wuhan, China, in December 2019. Environmental conditions necessary for survival and spread of 2019-nCoV are somewhat transparent but unlike animal coronaviruses. We are poorly aware of their survival in environment and precise factors of their transmission. Countries located in east and west of globe did not have a significant impact on prevalence of disease among communities, and on the other hand, north and south have provided a model for relative prediction of disease outbreaks. The 2019-nCoV can survive for up to 9 days at 25 \u00b0C, and if this temperature rises to 30 \u00b0C, its lifespan will be shorter. The 2019-nCoV is sensitive to humidity, and lifespan of viruses in 50% humidity is longer than that of 30%. Also, temperature and humidity are important factors influencing the COVID-19 mortality rate and may facilitate 2019-nCoV transmission. Thus, considering the available and recent evidence, it seems that low temperatures, as well as dry and unventilated air, may affect stability and transmissibility of 2019-nCoV.", "qid": 15, "docid": "zqsfw75p", "rank": 4, "score": 0.8399458527565002}, {"content": "Title: Persistence of coronaviruses on inanimate surfaces and their inactivation with biocidal agents Content: Currently, the emergence of a novel human coronavirus, SARS-CoV-2, has become a global health concern causing severe respiratory tract infections in humans. Human-to-human transmissions have been described with incubation times between 2-10 days, facilitating its spread via droplets, contaminated hands or surfaces. We therefore reviewed the literature on all available information about the persistence of human and veterinary coronaviruses on inanimate surfaces as well as inactivation strategies with biocidal agents used for chemical disinfection, e.g. in healthcare facilities. The analysis of 22 studies reveals that human coronaviruses such as Severe Acute Respiratory Syndrome (SARS) coronavirus, Middle East Respiratory Syndrome (MERS) coronavirus or endemic human coronaviruses (HCoV) can persist on inanimate surfaces like metal, glass or plastic for up to 9 days, but can be efficiently inactivated by surface disinfection procedures with 62-71% ethanol, 0.5% hydrogen peroxide or 0.1% sodium hypochlorite within 1 minute. Other biocidal agents such as 0.05-0.2% benzalkonium chloride or 0.02% chlorhexidine digluconate are less effective. As no specific therapies are available for SARS-CoV-2, early containment and prevention of further spread will be crucial to stop the ongoing outbreak and to control this novel infectious thread.", "qid": 15, "docid": "ssq0dwmn", "rank": 5, "score": 0.8360067009925842}, {"content": "Title: Persistence of coronaviruses on inanimate surfaces and their inactivation with biocidal agents Content: Summary Currently, the emergence of a novel human coronavirus, SARS-CoV-2, has become a global health concern causing severe respiratory tract infections in humans. Human-to-human transmissions have been described with incubation times between 2-10 days, facilitating its spread via droplets, contaminated hands or surfaces. We therefore reviewed the literature on all available information about the persistence of human and veterinary coronaviruses on inanimate surfaces as well as inactivation strategies with biocidal agents used for chemical disinfection, e.g. in healthcare facilities. The analysis of 22 studies reveals that human coronaviruses such as Severe Acute Respiratory Syndrome (SARS) coronavirus, Middle East Respiratory Syndrome (MERS) coronavirus or endemic human coronaviruses (HCoV) can persist on inanimate surfaces like metal, glass or plastic for up to 9 days, but can be efficiently inactivated by surface disinfection procedures with 62\u201371% ethanol, 0.5% hydrogen peroxide or 0.1% sodium hypochlorite within 1 minute. Other biocidal agents such as 0.05\u20130.2% benzalkonium chloride or 0.02% chlorhexidine digluconate are less effective. As no specific therapies are available for SARS-CoV-2, early containment and prevention of further spread will be crucial to stop the ongoing outbreak and to control this novel infectious thread.", "qid": 15, "docid": "k9xhphpl", "rank": 6, "score": 0.834780216217041}, {"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": 15, "docid": "gp3ib74q", "rank": 7, "score": 0.8340603113174438}, {"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": 15, "docid": "ycrrsr5c", "rank": 8, "score": 0.8311665654182434}, {"content": "Title: Incubation period of 2019 novel coronavirus (2019-nCoV) infections among travellers from Wuhan, China, 20-28 January 2020 Content: A novel coronavirus (2019-nCoV) is causing an outbreak of viral pneumonia that started in Wuhan, China. Using the travel history and symptom onset of 88 confirmed cases that were detected outside Wuhan in the early outbreak phase, we estimate the mean incubation period to be 6.4 days (95% credible interval: 5.6-7.7), ranging from 2.1 to 11.1 days (2.5th to 97.5th percentile). These values should help inform 2019-nCoV case definitions and appropriate quarantine durations.", "qid": 15, "docid": "mx7rn5lt", "rank": 9, "score": 0.8307111859321594}, {"content": "Title: Incubation period of 2019 novel coronavirus (2019-nCoV) infections among travellers from Wuhan, China, 20\u201328 January 2020 Content: A novel coronavirus (2019-nCoV) is causing an outbreak of viral pneumonia that started in Wuhan, China. Using the travel history and symptom onset of 88 confirmed cases that were detected outside Wuhan in the early outbreak phase, we estimate the mean incubation period to be 6.4 days (95% credible interval: 5.6\u20137.7), ranging from 2.1 to 11.1 days (2.5th to 97.5th percentile). These values should help inform 2019-nCoV case definitions and appropriate quarantine durations.", "qid": 15, "docid": "jat60k8t", "rank": 10, "score": 0.8306021690368652}, {"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": 15, "docid": "ej93duxi", "rank": 11, "score": 0.8305943012237549}, {"content": "Title: Persistence of SARS-CoV-2 in the environment and COVID-19 transmission risk from environmental matrices and surfaces Content: The Coronavirus disease 2019 (COVID-19) is spreading around the world, representing a global pandemic, counting, as of June 5th, 2020, over 6,600,000 confirmed cases and more than 390,000 deaths, with exponentially increasing numbers. In the first half of 2020, because of the widespread of the COVID-19, researches were focused on the monitoring of SARS-CoV-2 in water, wastewater, sludge, air, and on surfaces, in order to assess the risk of contracting the viral infection from contaminated environments. So far, the survival of the novel Coronavirus out of the human body has been reported for short time periods (from hours to few days, in optimized in vitro conditions), mainly because of the need of an host organism which could consent the viral attack, and due to the weak external membrane of the virus. SARS-CoV-2 viral shedding strategies in the environment, either through animate and unanimate matrices, or exploiting the organic matter in water, wastewater, and waste in general, have been discussed in the present article. We concluded that, besides the high infectuousness of the novel Coronavirus, the transmission of the pathogen may be efficiently contained applying the adequate preventive measures (e.g., personal protection equipments, and disinfecting agents), indicated by national and international health authories.", "qid": 15, "docid": "b5lcv77o", "rank": 12, "score": 0.8288873434066772}, {"content": "Title: Persistence of SARS-CoV-2 in the environment and COVID-19 transmission risk from environmental matrices and surfaces() Content: The Coronavirus disease 2019 (COVID-19) is spreading around the world, representing a global pandemic, counting, as of June 5th, 2020, over 6,600,000 confirmed cases and more than 390,000 deaths, with exponentially increasing numbers. In the first half of 2020, because of the widespread of the COVID-19, researches were focused on the monitoring of SARS-CoV-2 in water, wastewater, sludge, air, and on surfaces, in order to assess the risk of contracting the viral infection from contaminated environments. So far, the survival of the novel Coronavirus out of the human body has been reported for short time periods (from hours to few days, in optimized in vitro conditions), mainly because of the need of an host organism which could consent the viral attack, and due to the weak external membrane of the virus. SARS-CoV-2 viral shedding strategies in the environment, either through animate and unanimate matrices, or exploiting the organic matter in water, wastewater, and waste in general, have been discussed in the present article. We concluded that, besides the high infectuousness of the novel Coronavirus, the transmission of the pathogen may be efficiently contained applying the adequate preventive measures (e.g., personal protection equipments, and disinfecting agents), indicated by national and international health authories.", "qid": 15, "docid": "kxyd5uzp", "rank": 13, "score": 0.8288872838020325}, {"content": "Title: Coronaviruses: a paradigm of new emerging zoonotic diseases Content: A novel type of coronavirus (2019-nCoV) infecting humans appeared in Wuhan, China, at the end of December 2019. Since the identification of the outbreak the infection quickly spread involving in one month more than 31,000 confirmed cases with 638 death. Molecular analysis suggest that 2019-nCoV could be originated from bats after passaging in intermediate hosts, highlighting the high zoonotic potential of coronaviruses.", "qid": 15, "docid": "1bvsn9e8", "rank": 14, "score": 0.8288050889968872}, {"content": "Title: Inanimate surfaces as potential source of 2019-nCoV spread and their disinfection with biocidal agents Content: The WHO has declared COVID-19 illness a global health concern which is caused by 2019-nCoV, causing severe respiratory tract infections in humans. Transmissibility among individual to individual have been reported through droplets and probably also via contaminated surfaces and hands. Human coronaviruses can persist on inanimate surfaces such as plastic, glass, fibers and metals up to nine days. 2019-nCoV remains infectious in air for 3 h and on inanimate surfaces such as cardboard, copper, plastic and steel up to 24, 4, 72 and 48 h respectively. Disinfectant activity of various biocidal agents against coronaviruses like ethanol (62\u201371%), sodium hypochlorite (0.1%) and hydrogen peroxide (0.5%) can be regarded effective against 2019-nCoV as well. As no vaccine and antiviral therapies have been discovered for 2019-nCoV, prevention of further spread will viable option to control the ongoing and future outbreaks.", "qid": 15, "docid": "esvutpel", "rank": 15, "score": 0.8278086185455322}, {"content": "Title: Profile of RT-PCR for SARS-CoV-2: a preliminary study from 56 COVID-19 patients Content: A novel coronavirus (COVID-19) pandemic threatens the world. Here, we first studied the dynamics profile of SARS-CoV-2 from 56 recovered COVID-19 patients. We found virus shedding was up to 6 weeks after onset of symptoms. Prolonged observation period is necessary for older patients.", "qid": 15, "docid": "4awl1ocd", "rank": 16, "score": 0.8267593383789062}, {"content": "Title: Digitally aided telemedicine during the SARS\u2010CoV\u20102 pandemic to screen oral medicine emergencies Content: A new human coronavirus, known as severe acute respiratory coronavirus 2 syndrome (SARS\u2010CoV\u20102), emerged at the end of 2019 in Wuhan, China, and we are now facing a pandemic (WHO 2020). The virus has been found in saliva (Meng et al 2020, Sabino et al 2020). In vitro experimental findings suggest that SARS\u2010CoV\u20102 remained viable in aerosols for 3 hours (van Doremalen et al 2020).", "qid": 15, "docid": "jk73ojkp", "rank": 17, "score": 0.8251502513885498}, {"content": "Title: The incubation period of 2019-nCoV infections among travellers from Wuhan, China Content: Currently, a novel coronavirus 2019-nCoV causes an outbreak of viral pneumonia in Wuhan, China. Little is known about its epidemiological characteristics. Using the travel history and symptom onset of 88 confirmed cases that were detected outside Wuhan, we estimate the mean incubation period to be 6.4 (5.6 - 7.7, 95% CI) days, ranging from 2.1 to 11.1 days (2.5th to 97.5th percentile). These values help to inform case definitions for 2019-nCoV and appropriate durations for quarantine.", "qid": 15, "docid": "u8goc7io", "rank": 18, "score": 0.8246524930000305}, {"content": "Title: COVID-19: Dados Atualizados e sua Rela\u00e7\u00e3o Com o Sistema Cardiovascular./ COVID-19: Dados Atualizados e sua Rela\u00e7\u00e3o Com o Sistema Cardiovascular./ 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": 15, "docid": "yj0png0x", "rank": 19, "score": 0.8242686986923218}, {"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": 15, "docid": "8hvv7gsm", "rank": 20, "score": 0.8242686986923218}, {"content": "Title: Clinical and Epidemiological Features of a Family Cluster of Symptomatic and Asymptomatic Severe Acute Respiratory Syndrome Coronavirus 2 Infection Content: In a family experiencing coronavirus disease 2019, the parents and 2 children aged 2 and 5 years became infected but the youngest child was not infected. Both children initially shed infectious virus, but cleared the virus after 5 to 6 days in the nasopharynx. However, viral RNA was continuously detected in the children\u2019s stool for more than 4 weeks.", "qid": 15, "docid": "zz5bpas1", "rank": 21, "score": 0.8230854272842407}, {"content": "Title: Digital prosthetic workflow during COVID\u201019 pandemic to limit infection risk in dental practice Content: A novel human coronavirus(SARS\u2010CoV\u20102) causing a severe acute respiratory syndrome, coronavirus disease 2019 (COVID\u201019), was reported in Wuhan, China at the end of 2019(Wang, Horby, Hayden, & Gao,2020; Khan, Ali, Siddique, Nabi, 2020).The infectionhas an estimated incubation period of 1\u201014 days and its clinical manifestations and symptoms include cough, fever and shortness of breath (Zhuet al., 2020).", "qid": 15, "docid": "oznelaus", "rank": 22, "score": 0.8222529888153076}, {"content": "Title: The Rheumatologist's Role in Covid-19. Content: The novel coronavirus (SARS-CoV-2) pandemic has spread rapidly throughout the planet. It is believed to have originated in the Wuhan province of China, but this highly contagious respiratory virus has spread to over 140 countries on 6 continents as of mid-March 2020 according to the World Health Organization (WHO). Worldwide, there have been over 164,000 cases identified and over 6,500 deaths attributed to the viral infection. As of March 15, 2020, there are over 3,700 confirmed cases and 68 deaths ascribed to Covid-19 (the disease caused by SARS-CoV-2) in the United States [https://www.livescience.com/coronavirus-updates-unitedstates.html].", "qid": 15, "docid": "8m7l0uid", "rank": 23, "score": 0.8221872448921204}, {"content": "Title: Duration of viral detection in throat and rectum of a patient with COVID-19 Content: The rapid spread of coronavirus disease 2019 (COVID-19) raises concern about a global pandemic. Knowledge about the duration of viral shedding remains important for patient management and infection control. We report the duration of viral detection in throat and rectum of a COVID-19 patient treated at the Hospital for Tropical Diseases in Ho Chi Minh City, Vietnam. Despite clinical recovery, SARS-CoV-2 RNA remained detectable by real time RT-PCR in throat and rectal swabs until day 11 and 18 of hospitalization, respectively. Because live SARS-CoV-2 has been successfully isolated from a stool sample from a COVID-19 patient in China, the results demonstrate that COVID-19 patients may remain infectious for long periods, and fecal-oral transmission may be possible. Therefore, our finding has important implications for infection control.", "qid": 15, "docid": "q4i9kh65", "rank": 24, "score": 0.8217957019805908}, {"content": "Title: Human Coronaviruses: Insights into Environmental Resistance and Its Influence on the Development of New Antiseptic Strategies Content: The Coronaviridae family, an enveloped RNA virus family, and, more particularly, human coronaviruses (HCoV), were historically known to be responsible for a large portion of common colds and other upper respiratory tract infections. HCoV are now known to be involved in more serious respiratory diseases, i.e. bronchitis, bronchiolitis or pneumonia, especially in young children and neonates, elderly people and immunosuppressed patients. They have also been involved in nosocomial viral infections. In 2002\u20132003, the outbreak of severe acute respiratory syndrome (SARS), due to a newly discovered coronavirus, the SARS-associated coronavirus (SARS-CoV); led to a new awareness of the medical importance of the Coronaviridae family. This pathogen, responsible for an emerging disease in humans, with high risk of fatal outcome; underline the pressing need for new approaches to the management of the infection, and primarily to its prevention. Another interesting feature of coronaviruses is their potential environmental resistance, despite the accepted fragility of enveloped viruses. Indeed, several studies have described the ability of HCoVs (i.e. HCoV 229E, HCoV OC43 (also known as betacoronavirus 1), NL63, HKU1 or SARS-CoV) to survive in different environmental conditions (e.g. temperature and humidity), on different supports found in hospital settings such as aluminum, sterile sponges or latex surgical gloves or in biological fluids. Finally, taking into account the persisting lack of specific antiviral treatments (there is, in fact, no specific treatment available to fight coronaviruses infections), the Coronaviridae specificities (i.e. pathogenicity, potential environmental resistance) make them a challenging model for the development of efficient means of prevention, as an adapted antisepsis-disinfection, to prevent the environmental spread of such infective agents. This review will summarize current knowledge on the capacity of human coronaviruses to survive in the environment and the efficacy of well-known antiseptic-disinfectants against them, with particular focus on the development of new methodologies to evaluate the activity of new antiseptic-disinfectants on viruses.", "qid": 15, "docid": "bp6st31f", "rank": 25, "score": 0.8213438987731934}, {"content": "Title: The Novel Coronavirus, 2019-nCoV, is Highly Contagious and More Infectious Than Initially Estimated Content: The novel coronavirus (2019-nCoV) is a recently emerged human pathogen that has spread widely since January 2020. Initially, the basic reproductive number, R0, was estimated to be 2.2 to 2.7. Here we provide a new estimate of this quantity. We collected extensive individual case reports and estimated key epidemiology parameters, including the incubation period. Integrating these estimates and high-resolution real-time human travel and infection data with mathematical models, we estimated that the number of infected individuals during early epidemic double every 2.4 days, and the R0 value is likely to be between 4.7 and 6.6. We further show that quarantine and contact tracing of symptomatic individuals alone may not be effective and early, strong control measures are needed to stop transmission of the virus.", "qid": 15, "docid": "myqli11j", "rank": 26, "score": 0.8211410641670227}, {"content": "Title: Potential role of inanimate surfaces for the spread of coronaviruses and their inactivation with disinfectant agents Content: Summary The novel human coronavirus SARS-CoV-2 has become a global health concern causing severe respiratory tract infections in humans. Human-to-human transmissions have been described, probably via droplets but possibly also via contaminated hands or surfaces. In a recent review on the persistence of human and veterinary coronaviruses on inanimate surfaces it was shown that human coronaviruses such as Severe Acute Respiratory Syndrome (SARS) coronavirus, Middle East Respiratory Syndrome (MERS) coronavirus or endemic human coronaviruses (HCoV) can persist on inanimate surfaces like metal, glass or plastic for up to 9 days. Some disinfectant agents effectively reduce coronavirus infectivity within 1 minute such 62%\u201371% ethanol, 0.5% hydrogen peroxide or 0.1% sodium hypochlorite. Other compounds such as 0.05%\u20130.2% benzalkonium chloride or 0.02% chlorhexidine digluconate are less effective. An effective surface disinfection may help to ensure an early containment and prevention of further viral spread.", "qid": 15, "docid": "80dfqjql", "rank": 27, "score": 0.8211389183998108}, {"content": "Title: COVID-19: Structural Predictions of Viral Success Content: Since the beginning of the 21st century, three coronaviruses have crossed the species barrier and caused serious human disease: severe acute respiratory syndrome coronavirus (SARS-CoV) in November 2002 [1, 2], Middle-East respiratory syndrome coronavirus (MERS-CoV) in 2012 [3, 4], and SARS-CoV-2 in 2019 [5, 6]. SARS-CoV-2 [7], initially called 2019-nCoV, is the etiological agent of COVID-19, a highly contagious infectious illness that was first reported in December 2019 in Wuhan, China and subsequently spread globally [8]. As of May 24, 2020, COVID-19 has caused >5,370,000 infections and >343,000 deaths worldwide [9].", "qid": 15, "docid": "p6r7d0sh", "rank": 28, "score": 0.8203262686729431}, {"content": "Title: COVID-19: Emergence, Spread, Possible Treatments, and Global Burden Content: The Coronavirus (CoV) is a large family of viruses known to cause illnesses ranging from the common cold to acute respiratory tract infection. The severity of the infection may be visible as pneumonia, acute respiratory syndrome, and even death. Until the outbreak of SARS, this group of viruses was greatly overlooked. However, since the SARS and MERS outbreaks, these viruses have been studied in greater detail, propelling the vaccine research. On December 31, 2019, mysterious cases of pneumonia were detected in the city of Wuhan in China's Hubei Province. On January 7, 2020, the causative agent was identified as a new coronavirus (2019-nCoV), and the disease was later named as COVID-19 by the WHO. The virus spread extensively in the Wuhan region of China and has gained entry to over 210 countries and territories. Though experts suspected that the virus is transmitted from animals to humans, there are mixed reports on the origin of the virus. There are no treatment options available for the virus as such, limited to the use of anti-HIV drugs and/or other antivirals such as Remdesivir and Galidesivir. For the containment of the virus, it is recommended to quarantine the infected and to follow good hygiene practices. The virus has had a significant socio-economic impact globally. Economically, China is likely to experience a greater setback than other countries from the pandemic due to added trade war pressure, which have been discussed in this paper.", "qid": 15, "docid": "vx7ebtbp", "rank": 29, "score": 0.8202161192893982}, {"content": "Title: Estimation of incubation period and serial interval of COVID-19: analysis of 178 cases and 131 transmission chains in Hubei province, China Content: A novel coronavirus disease, designated as COVID-19, has become a pandemic worldwide. This study aims to estimate the incubation period and serial interval of COVID-19. We collected contact tracing data in a municipality in Hubei province during a full outbreak period. The date of infection and infector\u2013infectee pairs were inferred from the history of travel in Wuhan or exposed to confirmed cases. The incubation periods and serial intervals were estimated using parametric accelerated failure time models, accounting for interval censoring of the exposures. Our estimated median incubation period of COVID-19 is 5.4 days (bootstrapped 95% confidence interval (CI) 4.8\u20136.0), and the 2.5th and 97.5th percentiles are 1 and 15 days, respectively; while the estimated serial interval of COVID-19 falls within the range of \u22124 to 13 days with 95% confidence and has a median of 4.6 days (95% CI 3.7\u20135.5). Ninety-five per cent of symptomatic cases showed symptoms by 13.7 days (95% CI 12.5\u201314.9). The incubation periods and serial intervals were not significantly different between male and female, and among age groups. Our results suggest a considerable proportion of secondary transmission occurred prior to symptom onset. And the current practice of 14-day quarantine period in many regions is reasonable.", "qid": 15, "docid": "7f1o9fvx", "rank": 30, "score": 0.8199646472930908}, {"content": "Title: Stability and inactivation of SARS coronavirus Content: The SARS-coronavirus (SARS-CoV) is a newly emerged, highly pathogenic agent that caused over 8,000 human infections with nearly 800 deaths between November 2002 and September 2003. While direct person-to-person transmission via respiratory droplets accounted for most cases, other modes have not been ruled out. Faecal shedding is common and prolonged and has caused an outbreak in Hong Kong. We studied the stability of SARS-CoV under different conditions, both in suspension and dried on surfaces, in comparison with other human-pathogenic viruses, including human coronavirus HCoV-229E. In suspension, HCoV-229E gradually lost its infectivity completely while SARS-CoV retained its infectivity for up to 9 days; in the dried state, survival times were 24 h versus 6 days. Thermal inactivation at 56\u00b0C was highly effective in the absence of protein, reducing the virus titre to below detectability; however, the addition of 20% protein exerted a protective effect resulting in residual infectivity. If protein-containing solutions are to be inactivated, heat treatment at 60\u00b0C for at least 30 min must be used. Different fixation procedures, e.g. for the preparation of immunofluorescence slides, as well as chemical means of virus inactivation commonly used in hospital and laboratory settings were generally found to be effective. Our investigations confirm that it is possible to care for SARS patients and to conduct laboratory scientific studies on SARS-CoV safely. Nevertheless, the agent\u2019s tenacity is considerably higher than that of HCoV-229E, and should SARS re-emerge, increased efforts need to be devoted to questions of environmental hygiene.", "qid": 15, "docid": "8s9671zf", "rank": 31, "score": 0.8199172616004944}, {"content": "Title: Estimation of incubation period and serial interval of COVID-19: analysis of 178 cases and 131 transmission chains in Hubei province, China Content: A novel coronavirus disease, designated as COVID-19, has become a pandemic worldwide. This study aims to estimate the incubation period and serial interval of COVID-19. We collected contact tracing data in a municipality in Hubei province during a full outbreak period. The date of infection and infector-infectee pairs were inferred from the history of travel in Wuhan or exposed to confirmed cases. The incubation periods and serial intervals were estimated using parametric accelerated failure time models, accounting for interval censoring of the exposures. Our estimated median incubation period of COVID-19 is 5.4 days (bootstrapped 95% confidence interval (CI) 4.8-6.0), and the 2.5th and 97.5th percentiles are 1 and 15 days, respectively; while the estimated serial interval of COVID-19 falls within the range of -4 to 13 days with 95% confidence and has a median of 4.6 days (95% CI 3.7-5.5). Ninety-five per cent of symptomatic cases showed symptoms by 13.7 days (95% CI 12.5-14.9). The incubation periods and serial intervals were not significantly different between male and female, and among age groups. Our results suggest a considerable proportion of secondary transmission occurred prior to symptom onset. And the current practice of 14-day quarantine period in many regions is reasonable.", "qid": 15, "docid": "3sehsl1x", "rank": 32, "score": 0.8197798728942871}, {"content": "Title: Pandemic Human Coronavirus \u2013 Characterization and Comparison of Selected Properties of Hcov-sars and Hcov-mers Content: It: Two Coronaviruses, HCoV-229E and HCoV-OC43, causing generally mild respiratory tract infections in humans, were described in the XX c Pandemic Coronaviruses were first discovered as late as in the XXI c : SARS-HCoV in 2002 \u2013 causing severe respiratory tract infections (SARS) in China;MERS-HCoV in 2012 \u2013 circulating mostly on the Arabian Peninsula The SARS epidemic ended in 2004 resulting in morbidity of &gt;8000 and &gt;770 deaths, while the MERS epidemic is still ongoing (&gt;2000 ill, &gt;700 deaths) although its intensity decreased Both viruses are zoonotic and require at least two \u201chost jumps\u201d for the transmission of the infection to humans: for HCoV-SARS \u2013 from bat to palm civet and then to human;for HCoV-MERS \u2013 from bats to camels and subsequently to humans Primary mode of transmission is droplet in close contact (&lt;1 m), but both viruses remain active in aerosol (up to 24 h), so infection can be also spread by air (ventilation) The ability for human-to-human transmission is higher for HCoV-SARS than for HCoV-MERS (8 generations vs 4, respectively) Moreover, there are differences in genome structure and pathogenic mechanisms: different receptor, cell entry mechanism, different way of host response modulation (e g inhibition of IFN\u03b2 cascade), etc Probably, these differences influence the overall manifestation of the disease in humans Infection caused by HCoV-MERS might manifest itself as ARDS, a mild-mannered and asymptomatic disease HCoV-SARS infections seem to be associated with severe disease only In this paper, a comparison of the structure of these viruses, the mechanisms underlying their ability to cross the interspecies barrier and to multiply in the human body, including modulation of IFN\u03b2 cascade, as well as routes of infection transmission and symptoms caused, were presented", "qid": 15, "docid": "9eso10is", "rank": 33, "score": 0.81964510679245}, {"content": "Title: Grundlagen der Replikation und der Immunologie von SARS-CoV-2 Content: Coronaviruses are a genetically highly variable family of viruses that infect vertebrates and have succeeded in infecting humans many times by overcoming the species barrier. The severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), which initially appeared in China at the end of 2019, exhibits a high infectivity and pathogenicity compared to other coronaviruses. As the viral coat and other viral components are recognized as being foreign by the immune system, this can lead to initial symptoms, which are induced by the very efficiently working immune defense system via the respiratory epithelium. During severe courses a systemically expressed proinflammatory cytokine storm and subsequent changes in the coagulation and complement systems can occur. Virus-specific antibodies, the long-term expression of which is ensured by the formation of B memory cell clones, generate a specific immune response that is also detectable in blood (seroconversion). Specifically effective cytotoxic CD8+ T\u2011cell populations are also formed, which recognize viral epitopes as pathogen-specific patterns in combination with MHC presentation on the cell surface of virus-infected cells and destroy these cells. At the current point in time it is unclear how regular, robust and durable this immune status is constructed. Experiences with other coronavirus infections (SARS and Middle East respiratory syndrome, MERS) indicate that the immunity could persist for several years. Based on animal experiments, already acquired data on other coronavirus types and plausibility assumptions, it can be assumed that seroconverted patients have an immunity of limited duration and only a very low risk of reinfection. Knowledge of the molecular mechanisms of viral cycles and immunity is an important prerequisite for the development of vaccination strategies and development of effective drugs.", "qid": 15, "docid": "neq2vqym", "rank": 34, "score": 0.8194621801376343}, {"content": "Title: Current perspectives on Coronavirus 2019 (COVID-19) and cardiovascular disease: A white paper by the JAHA editors. Content: Coronavirus Disease 2019 (COVID-19), caused by the Severe Acute Respiratory Syndrome Coronavirus-2 (SARS-CoV-2), has infected more than 3.0 million people worldwide and killed more than 200,000 as of April 27, 2020, making it the most lethal pandemic since the Spanish flu of 1918.1, 2 COVID-19 may preferentially infect individuals with cardiovascular conditions, is more severe in subjects with cardiovascular comorbidities, may directly or indirectly affect the heart and may interact with cardiovascular medications.3 In addition, the widespread effects of the pandemic on the global healthcare system affects the routine and emergency cardiac care for patients who are, may be, or are not infected with COVID-19.", "qid": 15, "docid": "tr5whji0", "rank": 35, "score": 0.8188539147377014}, {"content": "Title: COVID-19, a worldwide public health emergency Content: Abstract A new coronavirus outbreak emerged on the 31st of December 2019 in Wuhan, China, causing commotion among the medical community and the rest of the world. This new species of coronavirus has been termed 2019-nCoV and has caused a considerable number of cases of infection and deaths in China and, to a growing degree, beyond China, becoming a worldwide public health emergency. 2019-nCoV has high homology to other pathogenic coronaviruses, such as those originating from bat-related zoonosis (SARS-CoV), which caused approximately 646 deaths in China at the start of the decade. The mortality rate for 2019-nCoV is not as high (approximately 2\u20133%), but its rapid propagation has resulted in the activation of protocols to stop its spread. This pathogen has the potential to become a pandemic. It is therefore vital to follow the personal care recommendations issued by the World Health Organization.", "qid": 15, "docid": "bjhdy8mg", "rank": 36, "score": 0.8187975883483887}, {"content": "Title: Survival of human coronaviruses 229E and OC43 in suspension and after drying onsurfaces: a possible source ofhospital-acquired infections Content: Abstract Strains OC43 and 229E of human coronaviruses (HCoV) cause one-third of common colds and hospital-acquired upper respiratory tract HCoV infections have been reported in premature newborns. To evaluate possible sources of infection, virus survival was studied in aqueous suspensions and on absorptive and non-absorptive surfaces representative of a hospital environment. Virus susceptibility to chemical disinfection with standard products was also characterized. Virus survived in saline solution for as long as six days but less in culture medium, with or without added cells. After drying, HCoV-229E infectivity was still detectable after 3h on various surfaces (aluminum, sterile latex surgical gloves, sterile sponges) but HCoV-OC43 survived 1h or less. Of the various chemical disinfectants tested, Proviodine\u00ae reduced the virus infectious titre by at least 50%. This study suggests that surfaces and suspensions can be considered as possible sources of contamination that may lead to hospital-acquired infections with HCoV and should be appropriately disinfected.", "qid": 15, "docid": "5gayhkxx", "rank": 37, "score": 0.8187968134880066}, {"content": "Title: 2019 Novel Coronavirus Outbreak: SOS Alert for Dentists Content: On January 31, 2020, novel coronavirus (nCoV), a zoonotic virus yet to be identified into the taxonomy, created a powerful ripple through mankind that the World Health Organization has declared a global health emergency.1 This is definitely not the first time that an alarm has been rung by this family of viruses. Epidemic impact of severe acute respiratory syndrome (SARS) due to SARS CoV and Middle East respiratory syndrome (MERS) by MERS CoV has engraved their place in the scientific literature.2 In general, CoV is known to cause respiratory diseases in humans and accounts for one-third of common cold infections.3 The current outbreak by 2019 nCoV in the Chinese city of Wuhan began in December 2019, has infected nearly 102,188 with 3,491 deaths reported as of March 7, 2020, and has spread to nearly 92 countries.1,4 An assumed incubation period between 2 and 14 days, with flu-like symptoms, may progress into severe pneumonia or acute respiratory distress syndrome which may be the reason for mortality.5,6.", "qid": 15, "docid": "sjya1rzc", "rank": 38, "score": 0.818696141242981}, {"content": "Title: 2019 Novel Coronavirus Outbreak: SOS Alert for Dentists. Content: On January 31, 2020, novel coronavirus (nCoV), a zoonotic virus yet to be identified into the taxonomy, created a powerful ripple through mankind that the World Health Organization has declared a global health emergency.1 This is definitely not the first time that an alarm has been rung by this family of viruses. Epidemic impact of severe acute respiratory syndrome (SARS) due to SARS CoV and Middle East respiratory syndrome (MERS) by MERS CoV has engraved their place in the scientific literature.2 In general, CoV is known to cause respiratory diseases in humans and accounts for one-third of common cold infections.3 The current outbreak by 2019 nCoV in the Chinese city of Wuhan began in December 2019, has infected nearly 102,188 with 3,491 deaths reported as of March 7, 2020, and has spread to nearly 92 countries.1,4 An assumed incubation period between 2 and 14 days, with flu-like symptoms, may progress into severe pneumonia or acute respiratory distress syndrome which may be the reason for mortality.5,6.", "qid": 15, "docid": "vu0wonwu", "rank": 39, "score": 0.8186960220336914}, {"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": 15, "docid": "x51o4gyn", "rank": 40, "score": 0.818092405796051}, {"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": 15, "docid": "tjplc5j6", "rank": 41, "score": 0.8180223703384399}, {"content": "Title: Grundlagen der Replikation und der Immunologie von SARS-CoV-2./ [Basic principles of replication and immunology of SARS-CoV-2] Content: Coronaviruses are a genetically highly variable family of viruses that infect vertebrates and have succeeded in infecting humans many times by overcoming the species barrier. The severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), which initially appeared in China at the end of 2019, exhibits a high infectivity and pathogenicity compared to other coronaviruses. As the viral coat and other viral components are recognized as being foreign by the immune system, this can lead to initial symptoms, which are induced by the very efficiently working immune defense system via the respiratory epithelium. During severe courses a systemically expressed proinflammatory cytokine storm and subsequent changes in the coagulation and complement systems can occur. Virus-specific antibodies, the long-term expression of which is ensured by the formation of B memory cell clones, generate a specific immune response that is also detectable in blood (seroconversion). Specifically effective cytotoxic CD8+ T\u00adcell populations are also formed, which recognize viral epitopes as pathogen-specific patterns in combination with MHC presentation on the cell surface of virus-infected cells and destroy these cells. At the current point in time it is unclear how regular, robust and durable this immune status is constructed. Experiences with other coronavirus infections (SARS and Middle East respiratory syndrome, MERS) indicate that the immunity could persist for several years. Based on animal experiments, already acquired data on other coronavirus types and plausibility assumptions, it can be assumed that seroconverted patients have an immunity of limited duration and only a very low risk of reinfection. Knowledge of the molecular mechanisms of viral cycles and immunity is an important prerequisite for the development of vaccination strategies and development of effective drugs.", "qid": 15, "docid": "r6y70to9", "rank": 42, "score": 0.817913293838501}, {"content": "Title: Coronaviruses and SARS-COV-2 Content: Coronaviruses (CoVs) cause a broad spectrum of diseases in domestic and wild animals, poultry, and rodents, ranging from mild to severe enteric, respiratory, and systemic disease, and also cause the common cold or pneumonia in humans. Seven coronavirus species are known to cause human infection, 4 of which, HCoV 229E, HCoV NL63, HCoV HKU1 and HCoV OC43, typically cause cold symptoms in immunocompetent individuals. The others namely SARS-CoV (severe acute respiratory syndrome coronavirus), MERS-CoV (Middle East respiratory syndrome coronavirus) were zoonotic in origin and cause severe respiratory illness and fatalities. On 31 December 2019, the existence of patients with pneumonia of an unknown aetiology was reported to WHO by the national authorities in China. This virus was officially identified by the coronavirus study group as severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), and the present outbreak of a coronavirus-associated acute respiratory disease was labelled coronavirus disease 19 (COVID-19). COVID-19's first cases were seen in Turkey on March 10, 2020 and was number 47,029 cases and 1006 deaths after 1 month. Infections with SARS-CoV-2 are now widespread, and as of 10 April 2020, 1,727,602 cases have been confirmed in more than 210 countries, with 105,728 deaths.", "qid": 15, "docid": "lm9urlat", "rank": 43, "score": 0.8179008960723877}, {"content": "Title: Emerging novel coronavirus (2019-nCoV)-current scenario, evolutionary perspective based on genome analysis and recent developments Content: Coronaviruses are the well-known cause of severe respiratory, enteric and systemic infections in a wide range of hosts including man, mammals, fish, and avian. The scientific interest on coronaviruses increased after the emergence of Severe Acute Respiratory Syndrome coronavirus (SARS-CoV) outbreaks in 2002-2003 followed by Middle East Respiratory Syndrome CoV (MERS-CoV). This decade's first CoV, named 2019-nCoV, emerged from Wuhan, China, and declared as 'Public Health Emergency of International Concern' on January 30th, 2020 by the World Health Organization (WHO). As on February 4, 2020, 425 deaths reported in China only and one death outside China (Philippines). In a short span of time, the virus spread has been noted in 24 countries. The zoonotic transmission (animal-to-human) is suspected as the route of disease origin. The genetic analyses predict bats as the most probable source of 2019-nCoV though further investigations needed to confirm the origin of the novel virus. The ongoing nCoV outbreak highlights the hidden wild animal reservoir of the deadly viruses and possible threat of spillover zoonoses as well. The successful virus isolation attempts have made doors open for developing better diagnostics and effective vaccines helping in combating the spread of the virus to newer areas.", "qid": 15, "docid": "22fc1qly", "rank": 44, "score": 0.8176610469818115}, {"content": "Title: A cross-sectional comparison of epidemiological and clinical features of patients with coronavirus disease (COVID-19) in Wuhan and outside Wuhan, China Content: BACKGROUND: Coronavirus disease 2019 (COVID-19) has spread outside the initial epicenter of Wuhan. We compared cases in Guangzhou and Wuhan to illustrate potential changes in pathogenicity and epidemiological characteristics as the epidemic has progressed. METHODS: We studied 20 patients admitted to the Third Affiliated Hospital of Sun Yat-Sen University in Guangzhou, China from January 22 to February 12, 2020. Data were extracted from medical records. These cases were compared with the 99 cases, previously published in Lancet, from Wuhan Jinyintan Hospital from January 1 to January 20, 2020. RESULTS: Guangzhou patients were younger and had better prognosis than Wuhan patients. The Wuhan patients were more likely to be admitted to the ICU (23% vs 5%) and had a higher mortality rate (11% vs 0%). Cases in Guangzhou tended to be more community clustered. Diarrhea and vomiting were more common among Guangzhou patients and SARS-CoV-2 RNA was found in feces. Fecal SARA-CoV-2 RNA remained positive when nasopharyngeal swabs turned negative in some patients. CONCLUSIONS: This study indicates possible diminishing virulence of the virus in the process of transmission. Yet persistent positive RNA in feces after negative nasopharyngeal swabs suggests a possible prolonged transmission period that challenges current quarantine practices.", "qid": 15, "docid": "joabbbvf", "rank": 45, "score": 0.8176287412643433}, {"content": "Title: Stability and infectivity of coronaviruses in inanimate environments Content: Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) is a highly contagious virus that can transmit through respiratory droplets, aerosols, or contacts. Frequent touching of contaminated surfaces in public areas is therefore a potential route of SARS-CoV-2 transmission. The inanimate surfaces have often been described as a source of nosocomial infections. However, summaries on the transmissibility of coronaviruses from contaminated surfaces to induce the coronavirus disease 2019 are rare at present. This review aims to summarize data on the persistence of different coronaviruses on inanimate surfaces. The literature was systematically searched on Medline without language restrictions. All reports with experimental evidence on the duration persistence of coronaviruses on any type of surface were included. Most viruses from the respiratory tract, such as coronaviruses, influenza, SARS-CoV, or rhinovirus, can persist on surfaces for a few days. Persistence time on inanimate surfaces varied from minutes to up to one month, depending on the environmental conditions. SARS-CoV-2 can be sustained in air in closed unventilated buses for at least 30 min without losing infectivity. The most common coronaviruses may well survive or persist on surfaces for up to one month. Viruses in respiratory or fecal specimens can maintain infectivity for quite a long time at room temperature. Absorbent materials like cotton are safer than unabsorbent materials for protection from virus infection. The risk of transmission via touching contaminated paper is low. Preventive strategies such as washing hands and wearing masks are critical to the control of coronavirus disease 2019.", "qid": 15, "docid": "ou7w3zkv", "rank": 46, "score": 0.817237913608551}, {"content": "Title: Epidemiology of COVID-19 Content: It seems that coronaviruses take an important place in the 21th century history. Five of seven human coronavirus was isolated in this century. Unfortunately, last three of them entered our life with a fear of outbreak, pandemic or death. Last human coronavirus which emerged world from Wuhan China, SARS CoV-2 and its clinical expression, Coronavirus disease (COVID-19) recently taken a significant place in our daily practice. Initial reports showed that, its origin was bats. It transmitted human to human by droplet and contact routes, but some doubt about airborne, fecal or intrauterine transmission also should be removed. Its R0 value is 2.3 but it could be as high as 5.7. Its case fatality rate was 6.3, but it was different in different ages and counties, and it could be over 15%. According to early models total 10\u201312 weeks is required to control an outbreak in the community. While different countries show different daily case numbers, total number of case, case mortality rates or R0, it seems they show a similar epidemic curve. Every day we learn new data about the current outbreak. Since the outbreak is not over yet, every detail should be evaluated carefully and the updates should be followed closely to monitor the epidemiological properties of COVID-19.", "qid": 15, "docid": "w7ej6jfg", "rank": 47, "score": 0.8171022534370422}, {"content": "Title: Complete title: Codon bias analysis may be insufficient for identifying host(s) of a novel virus Content: A novel kind of coronavirus has infected more than 1, 600, 000 people, claimed over 100, 000 lives, and spread to 212 countries and territories since December 2019.(1) The virus has been named SARS\u2010CoV\u20102 (provisionally termed 2019\u2010nCoV before(2)), and the pneumonia caused by it is COVID\u201019. Though many scientists and researchers are trying to identify the animals harboring SARS\u2010CoV\u20102, the intermediate host remains under the veil. This article is protected by copyright. All rights reserved.", "qid": 15, "docid": "5tx3y16o", "rank": 48, "score": 0.8169742822647095}, {"content": "Title: BETS: The dangers of selection bias in early analyses of the coronavirus disease (COVID-19) pandemic Content: The coronavirus disease 2019 (COVID-19) has quickly grown from a regional outbreak in Wuhan, China to a global pandemic. Early estimates of the epidemic growth and incubation period of COVID-19 may have been biased due to sample selection. Using detailed case reports from 14 locations in and outside mainland China, we obtained 378 Wuhan-exported cases who left Wuhan before an abrupt travel quarantine. We developed a generative model we call BETS for four key epidemiological events---Beginning of exposure, End of exposure, time of Transmission, and time of Symptom onset (BETS)---and derived explicit formulas to correct for the sample selection. We gave a detailed illustration of why some early and highly influential analyses of the COVID-19 pandemic were severely biased. All our analyses, regardless of which subsample and model were being used, point to an epidemic doubling time of 2 to 2.5 days during the early outbreak in Wuhan. A Bayesian nonparametric analysis further suggests that about 5% of the symptomatic cases may not develop symptoms within 14 days of infection and that men may be much more likely than women to develop symptoms within 2 days of infection.", "qid": 15, "docid": "3087o3g0", "rank": 49, "score": 0.8167872428894043}, {"content": "Title: The Incubation Period of Coronavirus Disease 2019 (COVID-19) From Publicly Reported Confirmed Cases: Estimation and Application Content: BACKGROUND: A novel human coronavirus, severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), was identified in China in December 2019. There is limited support for many of its key epidemiologic features, including the incubation period for clinical disease (coronavirus disease 2019 [COVID-19]), which has important implications for surveillance and control activities. OBJECTIVE: To estimate the length of the incubation period of COVID-19 and describe its public health implications. DESIGN: Pooled analysis of confirmed COVID-19 cases reported between 4 January 2020 and 24 February 2020. SETTING: News reports and press releases from 50 provinces, regions, and countries outside Wuhan, Hubei province, China. PARTICIPANTS: Persons with confirmed SARS-CoV-2 infection outside Hubei province, China. MEASUREMENTS: Patient demographic characteristics and dates and times of possible exposure, symptom onset, fever onset, and hospitalization. RESULTS: There were 181 confirmed cases with identifiable exposure and symptom onset windows to estimate the incubation period of COVID-19. The median incubation period was estimated to be 5.1 days (95% CI, 4.5 to 5.8 days), and 97.5% of those who develop symptoms will do so within 11.5 days (CI, 8.2 to 15.6 days) of infection. These estimates imply that, under conservative assumptions, 101 out of every 10 000 cases (99th percentile, 482) will develop symptoms after 14 days of active monitoring or quarantine. LIMITATION: Publicly reported cases may overrepresent severe cases, the incubation period for which may differ from that of mild cases. CONCLUSION: This work provides additional evidence for a median incubation period for COVID-19 of approximately 5 days, similar to SARS. Our results support current proposals for the length of quarantine or active monitoring of persons potentially exposed to SARS-CoV-2, although longer monitoring periods might be justified in extreme cases. PRIMARY FUNDING SOURCE: U.S. Centers for Disease Control and Prevention, National Institute of Allergy and Infectious Diseases, National Institute of General Medical Sciences, and Alexander von Humboldt Foundation.", "qid": 15, "docid": "8anqfkmo", "rank": 50, "score": 0.816778838634491}, {"content": "Title: The Incubation Period of Coronavirus Disease 2019 (COVID-19) From Publicly Reported Confirmed Cases: Estimation and Application Content: Background: A novel human coronavirus, severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), was identified in China in December 2019. There is limited support for many of its key epidemiologic features, including the incubation period for clinical disease (coronavirus disease 2019 [COVID-19]), which has important implications for surveillance and control activities. Objective: To estimate the length of the incubation period of COVID-19 and describe its public health implications. Design: Pooled analysis of confirmed COVID-19 cases reported between 4 January 2020 and 24 February 2020. Setting: News reports and press releases from 50 provinces, regions, and countries outside Wuhan, Hubei province, China. Participants: Persons with confirmed SARS-CoV-2 infection outside Hubei province, China. Measurements: Patient demographic characteristics and dates and times of possible exposure, symptom onset, fever onset, and hospitalization. Results: There were 181 confirmed cases with identifiable exposure and symptom onset windows to estimate the incubation period of COVID-19. The median incubation period was estimated to be 5.1 days (95% CI, 4.5 to 5.8 days), and 97.5% of those who develop symptoms will do so within 11.5 days (CI, 8.2 to 15.6 days) of infection. These estimates imply that, under conservative assumptions, 101 out of every 10 000 cases (99th percentile, 482) will develop symptoms after 14 days of active monitoring or quarantine. Limitation: Publicly reported cases may overrepresent severe cases, the incubation period for which may differ from that of mild cases. Conclusion: This work provides additional evidence for a median incubation period for COVID-19 of approximately 5 days, similar to SARS. Our results support current proposals for the length of quarantine or active monitoring of persons potentially exposed to SARS-CoV-2, although longer monitoring periods might be justified in extreme cases. Primary Funding Source: U.S. Centers for Disease Control and Prevention, National Institute of Allergy and Infectious Diseases, National Institute of General Medical Sciences, and Alexander von Humboldt Foundation.", "qid": 15, "docid": "42pyo6gi", "rank": 51, "score": 0.816778838634491}, {"content": "Title: The Effects of Temperature and Relative Humidity on the Viability of the SARS Coronavirus Content: The main route of transmission of SARS CoV infection is presumed to be respiratory droplets. However the virus is also detectable in other body fluids and excreta. The stability of the virus at different temperatures and relative humidity on smooth surfaces were studied. The dried virus on smooth surfaces retained its viability for over 5 days at temperatures of 22\u201325\u00b0C and relative humidity of 40\u201350%, that is, typical air-conditioned environments. However, virus viability was rapidly lost (>3 log(10)) at higher temperatures and higher relative humidity (e.g., 38\u00b0C, and relative humidity of >95%). The better stability of SARS coronavirus at low temperature and low humidity environment may facilitate its transmission in community in subtropical area (such as Hong Kong) during the spring and in air-conditioned environments. It may also explain why some Asian countries in tropical area (such as Malaysia, Indonesia or Thailand) with high temperature and high relative humidity environment did not have major community outbreaks of SARS.", "qid": 15, "docid": "x3b6j5d0", "rank": 52, "score": 0.8166823387145996}, {"content": "Title: Evidence of person-to-person transmission within a family cluster of novel coronavirus infections, United Kingdom, February 2013. Content: In February 2013, novel coronavirus (nCoV) infection was diagnosed in an adult male in the United Kingdom with severe respiratory illness, who had travelled to Pakistan and Saudi Arabia 10 days before symptom onset. Contact tracing identified two secondary cases among family members without recent travel: one developed severe respiratory illness and died, the other an influenza-like illness. No other severe cases were identified or nCoV detected in respiratory samples among 135 contacts followed for 10 days.", "qid": 15, "docid": "v83tcvm5", "rank": 53, "score": 0.8164920806884766}, {"content": "Title: COVID-19 Surface Persistence: A Recent Data Summary and Its Importance for Medical and Dental Settings Content: Recently, due to the coronavirus pandemic, many guidelines and anti-contagion strategies continue to report unclear information about the persistence of coronavirus disease 2019 (COVID-19) in the environment. This certainly generates insecurity and fear in people, with an important psychological component that is not to be underestimated at this stage of the pandemic. The purpose of this article is to highlight all the sources currently present in the literature concerning the persistence of the different coronaviruses in the environment as well as in medical and dental settings. As this was a current study, there are still not many sources in the literature, and scientific strategies are moving towards therapy and diagnosis, rather than knowing the characteristics of the virus. Such an article could be an aid to summarize virus features and formulate new guidelines and anti-spread strategies.", "qid": 15, "docid": "6fmuh2or", "rank": 54, "score": 0.8162803649902344}, {"content": "Title: Estimating the distribution of the incubation period of 2019 novel coronavirus (COVID-19) infection between travelers to Hubei, China and non-travelers Content: Objectives: Amid the continuing spread of the novel coronavirus (COVID-19), the incubation period of COVID-19 should be regularly re-assessed as more information is available upon the increase in reported cases. The present work estimated the distribution of incubation periods of patients infected in and outside Hubei province of China. Methods: Clinical data were collected from the individual cases reported by the media as they were not fully available on the official pages of the Chinese health authorities. MLE was used to estimate the distributions of the incubation period. Results: It was found that the incubation period of patients with no travel history to Hubei was longer and more volatile. Conclusion: It is recommended that the duration of quarantine should be extended to at least 3 weeks.", "qid": 15, "docid": "ibx89gqw", "rank": 55, "score": 0.8160985708236694}, {"content": "Title: Obesity \u00ad a risk factor for increased COVID\u00ad19 prevalence, severity and lethality (Review) Content: Coronaviruses (CoVs), enveloped positive-sense RNA viruses, are a group of viruses that cause infections in the human respiratory tract, which can be characterized clinically from mild to fatal. The severe acute respiratory syndrome coronavirus 2 (SARS\u00adCoV\u00ad2) is the virus responsible. The global spread of COVID\u00ad19 can be described as the worst pandemic in humanity in the last century. To date, COVID\u00ad19 has infected more than 3,000,000 people worldwide and killed more than 200,000 people. All age groups can be infected from the virus, but more serious symptoms that can possibly result in death are observed in older people and those with underlying medical conditions such as cardiovascular and pulmonary disease. Novel data report more severe symptoms and even a negative prognosis for the obese patients. A growing body of evidence connects obesity with COVID\u00ad19 and a number of mechanisms from immune system activity attenuation to chronic inflammation are implicated. Lipid peroxidation creates reactive lipid aldehydes which in a patient with metabolic disorder and COVID\u00ad19 will affect its prognosis. Finally, pregnancy\u00adassociated obesity needs to be studied further in connection to COVID\u00ad19 as this infection could pose high risk both to pregnant women and the fetus.", "qid": 15, "docid": "q4bzy9yi", "rank": 56, "score": 0.8153712153434753}, {"content": "Title: Incubation Period and Other Epidemiological Characteristics of 2019 Novel Coronavirus Infections with Right Truncation: A Statistical Analysis of Publicly Available Case Data Content: The geographic spread of 2019 novel coronavirus (COVID-19) infections from the epicenter of Wuhan, China, has provided an opportunity to study the natural history of the recently emerged virus. Using publicly available event-date data from the ongoing epidemic, the present study investigated the incubation period and other time intervals that govern the epidemiological dynamics of COVID-19 infections. Our results show that the incubation period falls within the range of 2-14 days with 95% confidence and has a mean of around 5 days when approximated using the best-fit lognormal distribution. The mean time from illness onset to hospital admission (for treatment and/or isolation) was estimated at 3-4 days without truncation and at 5-9 days when right truncated. Based on the 95th percentile estimate of the incubation period, we recommend that the length of quarantine should be at least 14 days. The median time delay of 13 days from illness onset to death (17 days with right truncation) should be considered when estimating the COVID-19 case fatality risk.", "qid": 15, "docid": "ykofrn9i", "rank": 57, "score": 0.8150695562362671}, {"content": "Title: Far-UVC light (222 nm) efficiently and safely inactivates airborne human coronaviruses Content: A direct approach to limit airborne viral transmissions is to inactivate them within a short time of their production. Germicidal ultraviolet light, typically at 254 nm, is effective in this context but, used directly, can be a health hazard to skin and eyes. By contrast, far-UVC light (207\u2013222 nm) efficiently kills pathogens potentially without harm to exposed human tissues. We previously demonstrated that 222-nm far-UVC light efficiently kills airborne influenza virus and we extend those studies to explore far-UVC efficacy against airborne human coronaviruses alpha HCoV-229E and beta HCoV-OC43. Low doses of 1.7 and 1.2 mJ/cm(2) inactivated 99.9% of aerosolized coronavirus 229E and OC43, respectively. As all human coronaviruses have similar genomic sizes, far-UVC light would be expected to show similar inactivation efficiency against other human coronaviruses including SARS-CoV-2. Based on the beta-HCoV-OC43 results, continuous far-UVC exposure in occupied public locations at the current regulatory exposure limit (~3 mJ/cm(2)/hour) would result in ~90% viral inactivation in ~8 minutes, 95% in ~11 minutes, 99% in ~16 minutes and 99.9% inactivation in ~25 minutes. Thus while staying within current regulatory dose limits, low-dose-rate far-UVC exposure can potentially safely provide a major reduction in the ambient level of airborne coronaviruses in occupied public locations.", "qid": 15, "docid": "x7ffgtrd", "rank": 58, "score": 0.8150562047958374}, {"content": "Title: M gene evolution of canine coronavirus in naturally infected dogs. Content: Two stray pups (A and B), three and five months old, respectively, both naturally infected with canine coronavirus (CCoV), were studied for 180 days. The virus was detected intermittently in the pups' faeces by PCR for periods of 156 and 146 days, respectively. Sequence analysis of a fragment of the gene encoding the M protein revealed that the viruses detected at the onset of the infection were very similar to typical strains of CCoV, whereas from 42 days after infection in pup A and 40 days after infection in pup B the viruses had nucleotide and amino acid mutations resembling sequences in feline coronavirus.", "qid": 15, "docid": "a30ybnzf", "rank": 59, "score": 0.8150443434715271}, {"content": "Title: Incubation Period and Other Epidemiological Characteristics of 2019 Novel Coronavirus Infections with Right Truncation: A Statistical Analysis of Publicly Available Case Data Content: The geographic spread of 2019 novel coronavirus (COVID-19) infections from the epicenter of Wuhan, China, has provided an opportunity to study the natural history of the recently emerged virus. Using publicly available event-date data from the ongoing epidemic, the present study investigated the incubation period and other time intervals that govern the epidemiological dynamics of COVID-19 infections. Our results show that the incubation period falls within the range of 2\u201314 days with 95% confidence and has a mean of around 5 days when approximated using the best-fit lognormal distribution. The mean time from illness onset to hospital admission (for treatment and/or isolation) was estimated at 3\u20134 days without truncation and at 5\u20139 days when right truncated. Based on the 95th percentile estimate of the incubation period, we recommend that the length of quarantine should be at least 14 days. The median time delay of 13 days from illness onset to death (17 days with right truncation) should be considered when estimating the COVID-19 case fatality risk.", "qid": 15, "docid": "4vrqzbof", "rank": 60, "score": 0.8149222135543823}, {"content": "Title: Novel coronavirus and central nervous system. Content: An outbreak of a novel coronavirus (2019-nCoV) that emerged in Wuhan has rapidly spread throughout China and has now become a global public health concern. As of the early March, a total of 100,000 cases have been confirmed in multiple countries. Clinical characteristics of 2019-nCoV that respiratory symptoms, such as cough, are the most common.[1] This is consistent with the finding that the majority of patients are virus-positive in nasopharyngeal and oropharyngeal swabs suggesting it mainly invades and infects the respiratory system, a hypothesis supported by pathological data.[2] In addition, it has been reported that patients' stool has tested positive for 2019-nCoV, indicating that the virus could spread from the respiratory tract to the digestive tract, or that individuals could be infected via the faecal-oral route. However, the neuroinvasive potential of 2019-nCoV remains poorly understood.", "qid": 15, "docid": "o4rvq84o", "rank": 61, "score": 0.8147609233856201}, {"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": 15, "docid": "mcf0zvaf", "rank": 62, "score": 0.8145622611045837}, {"content": "Title: Neurological manifestations of patients with COVID-19: potential routes of SARS-CoV-2 neuroinvasion from the periphery to the brain Content: Coronavirus disease 2019 (COVID-19), caused by severe acute respiratory syndrome Coronavirus 2 (SARS-CoV-2), has caused a global pandemic in only 3 months. In addition to major respiratory distress, characteristic neurological manifestations are also described, indicating that SARS-CoV-2 may be an underestimated opportunistic pathogen of the brain. Based on previous studies of neuroinvasive human respiratory coronaviruses, it is proposed that after physical contact with the nasal mucosa, laryngopharynx, trachea, lower respiratory tract, alveoli epithelium, or gastrointestinal mucosa, SARS-CoV-2 can induce intrinsic and innate immune responses in the host involving increased cytokine release, tissue damage, and high neurosusceptibility to COVID-19, especially in the hypoxic conditions caused by lung injury. In some immune-compromised individuals, the virus may invade the brain through multiple routes, such as the vasculature and peripheral nerves. Therefore, in addition to drug treatments, such as pharmaceuticals and traditional Chinese medicine, non-pharmaceutical precautions, including facemasks and hand hygiene, are critically important.", "qid": 15, "docid": "z1jsowv4", "rank": 63, "score": 0.8144398331642151}, {"content": "Title: Epidemiological Characteristics of COVID-19: A Systemic Review and Meta-Analysis Content: Background: Our understanding of the corona virus disease 2019 (COVID-19) continues to evolve. However, there are many unknowns about its epidemiology. Purpose: To synthesize the number of deaths from confirmed COVID-19 cases, incubation period, as well as time from onset of COVID-19 symptoms to first medical visit, ICU admission, recovery and death of COVID-19. Data Sources: MEDLINE, Embase, and Google Scholar from December 01, 2019 through to March 11, 2020 without language restrictions as well as bibliographies of relevant articles. Study Selection: Quantitative studies that recruited people living with or died due to COVID-19. Data Extraction: Two independent reviewers extracted the data. Conflicts were resolved through discussion with a senior author. Data Synthesis: Out of 1675 non-duplicate studies identified, 57 were included. Pooled mean incubation period was 5.84 (99% CI: 4.83, 6.85) days. Pooled mean number of days from the onset of COVID-19 symptoms to first clinical visit was 4.82 (95% CI: 3.48, 6.15), ICU admission was 10.48 (95% CI: 9.80, 11.16), recovery was 17.76 (95% CI: 12.64, 22.87), and until death was 15.93 (95% CI: 13.07, 18.79). Pooled probability of COVID-19-related death was 0.02 (95% CI: 0.02, 0.03). Limitations: Studies are observational and findings are mainly based on studies that recruited patient from clinics and hospitals and so may be biased toward more severe cases. Conclusion: We found that the incubation period and lag between the onset of symptoms and diagnosis of COVID-19 is longer than other respiratory viral infections including MERS and SARS; however, the current policy of 14 days of mandatory quarantine for everyone might be too conservative. Longer quarantine periods might be more justified for extreme cases.", "qid": 15, "docid": "e3t1f0rt", "rank": 64, "score": 0.8144359588623047}, {"content": "Title: Making waves: Coronavirus detection, presence and persistence in the water environment: State of the art and knowledge needs for public health Content: The main route of transmission of the human coronaviruses (HCoVs), and presumably also of the new pandemic SARS-CoV-2, is via droplets and close contacts, however their fecal elimination also suggests the possible spread via water. A scientific literature search was thus carried out to highlight the current state of the art and knowledge gaps regarding coronavirus in water. Since 1978 only 22 studies have met the inclusion criteria, and considered heterogeneous purposes, detection methods and types of water. In vitro experiments have addressed the recovery efficiency of analytical methods, survival in different types of water and the removal efficiency of water treatments. Field studies have monitored coronaviruses in surface waters, sewage, slurry, and biosolids. Overall, at the lab scale, HCoVs or surrogates can survive for several days at 4 \u00b0C, however their persistence is lower compared with non-enveloped viruses and is strongly influenced by temperature and organic or microbial pollution. HCoVs have rarely been detected in field investigations, however may be due to the low recovery efficiency of the analytical methods. The scarcity of information on HCoV in the environment suggests that research is needed to understand the fate of these viruses in the water cycle.", "qid": 15, "docid": "vuzf3dnr", "rank": 65, "score": 0.8143807649612427}, {"content": "Title: Making Waves: Coronavirus detection, presence and persistence in the water environment: State of the art and knowledge needs for public health Content: The main route of transmission of the human coronaviruses (HCoVs), and presumably also of the new pandemic SARS-CoV-2, is via droplets and close contacts, however their fecal elimination also suggests the possible spread via water. A scientific literature search was thus carried out to highlight the current state of the art and knowledge gaps regarding coronavirus in water. Since 1978 only 22 studies have met the inclusion criteria, and considered heterogeneous purposes, detection methods and types of water. In vitro experiments have addressed the recovery efficiency of analytical methods, survival in different types of water and the removal efficiency of water treatments. Field studies have monitored coronaviruses in surface waters, sewage, slurry, and biosolids. Overall, at the lab scale, HCoVs or surrogates can survive for several days at 4 \u00b0C, however their persistence is lower compared with non-enveloped viruses and is strongly influenced by temperature and organic or microbial pollution. HCoVs have rarely been detected in field investigations, however may be due to the low recovery efficiency of the analytical methods. The scarcity of information on HCoV in the environment suggests that research is needed to understand the fate of these viruses in the water cycle.", "qid": 15, "docid": "c17eijdt", "rank": 66, "score": 0.8143807649612427}, {"content": "Title: Human respiratory coronaviruses : neuroinvasive, neurotropic and potentially neurovirulent pathogens. Content: In humans, viral infections of the respiratory tract are a leading cause of morbidity and mortality worldwide. Among the various respiratory viruses, coronaviruses are important ubiquitous pathogens of humans and animals. Since the late 1960's, human coronaviruses (HCoV) are recognized pathogens of the upper respiratory tract, being mainly associated with mild pathologies such as the common cold. However, in vulnerable populations, (newborns, infants, the elderly and immune-compromised individuals), they can affect the lower respiratory tract, leading to pneumonia, exacerbations of asthma, respiratory distress syndrome or even severe acute respiratory syndrome (SARS). For almost three decades now, the scientific literature has also demonstrated that HCoV are neuroinvasive and neurotropic: neurons are often the target cell in the central nervous system (CNS), inducing neurodegeneration and eventually death. Moreover, HCoV can contribute to an overactivation of the immune system that could lead to autoimmunity in the CNS of susceptible individuals. Given all these properties, it has been suggested that HCoV could be associated with the triggering or the exacerbation of human neurological diseases for which the etiology remains unknown or poorly understood.", "qid": 15, "docid": "9yysz7n8", "rank": 67, "score": 0.814355731010437}, {"content": "Title: A cross-sectional comparison of epidemiological and clinical features of patients with coronavirus disease (COVID-19) in Wuhan and outside Wuhan, China Content: Abstract Background Coronavirus disease 2019 (COVID-19) has spread outside the initial epicenter of Wuhan. We compared cases in Guangzhou and Wuhan to illustrate potential changes in pathogenicity and epidemiological characteristics as the epidemic has progressed. Methods We studied 20 patients admitted to the Third Affiliated Hospital of Sun Yat-Sen University in Guangzhou, China from January 22 to February 12, 2020. Data were extracted from medical records. These cases were compared with the 99 cases, previously published in Lancet, from Wuhan Jinyintan Hospital from January 1 to January 20, 2020. Results Guangzhou patients were younger and had better prognosis than Wuhan patients. The Wuhan patients were more likely to be admitted to the ICU (23% vs 5%) and had a higher mortality rate (11% vs 0%). Cases in Guangzhou tended to be more community clustered. Diarrhea and vomiting were more common among Guangzhou patients and SARS-CoV-2 RNA was found in feces. Fecal SARA-CoV-2 RNA remained positive when nasopharyngeal swabs turned negative in some patients. Conclusions This study indicates possible diminishing virulence of the virus in the process of transmission. Yet persistent positive RNA in feces after negative nasopharyngeal swabs suggests a possible prolonged transmission period that challenges current quarantine practices.", "qid": 15, "docid": "20jf7jum", "rank": 68, "score": 0.8142217397689819}, {"content": "Title: Far-UVC light (222 nm) efficiently and safely inactivates airborne human coronaviruses Content: A direct approach to limit airborne viral transmissions is to inactivate them within a short time of their production. Germicidal ultraviolet light, typically at 254 nm, is effective in this context but, used directly, can be a health hazard to skin and eyes. By contrast, far-UVC light (207-222 nm) efficiently kills pathogens potentially without harm to exposed human tissues. We previously demonstrated that 222-nm far-UVC light efficiently kills airborne influenza virus and we extend those studies to explore far-UVC efficacy against airborne human coronaviruses alpha HCoV-229E and beta HCoV-OC43. Low doses of 1.7 and 1.2 mJ/cm2 inactivated 99.9% of aerosolized coronavirus 229E and OC43, respectively. As all human coronaviruses have similar genomic sizes, far-UVC light would be expected to show similar inactivation efficiency against other human coronaviruses including SARS-CoV-2. Based on the beta-HCoV-OC43 results, continuous far-UVC exposure in occupied public locations at the current regulatory exposure limit (~3 mJ/cm2/hour) would result in ~90% viral inactivation in ~8 minutes, 95% in ~11 minutes, 99% in ~16 minutes and 99.9% inactivation in ~25 minutes. Thus while staying within current regulatory dose limits, low-dose-rate far-UVC exposure can potentially safely provide a major reduction in the ambient level of airborne coronaviruses in occupied public locations.", "qid": 15, "docid": "imxcqf3o", "rank": 69, "score": 0.8141231536865234}, {"content": "Title: Obesity - a risk factor for increased COVID-19 prevalence, severity and lethality Content: Coronaviruses (CoVs), enveloped positive-sense RNA viruses, are a group of viruses that cause infections in the human respiratory tract, which can be characterized clinically from mild to fatal. The severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) is the virus responsible. The global spread of COVID-19 can be described as the worst pandemic in humanity in the last century. To date, COVID-19 has infected more than 3,000,000 people worldwide and killed more than 200,000 people. All age groups can be infected from the virus, but more serious symptoms that can possibly result in death are observed in older people and those with underlying medical conditions such as cardiovascular and pulmonary disease. Novel data report more severe symptoms and even a negative prognosis for the obese patients. A growing body of evidence connects obesity with COVID-19 and a number of mechanisms from immune system activity attenuation to chronic inflammation are implicated. Lipid peroxidation creates reactive lipid aldehydes which in a patient with metabolic disorder and COVID-19 will affect its prognosis. Finally, pregnancy-associated obesity needs to be studied further in connection to COVID-19 as this infection could pose high risk both to pregnant women and the fetus.", "qid": 15, "docid": "y8wlbik5", "rank": 70, "score": 0.8141209483146667}, {"content": "Title: Case Report: Viral Shedding for 60 Days in a Woman with COVID-19 Content: Novel coronavirus disease (COVID-19) caused by severe acute respiratory syndrome-coronavirus-2 (SARS-CoV-2) has become a public health emergency of international concern. This was first noted in Wuhan, Hubei Province, China, and since then has become widespread globally. We report a 71-year-old woman with documented viral shedding (based on reverse transcription\u2013polymerase chain reaction (RT-PCR) testing) of SARS-CoV-2 for 60 days from the onset of symptoms (55 days from her first positive test and 36 days after complete resolution of symptoms). This is to our knowledge the longest duration of viral shedding reported to date. This case demonstrates that viral shedding after COVID-19 diagnosis can be prolonged.", "qid": 15, "docid": "vvzga2tm", "rank": 71, "score": 0.814014196395874}, {"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": 72, "score": 0.8139050006866455}, {"content": "Title: Estimated Inactivation of Coronaviruses by Solar Radiation With Special Reference to COVID-19 Content: Using a model developed for estimating solar inactivation of viruses of biodefense concerns, we calculated the expected inactivation of SARS-CoV-2 virus, cause of COVID-19 pandemic, by artificial UVC and by solar ultraviolet radiation in several cities of the world during different times of the year. The UV sensitivity estimated here for SARS-CoV-2 is compared with those reported for other ssRNA viruses, including influenza A virus. The results indicate that SARS-CoV-2 aerosolized from infected patients and deposited on surfaces could remain infectious outdoors for considerable time during the winter in many temperate-zone cities, with continued risk for re-aerosolization and human infection. Conversely, the presented data indicate that SARS-CoV-2 should be inactivated relatively fast (faster than influenza A) during summer in many populous cities of the world, indicating that sunlight should have a role in the occurrence, spread rate, and duration of coronavirus pandemics.", "qid": 15, "docid": "7emv2bao", "rank": 73, "score": 0.8138128519058228}, {"content": "Title: COVID-19 in a patient with long-term use of glucocorticoids: A study of a familial cluster Content: Clusters of patients with novel coronavirus disease 2019 (COVID-19) have been successively reported globally. Studies show clear person-to-person transmission. The average incubation period is 2-14 days, and mostly 3-7 days. However, in some patients, this period may be longer. Here, we report a familial cluster of COVID-19 where a 47-year-old woman with long-term use of glucocorticoids did not develop any symptoms within the 14-day quarantine period but was confirmed with COVID-19 by tested positive of antibody on day 40 after she left Wuhan. Almost at the same time, her father and sister were diagnosed with COVID-19. The results suggest that the long-term use of glucocorticoids might cause atypical infections, a long incubation period, and extra transmission of COVID-19.", "qid": 15, "docid": "bnlqlx1y", "rank": 74, "score": 0.81376051902771}, {"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": 15, "docid": "rhpjosih", "rank": 75, "score": 0.813742995262146}, {"content": "Title: Virus survival in evaporated saliva microdroplets deposited on inanimate surfaces Content: The novel coronavirus respiratory syndrome (COVID-19) has now spread worldwide. The relative contribution of viral transmission via fomites is still unclear. SARS-CoV-2 has been shown to survive on inanimate surfaces for several days, yet the factors that determine its survival on surfaces are not well understood. Here we combine microscopy imaging with virus viability assays to study survival of three bacteriophages suggested as good models for human respiratory pathogens: the enveloped Phi6 (a surrogate for SARS-CoV-2), and the non-enveloped PhiX174 and MS2. We measured virus viability in human saliva microdroplets, SM buffer, and water following deposition on glass surfaces at various relative humidities (RH). Although saliva microdroplets dried out rapidly at all tested RH levels (unlike SM that remained hydrated at RH \u2265 57%), survival of all three viruses in dry saliva microdroplets was significantly higher than in water or SM. Thus, RH and hydration conditions are not sufficient to explain virus survival, indicating that the suspended medium, and association with saliva components in particular, likely affect physicochemical properties that determine virus survival. The observed high virus survival in dry saliva deposited on surfaces, under a wide range of RH levels, can have profound implications for human public health, specifically the COVID-19 pandemic.", "qid": 15, "docid": "atisrhas", "rank": 76, "score": 0.8136852383613586}, {"content": "Title: Studies on the survival of canine coronavirus under different environmental conditions Content: Abstract Canine coronavirus (CCV) is a common faecal agent which is difficult to isolate. This study shows CCV to survive well at temperatures below \u221220\u00b0C but not at temperatures above 4\u00b0C. The presence of faecal material markedly reduced CCV survival times at temperatures ranging from 20\u00b0C to \u221270\u00b0C. Thus, it is suggested that diagnostic faecal material should be diluted 1:10 (w/v) with growth medium and examined at the earliest opportunity.", "qid": 15, "docid": "fpckqvr5", "rank": 77, "score": 0.813501238822937}, {"content": "Title: Virological assessment of hospitalized patients with COVID-2019. Content: Coronavirus disease 2019 (COVID-19) is an acute respiratory tract infection that emerged in late 20191,2. Initial outbreaks in China involved 13.8% cases with severe, and 6.1% with critical courses3. This severe presentation corresponds to the usage of a virus receptor that is expressed predominantly in the lung2,4. By causing an early onset of severe symptoms, this same receptor tropism is thought to have determined pathogenicity, but also aided the control, of severe acute respiratory syndrome (SARS) in 20035. However, there are reports of COVID-19 cases with mild upper respiratory tract symptoms, suggesting the potential for pre- or oligosymptomatic transmission6-8. There is an urgent need for information on body site-specific virus replication, immunity, and infectivity. Here we provide a detailed virological analysis of nine cases, providing proof of active virus replication in upper respiratory tract tissues. Pharyngeal virus shedding was very high during the first week of symptoms (peak at 7.11 \u00d7 108 RNA copies per throat swab, day 4). Infectious virus was readily isolated from throat- and lung-derived samples, but not from stool samples, in spite of high virus RNA concentration. Blood and urine never yielded virus. Active replication in the throat was confirmed by viral replicative RNA intermediates in throat samples. Sequence-distinct virus populations were consistently detected in throat and lung samples from the same patient, proving independent replication. Shedding of viral RNA from sputum outlasted the end of symptoms. Seroconversion occurred after 7 days in 50% of patients (14 days in all), but was not followed by a rapid decline in viral load. COVID-19 can present as a mild upper respiratory tract illness. Active virus replication in the upper respiratory tract puts the prospects of COVID-19 containment in perspective.", "qid": 15, "docid": "7kxi7px1", "rank": 78, "score": 0.8134571313858032}, {"content": "Title: Aerosol and surface stability of HCoV-19 (SARS-CoV-2) compared to SARS-CoV-1 Content: A novel human coronavirus, now named severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2, referred to as HCoV-19 here) that emerged in Wuhan, China in late 2019 is now causing a pandemic. Here, we analyze the aerosol and surface stability of HCoV-19 and compare it with SARS-CoV-1, the most closely related human coronavirus.2 We evaluated the stability of HCoV-19 and SARS-CoV-1 in aerosols and on different surfaces and estimated their decay rates using a Bayesian regression model", "qid": 15, "docid": "hiw576og", "rank": 79, "score": 0.8133193254470825}, {"content": "Title: Estimated Inactivation of Coronaviruses by Solar Radiation With Special Reference to COVID-19 Content: Using a model developed for estimating solar inactivation of viruses of biodefense concerns, we calculated the expected inactivation of SARS-CoV-2 virus, cause of COVID-19 pandemic, by artificial UVC and by solar ultraviolet radiation in several cities of the world during different times of the year. The UV sensitivity estimated here for SARS-CoV-2 is compared with those reported for other ssRNA viruses, including influenza A virus. The results indicate that SARS-CoV-2 aerosolized from infected patients and deposited on surfaces could remain infectious outdoors for considerable time during the winter in many temperate-zone cities, with continued risk for re-aerosolization and human infection. Conversely, the presented data indicate that SARS-CoV-2 should be inactivated relatively fast (faster than influenza A) during summer in many populous cities of the world, indicating that sunlight should have a role in the occurrence, spread rate and duration of coronavirus pandemics.", "qid": 15, "docid": "4xijeti6", "rank": 80, "score": 0.8133133053779602}, {"content": "Title: Coronavirus infections: Epidemiological, clinical and immunological features and hypotheses Content: Coronaviruses (CoVs) are a large family of enveloped, positive-strand RNA viruses Four human CoVs (HCoVs), the non-severe acute respiratory syndrome (SARS)-like HCoVs (namely HCoV 229E, NL63, OC43, and HKU1), are globally endemic and account for a substantial fraction of upper respiratory tract infections Non-SARS-like CoV can occasionally produce severe diseases in frail subjects but do not cause any major (fatal) epidemics In contrast, SARS like CoVs (namely SARS-CoV and Middle-East respiratory syndrome coronavirus, MERS-CoV) can cause intense short-lived fatal outbreaks The current epidemic caused by the highly contagious SARS-CoV-2 and its rapid spread globally is of major concern There is scanty knowledge on the actual pandemic potential of this new SARS-like virus It might be speculated that SARS-CoV-2 epidemic is grossly underdiagnosed and that the infection is silently spreading across the globe with two consequences: (i) clusters of severe infections among frail subjects could haphazardly occur linked to unrecognized index cases;(ii) the current epidemic could naturally fall into a low-level endemic phase when a significant number of subjects will have developed immunity Understanding the role of paucisymptomatic subjects and stratifying patients according to the risk of developing severe clinical presentations is pivotal for implementing reasonable measures to contain the infection and to reduce its mortality Whilst the future evolution of this epidemic remains unpredictable, classic public health strategies must follow rational patterns The emergence of yet another global epidemic underscores the permanent challenges that infectious diseases pose and underscores the need for global cooperation and preparedness, even during inter-epidemic periods", "qid": 15, "docid": "syt4r964", "rank": 81, "score": 0.8132634162902832}, {"content": "Title: Case Report: Viral Shedding for 60 Days in a Woman with COVID-19 Content: Novel coronavirus disease (COVID-19) caused by severe acute respiratory syndrome-coronavirus-2 (SARS-CoV-2) has become a public health emergency of international concern. This was first noted in Wuhan, Hubei Province, China, and since then has become widespread globally. We report a 71-year-old woman with documented viral shedding (based on reverse transcription-polymerase chain reaction (RT-PCR) testing) of SARS-CoV-2 for 60 days from the onset of symptoms (55 days from her first positive test and 36 days after complete resolution of symptoms). This is to our knowledge the longest duration of viral shedding reported to date. This case demonstrates that viral shedding after COVID-19 diagnosis can be prolonged.", "qid": 15, "docid": "1vba9l42", "rank": 82, "score": 0.8132369518280029}, {"content": "Title: The 2019 coronavirus: Learning curves, lessons, and the weakest link Content: In the space of just six weeks, a new coronavirus, from a family that historically was not viewed as a global health concern, has become daily headline news around the globe. The 21st century marked its arrival with the emergence of three previously unknown coronaviruses. SARS-CoV (severe acute respiratory syndrome coronavirus) was recognized in November 2002 [1, 2], MERS-CoV (Middle East respiratory syndrome coronavirus) in June 2012 [3, 4], and 2019-nCoV in December 2019 [5]. Previously, human coronaviruses, known since the 1960s, were viewed as being only marginally relevant to the clinic, except for infants, the elderly, and immunocompromised individuals [1, 6, 7].", "qid": 15, "docid": "qp13h0un", "rank": 83, "score": 0.813146710395813}, {"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": 15, "docid": "xkzvzonj", "rank": 84, "score": 0.8130673170089722}, {"content": "Title: Murine encephalitis caused by HCoV-OC43, a human coronavirus with broad species specificity, is partly immune-mediated Content: Abstract The human coronavirus HCoV-OC43 causes a significant fraction of upper respiratory tract infections. Most coronaviruses show a strong species specificity, although the SARS-Coronavirus crossed species from palm civet cats to infect humans. Similarly, HCoV-OC43, likely a member of the same coronavirus group as SARS-CoV, readily crossed the species barrier as evidenced by its rapid adaptation to the murine brain [McIntosh, K., Becker, W.B., Chanock, R.M., 1967. Growth in suckling-mouse brain of \u201cIBV-like\u201d viruses from patients with upper respiratory tract disease. Proc Natl Acad Sci U.S.A. 58, 2268\u201373]. Herein, we investigated two consequences of this plasticity in species tropism. First, we showed that HCoV-OC43 was able to infect cells from a large number of mammalian species. Second, we showed that virus that was passed exclusively in suckling mouse brains was highly virulent and caused a uniformly fatal encephalitis in adult mice. The surface glycoprotein is a major virulence factor in most coronavirus infections. We identified three changes in the HCoV-OC43 surface glycoprotein that correlated with enhanced neurovirulence in mice; these were located in the domain of the protein responsible for binding to host cells. These data suggest that some coronaviruses, including HCoV-OC43 and SARS-CoV, readily adapt to growth in cells from heterologous species. This adaptability has facilitated the isolation of HCoV-OC43 viral variants with markedly differing abilities to infect animals and tissue culture cells.", "qid": 15, "docid": "vuvgi8xx", "rank": 85, "score": 0.8128838539123535}, {"content": "Title: Factors affecting stability and infectivity of SARS-CoV-2 Content: BACKGROUND: In late 2019, a novel human coronavirus, SARS-CoV-2, emerged in Wuhan, China. This virus has caused a global pandemic involving more than 200 countries. SARS-CoV-2 is highly adapted to humans and readily transmits from person-to-person. AIM: The aim of this study was to investigate the infectivity of SARS-CoV-2 under various environmental factors, disinfectants and different pH conditions. The efficacy of a variety of laboratory virus inactivation methods and home disinfectants against SARS-CoV-2 were investigated. METHODS: The residual virus in dried form or in solution was titrated on Vero E6 cell line at day 0, 1, 3, 5, and 7 after incubation at different temperatures. The viability of virus was determined after treatment with different disinfectants and pH solutions at room temperature (20\u223c25(o)C). FINDINGS: SARS-CoV-2 was able to retain viability for 3-5 days in dried form or 7 days in solution at room temperature. SARS-CoV-2 could be detected under a wide range of pH conditions from pH4 to pH11 for several days and 1 to 2 days in stool at room temperature but lost 5 logs of infectivity. A variety of commonly used disinfectants and laboratory inactivation procedures were found to reduce viral viability effectively. CONCLUSION: This study demonstrates the stability of SARS-CoV-2 on environmental surfaces and raises the possibility of faecal-oral transmission. Commonly used fixatives, nucleic acid extraction methods and heat inactivation were found to significantly reduce viral infectivity that could ensure hospital and laboratory safety during the COVID-19 pandemic.", "qid": 15, "docid": "kngf6qpe", "rank": 86, "score": 0.8128769397735596}, {"content": "Title: Factors affecting stability and infectivity of SARS-CoV-2 Content: BACKGROUND: In late 2019, a novel human coronavirus, SARS-CoV-2, emerged in Wuhan, China. This virus has caused a global pandemic involving more than 200 countries. SARS-CoV-2 is highly adapted to humans and readily transmits from person-to-person. AIM: The aim of this study was to investigate the infectivity of SARS-CoV-2 under various environmental factors, disinfectants and different pH conditions. The efficacy of a variety of laboratory virus inactivation methods and home disinfectants against SARS-CoV-2 were investigated. METHODS: The residual virus in dried form or in solution was titrated on Vero E6 cell line at day 0, 1, 3, 5, and 7 after incubation at different temperatures. The viability of virus was determined after treatment with different disinfectants and pH solutions at room temperature (20\u00e2\u0088\u00bc25oC). FINDINGS: SARS-CoV-2 was able to retain viability for 3-5 days in dried form or 7 days in solution at room temperature. SARS-CoV-2 could be detected under a wide range of pH conditions from pH4 to pH11 for several days and 1 to 2 days in stool at room temperature but lost 5 logs of infectivity. A variety of commonly used disinfectants and laboratory inactivation procedures were found to reduce viral viability effectively. CONCLUSION: This study demonstrates the stability of SARS-CoV-2 on environmental surfaces and raises the possibility of faecal-oral transmission. Commonly used fixatives, nucleic acid extraction methods and heat inactivation were found to significantly reduce viral infectivity that could ensure hospital and laboratory safety during the COVID-19 pandemic.", "qid": 15, "docid": "eke4f5fn", "rank": 87, "score": 0.8127458095550537}, {"content": "Title: Epidemiology of COVID-19 Content: It seems that coronaviruses take an important place in the 21th century history. Five of seven human coronavirus was isolated in this century. Unfortunately, last three of them entered our life with a fear of outbreak, pandemic or death. Last human coronavirus which emerged world from Wuhan China, SARS CoV-2 and its clinical expression, Coronavirus disease (COVID-19) recently taken a significant place in our daily practice. Initial reports showed that, its origin was bats. It transmitted human to human by droplet and contact routes, but some doubt about airborne, fecal or intrauterine transmission also should be removed. Its R0 value is 2.3 but it could be as high as 5.7. Its case fatality rate was 6.3, but it was different in different ages and counties, and it could be over 15%. According to early models total 10\u00ad12 weeks is required to control an outbreak in the community. While different countries show different daily case numbers, total number of case, case mortality rates or R0, it seems they show a similar epidemic curve. Every day we learn new data about the current outbreak. Since the outbreak is not over yet, every detail should be evaluated carefully and the updates should be followed closely to monitor the epidemiological properties of COVID-19.", "qid": 15, "docid": "jg20ouix", "rank": 88, "score": 0.8127025365829468}, {"content": "Title: COVID-19 and animals: What do we know? Content: Coronaviruses, which were generally considered harmless to humans before 2003, have appeared again with a pandemic threatening the world since December 2019 after the epidemics of SARS and MERS. It is known that transmission from person to person is the most important way to spread. However, due to the widespread host diversity, a detailed examination of the role of animals in this pandemic is essential to effectively fight against the outbreak. Although coronavirus infections in pets are known to be predominantly related to the gastrointestinal tract, it has been observed that there are human-to-animal transmissions in this outbreak and some animals have similar symptoms to humans. Although animal-to-animal transmission has been shown to be possible, there is no evidence of animal-to-human transmission.", "qid": 15, "docid": "hbs9inah", "rank": 89, "score": 0.8125942945480347}, {"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": 15, "docid": "mhytn634", "rank": 90, "score": 0.8125649690628052}, {"content": "Title: Coronaviruses and SARS-COV-2 Content: Coronaviruses (CoVs) cause a broad spectrum of diseases in domestic and wild animals, poultry, and rodents, ranging from mild to severe enteric, respiratory, and systemic disease, and also cause the common cold or pneumonia in humans. Seven coronavirus species are known to cause human infection, 4 of which, HCoV 229E, HCoV NL63, HCoV HKU1 and HCoV OC43, typically cause cold symptoms in immunocompetent individuals. The others namely SARS-CoV (severe acute respiratory syndrome coronavirus), MERS-CoV (Middle East respiratory syndrome coronavirus) were zoonotic in origin and cause severe respiratory illness and fatalities. On 31 December 2019, the existence of patients with pneumonia of an unknown aetiology was reported to WHO by the national authorities in China. This virus was officially identified by the coronavirus study group as severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), and the present outbreak of a coronavirus-associated acute respiratory disease was labelled coronavirus disease 19 (COVID-19). COVID-19\u2019s first cases were seen in Turkey on March 10, 2020 and was number 47,029 cases and 1006 deaths after 1 month. Infections with SARS-CoV-2 are now widespread, and as of 10 April 2020, 1,727,602 cases have been confirmed in more than 210 countries, with 105,728 deaths.", "qid": 15, "docid": "gjdlp10q", "rank": 91, "score": 0.8124958276748657}, {"content": "Title: Transmission and risk factors of OF COVID-19 Content: SARS-CoV-2, the virus that causes COVID-19, is transmitted through respiratory secretions and saliva. The virus can also live for short periods of time (1 to several hours) on fomites such as doorknobs, handrails, and tables. Aerosolization of the virus can occur during procedures including bronchoscopy, endotracheal intubation, and administration of nebulized treatments. Asymptomatic shedding of the virus does occur and may account for up to 60% of cases. Risk factors for a more severe course of COVID-19 include age 65 and older, living in a nursing home or long term care facility, chronic lung disease, and others.", "qid": 15, "docid": "eimqd5b9", "rank": 92, "score": 0.8124353885650635}, {"content": "Title: Transmission and risk factors of OF COVID-19. Content: SARS-CoV-2, the virus that causes COVID-19, is transmitted through respiratory secretions and saliva. The virus can also live for short periods of time (1 to several hours) on fomites such as doorknobs, handrails, and tables. Aerosolization of the virus can occur during procedures including bronchoscopy, endotracheal intubation, and administration of nebulized treatments. Asymptomatic shedding of the virus does occur and may account for up to 60% of cases. Risk factors for a more severe course of COVID-19 include age 65 and older, living in a nursing home or long term care facility, chronic lung disease, and others.", "qid": 15, "docid": "l1nvnvkg", "rank": 93, "score": 0.8124353885650635}, {"content": "Title: Human coronavirus reinfection dynamics: lessons for SARS-CoV-2 Content: In the current SARS-CoV-2 pandemic a key unsolved question is the quality and duration of acquired immunity in recovered individuals. This is crucial to solve, however SARS-CoV-2 has circulated for under five months, precluding a direct study. We therefore monitored 10 subjects over a time span of 35 years (1985-2020), providing a total of 2473 follow up person-months, and determined a) their antibody levels following infection by any of the four seasonal human coronaviruses, and b) the time period after which reinfections by the same virus can occur. An alarmingly short duration of protective immunity to coronaviruses was found by both analyses. We saw frequent reinfections at 12 months post-infection and a substantial reduction in antibody levels as soon as 6 months post-infection.", "qid": 15, "docid": "u5nxm9tu", "rank": 94, "score": 0.8123726844787598}, {"content": "Title: [The preliminary analysis on the characteristics of the cluster for the Corona Virus Disease]. Content: Since December 2019, Corona Virus Disease (COVID-19), a new emerging infection disease occurred in Wuhan, has spread in 27 countries and regions. The clusters of many cases were reported with the epidemic progresses. We collected currently available information for 377 COVID-19 clusters (1 719 cases), excluded the hospital clusters and Hubei cases, during the period from January 1, 2020 to February 20, 2020. There were 297 family clusters (79%), case median 4; 39 clusters of dining (10%), case median 5; 23 clusters of shopping malls or supermarkets (6%), case median 13; 12 clusters of work units (3%), case median 6, and 6 clusters of transportation. We selected 325 cases to estimate the incubation period and found its range is 1 to 20 days, median was 7 days, and mode was 4 days. The analysis of the epidemic situation in a department store in China indicates that there is a possibility of patients as the source of infection during the incubation period of the epidemic. From February 5, 2020 to February 21, 2020, 634 persons were infected in the Diamond Princess Liner. All persons are susceptible to SARS-CoV-2. The older, patients during the incubation period and the worse environment may be the cause of the cases rising. The progress of the two typical outbreaks clearly demonstrates the spread of the early cases in Wuhan. Whatever happens, screening and isolating close contacts remains essential except for clinical treatment during the epidemic. Especially for the healthy people in the epidemic area, isolation is the key.", "qid": 15, "docid": "q7rnui5i", "rank": 95, "score": 0.8122040033340454}, {"content": "Title: The impact of the SARS\u2010CoV\u20102 outbreak on the safety and availability of blood transfusions in Italy Content: Coronaviruses are enveloped single-stranded RNA viruses belonging to the family of Coronaviridae. While initial research focused on their ability to cause enzootic infections, infections which have emerged in the past two decades demonstrate their ability to cross the species barrier and infect humans [1,2]. The ensuing epidemics have included Severe Acute Respiratory Syndrome (SARS) in 2002 and the more recent Middle East Respiratory Syndrome (MERS) in 2012, and have resulted in severe disease burden, mortality and economic disruption [3]. A novel flu-like coronavirus, emerging towards the end of 2019 and subsequently named SARS-CoV-2, has been associated with an epidemic initially focused in Wuhan, China.", "qid": 15, "docid": "7imgvale", "rank": 96, "score": 0.8120265007019043}, {"content": "Title: Survival characteristics of airborne human coronavirus 229E. Content: The survival of airborne human coronavirus 229E (HCV/229E) was studied under different conditions of temperature (20 +/- 1 degree C and 6 +/- 1 degree C) and low (30 +/- 5%), medium (50 +/- 5%) or high (80 +/- 5%) relative humidities (RH). At 20 +/- 1 degree C, aerosolized HCV/229E was found to survive best at 50% RH with a half-life of 67.33 +/- 8.24 h while at 30% RH the virus half-life was 26.76 +/- 6.21 h. At 50% RH nearly 20% infectious virus was still detectable at 6 days. High RH at 20 +/- 1 degree C, on the other hand, was found to be the least favourable to the survival of aerosolized virus and under these conditions the virus half-life was only about 3 h; no virus could be detected after 24 h in aerosol. At 6 +/- 1 degree C, in either 50% or 30% RH conditions, the survival of HCV/229E was significantly enhanced, with the decay pattern essentially similar to that seen at 20 +/- 1 degree C. At low temperature and high RH (80%), however, the survival pattern was completely reversed, with the HCV/229E half-life increasing to 86.01 +/- 5.28 h, nearly 30 times that found at 20 +/- 1 degree C and high RH. Although optimal survival at 6 degree C still occurred at 50% RH, the pronounced stabilizing effect of low temperature on the survival of HCV/229E at high RH indicates that the role of the environment on the survival of viruses in air may be more complex and significant than previously thought.", "qid": 15, "docid": "oi7karvd", "rank": 97, "score": 0.8119339346885681}, {"content": "Title: Molecular and serological investigation of 2019-nCoV infected patients: implication of multiple shedding routes Content: In December 2019, a novel coronavirus (2019-nCoV) caused an outbreak in Wuhan, China, and soon spread to other parts of the world. It was believed that 2019-nCoV was transmitted through respiratory tract and then induced pneumonia, thus molecular diagnosis based on oral swabs was used for confirmation of this disease. Likewise, patient will be released upon two times of negative detection from oral swabs. However, many coronaviruses can also be transmitted through oral-fecal route by infecting intestines. Whether 2019-nCoV infected patients also carry virus in other organs like intestine need to be tested. We conducted investigation on patients in a local hospital who were infected with this virus. We found the presence of 2019-nCoV in anal swabs and blood as well, and more anal swab positives than oral swab positives in a later stage of infection, suggesting shedding and thereby transmitted through oral-fecal route. We also showed serology test can improve detection positive rate thus should be used in future epidemiology. Our report provides a cautionary warning that 2019-nCoV may be shed through multiple routes.", "qid": 15, "docid": "zztydksw", "rank": 98, "score": 0.8119176626205444}, {"content": "Title: Thromboinflammation and the hypercoagulability of COVID-19. Content: The pathogenic coronavirus has been wreaking havoc worldwide since January. Infection with SARS-CoV-2 is problematic as no one has prior immunity, and no specific antiviral treatments are available. While many people with COVID-19 develop mild to moderate symptoms, some develop profound seemingly unchecked inflammatory responses leading to acute lung injury and hypoxemic respiratory failure, the most common cause for death.", "qid": 15, "docid": "svwkcuxf", "rank": 99, "score": 0.8118995428085327}, {"content": "Title: Coronaviruses: Molecular Biology Content: Coronaviruses (CoVs) are enveloped, positive-strand RNA viruses with characteristic spike glycoproteins that project outward like the rays of the sun (corona \u2013 Latin for \u2018crown\u2019), when visualized by electron microscopy. CoV are classified, together with the toroviruses, in the family Coronaviridae and the order Nidovirales. All nidoviruses have a common genome organization and generate a nested set (nido \u2013 Latin for \u2018nest\u2019) of 3\u2032 co-terminal mRNAs. CoVs have been isolated from a variety of species, including birds, livestock, domestic animals, and humans. CoV infections can cause respiratory, gastrointestinal, and neurologic disease, depending on the strain of the virus and the site of infection. Importantly, CoVs have been shown to cross species barriers and have emerged from animal reservoirs to infect humans and cause severe disease. The CoV responsible for an outbreak of severe acute respiratory disease (SARS-CoV) in 2002\u201303 likely originated as a bat coronavirus which, during replication in an intermediate host (such as the palm civet), evolved to be able to infect humans efficiently. SARS-CoV infected over 8000 people with approximately 10% mortality rate. The SARS-CoV outbreak was controlled by public health measures alone. However, emergence or re-emergence of CoV from animal reservoirs is a potential concern for public health.", "qid": 15, "docid": "tktqlfgd", "rank": 100, "score": 0.8118120431900024}]}
{"query": "how long does coronavirus remain stable  on surfaces?", "hits": [{"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": 1, "score": 0.8942448496818542}, {"content": "Title: Increasing Temperature and Relative Humidity Accelerates Inactivation of SARS-CoV-2 on Surfaces Content: Coronavirus disease 2019 (COVID-19) was first identified in China in late 2019 and is caused by newly identified severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). Previous studies had reported the stability of SARS-CoV-2 in cell culture media and deposited onto surfaces under a limited set of environmental conditions. Here, we broadly investigated the effects of relative humidity, temperature, and droplet size on the stability of SARS-CoV-2 in a simulated clinically relevant matrix dried on nonporous surfaces. The results show that SARS-CoV-2 decayed more rapidly when either humidity or temperature was increased but that droplet volume (1 to 50 \u00b5l) and surface type (stainless steel, plastic, or nitrile glove) did not significantly impact decay rate. At room temperature (24\u00b0C), virus half-life ranged from 6.3 to 18.6 h depending on the relative humidity but was reduced to 1.0 to 8.9 h when the temperature was increased to 35\u00b0C. These findings suggest that a potential for fomite transmission may persist for hours to days in indoor environments and have implications for assessment of the risk posed by surface contamination in indoor environments.IMPORTANCE Mitigating the transmission of SARS-CoV-2 in clinical settings and public spaces is critically important to reduce the number of COVID-19 cases while effective vaccines and therapeutics are under development. SARS-CoV-2 transmission is thought to primarily occur through direct person-to-person transfer of infectious respiratory droplets or through aerosol-generating medical procedures. However, contact with contaminated surfaces may also play a significant role. In this context, understanding the factors contributing to SARS-CoV-2 persistence on surfaces will enable a more accurate estimation of the risk of contact transmission and inform mitigation strategies. To this end, we have developed a simple mathematical model that can be used to estimate virus decay on nonporous surfaces under a range of conditions and which may be utilized operationally to identify indoor environments in which the virus is most persistent.", "qid": 16, "docid": "e2paoo2m", "rank": 2, "score": 0.8759937286376953}, {"content": "Title: Increasing Temperature and Relative Humidity Accelerates Inactivation of SARS-CoV-2 on Surfaces Content: Coronavirus disease 2019 (COVID-19) was first identified in China in late 2019 and is caused by newly identified severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). Previous studies had reported the stability of SARS-CoV-2 in cell culture media and deposited onto surfaces under a limited set of environmental conditions. Here, we broadly investigated the effects of relative humidity, temperature, and droplet size on the stability of SARS-CoV-2 in a simulated clinically relevant matrix dried on nonporous surfaces. The results show that SARS-CoV-2 decayed more rapidly when either humidity or temperature was increased but that droplet volume (1 to 50 \u03bcl) and surface type (stainless steel, plastic, or nitrile glove) did not significantly impact decay rate. At room temperature (24\u00b0C), virus half-life ranged from 6.3 to 18.6 h depending on the relative humidity but was reduced to 1.0 to 8.9 h when the temperature was increased to 35\u00b0C. These findings suggest that a potential for fomite transmission may persist for hours to days in indoor environments and have implications for assessment of the risk posed by surface contamination in indoor environments. IMPORTANCE Mitigating the transmission of SARS-CoV-2 in clinical settings and public spaces is critically important to reduce the number of COVID-19 cases while effective vaccines and therapeutics are under development. SARS-CoV-2 transmission is thought to primarily occur through direct person-to-person transfer of infectious respiratory droplets or through aerosol-generating medical procedures. However, contact with contaminated surfaces may also play a significant role. In this context, understanding the factors contributing to SARS-CoV-2 persistence on surfaces will enable a more accurate estimation of the risk of contact transmission and inform mitigation strategies. To this end, we have developed a simple mathematical model that can be used to estimate virus decay on nonporous surfaces under a range of conditions and which may be utilized operationally to identify indoor environments in which the virus is most persistent.", "qid": 16, "docid": "1vhprok9", "rank": 3, "score": 0.8758758306503296}, {"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": 4, "score": 0.8742330074310303}, {"content": "Title: Potential role of inanimate surfaces for the spread of coronaviruses and their inactivation with disinfectant agents Content: Summary The novel human coronavirus SARS-CoV-2 has become a global health concern causing severe respiratory tract infections in humans. Human-to-human transmissions have been described, probably via droplets but possibly also via contaminated hands or surfaces. In a recent review on the persistence of human and veterinary coronaviruses on inanimate surfaces it was shown that human coronaviruses such as Severe Acute Respiratory Syndrome (SARS) coronavirus, Middle East Respiratory Syndrome (MERS) coronavirus or endemic human coronaviruses (HCoV) can persist on inanimate surfaces like metal, glass or plastic for up to 9 days. Some disinfectant agents effectively reduce coronavirus infectivity within 1 minute such 62%\u201371% ethanol, 0.5% hydrogen peroxide or 0.1% sodium hypochlorite. Other compounds such as 0.05%\u20130.2% benzalkonium chloride or 0.02% chlorhexidine digluconate are less effective. An effective surface disinfection may help to ensure an early containment and prevention of further viral spread.", "qid": 16, "docid": "80dfqjql", "rank": 5, "score": 0.8732888698577881}, {"content": "Title: Stability and infectivity of coronaviruses in inanimate environments Content: Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) is a highly contagious virus that can transmit through respiratory droplets, aerosols, or contacts. Frequent touching of contaminated surfaces in public areas is therefore a potential route of SARS-CoV-2 transmission. The inanimate surfaces have often been described as a source of nosocomial infections. However, summaries on the transmissibility of coronaviruses from contaminated surfaces to induce the coronavirus disease 2019 are rare at present. This review aims to summarize data on the persistence of different coronaviruses on inanimate surfaces. The literature was systematically searched on Medline without language restrictions. All reports with experimental evidence on the duration persistence of coronaviruses on any type of surface were included. Most viruses from the respiratory tract, such as coronaviruses, influenza, SARS-CoV, or rhinovirus, can persist on surfaces for a few days. Persistence time on inanimate surfaces varied from minutes to up to one month, depending on the environmental conditions. SARS-CoV-2 can be sustained in air in closed unventilated buses for at least 30 min without losing infectivity. The most common coronaviruses may well survive or persist on surfaces for up to one month. Viruses in respiratory or fecal specimens can maintain infectivity for quite a long time at room temperature. Absorbent materials like cotton are safer than unabsorbent materials for protection from virus infection. The risk of transmission via touching contaminated paper is low. Preventive strategies such as washing hands and wearing masks are critical to the control of coronavirus disease 2019.", "qid": 16, "docid": "ou7w3zkv", "rank": 6, "score": 0.8689996600151062}, {"content": "Title: Effect of Environmental Conditions on SARS-CoV-2 Stability in Human Nasal Mucus and Sputum Content: We found that environmental conditions affect the stability of severe acute respiratory syndrome coronavirus 2 in nasal mucus and sputum. The virus is more stable at low-temperature and low-humidity conditions, whereas warmer temperature and higher humidity shortened half-life. Although infectious virus was undetectable after 48 hours, viral RNA remained detectable for 7 days.", "qid": 16, "docid": "04awj06g", "rank": 7, "score": 0.8616436123847961}, {"content": "Title: Effect of Environmental Conditions on SARS-CoV-2 Stability in Human Nasal Mucus and Sputum. Content: We found that environmental conditions affect the stability of severe acute respiratory syndrome coronavirus 2 in nasal mucus and sputum. The virus is more stable at low-temperature and low-humidity conditions, whereas warmer temperature and higher humidity shortened half-life. Although infectious virus was undetectable after 48 hours, viral RNA remained detectable for 7 days.", "qid": 16, "docid": "4819g00y", "rank": 8, "score": 0.8616436123847961}, {"content": "Title: Stability and inactivation of SARS coronavirus Content: The SARS-coronavirus (SARS-CoV) is a newly emerged, highly pathogenic agent that caused over 8,000 human infections with nearly 800 deaths between November 2002 and September 2003. While direct person-to-person transmission via respiratory droplets accounted for most cases, other modes have not been ruled out. Faecal shedding is common and prolonged and has caused an outbreak in Hong Kong. We studied the stability of SARS-CoV under different conditions, both in suspension and dried on surfaces, in comparison with other human-pathogenic viruses, including human coronavirus HCoV-229E. In suspension, HCoV-229E gradually lost its infectivity completely while SARS-CoV retained its infectivity for up to 9 days; in the dried state, survival times were 24 h versus 6 days. Thermal inactivation at 56\u00b0C was highly effective in the absence of protein, reducing the virus titre to below detectability; however, the addition of 20% protein exerted a protective effect resulting in residual infectivity. If protein-containing solutions are to be inactivated, heat treatment at 60\u00b0C for at least 30 min must be used. Different fixation procedures, e.g. for the preparation of immunofluorescence slides, as well as chemical means of virus inactivation commonly used in hospital and laboratory settings were generally found to be effective. Our investigations confirm that it is possible to care for SARS patients and to conduct laboratory scientific studies on SARS-CoV safely. Nevertheless, the agent\u2019s tenacity is considerably higher than that of HCoV-229E, and should SARS re-emerge, increased efforts need to be devoted to questions of environmental hygiene.", "qid": 16, "docid": "8s9671zf", "rank": 9, "score": 0.8600963354110718}, {"content": "Title: Coronaviruses widespread on nonliving surfaces: important questions and promising answers. Content: The world is facing, while writing this review, a global pandemic due to one of the types of the coronaviruses (i.e., COVID-19), which is a new virus. Among the most important reasons for the transmission of infection between humans is the presence of this virus active on the surfaces and materials. Here, we addressed important questions such as do coronaviruses remain active on the inanimate surfaces? Do the types of inanimate surfaces affect the activity of coronaviruses? What are the most suitable ingredients that used to inactivate viruses? This review article addressed many of the works that were done in the previous periods on the survival of many viruses from the coronaviruses family on various surfaces such as steel, glass, plastic, Teflon, ceramic tiles, silicon rubber and stainless steel copper alloys, Al surface, sterile sponges, surgical gloves and sterile latex. The impacts of environmental conditions such as temperature and humidity were presented and discussed. The most important active ingredients that can deactivate viruses on the surfaces were reported here. We hope that these active ingredients will have the same effect on COVID-19.", "qid": 16, "docid": "9xv9t5ba", "rank": 10, "score": 0.860093355178833}, {"content": "Title: Coronaviruses widespread on nonliving surfaces: important questions and promising answers Content: The world is facing, while writing this review, a global pandemic due to one of the types of the coronaviruses (i.e., COVID-19), which is a new virus. Among the most important reasons for the transmission of infection between humans is the presence of this virus active on the surfaces and materials. Here, we addressed important questions such as do coronaviruses remain active on the inanimate surfaces? Do the types of inanimate surfaces affect the activity of coronaviruses? What are the most suitable ingredients that used to inactivate viruses? This review article addressed many of the works that were done in the previous periods on the survival of many viruses from the coronaviruses family on various surfaces such as steel, glass, plastic, Teflon, ceramic tiles, silicon rubber and stainless steel copper alloys, Al surface, sterile sponges, surgical gloves and sterile latex. The impacts of environmental conditions such as temperature and humidity were presented and discussed. The most important active ingredients that can deactivate viruses on the surfaces were reported here. We hope that these active ingredients will have the same effect on COVID-19.", "qid": 16, "docid": "fxx5vrg0", "rank": 11, "score": 0.8600932955741882}, {"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": 12, "score": 0.8594462871551514}, {"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": 13, "score": 0.8587381839752197}, {"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": 14, "score": 0.8582572937011719}, {"content": "Title: Persistence of coronaviruses on inanimate surfaces and their inactivation with biocidal agents Content: Currently, the emergence of a novel human coronavirus, SARS-CoV-2, has become a global health concern causing severe respiratory tract infections in humans. Human-to-human transmissions have been described with incubation times between 2-10 days, facilitating its spread via droplets, contaminated hands or surfaces. We therefore reviewed the literature on all available information about the persistence of human and veterinary coronaviruses on inanimate surfaces as well as inactivation strategies with biocidal agents used for chemical disinfection, e.g. in healthcare facilities. The analysis of 22 studies reveals that human coronaviruses such as Severe Acute Respiratory Syndrome (SARS) coronavirus, Middle East Respiratory Syndrome (MERS) coronavirus or endemic human coronaviruses (HCoV) can persist on inanimate surfaces like metal, glass or plastic for up to 9 days, but can be efficiently inactivated by surface disinfection procedures with 62-71% ethanol, 0.5% hydrogen peroxide or 0.1% sodium hypochlorite within 1 minute. Other biocidal agents such as 0.05-0.2% benzalkonium chloride or 0.02% chlorhexidine digluconate are less effective. As no specific therapies are available for SARS-CoV-2, early containment and prevention of further spread will be crucial to stop the ongoing outbreak and to control this novel infectious thread.", "qid": 16, "docid": "ssq0dwmn", "rank": 15, "score": 0.8582318425178528}, {"content": "Title: The Effects of Temperature and Relative Humidity on the Viability of the SARS Coronavirus Content: The main route of transmission of SARS CoV infection is presumed to be respiratory droplets. However the virus is also detectable in other body fluids and excreta. The stability of the virus at different temperatures and relative humidity on smooth surfaces were studied. The dried virus on smooth surfaces retained its viability for over 5 days at temperatures of 22\u201325\u00b0C and relative humidity of 40\u201350%, that is, typical air-conditioned environments. However, virus viability was rapidly lost (>3 log(10)) at higher temperatures and higher relative humidity (e.g., 38\u00b0C, and relative humidity of >95%). The better stability of SARS coronavirus at low temperature and low humidity environment may facilitate its transmission in community in subtropical area (such as Hong Kong) during the spring and in air-conditioned environments. It may also explain why some Asian countries in tropical area (such as Malaysia, Indonesia or Thailand) with high temperature and high relative humidity environment did not have major community outbreaks of SARS.", "qid": 16, "docid": "x3b6j5d0", "rank": 16, "score": 0.8571848273277283}, {"content": "Title: Persistence of coronaviruses on inanimate surfaces and their inactivation with biocidal agents Content: Summary Currently, the emergence of a novel human coronavirus, SARS-CoV-2, has become a global health concern causing severe respiratory tract infections in humans. Human-to-human transmissions have been described with incubation times between 2-10 days, facilitating its spread via droplets, contaminated hands or surfaces. We therefore reviewed the literature on all available information about the persistence of human and veterinary coronaviruses on inanimate surfaces as well as inactivation strategies with biocidal agents used for chemical disinfection, e.g. in healthcare facilities. The analysis of 22 studies reveals that human coronaviruses such as Severe Acute Respiratory Syndrome (SARS) coronavirus, Middle East Respiratory Syndrome (MERS) coronavirus or endemic human coronaviruses (HCoV) can persist on inanimate surfaces like metal, glass or plastic for up to 9 days, but can be efficiently inactivated by surface disinfection procedures with 62\u201371% ethanol, 0.5% hydrogen peroxide or 0.1% sodium hypochlorite within 1 minute. Other biocidal agents such as 0.05\u20130.2% benzalkonium chloride or 0.02% chlorhexidine digluconate are less effective. As no specific therapies are available for SARS-CoV-2, early containment and prevention of further spread will be crucial to stop the ongoing outbreak and to control this novel infectious thread.", "qid": 16, "docid": "k9xhphpl", "rank": 17, "score": 0.8570286631584167}, {"content": "Title: Aerosol and surface stability of HCoV-19 (SARS-CoV-2) compared to SARS-CoV-1 Content: A novel human coronavirus, now named severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2, referred to as HCoV-19 here) that emerged in Wuhan, China in late 2019 is now causing a pandemic. Here, we analyze the aerosol and surface stability of HCoV-19 and compare it with SARS-CoV-1, the most closely related human coronavirus.2 We evaluated the stability of HCoV-19 and SARS-CoV-1 in aerosols and on different surfaces and estimated their decay rates using a Bayesian regression model", "qid": 16, "docid": "hiw576og", "rank": 18, "score": 0.852784276008606}, {"content": "Title: Stability of SARS-CoV-2 and other coronaviruses in the environment and on common touch surfaces and the influence of climatic conditions: a review Content: Although the unprecedented efforts the world has been taking to control the spread of the human coronavirus disease (COVID-19) and its causative etiology [Severe Acute Respiratory Syndrome-Coronavirus-2 (SARS-CoV-2)], the number of confirmed cases has been increasing drastically. Therefore, there is an urgent need for devising more efficient preventive measures, to limit the spread of the infection until an effective treatment or vaccine is available. The preventive measures depend mainly on the understanding of the transmission routes of this virus, its environmental stability, and its persistence on common touch surfaces. Due to the very limited knowledge about SARS-CoV-2, we can speculate its stability in the light of previous studies conducted on other human and animal coronaviruses. In this review, we present the available data on the stability of coronaviruses (CoVs), including SARS-CoV-2, from previous reports to help understand its environmental survival. According to available data, possible airborne transmission of SARS-CoV-2 has been suggested. SARS-CoV-2 and other human and animal CoVs have remarkably short persistence on copper, latex, and surfaces with low porosity as compared to other surfaces like stainless steel, plastics, glass, and highly porous fabrics. It has also been reported that SARS-CoV-2 is associated with diarrhea and that it is shed in the feces of COVID-19 patients. Some CoVs show persistence in human excrement, sewage, and waters for a few days. These findings suggest a possible risk of fecal-oral, foodborne, and waterborne transmission of SARS-CoV-2 in developing countries that often use sewage-polluted waters in irrigation and have poor water treatment systems. CoVs survive longer in the environment at lower temperatures and lower relative humidity. It has been suggested that large numbers of COVID-19 cases are associated with cold and dry climates in temperate regions of the world and that seasonality of the virus spread is suspected.", "qid": 16, "docid": "z4vfjlbg", "rank": 19, "score": 0.8514930009841919}, {"content": "Title: Inanimate surfaces as potential source of 2019-nCoV spread and their disinfection with biocidal agents Content: The WHO has declared COVID-19 illness a global health concern which is caused by 2019-nCoV, causing severe respiratory tract infections in humans. Transmissibility among individual to individual have been reported through droplets and probably also via contaminated surfaces and hands. Human coronaviruses can persist on inanimate surfaces such as plastic, glass, fibers and metals up to nine days. 2019-nCoV remains infectious in air for 3 h and on inanimate surfaces such as cardboard, copper, plastic and steel up to 24, 4, 72 and 48 h respectively. Disinfectant activity of various biocidal agents against coronaviruses like ethanol (62\u201371%), sodium hypochlorite (0.1%) and hydrogen peroxide (0.5%) can be regarded effective against 2019-nCoV as well. As no vaccine and antiviral therapies have been discovered for 2019-nCoV, prevention of further spread will viable option to control the ongoing and future outbreaks.", "qid": 16, "docid": "esvutpel", "rank": 20, "score": 0.8514625430107117}, {"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": 21, "score": 0.8478645086288452}, {"content": "Title: Stability of SARS\u2010CoV\u20102 and other coronaviruses in the environment and on common touch surfaces and the influence of climatic conditions: A review Content: Although the unprecedented efforts the world has been taking to control the spread of the human coronavirus disease (COVID\u201019) and its causative aetiology [severe acute respiratory syndrome coronavirus 2 (SARS\u2010CoV\u20102)], the number of confirmed cases has been increasing drastically. Therefore, there is an urgent need for devising more efficient preventive measures, to limit the spread of the infection until an effective treatment or vaccine is available. The preventive measures depend mainly on the understanding of the transmission routes of this virus, its environmental stability, and its persistence on common touch surfaces. Due to the very limited knowledge about SARS\u2010CoV\u20102, we can speculate its stability in the light of previous studies conducted on other human and animal coronaviruses. In this review, we present the available data on the stability of coronaviruses (CoVs), including SARS\u2010CoV\u20102, from previous reports to help understand its environmental survival. According to available data, possible airborne transmission of SARS\u2010CoV\u20102 has been suggested. SARS\u2010CoV\u20102 and other human and animal CoVs have remarkably short persistence on copper, latex and surfaces with low porosity as compared to other surfaces like stainless steel, plastics, glass and highly porous fabrics. It has also been reported that SARS\u2010CoV\u20102 is associated with diarrhoea and that it is shed in the faeces of COVID\u201019 patients. Some CoVs show persistence in human excrement, sewage and waters for a few days. These findings suggest a possible risk of faecal\u2013oral, foodborne and waterborne transmission of SARS\u2010CoV\u20102 in developing countries that often use sewage\u2010polluted waters in irrigation and have poor water treatment systems. CoVs survive longer in the environment at lower temperatures and lower relative humidity. It has been suggested that large numbers of COVID\u201019 cases are associated with cold and dry climates in temperate regions of the world and that seasonality of the virus spread is suspected.", "qid": 16, "docid": "rhfwbyav", "rank": 22, "score": 0.8470696210861206}, {"content": "Title: A Continuously Active Antimicrobial Coating effective against Human Coronavirus 229E Content: The disinfection of high-contact surfaces is seen as an infection control practice to prevent the spread of pathogens by fomites. Unfortunately, recontamination of these surfaces can occur any time after the use of common disinfectants. We recently reported on a novel continuously active antimicrobial coating which was shown to reduce the spread of healthcare acquired infections in hospitals. We evaluated a modified coating that demonstrated a residual efficacy against viruses. The coated surfaces were found to be effective against human coronavirus (HCoV) 229E, reducing the concentration of these viruses by greater than 90% in 10 minutes and by greater than 99.9% after two hours of contact. The coating formulation when tested in suspension yielded a greater than 99.99% reduction of HCoV 229E within ten minutes of contact. This outcome presents an opportunity for controlling the transmission of COVID-19 from contaminated fomites.", "qid": 16, "docid": "itm0bldp", "rank": 23, "score": 0.8469850420951843}, {"content": "Title: A Surface Coating that Rapidly Inactivates SARS-CoV-2. Content: SARS-CoV-2, the virus that causes the disease COVID-19, remains viable on solids for periods of up to one week, so one potential route for human infection is via exposure to an infectious dose from a solid. We have fabricated and tested a coating that is designed to reduce the longevity of SARS-CoV-2 on solids. The coating consists of cuprous oxide (Cu2O) particles bound with polyurethane. After one hour on coated glass or stainless steel, the viral titer was reduced by about 99.9% on average compared to the uncoated sample. An advantage of a polyurethane-based coating is that polyurethane is already used to coat a large number of everyday objects. Our coating adheres well to glass and stainless steel, as well as everyday items that people may fear to touch during a pandemic, such as a doorknob, a pen, and a credit card keypad button. The coating performs well in the cross-hatch durability test and remains intact and active after 13 days immersed in water, or after exposure to multiple cycles of exposure to virus and disinfection.", "qid": 16, "docid": "gxo13x70", "rank": 24, "score": 0.845562219619751}, {"content": "Title: Stability of SARS-CoV-2 on Critical Personal Protective Equipment Content: The spread of COVID-19 in healthcare settings is concerning, with healthcare workers representing a disproportionately high percentage of confirmed cases. Although SARS-CoV-2 virus has been found to persist on surfaces for a number of days, the extent and duration of fomites as a mode of transmission, particularly in healthcare settings, has not been fully characterized. To shed light on this critical matter, the present study provides the first comprehensive assessment of SARS-CoV-2 stability on experimentally contaminated personal protective equipment (PPE) widely used by healthcare workers and the general public. Persistence of viable virus was monitored over 21 days on eight different materials, including nitrile medical examination gloves, reinforced chemical resistant gloves, N-95 and N-100 particulate respirator masks, Tyvek, plastic, cotton, and stainless steel. Unlike previous reports, viable SARS-CoV-2 in the presence of a soil load persisted for up to 21 days on experimentally inoculated PPE, including materials from filtering facepiece respirators (N-95 and N-100 masks) and a plastic visor. Conversely, when applied to 100% cotton fabric, the virus underwent rapid degradation and became undetectable in less than 24 hours. These findings underline the importance of appropriate handling of contaminated PPE during and following use in high-risk settings and provide interesting insight into the potential utility of cotton, including cotton masks, in limiting COVID-19 transmission.", "qid": 16, "docid": "qpc4hyvl", "rank": 25, "score": 0.8440231680870056}, {"content": "Title: Simulated Sunlight Rapidly Inactivates SARS-CoV-2 on Surfaces Content: Previous studies have demonstrated that SARS-CoV-2 is stable on surfaces for extended periods under indoor conditions. In the present study, simulated sunlight rapidly inactivated SARS-CoV-2 suspended in either simulated saliva or culture media and dried on stainless steel coupons. Ninety percent of infectious virus was inactivated every 6.8 minutes in simulated saliva and every 14.3 minutes in culture media when exposed to simulated sunlight representative of the summer solstice at 40\u00b0N latitude at sea level on a clear day. Significant inactivation also occurred, albeit at a slower rate, under lower simulated sunlight levels. The present study provides the first evidence that sunlight may rapidly inactivate SARS-CoV-2 on surfaces, suggesting that persistence, and subsequently exposure risk, may vary significantly between indoor and outdoor environments. Additionally, these data indicate that natural sunlight may be effective as a disinfectant for contaminated nonporous materials.", "qid": 16, "docid": "mixy6roy", "rank": 26, "score": 0.8437881469726562}, {"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": 16, "docid": "zmaw9lbz", "rank": 27, "score": 0.8422231674194336}, {"content": "Title: Virus survival in evaporated saliva microdroplets deposited on inanimate surfaces Content: The novel coronavirus respiratory syndrome (COVID-19) has now spread worldwide. The relative contribution of viral transmission via fomites is still unclear. SARS-CoV-2 has been shown to survive on inanimate surfaces for several days, yet the factors that determine its survival on surfaces are not well understood. Here we combine microscopy imaging with virus viability assays to study survival of three bacteriophages suggested as good models for human respiratory pathogens: the enveloped Phi6 (a surrogate for SARS-CoV-2), and the non-enveloped PhiX174 and MS2. We measured virus viability in human saliva microdroplets, SM buffer, and water following deposition on glass surfaces at various relative humidities (RH). Although saliva microdroplets dried out rapidly at all tested RH levels (unlike SM that remained hydrated at RH \u2265 57%), survival of all three viruses in dry saliva microdroplets was significantly higher than in water or SM. Thus, RH and hydration conditions are not sufficient to explain virus survival, indicating that the suspended medium, and association with saliva components in particular, likely affect physicochemical properties that determine virus survival. The observed high virus survival in dry saliva deposited on surfaces, under a wide range of RH levels, can have profound implications for human public health, specifically the COVID-19 pandemic.", "qid": 16, "docid": "atisrhas", "rank": 28, "score": 0.8421558141708374}, {"content": "Title: Experimental aerosol survival of SARS-CoV-2 in artificial saliva and tissue culture media at medium and high humidity Content: SARS-CoV-2, the causative agent of the COVID-19 pandemic, may be transmitted via airborne droplets or contact with surfaces onto which droplets have deposited. In this study, the ability of SARS-CoV-2 to survive in the dark, at two different relative humidity values and within artificial saliva, a clinically relevant matrix, was investigated. SARS-CoV-2 was found to be stable, in the dark, in a dynamic small particle aerosol under the four experimental conditions we tested and viable virus could still be detected after 90 minutes. The decay rate and half-life was determined and decay rates ranged from 0.4 to 2.27 % per minute and the half lives ranged from 30 to 177 minutes for the different conditions. This information can be used for advice and modelling and potential mitigation strategies.", "qid": 16, "docid": "txc0k2vb", "rank": 29, "score": 0.8410736322402954}, {"content": "Title: Sustainability of Coronavirus on different surfaces Content: Abstract COVID-19 is the name of the disease supposedly manifested in December 2019 from Wuhan, because of virus named as SARS-CoV-2. Now this disease has spread to almost all other parts of the world. COVID-19 pandemic has various reasons for its dramatic worldwide increase. Here, we have studied Coronavirus sustainability on various surfaces. Various disinfectants and their roles are discussed from the available literature. The infection capabilities of SARS-CoV-1 and SARS-CoV-2 for different materials are discussed and finally studies infection decay for SARS-CoV-1 and SARS-CoV-2.", "qid": 16, "docid": "f7gr98eb", "rank": 30, "score": 0.8407106399536133}, {"content": "Title: Effective Heat Inactivation of SARS-CoV-2 Content: The outbreak of the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2 or 2019-nCoV) has quickly turned into a global pandemic. Infectious viruses had been isolated from oro- or naso-pharyngeal swabs, sputum and possibly stool samples of infected individuals. Handling these clinical specimens therefore poses a biosafety risk to both healthcare professionals and laboratory workers. In this study, we aimed to evaluate the stability of SARS-CoV-2 under different heat conditions and report that the virus is stable at 37 C for at least 24 hours. Heating at 56 C for 30 minutes, however, effectively inactivated the virus while preserved the stability of viral RNA in both human sera and sputum samples. These findings provide critical information regarding the biology of the virus as well as a practical way to inactivate infectious virus that is potentially found in clinical specimens.", "qid": 16, "docid": "og69izi3", "rank": 31, "score": 0.8406058549880981}, {"content": "Title: Stability of Middle East respiratory syndrome coronavirus (MERS-CoV) under different environmental conditions. Content: The stability of Middle East respiratory syndrome coronavirus (MERS-CoV) was determined at 20\u00b0C--40% relative humidity (RH); 30\u00b0C--30% RH and 30\u00b0C--80% RH. MERS-CoV was more stable at low temperature/low humidity conditions and could still be recovered after 48 hours. During aerosolisation of MERS-CoV, no decrease in stability was observed at 20\u00b0C--40% RH. These data suggest the potential of MERS-CoV to be transmitted via contact or fomite transmission due to prolonged environmental presence.", "qid": 16, "docid": "0wlapuuq", "rank": 32, "score": 0.8403527736663818}, {"content": "Title: Survival of human coronaviruses 229E and OC43 in suspension and after drying onsurfaces: a possible source ofhospital-acquired infections Content: Abstract Strains OC43 and 229E of human coronaviruses (HCoV) cause one-third of common colds and hospital-acquired upper respiratory tract HCoV infections have been reported in premature newborns. To evaluate possible sources of infection, virus survival was studied in aqueous suspensions and on absorptive and non-absorptive surfaces representative of a hospital environment. Virus susceptibility to chemical disinfection with standard products was also characterized. Virus survived in saline solution for as long as six days but less in culture medium, with or without added cells. After drying, HCoV-229E infectivity was still detectable after 3h on various surfaces (aluminum, sterile latex surgical gloves, sterile sponges) but HCoV-OC43 survived 1h or less. Of the various chemical disinfectants tested, Proviodine\u00ae reduced the virus infectious titre by at least 50%. This study suggests that surfaces and suspensions can be considered as possible sources of contamination that may lead to hospital-acquired infections with HCoV and should be appropriately disinfected.", "qid": 16, "docid": "5gayhkxx", "rank": 33, "score": 0.8396974802017212}, {"content": "Title: Sustainability of Coronavirus on different surfaces Content: COVID-19 is the name of the disease supposedly manifested in December 2019 from Wuhan, because of virus named as SARS-CoV-2. Now this disease has spread to almost all other parts of the world. COVID-19 pandemic has various reasons for its dramatic worldwide increase. Here, we have studied Coronavirus sustainability on various surfaces. Various disinfectants and their roles are discussed from the available literature. The infection capabilities of SARS-CoV-1 and SARS-CoV-2 for different materials are discussed and finally studies infection decay for SARS-CoV-1 and SARS-CoV-2.", "qid": 16, "docid": "9fnpfncr", "rank": 34, "score": 0.8384222984313965}, {"content": "Title: Effect of pH and temperature on the infectivity of human coronavirus 229E. Content: The stability of human coronavirus 229E infectivity was maximum at pH 6.0 when incubated at either 4 or 33 degrees C. However, the influence of pH was more pronounced at 33 degrees C. Viral infectivity was completely lost after a 14-day incubation period at 22, 33, or 37 degrees C but remained relatively constant at 4 degrees C for the same length of time. Finally, the infectious titer did not show any significant reduction when subjected to 25 cycles of thawing and freezing. These studies will contribute to optimize virus growth and storage conditions, which will facilitate the molecular characterization of this important pathogen.", "qid": 16, "docid": "jpw8f2op", "rank": 35, "score": 0.8376299142837524}, {"content": "Title: Modelling the thermal inactivation of viruses from the Coronaviridae family in suspensions or on surfaces with various relative humidities. Content: Temperature and relative humidity are major factors determining virus inactivation in the environment. This article reviews inactivation data of coronaviruses on surfaces and in liquids from published studies and develops secondary models to predict coronaviruses inactivation as a function of temperature and relative humidity. A total of 102 D-values (time to obtain a log10 reduction of virus infectivity), including values for SARS-CoV-2, were collected from 26 published studies. The values obtained from the different coronaviruses and studies were found to be generally consistent. Five different models were fitted to the global dataset of D-values. The most appropriate model considered temperature and relative humidity. A spreadsheet predicting the inactivation of coronaviruses and the associated uncertainty is presented and can be used to predict virus inactivation for untested temperatures, time points or new coronavirus strains.", "qid": 16, "docid": "4hbwg18z", "rank": 36, "score": 0.8362630009651184}, {"content": "Title: Environmental contamination by SARS-CoV-2 of an imported case during incubation period Content: We collected environmental surface samples prior to and after disinfection of a quarantine room to evaluate the stability of SARS-CoV-2 during the incubation period of an imported case traveling to Qingdao, China. Overall, 11 of 23 (47.8%) of the first batch of environmental surface samples (within 4 h after case confirmation) were tested positive for SARS-CoV-2. Whereas only 2 of 23 (8.7%) of the second batch of environmental samples (after first disinfection) were tested positive for SARS-CoV-2. The majority of samples from the bedroom (70%) were positive for SARS-CoV-2, followed by 50% of samples from the bathroom and that of 33% from the corridor. The inner walls of toilet bowl and sewer inlet were the most contaminated sites with the highest viral loads. SARS-CoV-2 was widely distributed on object surfaces in a quarantine room of a later diagnosed COVID-19 case during the incubation period. Proper disinfection is crucial to minimize community transmission of this highly contagious virus.", "qid": 16, "docid": "sh3h6ggg", "rank": 37, "score": 0.8357794284820557}, {"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": 38, "score": 0.8344677686691284}, {"content": "Title: Environmental contamination by SARS-CoV-2 of an imported case during incubation period Content: Abstract We collected environmental surface samples prior to and after disinfection of a quarantine room to evaluate the stability of SARS-CoV-2 during the incubation period of an imported case traveling to Qingdao, China. Overall, 11 of 23 (47.8%) of the first batch of environmental surface samples (within 4 h after case confirmation) were tested positive for SARS-CoV-2. Whereas only 2 of 23 (8.7%) of the second batch of environmental samples (after first disinfection) were tested positive for SARS-CoV-2. The majority of samples from the bedroom (70%) were positive for SARS-CoV-2, followed by 50% of samples from the bathroom and that of 33% from the corridor. The inner walls of toilet bowl and sewer inlet were the most contaminated sites with the highest viral loads. SARS-CoV-2 was widely distributed on object surfaces in a quarantine room of a later diagnosed COVID-19 case during the incubation period. Proper disinfection is crucial to minimize community transmission of this highly contagious virus.", "qid": 16, "docid": "bfq7vvef", "rank": 39, "score": 0.8335661888122559}, {"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": 40, "score": 0.8325559496879578}, {"content": "Title: Environmental concern regarding the effect of humidity and temperature on 2019-nCoV survival: fact or fiction Content: The new coronavirus, called 2019-nCoV, is a new type of virus that was first identified in Wuhan, China, in December 2019. Environmental conditions necessary for survival and spread of 2019-nCoV are somewhat transparent but unlike animal coronaviruses. We are poorly aware of their survival in environment and precise factors of their transmission. Countries located in east and west of globe did not have a significant impact on prevalence of disease among communities, and on the other hand, north and south have provided a model for relative prediction of disease outbreaks. The 2019-nCoV can survive for up to 9 days at 25 \u00b0C, and if this temperature rises to 30 \u00b0C, its lifespan will be shorter. The 2019-nCoV is sensitive to humidity, and lifespan of viruses in 50% humidity is longer than that of 30%. Also, temperature and humidity are important factors influencing the COVID-19 mortality rate and may facilitate 2019-nCoV transmission. Thus, considering the available and recent evidence, it seems that low temperatures, as well as dry and unventilated air, may affect stability and transmissibility of 2019-nCoV.", "qid": 16, "docid": "zqsfw75p", "rank": 41, "score": 0.8323067426681519}, {"content": "Title: Persistence of SARS-CoV-2 in the environment and COVID-19 transmission risk from environmental matrices and surfaces Content: The Coronavirus disease 2019 (COVID-19) is spreading around the world, representing a global pandemic, counting, as of June 5th, 2020, over 6,600,000 confirmed cases and more than 390,000 deaths, with exponentially increasing numbers. In the first half of 2020, because of the widespread of the COVID-19, researches were focused on the monitoring of SARS-CoV-2 in water, wastewater, sludge, air, and on surfaces, in order to assess the risk of contracting the viral infection from contaminated environments. So far, the survival of the novel Coronavirus out of the human body has been reported for short time periods (from hours to few days, in optimized in vitro conditions), mainly because of the need of an host organism which could consent the viral attack, and due to the weak external membrane of the virus. SARS-CoV-2 viral shedding strategies in the environment, either through animate and unanimate matrices, or exploiting the organic matter in water, wastewater, and waste in general, have been discussed in the present article. We concluded that, besides the high infectuousness of the novel Coronavirus, the transmission of the pathogen may be efficiently contained applying the adequate preventive measures (e.g., personal protection equipments, and disinfecting agents), indicated by national and international health authories.", "qid": 16, "docid": "b5lcv77o", "rank": 42, "score": 0.8316357731819153}, {"content": "Title: Persistence of SARS-CoV-2 in the environment and COVID-19 transmission risk from environmental matrices and surfaces() Content: The Coronavirus disease 2019 (COVID-19) is spreading around the world, representing a global pandemic, counting, as of June 5th, 2020, over 6,600,000 confirmed cases and more than 390,000 deaths, with exponentially increasing numbers. In the first half of 2020, because of the widespread of the COVID-19, researches were focused on the monitoring of SARS-CoV-2 in water, wastewater, sludge, air, and on surfaces, in order to assess the risk of contracting the viral infection from contaminated environments. So far, the survival of the novel Coronavirus out of the human body has been reported for short time periods (from hours to few days, in optimized in vitro conditions), mainly because of the need of an host organism which could consent the viral attack, and due to the weak external membrane of the virus. SARS-CoV-2 viral shedding strategies in the environment, either through animate and unanimate matrices, or exploiting the organic matter in water, wastewater, and waste in general, have been discussed in the present article. We concluded that, besides the high infectuousness of the novel Coronavirus, the transmission of the pathogen may be efficiently contained applying the adequate preventive measures (e.g., personal protection equipments, and disinfecting agents), indicated by national and international health authories.", "qid": 16, "docid": "kxyd5uzp", "rank": 43, "score": 0.8316357135772705}, {"content": "Title: Profile of RT-PCR for SARS-CoV-2: a preliminary study from 56 COVID-19 patients Content: A novel coronavirus (COVID-19) pandemic threatens the world. Here, we first studied the dynamics profile of SARS-CoV-2 from 56 recovered COVID-19 patients. We found virus shedding was up to 6 weeks after onset of symptoms. Prolonged observation period is necessary for older patients.", "qid": 16, "docid": "4awl1ocd", "rank": 44, "score": 0.8287403583526611}, {"content": "Title: Persistence of Severe Acute Respiratory Syndrome Coronavirus 2 in Aerosol Suspensions Content: We aerosolized severe acute respiratory syndrome coronavirus 2 and determined that its dynamic aerosol efficiency surpassed those of severe acute respiratory syndrome coronavirus and Middle East respiratory syndrome. Although we performed experiment only once across several laboratories, our findings suggest retained infectivity and virion integrity for up to 16 hours in respirable-sized aerosols.", "qid": 16, "docid": "34ayx062", "rank": 45, "score": 0.8283275365829468}, {"content": "Title: Persistence of Severe Acute Respiratory Syndrome Coronavirus 2 in Aerosol Suspensions. Content: We aerosolized severe acute respiratory syndrome coronavirus 2 and determined that its dynamic aerosol efficiency surpassed those of severe acute respiratory syndrome coronavirus and Middle East respiratory syndrome. Although we performed experiment only once across several laboratories, our findings suggest retained infectivity and virion integrity for up to 16 hours in respirable-sized aerosols.", "qid": 16, "docid": "jincu9xx", "rank": 46, "score": 0.8283275365829468}, {"content": "Title: Establishment and maintenance of a persistent infection of L132 cells by human coronavirus strain 229E Content: A persistent infection by human coronavirus 229E (HCV/229E) was established in a human continuous cell line (L132). Following the initial infection with stock HCV/229E, several cultures were established of which two (HV1 and HV4) have been maintained by continuous passage for two years. These cultures have shed high titres of infectious virus continuously into the supernatant fluid since their initiation. The persistently infected cells were resistant to homologous super-infection but supported polio virus replication to normal titres. Preliminary tests indicated that 50\u2013100 percent of the cells contain virus. Neither interferon nor reverse transcriptase could be detected in these cultures and the presence of defective interfering particles could not be demonstrated. VH1 and VH4 coronaviruses, isolated from these persistently infected cultures (HV) and identified by 229E antiserum neutralization, were more cytocidal than the parent virus as judged by plaque characteristics and CPE however, they were indistinguishable on the basis of density, EM morphology, and genome size. Present evidence indicates that temperature plays an important but as yet undetermined role in the establishment and maintenance of stable 229E persistently infected cell cultures.", "qid": 16, "docid": "6id8rb35", "rank": 47, "score": 0.827316164970398}, {"content": "Title: Prolonged Infectivity of SARS-CoV-2 in Fomites Content: We spotted severe acute respiratory syndrome coronavirus 2 on polystyrene plastic, aluminum, and glass for 96 hours with and without bovine serum albumin (3 g/L). We observed a steady infectivity (<1 log10 drop) on plastic, a 3.5 log10 decrease on glass, and a 6 log10 drop on aluminum. The presence of proteins noticeably prolonged infectivity.", "qid": 16, "docid": "3mcvp0h6", "rank": 48, "score": 0.8270916938781738}, {"content": "Title: Prolonged Infectivity of SARS-CoV-2 in Fomites. Content: We spotted severe acute respiratory syndrome coronavirus 2 on polystyrene plastic, aluminum, and glass for 96 hours with and without bovine serum albumin (3 g/L). We observed a steady infectivity (<1 log10 drop) on plastic, a 3.5 log10 decrease on glass, and a 6 log10 drop on aluminum. The presence of proteins noticeably prolonged infectivity.", "qid": 16, "docid": "vwmjf326", "rank": 49, "score": 0.8270916938781738}, {"content": "Title: Survival of Enveloped and Non-Enveloped Viruses on Inanimate Surfaces Content: In the present study, we evaluated the viability of non-enveloped viruses, minute virus of mice (MVM) and coxsackievirus B4 (CVB4), and enveloped-viruses, influenza A virus (H1N1) and herpes simplex virus type 1 (HSV-1), on surfaces. We also investigated the impact of the initial concentration of proteins and sodium chloride on the persistence of infectious CVB4 on surfaces. Viral suspensions (>10(4.5) TCID(50)) were applied to petri dish lids and dried under the air flow of a biosafety cabinet. The recovered viral preparations were titered on appropriate cell lines. Enveloped viruses persisted for less than 5 days while CVB4 and MVM persisted for weeks. However, repetitive cycles of drying and resuspension had a stronger virucidal effect on CVB4 than on H1N1 and HSV-1. These repetitive cycles had no effect on the infectious titer of MVM. When exposed to drying, the initial concentrations of bovine serum albumin (from 0 to 90 mg mL(\u22121)), fetal calf serum (from 0 to 100%), and sodium chloride (from 0 to 300 mg mL(\u22121)) affected the viability of CVB4. CVB4 was more likely to be inactivated by drying in a protein-rich medium, whereas the impact of drying was reduced in the presence of sodium chloride. The results of the present study demonstrated that the resistance of viruses to drying, as suggested by iterative drying, was not due to the heterogeneity of viral subpopulations, but was influenced by media compositions and component concentrations, as illustrated in the model of CVB4.", "qid": 16, "docid": "hrcffnpt", "rank": 50, "score": 0.8251254558563232}, {"content": "Title: Studies on the survival of canine coronavirus under different environmental conditions Content: Abstract Canine coronavirus (CCV) is a common faecal agent which is difficult to isolate. This study shows CCV to survive well at temperatures below \u221220\u00b0C but not at temperatures above 4\u00b0C. The presence of faecal material markedly reduced CCV survival times at temperatures ranging from 20\u00b0C to \u221270\u00b0C. Thus, it is suggested that diagnostic faecal material should be diluted 1:10 (w/v) with growth medium and examined at the earliest opportunity.", "qid": 16, "docid": "fpckqvr5", "rank": 51, "score": 0.82467120885849}, {"content": "Title: Survival of Severe Acute Respiratory Syndrome Coronavirus Content: Background. The primary modes of transmission of severe acute respiratory syndrome (SARS) coronavirus (SARS-CoV) appear to be direct mucus membrane contact with infectious droplets and through exposure to formites. Knowledge of the survival characteristics of the virus is essential for formulating appropriate infection-control measures. Methods. Survival of SARS-CoV strain GVU6109 was studied in stool and respiratory specimens. Survival of the virus on different environmental surfaces, including a laboratory request form, an impervious disposable gown, and a cotton nondisposable gown, was investigated. The virucidal effects of sodium hypochlorite, house detergent, and a peroxygen compound (Virkon S; Antec International) on the virus were also studied. Results. SARS-CoV GVU6109 can survive for 4 days in diarrheal stool samples with an alkaline pH, and it can remain infectious in respiratory specimens for >7 days at room temperature. Even at a relatively high concentration (10(4) tissue culture infective doses/mL), the virus could not be recovered after drying of a paper request form, and its infectivity was shown to last longer on the disposable gown than on the cotton gown. All disinfectants tested were shown to be able to reduce the virus load by >3 log within 5 min. Conclusions. Fecal and respiratory samples can remain infectious for a long period of time at room temperature. The risk of infection via contact with droplet-contaminated paper is small. Absorbent material, such as cotton, is preferred to nonabsorptive material for personal protective clothing for routine patient care where risk of large spillage is unlikely. The virus is easily inactivated by commonly used disinfectants.", "qid": 16, "docid": "h9gj814e", "rank": 52, "score": 0.8246381282806396}, {"content": "Title: Isothermal evaporation rate of deposited liquid aerosols and the SARS-CoV-2 coronavirus survival Content: It is shown that the evaporation rate of a liquid sample containing the culture of coronavirus affects its survival on a substrate. Possible mechanisms of such influence can be due to the appearance of large, about 140 bar, non comprehensive capillary pressures and the associated dynamic forces during the movement of the evaporation front in a sample with the virus. A simulation of isothermal evaporation of a thin liquid sample based on the Stefan problem was performed. The comparison of simulation data and recent experiments on the coronavirus survival on various surfaces showed that the rate of isothermal evaporation of aqueous samples, which is higher for heat-conducting materials, correlates well with the lifetime of the coronavirus on these surfaces.", "qid": 16, "docid": "80ev0j5a", "rank": 53, "score": 0.8240793943405151}, {"content": "Title: Extended Storage of SARS-CoV2 Nasopharyngeal Swabs Does Not Negatively Impact Results of Molecular-Based Testing Content: With the global outbreak of the novel coronavirus disease 2019, the demand for testing rapidly increased and quickly exceeded the testing capacities for many laboratories. Clinical tests which receive CE and FDA authorizations cannot always be tested thoroughly in a real-world environment. Here we demonstrate the long-term stability of nasopharyngeal swab specimens for SARS-CoV-2 molecular testing across three assays recently approved by the U.S. FDA under Emergency Use Authorization. This study demonstrates that nasopharyngeal swab specimens can be stored under refrigeration or even ambient conditions for 21 days without clinically impacting the results of the real-time RT-PCR testing.", "qid": 16, "docid": "hhk900c1", "rank": 54, "score": 0.8239579200744629}, {"content": "Title: On the airborne aspect of COVID-19 coronovirus Content: It is a widely accepted view that COVID 19 is either transmitted via surface contamination or via close contact of an un-infected person with an infected person. Surface contamination usually happens when infected water droplets from exhalation/sneeze/cough of COVID sick person settle on nearby surfaces. To curb this, social distancing and good hand hygiene advise is advocated by World health Organization (WHO). We argue that COVID 19 coronovirus can also be airborne in a puff cloud loaded with infected droplets generated by COVID sick person. An elementary calculation shows that a $5~\\mu m$ respiratory infected droplet can remain suspended for about 9.0 minutes and a $2~\\mu m$ droplet can remain suspended for about an hour! And social distancing advise of 3 feet by WHO and 6 feet by CDC (Centers for Disease Control and Prevention) may not be sufficient in some circumstances as discussed in the text.", "qid": 16, "docid": "a47onmje", "rank": 55, "score": 0.8239307403564453}, {"content": "Title: Environmental and decontamination issues for human coronaviruses and their potential surrogates Content: Pandemic coronavirus disease-2019 (COVID-19) gives ample reason to generally review coronavirus (CoV) containment. For establishing some preliminary views on decontamination and disinfection, surrogate CoVs have commonly been assessed. This review serves to examine the existing science in regard to CoV containment generically and then to translate these findings into timely applications for COVID-19. There is widespread dissemination of CoVs in the immediate patient environment, and CoVs can potentially be spread via respiratory secretions, urine, and stool. Interpretations of the spread however must consider whether studies examine for viral RNA, virus viability by culture, or both. Presymptomatic, asymptomatic, and post-14 day virus excretion from patients may complicate the epidemiology. Whereas droplet spread is accepted, there continues to be controversy over the extent of possible airborne spread and especially now for severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). CoVs are stable in body secretions and sewage at reduced temperatures. In addition to temperature, dryness or relative humidity, initial viral burden, concomitant presence of bioburden, and the type of surface can all affect stability. Generalizing, CoVs can be susceptible to radiation, temperature extremes, pH extremes, peroxides, halogens, aldehydes, many solvents, and several alcohols. Whereas detergent surfactants can have some direct activity, these agents are better used as complements to a complex disinfectant solution. Disinfectants with multiple agents and adverse pH are more likely to be best active at higher water temperatures. Real-life assessments should be encouraged with working dilutions. The use of decontamination and disinfection should be balanced with considerations of patient and caregiver safety. Processes should also be balanced with considerations for other potential pathogens that must be targeted. Given some CoV differences and given that surrogate testing provides experimental correlates at best, direct assessments with SARS-CoV, Middle East respiratory syndrome-related coronavirus (MERS-CoV), and SARS-CoV-2 are required.", "qid": 16, "docid": "ou8lm4yl", "rank": 56, "score": 0.823367178440094}, {"content": "Title: Transmission of SARS and MERS coronaviruses and influenza virus in healthcare settings: the possible role of dry surface contamination Content: Summary Viruses with pandemic potential including H1N1, H5N1, and H5N7 influenza viruses, and severe acute respiratory syndrome (SARS)/Middle East respiratory syndrome (MERS) coronaviruses (CoV) have emerged in recent years. SARS-CoV, MERS-CoV, and influenza virus can survive on surfaces for extended periods, sometimes up to months. Factors influencing the survival of these viruses on surfaces include: strain variation, titre, surface type, suspending medium, mode of deposition, temperature and relative humidity, and the method used to determine the viability of the virus. Environmental sampling has identified contamination in field-settings with SARS-CoV and influenza virus, although the frequent use of molecular detection methods may not necessarily represent the presence of viable virus. The importance of indirect contact transmission (involving contamination of inanimate surfaces) is uncertain compared with other transmission routes, principally direct contact transmission (independent of surface contamination), droplet, and airborne routes. However, influenza virus and SARS-CoV may be shed into the environment and be transferred from environmental surfaces to hands of patients and healthcare providers. Emerging data suggest that MERS-CoV also shares these properties. Once contaminated from the environment, hands can then initiate self-inoculation of mucous membranes of the nose, eyes or mouth. Mathematical and animal models, and intervention studies suggest that contact transmission is the most important route in some scenarios. Infection prevention and control implications include the need for hand hygiene and personal protective equipment to minimize self-contamination and to protect against inoculation of mucosal surfaces and the respiratory tract, and enhanced surface cleaning and disinfection in healthcare settings.", "qid": 16, "docid": "pk8u9m7h", "rank": 57, "score": 0.8233410716056824}, {"content": "Title: Ebola Virus Stability on Surfaces and in Fluids in Simulated Outbreak Environments. Content: We evaluated the stability of Ebola virus on surfaces and in fluids under simulated environmental conditions for the climate of West Africa and for climate-controlled hospitals. This virus remains viable for a longer duration on surfaces in hospital conditions than in African conditions and in liquid than in dried blood.", "qid": 16, "docid": "0ywzv96f", "rank": 58, "score": 0.8224713802337646}, {"content": "Title: Luminore CopperTouch\u00e2\u0084\u00a2 surface coating effectively inactivates SARS-CoV-2, Ebola and Marburg viruses in vitro Content: We investigated the ability of Luminore CopperTouch copper and copper-nickel surfaces to inactivate filoviruses and severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). For this purpose, we compared viral titers in Vero cells from viral droplets exposed to copper surfaces for 30 min. The copper and copper-nickel surfaces inactivated 99.9% of the viral titer of both Ebola and Marburg viruses. The copper surfaces also inactivated 99% of SARS-CoV-2 titers in 2 hours to close to the limit of detection. These data add Ebolavirus, Marburgvirus, and SARS-CoV-2 (COVID-19) to the list of pathogens that can be inactivated by exposure to copper ions, validating Luminore CopperTouch technology (currently the only Environmental Protection Agency [EPA]-registered cold spray antimicrobial surface technology) as an efficacious, cost-friendly tool to improve infection control in hospitals, long-term care facilities, schools, hotels, buses, trains, airports, and other highly trafficked areas.", "qid": 16, "docid": "v8rbfnhz", "rank": 59, "score": 0.8220057487487793}, {"content": "Title: An experimental study of the survival of turkey coronavirus at room temperature and +4\u00b0C Content: Turkey coronavirus (TCoV) is a gammacoronavirus (Coronaviridae, Nidovirales) responsible for digestive disorders in young turkeys. TCoV has been associated with poult enteritis complex, a syndrome that severely affects turkey production. No medical prophylaxis exists to control TCoV, therefore sanitary measures such as cleaning and disinfection are essential. It is thus important to evaluate temperatures that allow persistence of TCoV in the environment. Two series of aliquots of a suspension of a French isolate of TCoV (Fr TCoV) were stored at room temperature or +4\u00b0C for 0 to 40 days. As TCoV does not grow in cell culture, the presence of residual infectious TCoV in the stored samples was tested by inoculating embryonated specific pathogen free turkey eggs. As TCoV does not induce lesions in the embryo, virus replication in the jejunum and ileum of the embryos was detected 4 days post inoculation, using RNA extraction and a real-time reverse transcriptase-polymerase chain reaction based on the nucleocapsid gene. No surviving virus was detected after 10 days storage at +21.6\u00b11.4\u00b0C or after 40 days storage at +4.1\u00b11.6\u00b0C, these temperatures being representative of the mean summer and winter temperatures, respectively, in the major French poultry-producing region. The relatively short survival of the virus at room temperature should contribute to limited virus survival during summer months. However, infectious virus was still detected after 20 days storage at the cooler temperatures, a finding that suggests prolonged survival of Fr TCoV and easier transmission between poultry farms in a cool environment are possible.", "qid": 16, "docid": "ytx6sf3x", "rank": 60, "score": 0.8213239908218384}, {"content": "Title: COVID-19 Surface Persistence: A Recent Data Summary and Its Importance for Medical and Dental Settings Content: Recently, due to the coronavirus pandemic, many guidelines and anti-contagion strategies continue to report unclear information about the persistence of coronavirus disease 2019 (COVID-19) in the environment. This certainly generates insecurity and fear in people, with an important psychological component that is not to be underestimated at this stage of the pandemic. The purpose of this article is to highlight all the sources currently present in the literature concerning the persistence of the different coronaviruses in the environment as well as in medical and dental settings. As this was a current study, there are still not many sources in the literature, and scientific strategies are moving towards therapy and diagnosis, rather than knowing the characteristics of the virus. Such an article could be an aid to summarize virus features and formulate new guidelines and anti-spread strategies.", "qid": 16, "docid": "6fmuh2or", "rank": 61, "score": 0.8206923007965088}, {"content": "Title: Viral Shedding and Environmental Cleaning in Middle East Respiratory Syndrome Coronavirus Infection Content: Viral shedding lasted 31 and 19 days from symptom onset in two patients with east respiratory syndrome coronavirus (MERS-CoV) pneumonia, respectively. Environmental real-time RT-PCR was weakly positive for bed guardrail and monitors. Even after cleaning the monitors with 70% alcohol-based disinfectant, RT-PCR was still weakly positive, and converted to negative only after wiping with diluted sodium chlorite. Further studies are required to clarify the appropriate methods to clean environments during and after treatment of patients with MERS-CoV infection.", "qid": 16, "docid": "x11dr866", "rank": 62, "score": 0.8201704025268555}, {"content": "Title: Environmental and Decontamination Issues for Human Coronaviruses and Their Potential Surrogates Content: Pandemic COVID-19 gives ample reason to generally review coronavirus (CoV) containment. For establishing some preliminary views on decontamination and disinfection, surrogate CoVs have commonly been assessed. This review serves to examine the existing science in regards to CoV containment generically and then to translate these findings into timely applications for COVID-19. There is widespread dissemination of CoVs in the immediate patient environment, and CoVs can potentially be spread via respiratory secretions, urine, and stool. Interpretations of the spread however must consider whether studies examine for viral RNA, virus viability by culture, or both. Pre-symptomatic, asymptomatic, and post-fourteen day virus excretion from patients may complicate the epidemiology. Whereas droplet spread is accepted, there continues to be controversy over the extent of possible airborne spread and especially now for SARS-CoV-2. CoVs are stable in body secretions and sewage at reduced temperatures. In addition to temperature, dryness or relative humidity, initial viral burden, concomitant presence of bioburden, and the type of surface can all affect stability. Generalizing, CoVs can be susceptible to radiation, temperature extremes, pH extremes, peroxides, halogens, aldehydes, many solvents, and several alcohols. Whereas detergent surfactants can have some direct activity, these agents are better used as complements to a complex disinfectant solution. Disinfectants with multiple agents and adverse pH are more likely to be best active at higher water temperatures. Real-life assessments should be encouraged with working dilutions. The use of decontamination and disinfection should be balanced with considerations of patient and caregiver safety. Processes should also be balanced with considerations for other potential pathogens that must be targeted. Given some CoV differences and given that surrogate testing provides experimental correlates at best, direct assessments with SARS-CoV, MERS-CoV, and SARS-CoV-2 are required. This article is protected by copyright. All rights reserved.", "qid": 16, "docid": "tgrl1d24", "rank": 63, "score": 0.8196277618408203}, {"content": "Title: Factors affecting stability and infectivity of SARS-CoV-2 Content: BACKGROUND: In late 2019, a novel human coronavirus, SARS-CoV-2, emerged in Wuhan, China. This virus has caused a global pandemic involving more than 200 countries. SARS-CoV-2 is highly adapted to humans and readily transmits from person-to-person. AIM: The aim of this study was to investigate the infectivity of SARS-CoV-2 under various environmental factors, disinfectants and different pH conditions. The efficacy of a variety of laboratory virus inactivation methods and home disinfectants against SARS-CoV-2 were investigated. METHODS: The residual virus in dried form or in solution was titrated on Vero E6 cell line at day 0, 1, 3, 5, and 7 after incubation at different temperatures. The viability of virus was determined after treatment with different disinfectants and pH solutions at room temperature (20\u00e2\u0088\u00bc25oC). FINDINGS: SARS-CoV-2 was able to retain viability for 3-5 days in dried form or 7 days in solution at room temperature. SARS-CoV-2 could be detected under a wide range of pH conditions from pH4 to pH11 for several days and 1 to 2 days in stool at room temperature but lost 5 logs of infectivity. A variety of commonly used disinfectants and laboratory inactivation procedures were found to reduce viral viability effectively. CONCLUSION: This study demonstrates the stability of SARS-CoV-2 on environmental surfaces and raises the possibility of faecal-oral transmission. Commonly used fixatives, nucleic acid extraction methods and heat inactivation were found to significantly reduce viral infectivity that could ensure hospital and laboratory safety during the COVID-19 pandemic.", "qid": 16, "docid": "eke4f5fn", "rank": 64, "score": 0.8194851875305176}, {"content": "Title: Factors affecting stability and infectivity of SARS-CoV-2 Content: BACKGROUND: In late 2019, a novel human coronavirus, SARS-CoV-2, emerged in Wuhan, China. This virus has caused a global pandemic involving more than 200 countries. SARS-CoV-2 is highly adapted to humans and readily transmits from person-to-person. AIM: The aim of this study was to investigate the infectivity of SARS-CoV-2 under various environmental factors, disinfectants and different pH conditions. The efficacy of a variety of laboratory virus inactivation methods and home disinfectants against SARS-CoV-2 were investigated. METHODS: The residual virus in dried form or in solution was titrated on Vero E6 cell line at day 0, 1, 3, 5, and 7 after incubation at different temperatures. The viability of virus was determined after treatment with different disinfectants and pH solutions at room temperature (20\u223c25(o)C). FINDINGS: SARS-CoV-2 was able to retain viability for 3-5 days in dried form or 7 days in solution at room temperature. SARS-CoV-2 could be detected under a wide range of pH conditions from pH4 to pH11 for several days and 1 to 2 days in stool at room temperature but lost 5 logs of infectivity. A variety of commonly used disinfectants and laboratory inactivation procedures were found to reduce viral viability effectively. CONCLUSION: This study demonstrates the stability of SARS-CoV-2 on environmental surfaces and raises the possibility of faecal-oral transmission. Commonly used fixatives, nucleic acid extraction methods and heat inactivation were found to significantly reduce viral infectivity that could ensure hospital and laboratory safety during the COVID-19 pandemic.", "qid": 16, "docid": "kngf6qpe", "rank": 65, "score": 0.8192501068115234}, {"content": "Title: How long do nosocomial pathogens persist on inanimate surfaces? A systematic review Content: BACKGROUND: Inanimate surfaces have often been described as the source for outbreaks of nosocomial infections. The aim of this review is to summarize data on the persistence of different nosocomial pathogens on inanimate surfaces. METHODS: The literature was systematically reviewed in MedLine without language restrictions. In addition, cited articles in a report were assessed and standard textbooks on the topic were reviewed. All reports with experimental evidence on the duration of persistence of a nosocomial pathogen on any type of surface were included. RESULTS: Most gram-positive bacteria, such as Enterococcus spp. (including VRE), Staphylococcus aureus (including MRSA), or Streptococcus pyogenes, survive for months on dry surfaces. Many gram-negative species, such as Acinetobacter spp., Escherichia coli, Klebsiella spp., Pseudomonas aeruginosa, Serratia marcescens, or Shigella spp., can also survive for months. A few others, such as Bordetella pertussis, Haemophilus influenzae, Proteus vulgaris, or Vibrio cholerae, however, persist only for days. Mycobacteria, including Mycobacterium tuberculosis, and spore-forming bacteria, including Clostridium difficile, can also survive for months on surfaces. Candida albicans as the most important nosocomial fungal pathogen can survive up to 4 months on surfaces. Persistence of other yeasts, such as Torulopsis glabrata, was described to be similar (5 months) or shorter (Candida parapsilosis, 14 days). Most viruses from the respiratory tract, such as corona, coxsackie, influenza, SARS or rhino virus, can persist on surfaces for a few days. Viruses from the gastrointestinal tract, such as astrovirus, HAV, polio- or rota virus, persist for approximately 2 months. Blood-borne viruses, such as HBV or HIV, can persist for more than one week. Herpes viruses, such as CMV or HSV type 1 and 2, have been shown to persist from only a few hours up to 7 days. CONCLUSION: The most common nosocomial pathogens may well survive or persist on surfaces for months and can thereby be a continuous source of transmission if no regular preventive surface disinfection is performed.", "qid": 16, "docid": "90qq0xsw", "rank": 66, "score": 0.8188906908035278}, {"content": "Title: Digitally aided telemedicine during the SARS\u2010CoV\u20102 pandemic to screen oral medicine emergencies Content: A new human coronavirus, known as severe acute respiratory coronavirus 2 syndrome (SARS\u2010CoV\u20102), emerged at the end of 2019 in Wuhan, China, and we are now facing a pandemic (WHO 2020). The virus has been found in saliva (Meng et al 2020, Sabino et al 2020). In vitro experimental findings suggest that SARS\u2010CoV\u20102 remained viable in aerosols for 3 hours (van Doremalen et al 2020).", "qid": 16, "docid": "jk73ojkp", "rank": 67, "score": 0.8188475370407104}, {"content": "Title: Persistently positive severe acute respiratory syndrome coronavirus 2 (SARS-COV2) nasopharyngeal PCR in a kidney transplant recipient Content: Severe acute respiratory syndrome coronavirus 2 (SARS-COV2 ) infection is usually diagnosed by a positive PCR test in respiratory samples. While the respiratory PCR may remain positive for 2-3 weeks in the general population there have been occasional reports of persistent and recurrent positive SARS-COV2 PCR beyond 4 weeks despite clinical resolution 1-6 .", "qid": 16, "docid": "ua4dv4jo", "rank": 68, "score": 0.8187169432640076}, {"content": "Title: Persistently positive severe acute respiratory syndrome coronavirus 2 (SARS-COV2) nasopharyngeal PCR in a kidney transplant recipient. Content: Severe acute respiratory syndrome coronavirus 2 (SARS-COV2 ) infection is usually diagnosed by a positive PCR test in respiratory samples. While the respiratory PCR may remain positive for 2-3 weeks in the general population there have been occasional reports of persistent and recurrent positive SARS-COV2 PCR beyond 4 weeks despite clinical resolution 1-6 .", "qid": 16, "docid": "su2fueox", "rank": 69, "score": 0.8187169432640076}, {"content": "Title: Survival characteristics of airborne human coronavirus 229E. Content: The survival of airborne human coronavirus 229E (HCV/229E) was studied under different conditions of temperature (20 +/- 1 degree C and 6 +/- 1 degree C) and low (30 +/- 5%), medium (50 +/- 5%) or high (80 +/- 5%) relative humidities (RH). At 20 +/- 1 degree C, aerosolized HCV/229E was found to survive best at 50% RH with a half-life of 67.33 +/- 8.24 h while at 30% RH the virus half-life was 26.76 +/- 6.21 h. At 50% RH nearly 20% infectious virus was still detectable at 6 days. High RH at 20 +/- 1 degree C, on the other hand, was found to be the least favourable to the survival of aerosolized virus and under these conditions the virus half-life was only about 3 h; no virus could be detected after 24 h in aerosol. At 6 +/- 1 degree C, in either 50% or 30% RH conditions, the survival of HCV/229E was significantly enhanced, with the decay pattern essentially similar to that seen at 20 +/- 1 degree C. At low temperature and high RH (80%), however, the survival pattern was completely reversed, with the HCV/229E half-life increasing to 86.01 +/- 5.28 h, nearly 30 times that found at 20 +/- 1 degree C and high RH. Although optimal survival at 6 degree C still occurred at 50% RH, the pronounced stabilizing effect of low temperature on the survival of HCV/229E at high RH indicates that the role of the environment on the survival of viruses in air may be more complex and significant than previously thought.", "qid": 16, "docid": "oi7karvd", "rank": 70, "score": 0.8185244202613831}, {"content": "Title: Quantitation, biological and physicochemical properties of cell culture-adapted porcine epidemic diarrhea coronavirus (PEDV) Content: Abstract The porcine epidemic coronavirus (PEDV), tentatively classified as a coronavirus, was adapted to Vero cells and a plaque test developed for infectivity titration, allowing us to test the biological and biophysical properties of the virus. Growth kinetics showed peak titers of 105.5 plaque-forming units ml\u22121 15 h after infection. Filtration experiments and electron microscopy revealed a particle diameter between 100 and 200 nm. The bouyant density of the virus was 1.18. The particle lost its infectivity on treatment with lipid solvents. Virus replication could not be inhibited by 5-iodo-2\u2032-deoxyuridine. PEDV was moderately stable at 50\u00b0C, but heat sensitivity was not altered by divalent cations. At 4\u00b0C, the virus was stable between pH 5.0 and 9.0, but at 37\u00b0C stability was restricted to the pH range 6.5\u20137.5. Viral infectivity was not impaired by ultrasonication or by multiple freezing and thawing. PEDV was not neutralized by transmissible gastroenteritis virus antiserum. On the basis of the tests carried out, PEDV is a pleomorphic, enveloped RNA virus with a particle diameter of \u223c 150 nm and a bouyant density of 1.18. Infectivity depends on the presence of trypsin, and infected cells show a tendency to fuse and to form syncytia. All of these properties, as well as its physicochemical characteristics, allow PEDV to be classified as a coronavirus.", "qid": 16, "docid": "j7bpccog", "rank": 71, "score": 0.8177849650382996}, {"content": "Title: SARS-CoV-2 infection: the environmental endurance of the virus can be influenced by the increase of temperature Content: The COVID-19 disease, a respiratory disease transmitted by a new betacoronavirus SARS-CoV-2. As for other viral respiratory agents, SARS-CoV-2 spreads by person to person through respiratory droplets and direct contact and potentially by indirect contact through fomites. The goal of the current study is to evaluate whether the increase of temperature can influence the environmental endurance of SARS-CoV-2.We tested SARS-CoV-2 environmental stability in parallel at room temperature (RT, 20-25 Celsius degrees) and at average maximum temperature of June (JT) estimated at 28 Celsius degrees in Italy. The virus inoculated on plastic surface was harvested at predefined time-points and tested to evaluate viral titres on Vero cells by TCID50. Our results confirm that fomite transmission of the emerging SARS-CoV2 is possible, since the virus remains viable on surfaces up to 84 hours at both RT and JT. Moreover, a remarkable difference between the two temperatures exists, suggesting that virus vitality can be influenced by the environmental temperature. Our results support the hypothesis that in the hot season the increase of temperature could influence the environmental endurance of SARS-CoV2 and reduce Covid-19 transmission probability.", "qid": 16, "docid": "h81b4imf", "rank": 72, "score": 0.8174090385437012}, {"content": "Title: Persistence of Bacteriophage Phi 6 on Porous and Non-Porous Surfaces; Potential for use as Ebola or Coronavirus Surrogate Content: The infection of healthcare workers during the 2013 -2016 Ebola outbreak raised concerns about fomite transmission. In the wake of the Coronavirus Disease 2019 (COVID-19) pandemic, investigations are ongoing to determine the role of fomites in coronavirus transmission as well. The bacteriophage Phi 6 has a phospholipid envelope and is commonly used in environmental studies as a surrogate for human enveloped viruses. The persistence of Phi 6 was evaluated as a surrogate for EBOV and coronaviruses on porous and nonporous hospital surfaces. Phi 6 was suspended in a body fluid simulant and inoculated onto 1 cm2 coupons of steel, plastic, and two fabric curtain types. The coupons were placed at two controlled absolute humidity (AH) levels; a low AH of 3.0 g/m3 and a high AH of 14.4 g/m3 Phi 6 declined at a slower rate on all materials under low AH conditions with a decay rate of 0.06 log10PFU/d to 0.11 log10PFU/d, as compared to the higher AH conditions with a decay rate of 0.65 log10PFU/h to 1.42 log10PFU/d. There was a significant difference in decay rates between porous and non-porous surfaces at both low AH (P < 0.0001) and high AH (P < 0.0001). Under these laboratory-simulated conditions, Phi 6 was found to be a conservative surrogate for EBOV under low AH conditions, in that it persisted longer than Ebola virus in similar AH conditions. Additionally, some coronaviruses persist longer than phi6 under similar conditions, therefore Phi6 may not be a suitable surrogate for coronaviruses.IMPORTANCE Understanding the persistence of enveloped viruses helps inform infection control practices and procedures in healthcare facilities and community settings. These data convey to public health investigators that enveloped viruses can persist and remain infective on surfaces, thus demonstrating a potential risk for transmission. Under these laboratory-simulated western indoor hospital conditions, Phi 6 was used to assess suitability as a surrogate for environmental persistence research related to enveloped viruses, including EBOV and coronaviruses.", "qid": 16, "docid": "a27luzwj", "rank": 73, "score": 0.8172765374183655}, {"content": "Title: Persistence of Bacteriophage Phi 6 on Porous and Non-Porous Surfaces; Potential for use as Ebola or Coronavirus Surrogate. Content: The infection of healthcare workers during the 2013 -2016 Ebola outbreak raised concerns about fomite transmission. In the wake of the Coronavirus Disease 2019 (COVID-19) pandemic, investigations are ongoing to determine the role of fomites in coronavirus transmission as well. The bacteriophage Phi 6 has a phospholipid envelope and is commonly used in environmental studies as a surrogate for human enveloped viruses. The persistence of Phi 6 was evaluated as a surrogate for EBOV and coronaviruses on porous and nonporous hospital surfaces. Phi 6 was suspended in a body fluid simulant and inoculated onto 1 cm2 coupons of steel, plastic, and two fabric curtain types. The coupons were placed at two controlled absolute humidity (AH) levels; a low AH of 3.0 g/m3 and a high AH of 14.4 g/m3 Phi 6 declined at a slower rate on all materials under low AH conditions with a decay rate of 0.06 log10PFU/d to 0.11 log10PFU/d, as compared to the higher AH conditions with a decay rate of 0.65 log10PFU/h to 1.42 log10PFU/d. There was a significant difference in decay rates between porous and non-porous surfaces at both low AH (P < 0.0001) and high AH (P < 0.0001). Under these laboratory-simulated conditions, Phi 6 was found to be a conservative surrogate for EBOV under low AH conditions, in that it persisted longer than Ebola virus in similar AH conditions. Additionally, some coronaviruses persist longer than phi6 under similar conditions, therefore Phi6 may not be a suitable surrogate for coronaviruses.IMPORTANCE Understanding the persistence of enveloped viruses helps inform infection control practices and procedures in healthcare facilities and community settings. These data convey to public health investigators that enveloped viruses can persist and remain infective on surfaces, thus demonstrating a potential risk for transmission. Under these laboratory-simulated western indoor hospital conditions, Phi 6 was used to assess suitability as a surrogate for environmental persistence research related to enveloped viruses, including EBOV and coronaviruses.", "qid": 16, "docid": "bgodmbru", "rank": 74, "score": 0.8172765374183655}, {"content": "Title: Estimated Inactivation of Coronaviruses by Solar Radiation With Special Reference to COVID-19 Content: Using a model developed for estimating solar inactivation of viruses of biodefense concerns, we calculated the expected inactivation of SARS-CoV-2 virus, cause of COVID-19 pandemic, by artificial UVC and by solar ultraviolet radiation in several cities of the world during different times of the year. The UV sensitivity estimated here for SARS-CoV-2 is compared with those reported for other ssRNA viruses, including influenza A virus. The results indicate that SARS-CoV-2 aerosolized from infected patients and deposited on surfaces could remain infectious outdoors for considerable time during the winter in many temperate-zone cities, with continued risk for re-aerosolization and human infection. Conversely, the presented data indicate that SARS-CoV-2 should be inactivated relatively fast (faster than influenza A) during summer in many populous cities of the world, indicating that sunlight should have a role in the occurrence, spread rate, and duration of coronavirus pandemics.", "qid": 16, "docid": "7emv2bao", "rank": 75, "score": 0.8168141841888428}, {"content": "Title: Estimated Inactivation of Coronaviruses by Solar Radiation With Special Reference to COVID-19 Content: Using a model developed for estimating solar inactivation of viruses of biodefense concerns, we calculated the expected inactivation of SARS-CoV-2 virus, cause of COVID-19 pandemic, by artificial UVC and by solar ultraviolet radiation in several cities of the world during different times of the year. The UV sensitivity estimated here for SARS-CoV-2 is compared with those reported for other ssRNA viruses, including influenza A virus. The results indicate that SARS-CoV-2 aerosolized from infected patients and deposited on surfaces could remain infectious outdoors for considerable time during the winter in many temperate-zone cities, with continued risk for re-aerosolization and human infection. Conversely, the presented data indicate that SARS-CoV-2 should be inactivated relatively fast (faster than influenza A) during summer in many populous cities of the world, indicating that sunlight should have a role in the occurrence, spread rate and duration of coronavirus pandemics.", "qid": 16, "docid": "4xijeti6", "rank": 76, "score": 0.816326379776001}, {"content": "Title: Plaque assay for human coronavirus NL63 using human colon carcinoma cells Content: BACKGROUND: Coronaviruses cause a broad range of diseases in animals and humans. Human coronavirus (hCoV) NL63 is associated with up to 10% of common colds. Viral plaque assays enable the characterization of virus infectivity and allow for purifying virus stock solutions. They are essential for drug screening. Hitherto used cell cultures for hCoV-NL63 show low levels of virus replication and weak and diffuse cytopathogenic effects. It has not yet been possible to establish practicable plaque assays for this important human pathogen. RESULTS: 12 different cell cultures were tested for susceptibility to hCoV-NL63 infection. Human colon carcinoma cells (CaCo-2) replicated virus more than 100 fold more efficiently than commonly used African green monkey kidney cells (LLC-MK2). CaCo-2 cells showed cytopathogenic effects 4 days post infection. Avicel, agarose and carboxymethyl-cellulose overlays proved suitable for plaque assays. Best results were achieved with Avicel, which produced large and clear plaques from the 4(th )day of infection. The utility of plaque assays with agrose overlay was demonstrated for purifying virus, thereby increasing viral infectivity by 1 log 10 PFU/mL. CONCLUSION: CaCo-2 cells support hCoV-NL63 better than LLC-MK2 cells and enable cytopathogenic plaque assays. Avicel overlay is favourable for plaque quantification, and agarose overlay is preferred for plaque purification. HCoV-NL63 virus stock of increased infectivity will be beneficial in antiviral screening, animal modelling of disease, and other experimental tasks.", "qid": 16, "docid": "qm61azql", "rank": 77, "score": 0.8158063292503357}, {"content": "Title: Rapid detection and monitoring of human coronavirus infections Content: Human coronaviruses (CoVs) are increasingly recognized as important respiratory pathogens associated with a broad range of clinical diseases. We sought to increase the insight into clinically relevant CoV infections by monitoring antigen concentrations in six confirmed CoV-positive patients using a newly developed assay for rapid detection of CoV OC43 infections. Antigen positivity lasted 3 to 6 days in secondary infections and 13 days in primary infection. CoV infections are clinically diverse, are common, and cannot be diagnosed from clinical symptoms alone.", "qid": 16, "docid": "rl66trp0", "rank": 78, "score": 0.815644383430481}, {"content": "Title: Environmental and Decontamination Issues for Human Coronaviruses and Their Potential Surrogates Content: Pandemic COVID\u201019 gives ample reason to generally review coronavirus (CoV) containment. For establishing some preliminary views on decontamination and disinfection, surrogate CoVs have commonly been assessed. This review serves to examine the existing science in regards to CoV containment generically and then to translate these findings into timely applications for COVID\u201019. There is widespread dissemination of CoVs in the immediate patient environment, and CoVs can potentially be spread via respiratory secretions, urine, and stool. Interpretations of the spread however must consider whether studies examine for viral RNA, virus viability by culture, or both. Pre\u2010symptomatic, asymptomatic, and post\u2010fourteen day virus excretion from patients may complicate the epidemiology. Whereas droplet spread is accepted, there continues to be controversy over the extent of possible airborne spread and especially now for SARS\u2010CoV\u20102. CoVs are stable in body secretions and sewage at reduced temperatures. In addition to temperature, dryness or relative humidity, initial viral burden, concomitant presence of bioburden, and the type of surface can all affect stability. Generalizing, CoVs can be susceptible to radiation, temperature extremes, pH extremes, peroxides, halogens, aldehydes, many solvents, and several alcohols. Whereas detergent surfactants can have some direct activity, these agents are better used as complements to a complex disinfectant solution. Disinfectants with multiple agents and adverse pH are more likely to be best active at higher water temperatures. Real\u2010life assessments should be encouraged with working dilutions. The use of decontamination and disinfection should be balanced with considerations of patient and caregiver safety. Processes should also be balanced with considerations for other potential pathogens that must be targeted. Given some CoV differences and given that surrogate testing provides experimental correlates at best, direct assessments with SARS\u2010CoV, MERS\u2010CoV, and SARS\u2010CoV\u20102 are required. This article is protected by copyright. All rights reserved.", "qid": 16, "docid": "8rl0y45s", "rank": 79, "score": 0.8155546188354492}, {"content": "Title: Duration of viral detection in throat and rectum of a patient with COVID-19 Content: The rapid spread of coronavirus disease 2019 (COVID-19) raises concern about a global pandemic. Knowledge about the duration of viral shedding remains important for patient management and infection control. We report the duration of viral detection in throat and rectum of a COVID-19 patient treated at the Hospital for Tropical Diseases in Ho Chi Minh City, Vietnam. Despite clinical recovery, SARS-CoV-2 RNA remained detectable by real time RT-PCR in throat and rectal swabs until day 11 and 18 of hospitalization, respectively. Because live SARS-CoV-2 has been successfully isolated from a stool sample from a COVID-19 patient in China, the results demonstrate that COVID-19 patients may remain infectious for long periods, and fecal-oral transmission may be possible. Therefore, our finding has important implications for infection control.", "qid": 16, "docid": "q4i9kh65", "rank": 80, "score": 0.8152077198028564}, {"content": "Title: Tackling Corona Virus Disease 2019 (COVID 19) in Workplaces Content: Coronaviruses are zoonotic viruses and six species of Coronaviruses are known to cause human disease such as cause common cold, severe acute respiratory syndrome and the Middle East Respiratory Syndrome. In January 2020, scientists in Wuhan, China isolated a novel coronavirus (SARS-CoV-2), responsible for an outbreak of unknown pneumonia that had not been previously reported among humans. This virus spreads from person to person, through respiratory droplets, close contact, and by touching surfaces or objects contaminated by the virus. The incubation period varies between 2 days and 14 days. Symptoms usually include fever, cough, difficulty in breathing, pneumonia, severe acute respiratory syndrome. Older age and co-morbid conditions increase the fatality. Any person with a history of travel to and from COVID-19 affected countries in the past 14 days or any person who has had close contact with a laboratory confirmed COVID-19 are suspect cases and needs evaluation. Currently no vaccine is available and treatment is mainly supportive. Measures at workplace should include- avoiding non-essential travel, identifying and isolating sick employees at the earliest, hand hygiene, respiratory hygiene, environmental hygiene and social distancing.", "qid": 16, "docid": "rzr8qjw8", "rank": 81, "score": 0.815134584903717}, {"content": "Title: Maintenance of pluripotency in mouse embryonic stem cells persistently infected with murine coronavirus. Content: A persistently coronavirus-infected embryonic stem (ES) cell line A3/MHV was established by infecting an ES cell line, A3-1, with mouse hepatitis virus type-2. Although almost all A3/MHV cells were found infected, both A3/MHV and A3-1 cells expressed comparable levels of cell surface differentiation markers. In addition, A3/MHV cells retained the ability to form embryoid bodies. These results suggest that persistent coronavirus infection does not affect the differentiation of ES cells.", "qid": 16, "docid": "ann6dzmn", "rank": 82, "score": 0.8151092529296875}, {"content": "Title: Clinical and Epidemiological Features of a Family Cluster of Symptomatic and Asymptomatic Severe Acute Respiratory Syndrome Coronavirus 2 Infection Content: In a family experiencing coronavirus disease 2019, the parents and 2 children aged 2 and 5 years became infected but the youngest child was not infected. Both children initially shed infectious virus, but cleared the virus after 5 to 6 days in the nasopharynx. However, viral RNA was continuously detected in the children\u2019s stool for more than 4 weeks.", "qid": 16, "docid": "zz5bpas1", "rank": 83, "score": 0.8140803575515747}, {"content": "Title: COVID-19 in air suspensions Content: We analyse the stability of virus-carrying particles in air at equilibrium after the dissipation of the initial turbulent process produced by sneezing, coughing, breathing or speaking. Because the viruses are expelled mainly attached to small droplets, with diverse sizes and weights, and the external environmental conditions can also be diverse, the subsequent motion spannes different spatial and temporal scales. For droplet sizes larger than $100\\,\\mu m$, computing the time of decay to the ground and the distance travelled with a simple free fall model with empirical data extracted from the literature, we obtain distances in the range between $1$ to $3$ meters from the emitter, with a falling time of less than $1\\,s$, similar to known recommendations for safe social distancing. For droplets sizes less than $100\\,\\mu m$ a simple model of motion in a viscous medium predicts that isolated viruses could remain suspended in quiet air for more than a month, while small droplets of $1\\,\\mu m$ in size can remain suspended for several hours, in agreement with recent experimental results on virus stability in aerosols. These results give solid background for the discussion of prevention strategies, like the use of masks in closed environments.", "qid": 16, "docid": "qvqoncbk", "rank": 84, "score": 0.8137935996055603}, {"content": "Title: Inactivation of surrogate coronaviruses on hard surfaces by health care germicides Content: BACKGROUND: In the 2003 severe acute respiratory syndrome outbreak, finding viral nucleic acids on hospital surfaces suggested surfaces could play a role in spread in health care environments. Surface disinfection may interrupt transmission, but few data exist on the effectiveness of health care germicides against coronaviruses on surfaces. METHODS: The efficacy of health care germicides against 2 surrogate coronaviruses, mouse hepatitis virus (MHV) and transmissible gastroenteritis virus (TGEV), was tested using the quantitative carrier method on stainless steel surfaces. Germicides were o-phenylphenol/p-tertiary amylphenol) (a phenolic), 70% ethanol, 1:100 sodium hypochlorite, ortho-phthalaldehyde (OPA), instant hand sanitizer (62% ethanol), and hand sanitizing spray (71% ethanol). RESULTS: After 1-minute contact time, for TGEV, there was a log(10) reduction factor of 3.2 for 70% ethanol, 2.0 for phenolic, 2.3 for OPA, 0.35 for 1:100 hypochlorite, 4.0 for 62% ethanol, and 3.5 for 71% ethanol. For MHV, log(10) reduction factors were 3.9 for 70% ethanol, 1.3 for phenolic, 1.7 for OPA, 0.62 for 1:100 hypochlorite, 2.7 for 62% ethanol, and 2.0 for 71% ethanol. CONCLUSION: Only ethanol reduced infectivity of the 2 coronaviruses by >3-log(10) after 1 minute. Germicides must be chosen carefully to ensure they are effective against viruses such as severe acute respiratory syndrome coronavirus.", "qid": 16, "docid": "yr1dq258", "rank": 85, "score": 0.813673734664917}, {"content": "Title: Stability of the COVID-19 virus under wet, dry and acidic conditions Content: COVID-19 has become a pandemic and is spreading fast worldwide. The COVID-19 virus is transmitted mainly through respiratory droplets and close contact. However, the fecal-oral transmission of the virus has not been ruled out and it is important to ascertain how acidic condition in the stomach affects the infectivity of the virus. Besides, it is unclear how stable the COVID-19 virus is under dry and wet conditions. In the present study, we have shown that the COVID-19 virus is extremely infectious as manifested by the infection of Vero-E6 cells by one PFU (Plaque Forming Unit) of the virus. We then investigated the stability of the COVID-19 virus in wet, dry and acidic (pH2.2) environments at room temperature. Results showed that the COVID-19 virus could survive for three days in wet and dry environments, but the dry condition is less favorable for the survival of the virus. Our study also demonstrated that the COVID-19 virus at a relative high titer (1.2 x 103 PFU) exhibits a certain degree of tolerance to acidic environment at least for 60 minutes. When the virus titer was \u22641.0 x 103 PFU, acid treatment (pH2.2) for 30 or 60 minute resulted in virus inactivation. It suggests that the virus at a high concentration may survive in the acidic environment of the stomach. The finding of the present study will contribute to the control of the spread of the COVID-19 virus.", "qid": 16, "docid": "3cm44rbz", "rank": 86, "score": 0.813581109046936}, {"content": "Title: Viral survival Content: How long do viruses like cold, flu and coronavirus survive outside the body? What factors affect this?", "qid": 16, "docid": "959w9sln", "rank": 87, "score": 0.8134069442749023}, {"content": "Title: Case Report: Viral Shedding for 60 Days in a Woman with COVID-19 Content: Novel coronavirus disease (COVID-19) caused by severe acute respiratory syndrome-coronavirus-2 (SARS-CoV-2) has become a public health emergency of international concern. This was first noted in Wuhan, Hubei Province, China, and since then has become widespread globally. We report a 71-year-old woman with documented viral shedding (based on reverse transcription-polymerase chain reaction (RT-PCR) testing) of SARS-CoV-2 for 60 days from the onset of symptoms (55 days from her first positive test and 36 days after complete resolution of symptoms). This is to our knowledge the longest duration of viral shedding reported to date. This case demonstrates that viral shedding after COVID-19 diagnosis can be prolonged.", "qid": 16, "docid": "1vba9l42", "rank": 88, "score": 0.8133858442306519}, {"content": "Title: Case Report: Viral Shedding for 60 Days in a Woman with COVID-19 Content: Novel coronavirus disease (COVID-19) caused by severe acute respiratory syndrome-coronavirus-2 (SARS-CoV-2) has become a public health emergency of international concern. This was first noted in Wuhan, Hubei Province, China, and since then has become widespread globally. We report a 71-year-old woman with documented viral shedding (based on reverse transcription\u2013polymerase chain reaction (RT-PCR) testing) of SARS-CoV-2 for 60 days from the onset of symptoms (55 days from her first positive test and 36 days after complete resolution of symptoms). This is to our knowledge the longest duration of viral shedding reported to date. This case demonstrates that viral shedding after COVID-19 diagnosis can be prolonged.", "qid": 16, "docid": "vvzga2tm", "rank": 89, "score": 0.8133841753005981}, {"content": "Title: Comparative dynamic aerosol efficiencies of three emergent coronaviruses and the unusual persistence of SARS-CoV-2 in aerosol suspensions Content: The emergent coronavirus, designated severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2), is a zoonotic pathogen that has demonstrated remarkable transmissibility in the human population and is the etiological agent of a current global pandemic called COVID-19. We measured the dynamic (short-term) aerosol efficiencies of SARS-CoV-2 and compared the efficiencies with two other emerging coronaviruses, SARS-CoV (emerged in 2002) and Middle Eastern respiratory syndrome CoV (MERS-CoV; emerged starting in 2012). We also quantified the long-term persistence of SARS-CoV-2 and its ability to maintain infectivity when suspended in aerosols for up to 16 hours.", "qid": 16, "docid": "zfm6xjkh", "rank": 90, "score": 0.8133071660995483}, {"content": "Title: As We Went to Press: COVID-19 Continues to Spread Content: Updates on the coronavirus.", "qid": 16, "docid": "7t976vq8", "rank": 91, "score": 0.8132191896438599}, {"content": "Title: As We Went to Press: COVID-19 Continues to Spread. Content: Updates on the coronavirus.", "qid": 16, "docid": "sb1n3fra", "rank": 92, "score": 0.8132191896438599}, {"content": "Title: Protection and disinfection policies against SARS-CoV-2 (COVID-19) Content: In late December 2019, reports from China of the incidence of pneumonia with unknown etiology were sent to the World Health Organization (WHO). Shortly afterwards, the cause of this disease was identified as the novel beta-coronavirus, SARS-CoV-2, and its genetic sequence was published on January 12, 2020. Human-to-human transmission via respiratory droplets and contact with aerosol infected surfaces are the major ways of transmitting this virus. Here we attempted to collect information on virus stability in the air and on surfaces and ways of preventing of SARS-CoV-2 spreading.", "qid": 16, "docid": "erdos4yw", "rank": 93, "score": 0.8131705522537231}, {"content": "Title: Protection and disinfection policies against SARS-CoV-2 (COVID-19). Content: In late December 2019, reports from China of the incidence of pneumonia with unknown etiology were sent to the World Health Organization (WHO). Shortly afterwards, the cause of this disease was identified as the novel beta-coronavirus, SARS-CoV-2, and its genetic sequence was published on January 12, 2020. Human-to-human transmission via respiratory droplets and contact with aerosol infected surfaces are the major ways of transmitting this virus. Here we attempted to collect information on virus stability in the air and on surfaces and ways of preventing of SARS-CoV-2 spreading.", "qid": 16, "docid": "kuioq8o6", "rank": 94, "score": 0.8131705522537231}, {"content": "Title: Design of engineered surfaces for prospective detection of Sars-CoV-2 using quartz crystal microbalance based techniques Content: INTRODUCTION: Rapid transmission of the severe acute respiratory syndrome coronavirus 2 has affected the whole world and forced it to a halt (lockdown). A fast and label free detection method for the novel coronavirus needs to be developed along with the existing enzyme-linked immunosorbent assay (ELISA) and reverse transcription polymerase chain reaction (RT-PCR) based methods. AREAS COVERED: In this report, biophysical aspects of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) spike glycoprotein are outlined based on its recent reported electron microscopy structure. Protein binding sites are analyzed theoretically, which consisted of hydrophobic and positive charged amino acid residues. Different strategies to form mixed self-assembled monolayers (SAMs) of hydrophobic (CH3) and negatively charged (COOH) groups are discussed to be used for the specific and strong interactions with spike protein. Bio-interfacial interactions between the spike protein and device (sensor) surface and its implications towards designing suitable engineered surfaces are summarized. EXPERT OPINION: Implementation of the engineered surfaces in quartz crystal microbalance (QCM) based detection techniques for the diagnosis of the novel coronavirus from oral swab samples is highlighted. The proposed strategy can be explored for the label free and real time detection with sensitivity up to ng level. These engineered surfaces can be reused after desorption.", "qid": 16, "docid": "2ezuf5ce", "rank": 95, "score": 0.8127062320709229}, {"content": "Title: Surface Alterations to Impart Antiviral Properties to Combat COVID-19 Transmission Content: A global epidemic caused by highly transmittable COVID-19 is causing severe loss of human life. In this study, two aspects of reducing transmission of COVID-19 virus, due to surface contact, are discussed: first refers to the effect of nanocarbon fullerene C(60) coating on surface, that causes lipid peroxidation on the phospholipid layer present in the outer envelope of COVID-19; the second aspect refers to creating hydrophobic surfaces by texturing them, so that the contact area between virus and surface is minimized due to the presence of entrapped air between the topographies. These can be similar to micro-/nano-multiscale textured surfaces that have anti-biofouling properties. Fullerene-coated surfaces can be seen as a possible solution to decrease the adhesion of virus on the surface, as they will be hydrophobic as well as toxic to the envelope.", "qid": 16, "docid": "mczrufe0", "rank": 96, "score": 0.8120930194854736}, {"content": "Title: Design of engineered surfaces for prospective detection of Sars-CoV-2 using quartz crystal microbalance based techniques. Content: INTRODUCTION Rapid transmission of the severe acute respiratory syndrome coronavirus 2 has affected the whole world and forced it to a halt (lockdown). A fast and label free detection method for the novel coronavirus needs to be developed along with the existing enzyme-linked immunosorbent assay (ELISA) and reverse transcription polymerase chain reaction (RT-PCR) based methods. AREAS COVERED In this report, biophysical aspects of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) spike glycoprotein are outlined based on its recent reported electron microscopy structure. Protein binding sites are analyzed theoretically, which consisted of hydrophobic and positive charged amino acid residues. Different strategies to form mixed self-assembled monolayers (SAMs) of hydrophobic (CH3) and negatively charged (COOH) groups are discussed to be used for the specific and strong interactions with spike protein. Bio-interfacial interactions between the spike protein and device (sensor) surface and its implications towards designing suitable engineered surfaces are summarized. EXPERT OPINION Implementation of the engineered surfaces in quartz crystal microbalance (QCM) based detection techniques for the diagnosis of the novel coronavirus from oral swab samples is highlighted. The proposed strategy can be explored for the label free and real time detection with sensitivity up to ng level. These engineered surfaces can be reused after desorption.", "qid": 16, "docid": "yqsbt0l9", "rank": 97, "score": 0.8112640976905823}, {"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": 16, "docid": "cz3qt5qd", "rank": 98, "score": 0.8110498189926147}, {"content": "Title: Optimal temperature zone for the dispersal of COVID-19 Content: It is essential to know the environmental parameters within which the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) can survive to understand its global dispersal pattern. We found that 60.0% of the confirmed cases of coronavirus disease 2019 (COVID-19) occurred in places where the air temperature ranged from 5 \u00b0C to 15 \u00b0C, with a peak in cases at 11.54 \u00b0C. Moreover, approximately 73.8% of the confirmed cases were concentrated in regions with absolute humidity of 3 g/m3 to 10 g/m3. SARS-CoV-2 appears to be spreading toward higher latitudes. Our findings suggest that there is an optimal climatic zone in which the concentration of SARS-CoV-2 markedly increases in the ambient environment (including the surfaces of objects). These results strongly imply that the COVID-19 pandemic may spread cyclically and outbreaks may recur in large cities in the mid-latitudes in autumn 2020.", "qid": 16, "docid": "gdl4l9xo", "rank": 99, "score": 0.810928225517273}, {"content": "Title: Stability of SARS-CoV-2 in different environmental conditions Content: Stability of SARS-CoV-2 in different environmental conditions.", "qid": 16, "docid": "rbzl0txp", "rank": 100, "score": 0.8105030059814453}]}
{"query": "are there any clinical trials available for the coronavirus", "hits": [{"content": "Title: Clinical trials for the prevention and treatment of COVID-19: current state of play Content: Since coronavirus disease 2019 (COVID-19) emerged in Wuhan, China in December 2019 and spread around the world, over 1100 clinical studies have been registered globally on clinical trials registries, including over 500 randomised controlled trials. Such rapid development and launch of clinical trials is impressive but presents challenges, including the potential for duplication and competition. There is currently no known effective treatment for COVID-19. In order to focus on those studies most likely to influence clinical practice, we summarise the 31 currently registered randomised trials with a target sample size of at least 1000 participants. We have grouped these trials into four categories: prophylaxis; treatment of outpatients with mild COVID-19; treatment of hospitalised patients with moderate COVID-19; and treatment of hospitalised patients with moderate or severe disease. The most common therapeutic agent being trialled currently is hydroxychloroquine (24 trials with potential sample size of over 25 000 participants), followed by lopinavir-ritonavir (seven trials) and remdesevir (five trials) There are many candidate drugs in pre-clinical and early phase development, and these form a pipeline for future large clinical trials if current candidate therapies prove ineffective or unsafe.", "qid": 17, "docid": "pftu5qea", "rank": 1, "score": 0.8940824270248413}, {"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": 2, "score": 0.8867664337158203}, {"content": "Title: Clinical trials for the prevention and treatment of COVID\u201019: current state of play Content: Since coronavirus disease 2019 (COVID\u201019) emerged in Wuhan, China in December 2019 and spread around the world, over 1100 clinical studies have been registered globally on clinical trials registries, including over 500 randomised controlled trials. Such rapid development and launch of clinical trials is impressive but presents challenges, including the potential for duplication and competition. There is currently no known effective treatment for COVID\u201019. In order to focus on those studies most likely to influence clinical practice, we summarise the 31 currently registered randomised trials with a target sample size of at least 1000 participants. We have grouped these trials into four categories: prophylaxis; treatment of outpatients with mild COVID\u201019; treatment of hospitalised patients with moderate COVID\u201019; and treatment of hospitalised patients with moderate or severe disease. The most common therapeutic agent being trialled currently is hydroxychloroquine (24 trials with potential sample size of over 25 000 participants), followed by lopinavir\u2013ritonavir (seven trials) and remdesevir (five trials). There are many candidate drugs in pre\u2010clinical and early phase development, and these form a pipeline for future large clinical trials if current candidate therapies prove ineffective or unsafe.", "qid": 17, "docid": "6wszpqvx", "rank": 3, "score": 0.8855239748954773}, {"content": "Title: Major ongoing clinical trials for COVID-19 treatment and studies currently being conducted or scheduled in Japan Content: The outbreak of coronavirus disease 2019 (COVID-19) caused by the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) poses a serious threat to global public health and economies Currently, hundreds of clinical trials on a wide variety of treatments against COVID-19 are being conducted around the world Here, we conducted a search for ongoing clinical trials for the treatment of COVID-19 at the clinicaltrials gov database on April 2, 2020 In total, 48 clinical trials were identified, and of these, 41 trials adopted drug intervention and the other 7 trials utilized biological intervention The number of trials stratified by a chief country conducting the investigation were 18 in China, 5 in the United States, 4 in Canada, 3 in Italy, 2 in France and Brazil, and 4 trials are being performed multinationally The drugs utilized in more than one trials were remdesivir (6 trials), lopinavir/ritonavir (6 trials), hydroxychloroquine (6 trials), interferon (5 trials), methylprednisolone (3 trials), nitric oxide gas (3 trials), oseltamivir (2 trials), arbidol (2 trials), and vitamin C (2 trials) We also described the Japanese trials which are now being conducted or scheduled, utilizing lopinavir/ritonavir, remdesivir, favipiravir, ciclesonide and nafamostat", "qid": 17, "docid": "i4fz2c49", "rank": 4, "score": 0.8825829029083252}, {"content": "Title: Characteristics of registered clinical trials assessing treatments for COVID-19: a cross-sectional analysis Content: OBJECTIVES: The coronavirus disease 2019 (COVID-19) pandemic has prompted many initiatives to identify safe and efficacious treatments, yet little is known regarding where early efforts have focused. We aimed to characterise registered clinical trials assessing drugs or plasma treatments for COVID-19. DESIGN, SETTING AND PARTICIPANTS: Cross-sectional analysis of clinical trials for the treatment of COVID-19 that were registered in the USA or in countries contributing to the WHO's International Clinical Trials Registry Platform. Relevant trial entries of drugs or plasma were downloaded on 26 March 2020, deduplicated, verified with reviews of major medical journals and WHO websites and independently analysed by two reviewers. MAIN OUTCOMES: Trial intervention, sponsorship, critical design elements and specified outcomes RESULTS: Overall, 201 clinical trials were registered for testing the therapeutic benefits of 92 drugs or plasma, including 64 in monotherapy and 28 different combinations. Only eight (8.7%) products or combinations involved new molecular entities. The other test therapies had a wide range of prior medical uses, including as antivirals, antimalarials, immunosuppressants and oncology treatments. In 152 trials (75.7%), patients were randomised to treatment or comparator, including 55 trials with some form of blinding and 97 open-label studies. The 49 (24.4%) of trials without a randomised design included 29 single armed studies and 20 trials with some comparison group. Most trial designs featured multiple endpoints. Clinical endpoints were identified in 134 (66.7%) of trials and included COVID-19 symptoms, death, recovery, required intensive care and hospital discharge. Clinical scales were being used in 33 (16.4%) trials, most often measures of oxygenation and critical illness. Surrogate endpoints or biomarkers were studied in 88 (42.3%) of trials, primarily assays of viral load. Although the trials were initiated in more than 17 countries or regions, 100 (49.8%) were registered in China and 78 (37.8%) in the USA. Registered trials increased rapidly, with the number of registered trials doubling from 1 March to 26 March 2020. CONCLUSIONS: While accelerating morbidity and mortality from the COVID-19 pandemic has been paralleled by early and rapid clinical investigation, many trials lack features to optimise their scientific value. Global coordination and increased funding of high-quality research may help to maximise scientific progress in rapidly discovering safe and effective treatments.", "qid": 17, "docid": "k1eq4l3d", "rank": 5, "score": 0.8793090581893921}, {"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": 6, "score": 0.8780924081802368}, {"content": "Title: Characteristics of registered clinical trials assessing treatments for COVID-19: a cross-sectional analysis Content: OBJECTIVES: The coronavirus disease 2019 (COVID-19) pandemic has prompted many initiatives to identify safe and efficacious treatments, yet little is known regarding where early efforts have focused. We aimed to characterise registered clinical trials assessing drugs or plasma treatments for COVID-19. DESIGN, SETTING AND PARTICIPANTS: Cross-sectional analysis of clinical trials for the treatment of COVID-19 that were registered in the USA or in countries contributing to the WHO\u2019s International Clinical Trials Registry Platform. Relevant trial entries of drugs or plasma were downloaded on 26 March 2020, deduplicated, verified with reviews of major medical journals and WHO websites and independently analysed by two reviewers. MAIN OUTCOME(S): Trial intervention, sponsorship, critical design elements and specified outcomes RESULTS: Overall, 201 clinical trials were registered for testing the therapeutic benefits of 92 drugs or plasma, including 64 in monotherapy and 28 different combinations. Only eight (8.7%) products or combinations involved new molecular entities. The other test therapies had a wide range of prior medical uses, including as antivirals, antimalarials, immunosuppressants and oncology treatments. In 152 trials (75.7%), patients were randomised to treatment or comparator, including 55 trials with some form of blinding and 97 open-label studies. The 49 (24.4%) of trials without a randomised design included 29 single armed studies and 20 trials with some comparison group. Most trial designs featured multiple endpoints. Clinical endpoints were identified in 134 (66.7%) of trials and included COVID-19 symptoms, death, recovery, required intensive care and hospital discharge. Clinical scales were being used in 33 (16.4%) trials, most often measures of oxygenation and critical illness. Surrogate endpoints or biomarkers were studied in 88 (42.3%) of trials, primarily assays of viral load. Although the trials were initiated in more than 17 countries or regions, 100 (49.8%) were registered in China and 78 (37.8%) in the USA. Registered trials increased rapidly, with the number of registered trials doubling from 1 March to 26 March 2020. CONCLUSIONS: While accelerating morbidity and mortality from the COVID-19 pandemic has been paralleled by early and rapid clinical investigation, many trials lack features to optimise their scientific value. Global coordination and increased funding of high-quality research may help to maximise scientific progress in rapidly discovering safe and effective treatments.", "qid": 17, "docid": "uqsjl4re", "rank": 7, "score": 0.875775158405304}, {"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": 8, "score": 0.8716046810150146}, {"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": 9, "score": 0.8716045618057251}, {"content": "Title: An early assessment of the efficacy of medicines in the treatment of patients with COVID-19/ \u0420\u0410\u041d\u041d\u042f\u042f \u041e\u0426\u0415\u041d\u041a\u0410 \u042d\u0424\u0424\u0415\u041a\u0422\u0418\u0412\u041d\u041e\u0421\u0422\u0418 \u041b\u0415\u041a\u0410\u0420\u0421\u0422\u0412\u0415\u041d\u041d\u042b\u0425 \u0421\u0420\u0415\u0414\u0421\u0422\u0412 \u041f\u0420\u0418 \u041b\u0415\u0427\u0415\u041d\u0418\u0418 \u0411\u041e\u041b\u042c\u041d\u042b\u0425 \u0421 COVID-19 Content: Coronavirus infection 2019 is considered a modern challenge to the world community. In the absence of vaccines and antivirals, effective and safe medicines are an urgent request from the healthcare system. We have evaluated the medical technologies for COVID-19 which are being examined. The search was conducted on the \u0421linicalTrials.gov at the beginning of April 2020. As a result it was shown that the growth of new clinical trials in the world devoted to COVID-19 is growing by 65% per week. More often, interventional clinical trials of the II and III phases are carried out. Most studies are planned or conducted in Western Europe (n = 92), China (n = 79), and the United States (n = 51). Surrogate points are usually evaluated, such as: clinical recovery, symptom-based disease relief (fever, cough, diarrhea, myalgia, shortness of breath), lack of progression of shortness of breath, rate of artificial ventilation, rate of admission to the intensive care unit, etc. It is antimalarial drugs that are mainly studied. Currently, it is not possible to discuss the efficacy and safety of a drug in the treatment of COVID-19, as most studies have just begun. The therapeutic regimens proposed now in clinical recommendations have no evidence base, and the studies indicated in them are at best considered hypothesizing.", "qid": 17, "docid": "37ii08h8", "rank": 10, "score": 0.8707738518714905}, {"content": "Title: Covid-19 and drug therapy, what we learned Content: COVID-19, the disease associated in December 2019 with the novel coronavirus SARS-CoV-2, was observed for the first time in China and then spread worldwide becoming pandemic. Currently, there is still no licensed specific antiviral treatment for the human coronavirus disease and a vaccine will not be ready soon. However, based on experience from the use of other antiviral agents to treat similar virusses, some treatment options have been tried with some efficacy. Clinical trials for future therapies are still ongoing. In the meantime, prevention, control, active communication and investment in research are the only ways to overcome this challenge.", "qid": 17, "docid": "538mkxfu", "rank": 11, "score": 0.870712161064148}, {"content": "Title: Off\u2010Label Therapies for COVID\u201019\u2014Are We All In This Together? Content: SARS-CoV-2 continues to spread rapidly outside of mainland China. As of April 6, there are over 300,000 cases and 10,000 deaths in the US. Effective therapies for the novel Coronavirus are urgently needed and over 200 clinical trials are now underway across the globe. Recognizing the need for robust randomized control trials, the World Health Organization (WHO) recently organized a multinational randomized trial-the SOLIDARITY trial-to study the effect of drugs that have been identified as promising based on in-vitro data and the early clinical experience with COVID-19: Remdesivir, lopinavir and ritonavir; lopinavir and ritonavir + interferon; and chloroquine or hydroxychloroquine.", "qid": 17, "docid": "f5tpz8ze", "rank": 12, "score": 0.8706234693527222}, {"content": "Title: Comprehensive overview of COVID-19 clinical trials Content: Here, we present an overview of the clinical trials that are currently being conducted or have concluded to date on COVID-19 globally. A comprehensive search was conducted to present 16 trial registries from around the world. Collectively, there are 1,528 trials reported for COVID-19 to date. Out of them, 50 studies included paediatric age group from day 0 to less than or equal to 18 years of age. A few 18 studies involve only females and 20 only males. There are 2 trials currently underway in Bangladesh, 4 in Pakistan and 13 in India. Overall, 940 trials are related to medicines and/or interventions. They include standard of care for any viral illness, antivirals, anti-inflammatory and immune altering medications. Two out of 10 vaccine trials are novel vaccines. It is knowledgeable and resourceful to reach out to the concerned sponsor if a physician thinks his patient can benefit from the trials in the region.", "qid": 17, "docid": "7nm7s0l5", "rank": 13, "score": 0.8693194389343262}, {"content": "Title: Comprehensive overview of COVID-19 clinical trials. Content: Here, we present an overview of the clinical trials that are currently being conducted or have concluded to date on COVID-19 globally. A comprehensive search was conducted to present 16 trial registries from around the world. Collectively, there are 1,528 trials reported for COVID-19 to date. Out of them, 50 studies included paediatric age group from day 0 to less than or equal to 18 years of age. A few 18 studies involve only females and 20 only males. There are 2 trials currently underway in Bangladesh, 4 in Pakistan and 13 in India. Overall, 940 trials are related to medicines and/or interventions. They include standard of care for any viral illness, antivirals, anti-inflammatory and immune altering medications. Two out of 10 vaccine trials are novel vaccines. It is knowledgeable and resourceful to reach out to the concerned sponsor if a physician thinks his patient can benefit from the trials in the region.", "qid": 17, "docid": "fti60hts", "rank": 14, "score": 0.8693194389343262}, {"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": 15, "score": 0.8682936429977417}, {"content": "Title: Review and methodological analysis of trials currently testing treatment and prevention options for the novel coronavirus disease (COVID-19) globally. Content: Background: As novel coronavirus disease (COVID-19) cases continue to steeply rise globally within an unprecedented short period of time, solid evidence from large randomised controlled trials is still lacking. Currently, numerous trials testing potential treatment and preventative options are undertaken globally. Objectives: We summarised all currently registered clinical trials examining treatment and prevention options for COVID-19 pneumonia. Additionally, we evaluated the quality of the retrieved interventional studies. Data sources: The ClinicalTrials.gov, the Chinese Clinical Trial Registry and the European Union Clinical Trials Register were systematically searched. Study eligibility criteria: Registered clinical trials examining treatment and/or prevention options for COVID-19 were included. No language, country or study design restrictions were applied. Withdrawn, cancelled studies and trials not reporting therapeutic or preventative strategies for COVID-19 were excluded. Participants and interventions: No restrictions in terms of participants' age and medical background or type of intervention were enforced. Methods: The registries were searched using the term \"coronavirus\" or \"COVID-19\" from their inception until 26th March 2020. Additional manual search of the registries was also performed. Eligible studies were summarised and tabulated. Interventional trials were methodologically analysed, excluding expanded access studies and trials testing Traditional Chinese Medicine. Results: In total, 309 trials evaluating therapeutic management options, 23 studies assessing preventive strategies and 3 studies examining both were retrieved. Interventional treatment studies were mostly randomised (n=150, 76%) and open-label (n=73, 37%) with a median number of planned inclusions of 90 (IQR 40-200). Major categories of interventions that are currently being investigated are discussed. Conclusion: Numerous clinical trials have been registered since the onset of the COVID-19 pandemic. Summarised data on these trials will assist physicians and researchers to promote patient care and guide future research efforts for COVID-19 pandemic containment. However, up to the end of March, 2020, significant information concerning reported trials was lacking.", "qid": 17, "docid": "di23na30", "rank": 16, "score": 0.8670862913131714}, {"content": "Title: Pharmacological treatment for the novel coronavirus disease 2019 (COVID-19 infection) Content: As of March 22, 2020, a total of 292,142 confirmed coronavirus disease 2019 (COVID-19) cases have been reported globally. Although there are currently no specific antiviral agents but all coronaviruses shared similar key elements of target for currently approved antiviral or new drug development. Several agents might be considered as a possible treatment based on the efficacy in SARS and MERS.", "qid": 17, "docid": "6niqv4e4", "rank": 17, "score": 0.8666576743125916}, {"content": "Title: Medical treatment options for COVID-19 Content: Therapeutic options for coronavirus disease 2019 are desperately needed to respond to the ongoing severe acute respiratory syndrome coronavirus 2 pandemic. Both antiviral drugs and immunomodulators might have their place in the management of coronavirus disease 2019. Unfortunately, no drugs have been approved yet to treat infections with human coronaviruses. As it will take years to develop new therapies for severe acute respiratory syndrome coronavirus 2, the current focus is on the repurposing of drugs that have been approved or are in development for other conditions. Several clinical trials have already been conducted or are currently ongoing to evaluate the efficacy of such drugs. Here, we discuss the potential of these therapies for the treatment of coronavirus disease 2019.", "qid": 17, "docid": "7y87ktmi", "rank": 18, "score": 0.8647361397743225}, {"content": "Title: Review of trials currently testing treatment and prevention of COVID-19 Content: BACKGROUND: As COVID-19 cases continue to rise globally, evidence from large randomized controlled trials is still lacking. Currently, numerous trials testing potential treatment and preventative options are being undertaken all over the world. OBJECTIVES: We summarized all registered clinical trials examining treatment and prevention options for COVID-19. Additionally, we evaluated the quality of the retrieved studies. DATA SOURCES: Clinicaltrials.gov, the Chinese Clinical Trial Registry and the European Union Clinical Trials Register were systematically searched. STUDY ELIGIBILITY CRITERIA: Registered clinical trials examining treatment and/or prevention options for COVID-19 were included. No language, country or study design restrictions were applied. We excluded withdrawn or cancelled studies and trials not reporting therapeutic or preventative strategies for COVID-19. PARTICIPANTS AND INTERVENTIONS: No restrictions in terms of participants' age and medical background or type of intervention were enforced. METHODS: The registries were searched using the term 'coronavirus' or 'COVID-19' from their inception until 26 March 2020. Additional manual search of the registries was also performed. Eligible studies were summarized and tabulated. Interventional trials were methodologically analysed, excluding expanded access studies and trials testing traditional Chinese medicine. RESULTS: In total, 309 trials evaluating therapeutic management options, 23 studies assessing preventive strategies and three studies examining both were retrieved. Finally, 214 studies were methodologically reviewed. Interventional treatment studies were mostly randomized (n = 150/198, 76%) and open label (n = 73/198, 37%) with a median number of planned inclusions of 90 (interquartile range 40-200). Major categories of interventions that are currently being investigated are discussed. CONCLUSIONS: Numerous clinical trials have been registered since the onset of the COVID-19 pandemic. Summarized data on these trials will assist physicians and researchers to promote patient care and guide future research efforts for COVID-19 pandemic containment.", "qid": 17, "docid": "0t974igx", "rank": 19, "score": 0.8645925521850586}, {"content": "Title: Implications of the lack of a unified research project framework: an investigation into the registration of clinical trials of COVID-19. Content: Objective: The aim of this study was to provide recommendations for improving the design of subsequent studies through analysis of the registered coronavirus disease 2019 (COVID-19) clinical trials.Methods: A retrospective analysis of 189 trials retrievals achieved on February 20, 2020.Results: A total of 189 trials are included in the study. There were 69.3% interventional studies, 21.7% observational studies, 5.3% diagnostic tests, and 3.7% other studies. The following statistics are provided only for the interventional studies. Severity of disease: 5.3% light and common type, 17.6% severe and critically ill, and 59.6% with no restricted classification. Medication use: 51.1% Western medicine, 32.1% Chinese medicine, 10.7% blood related product, and 6.1% non-drug therapy. The median and inner quantile range of the sample sizes included in these studies: 104 (IQR: 60, 200). Primary outcome type most used: 45.8% with clinical characteristics and 21.4% with virological. Study design characteristics: 71% of all studies were randomized, 5% of all studies were blinded, 18% of all studies were multicenter, and 76% of all studies were single-center.Conclusion: Although many COVID-19 studies include randomization in their design, the lack of additional double-blind and placebo-controlled elements in their designs result in a less robust evaluation of intervention safety and efficacy. Furthermore, similar or repeated research and small sample studies that have less promise in gains of new information have possibly led to a shortage of recruitable patients and become a barrier to the completion of large multicenter clinical trial studies.", "qid": 17, "docid": "yjx1rx3k", "rank": 20, "score": 0.8645615577697754}, {"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": 17, "docid": "natp8lbj", "rank": 21, "score": 0.8644393682479858}, {"content": "Title: COVID-19 trials in Italy: A call for simplicity, top standards and global pooling Content: The novel coronavirus disease, affecting ~9 million people in the past five months and causing >460,000 deaths worldwide, is completely new to mankind. More than 2,000 research projects registered at ClinTrials.gov are aiming at finding effective treatments for rapid transfer to clinical practice. Unfortunately, just few studies have a sufficiently valid design to provide reliable information for clinical practice.", "qid": 17, "docid": "edy3mvur", "rank": 22, "score": 0.8641538619995117}, {"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": 17, "docid": "tsms3303", "rank": 23, "score": 0.8635114431381226}, {"content": "Title: Characteristics of registered studies for Coronavirus disease 2019 (COVID-19): A systematic review Content: Abstract Background The World Health Organization characterized the Coronavirus disease 2019 (COVID-19) as a pandemic on March 11th. Many clinical trials on COVID-19 have been registered, and we aim to review the study characteristics and provide guidance for future trials to avoid duplicated effort. Methods Studies on COVID-19 registered before March 3rd, 2020 on eight registry platforms worldwide were searched and the data of design, participants, interventions, and outcomes were extracted and analyzed. Results Three hundred and ninety-three studies were identified and 380 (96.7%) were from mainland China, while 3 in Japan, 3 in France, 2 in the US, and 3 were international collaborative studies. Two hundred and sixty-six (67.7%) aimed at therapeutic effect, others were for prevention, diagnosis, prognosis, etc. Two hundred and two studies (51.4%) were randomized controlled trials. Two third of therapeutic studies tested Western medicines including antiviral drugs (17.7%), stem cell and cord blood therapy (10.2%), chloroquine and derivatives (8.3%), 16 (6.0%) on Chinese medicines, and 73 (27.4%) on integrated therapy of Western and Chinese medicines. Thirty-one studies among 266 therapeutic studies (11.7%) used mortality as primary outcome, while the most designed secondary outcomes were symptoms and signs (47.0%). Half of the studies (45.5%) had not started recruiting till March 3rd. Conclusions Inappropriate outcome setting, delayed recruitment and insufficient numbers of new cases in China implied many studies may fail to complete. Strategies and protocols of the studies with robust and rapid data sharing are warranted for emergency public health events, helping the timely evidence-based decision-making.", "qid": 17, "docid": "vhfu020h", "rank": 24, "score": 0.8633220195770264}, {"content": "Title: Implications of the lack of a unified research project framework: an investigation into the registration of clinical trials of COVID-19 Content: Objective: The aim of this study was to provide recommendations for improving the design of subsequent studies through analysis of the registered coronavirus disease 2019 (COVID-19) clinical trials.Methods: A retrospective analysis of 189 trial retrievals achieved on 20 February 2020.Results: A total of 189 trials are included in the study. There were 69.3% interventional studies, 21.7% observational studies, 5.3% diagnostic tests and 3.7% other studies. The following statistics are provided only for the interventional studies. Severity of disease: 5.3% light and common type, 17.6% severe and critically ill and 59.6% with no restricted classification. Medication use: 51.1% Western medicine, 32.1% Chinese medicine, 10.7% blood related product and 6.1% non-drug therapy. The median and inner quantile range of the sample sizes included in these studies: 104 (IQR: 60, 200). Primary outcome type most used: 45.8% with clinical characteristics and 21.4% with virological. Study design characteristics: 71% of all studies were randomized, 5% of all studies were blinded, 18% of all studies were multicenter and 76% of all studies were single center.Conclusion: Although many COVID-19 studies include randomization in their design, the lack of additional double-blind and placebo-controlled elements in their designs result in a less robust evaluation of intervention safety and efficacy. Furthermore, similar or repeated research and small sample studies that have less promise in gains of new information have possibly led to a shortage of recruitable patients and become a barrier to the completion of large multicenter clinical trial studies.", "qid": 17, "docid": "itpizzzh", "rank": 25, "score": 0.8632153272628784}, {"content": "Title: Current evidence for directed and supportive investigational therapies against COVID-19 Content: Coronavirus disease 2019 (COVID-19) is a global health crisis. There is currently a great need for effective and safe therapies directed at the disease, but no drugs are presently registered for use in COVID-19. Several directed therapies have been proposed, and most are still in clinical trials. Currently available published, peer-reviewed results mostly involve small sample sizes with study limitations restricting the interpretation of the findings. Many trials currently published also do not have a control group, limiting the interpretation of the effect of the intervention. Investigational directed therapies as well as investigational supportive therapies against COVID-19 are reviewed here. Chloroquine and hydroxychloroquine show promise as directed therapies, but current trial results are conflicting. Lopinavir/ritonavir also shows potential, but was started late in the disease course in most trials. No randomised controlled evidence is currently available for remdesivir and favipiravir. Corticosteroid use is not recommended for directed therapy against COVID-19, and the role of tocilizumab is currently unclear, based on limited evidence. Early initiation of investigational directed therapies may provide benefit in selected patients. The results from larger randomised controlled trials will clarify the place of these therapies in COVID-19 treatment.", "qid": 17, "docid": "f33eb1nf", "rank": 26, "score": 0.861926794052124}, {"content": "Title: Treatment of SARS-CoV-2: How far have we reached? Content: The virus severe acute respiratory syndrome-coronavirus-2 (SARS-CoV-2) is currently affecting more than 200 countries and territories worldwide. It has been declared as pandemic by World Health Organization (WHO) and the whole world is suffering from corona virus disease 2019 (COVID-19). Currently, no treatment for SARS-CoV-2 are approved because of lack of evidence, but a number of clinical trials are in process and we are expecting fruitful results very soon. This review focuses on various approaches of treatment and few of the most recent clinical trials carried out in this field.", "qid": 17, "docid": "lgzmwx3j", "rank": 27, "score": 0.8612414598464966}, {"content": "Title: Antiviral therapy in management of COVID-19: a systematic review on current evidence Content: BACKGROUND: The purpose of the current systematic review is to evaluate the efficacy of antiviral therapies in treatment of COVID-19. In addition, clinical trials on the efficacy of antiviral therapies in the management of Severe Acute Respiratory Syndrome coronavirus (SARS-Cov) or Middle East Respiratory Syndrome coronavirus (MERS-CoV) have also been reviewed, in order to identify potential treatment options for COVID-19. METHOD: An extensive search was performed in Medline, Embase, Scopus, Web of Science and CENTRAL databases until the end of March 15, 2020. Two independent researchers performed the screening, and finally the related studies were included. RESULTS: Only one clinical trial on the efficacy of antiviral therapy in management of COVID-19 was found. The results depicted that adding Lopinavir-Ritonavir to the standard treatment regimen of patients with severe COVID-19 has no benefits. Moreover, 21 case-series and case-report studies reported the prescription of antiviral agents in COVID-19, none of which can be used to determine the efficacy of antiviral therapies in confronting COVID-19. In addition, no clinical trials were found to be performed on the efficacy of antiviral agents in the management of SARS-CoV and MERS-CoV. CONCLUSION: The current evidence impede researchers from proposing an appropriate antiviral therapy against COVID-19, making the current situation a serious concern for international organizations such as World Health Organization (WHO). In the time of the current pandemic and future epidemics, organizations such as WHO should pursue more proactive actions and plan well-designed clinical trials so that their results can be used in managing future epidemics.", "qid": 17, "docid": "jlqee1b8", "rank": 28, "score": 0.8609784841537476}, {"content": "Title: Battling COVID-19: using old weapons for a new enemy Content: Coronavirus disease-19 (COVID-19) has reached pandemic proportions. Most of the drugs that are being tried for the treatment have not been evaluated in any randomized controlled trials. The purpose of this review was to summarize the in-vitro and in-vivo efficacy of these drugs on Severe Acute Respiratory Syndrome (SARS-CoV-2) and related viruses (SARS and Middle East Respiratory Syndrome) and evaluate their potential for re-purposing them in the management of COVID-19.", "qid": 17, "docid": "yn7x9uit", "rank": 29, "score": 0.8608022928237915}, {"content": "Title: COVID-19 and toxicity from potential treatments: Panacea or poison Content: Since December 2019, coronavirus disease (COVID-19) has been increasingly spreading from its origin in Wuhan, China to many countries around the world eventuating in morbidity and mortality affecting millions of people. This pandemic has proven to be a challenge given that there is no immediate cure, no vaccine is currently available and medications or treatments being used are still undergoing clinical trials. There have already been examples of self-medication and overdose. Clearly, there is a need to further define the efficacy of treatments used in the management of COVID-19. This evidence needs to be backed by large randomised-controlled clinical trials. In the meantime, there will no doubt be further off-label use of these medications by patients and practitioners and possibly related toxicity.", "qid": 17, "docid": "kpnuuvz6", "rank": 30, "score": 0.8604204058647156}, {"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": 17, "docid": "azvbl4ie", "rank": 31, "score": 0.8602689504623413}, {"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": 17, "docid": "eitnkdi9", "rank": 32, "score": 0.8599692583084106}, {"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": 17, "docid": "x82yaoxc", "rank": 33, "score": 0.8598438501358032}, {"content": "Title: The Efficacy and Safety of Triazavirin for COVID-19: A Trial Protocol Content: The coronavirus disease 2019 (COVID-19), a pneumonia caused by a novel coronavirus, was reported in December 2019. COVID-19 is highly contagious and has rapidly developed from a regional epidemic into a global pandemic. As yet, no effective drugs have been found to treat this virus. This study, an ongoing multicenter and blind randomized controlled trial (RCT), is being conducted at ten study sites in Heilongjiang Province, China, to investigate the efficacy and safety of Triazavirin (TZV) versus its placebo in COVID-19 patients. A total of 240 participants with COVID-19 are scheduled to be enrolled in this trial. Participants with positive tests of throat swab virus nucleic acid are randomized (1:1) into two groups: standard therapy plus TZV or standard therapy plus placebo for a 7-day treatment with a 21-day follow-up. The primary outcome is the time to clinical improvement of the subjects. Secondary outcomes include clinical improvement rate, time to alleviation of fever, mean time and proportion of obvious inflammatory absorption in the lung, conversion rate of repeated negative virus nucleic acid tests, mortality rate, and conversion rate to severe and critically severe patients. Adverse events, serious adverse events, liver function, kidney function and concurrent treatments will be monitored and recorded throughout the trial. The results of this trial should provide evidence-based recommendations to clinicians for the treatment of COVID-19.", "qid": 17, "docid": "njemjpv2", "rank": 34, "score": 0.8597765564918518}, {"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": 17, "docid": "nedsqmr0", "rank": 35, "score": 0.859341025352478}, {"content": "Title: Can a century-old TB vaccine steel the immune system against the new coronavirus? Content: Researchers in four countries will soon start a clinical trial of an unorthodox approach to the new coronavirus They will test whether a century-old vaccine against tuberculosis (TB), a bacterial disease, can rev up the human immune system in a broad way, allowing it to better fight the virus that causes coronavirus disease 2019 and, perhaps, prevent infection with it altogether The studies will be done in physicians and nurses, who are at higher risk of becoming infected with the respiratory disease than the general population, and in the elderly, who are at higher risk of serious illness if they become infected", "qid": 17, "docid": "9xome3no", "rank": 36, "score": 0.8590935468673706}, {"content": "Title: Review of trials currently testing treatment and prevention of COVID-19 Content: BACKGROUND: As COVID-19 cases continue to rise globally, evidence from large randomised controlled trials is still lacking. Currently, numerous trials testing potential treatment and preventative options are undertaken all over the world. OBJECTIVES: We summarised all registered clinical trials examining treatment and prevention options for COVID-19. Additionally, we evaluated the quality of the retrieved studies. DATA SOURCES: Clinicaltrials.gov, the Chinese Clinical Trial Registry and the European Union Clinical Trials Register were systematically searched. STUDY ELIGIBILITY CRITERIA: Registered clinical trials examining treatment and/or prevention options for COVID-19 were included. No language, country or study design restrictions were applied. We excluded withdrawn or cancelled studies and trials not reporting therapeutic or preventative strategies for COVID-19. PARTICIPANTS: and interventions: No restrictions in terms of participants\u2019 age and medical background or type of intervention were enforced. METHODS: The registries were searched using the term \u201ccoronavirus\u201d or \u201cCOVID-19\u201d from their inception until 26(th) March 2020.Additional manual search of the registries was also performed. Eligible studies were summarised and tabulated. Interventional trials were methodologically analysed, excluding expanded access studies and trials testing Traditional Chinese Medicine. RESULTS: In total, 309 trials evaluating therapeutic management options, 23 studies assessing preventive strategies and 3 studies examining both were retrieved. Finally, 214 studies were methodologically reviewed. Interventional treatment studies were mostly randomised (n=150, 76%) and open-label (n=73, 37%) with a median number of planned inclusions of 90 (IQR 40-200). Major categories of interventions that are currently being investigated are discussed. CONCLUSION: Numerous clinical trials have been registered since the onset of the COVID-19 pandemic. Summarised data on these trials will assist physicians and researchers to promote patient care and guide future research efforts for COVID-19 pandemic containment.", "qid": 17, "docid": "dsjq98ks", "rank": 37, "score": 0.8589349985122681}, {"content": "Title: Ongoing Clinical Trials for the Management of the COVID-19 Pandemic Content: COVID-19 has rapidly developed into a worldwide pandemic with a significant health and economic burden. There are currently no approved treatments or preventative therapeutic strategies. Hundreds of clinical studies have been registered with the intention of discovering effective treatments. Here, we review currently registered interventional clinical trials for the treatment and prevention of COVID-19 to provide an overall summary and insight into the global response.", "qid": 17, "docid": "ibuqz948", "rank": 38, "score": 0.8587496876716614}, {"content": "Title: Emergence of novel coronavirus and progress toward treatment and vaccine Content: In late December 2019, a group of patients was observed with pneumonia-like symptoms that were linked with a wet market in Wuhan, China. The patients were found to have a novel coronavirus genetically related to a bat coronavirus that was termed SARS-CoV-2. The virus gradually spread worldwide and was declared a pandemic by WHO. Scientists have started trials on potential preventive and treatment options. Currently, there is no specific approved treatment for SARS-CoV-2, and various clinical trials are underway to explore better treatments. Some previously approved antiviral and other drugs have shown some in vitro activity. Here we summarize the fight against this novel coronavirus with particular focus on the different treatment options and clinical trials exploring treatment as well as work done toward development of vaccines.", "qid": 17, "docid": "uw7qhwne", "rank": 39, "score": 0.8584851026535034}, {"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": 40, "score": 0.8582097887992859}, {"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": 41, "score": 0.8575947284698486}, {"content": "Title: Clinical trials for coronavirus disease 2019: What is being evaluated and what is not Content: Since the report of the first case of coronavirus disease 2019 (COVID-19) in China in late December 2019, there have been 204 610 cases worldwide as of 18 March, 2020. As part of the response to this outbreak, there has been an impressive amount of research undertaken to better characterize the disease and to evaluate therapeutic options. By March 12, 2020, there are more than 382 studies registered in the clinical trials databases addressing COVID-19 including more than 80 randomized controlled trials.", "qid": 17, "docid": "jwrheaph", "rank": 42, "score": 0.8574850559234619}, {"content": "Title: Antiviral therapy in management of COVID-19: a systematic review on current evidence. Content: Background The purpose of the current systematic review is to evaluate the efficacy of antiviral therapies in treatment of COVID-19. In addition, clinical trials on the efficacy of antiviral therapies in the management of Severe Acute Respiratory Syndrome coronavirus (SARS-Cov) or Middle East Respiratory Syndrome coronavirus (MERS-CoV) have also been reviewed, in order to identify potential treatment options for COVID-19. Method An extensive search was performed in Medline, Embase, Scopus, Web of Science and CENTRAL databases until the end of March 15, 2020. Two independent researchers performed the screening, and finally the related studies were included. Results Only one clinical trial on the efficacy of antiviral therapy in management of COVID-19 was found. The results depicted that adding Lopinavir-Ritonavir to the standard treatment regimen of patients with severe COVID-19 has no benefits. Moreover, 21 case-series and case-report studies reported the prescription of antiviral agents in COVID-19, none of which can be used to determine the efficacy of antiviral therapies in confronting COVID-19. In addition, no clinical trials were found to be performed on the efficacy of antiviral agents in the management of SARS-CoV and MERS-CoV. Conclusion The current evidence impede researchers from proposing an appropriate antiviral therapy against COVID-19, making the current situation a serious concern for international organizations such as World Health Organization (WHO). In the time of the current pandemic and future epidemics, organizations such as WHO should pursue more proactive actions and plan well-designed clinical trials so that their results can be used in managing future epidemics.", "qid": 17, "docid": "bfchqn2g", "rank": 43, "score": 0.8570919036865234}, {"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": 17, "docid": "303b23dd", "rank": 44, "score": 0.8568416237831116}, {"content": "Title: Effectiveness and safety of antiviral or antibody treatments for coronavirus: A rapid review Content: Background: To identify safe and effective medical countermeasures (e.g., antivirals/antibodies) to address the current outbreak of a novel coronavirus (COVID-19) Methods: Comprehensive literature searches were developed by an experienced librarian for MEDLINE, EMBASE, the Cochrane Library, and biorxiv.org/medrxiv.org; additional searches for ongoing trials and unpublished studies were conducted in clinicaltrials.gov and the Global Infectious Diseases and Epidemiology Network (GIDEON). Title/abstract and full-text screening, data abstraction, and risk of bias appraisal were carried out by single reviewers. Results: 54 studies were included in the review: three controlled trials, 10 cohort studies, seven retrospective medical record/database studies, and 34 case reports or series. These studies included patients with severe acute respiratory syndrome (SARs, n=33), middle east respiratory syndrome (MERS, n=16), COVID-19 (n=3), and unspecified coronavirus (n=2). The most common treatment was ribavirin (n=41), followed by oseltamivir (n=10) and the combination of lopinavir/ritonavir (n=7). Additional therapies included broad spectrum antibiotics (n=30), steroids (n=39) or various interferons (n=12). No eligible studies examining monoclonal antibodies for COVID-19 were identified. One trial found that ribavirin prophylactic treatment statistically significantly reduced risk of MERS infection in people who had been exposed to the virus. Of the 21 studies reporting rates of ICU admission in hospitalized SARS or MERS patients, none reported statistically significant results in favour of or against antiviral therapies. Of the 40 studies reporting mortality rates in hospitalized SARS or MERS patients, one cohort study (MERS) and one retrospective study (SARS) found a statistically significant increase in the mortality rate for patients treated with ribavirin. Eighteen studies reported potential drug-related adverse effects including gastrointestinal symptoms, anemia, and altered liver function in patients receiving ribavirin. Conclusion: The current evidence for the effectiveness and safety of antiviral therapies for coronavirus is inconclusive and suffers from a lack of well-designed prospective trials or observational studies, preventing any treatment recommendations from being made. However, it is clear that the existing body of evidence is weighted heavily towards ribavirin (41/54 studies), which has not shown conclusive evidence of effectiveness and may cause harmful adverse events so future investigations may consider focusing on other candidates for antiviral therapy.", "qid": 17, "docid": "ptnmtvzj", "rank": 45, "score": 0.8566893339157104}, {"content": "Title: Drug treatment options for the 2019-new coronavirus (2019-nCoV) Content: As of January 22, 2020, a total of 571 cases of the 2019-new coronavirus (2019-nCoV) have been reported in 25 provinces (districts and cities) in China. At present, there is no vaccine or antiviral treatment for human and animal coronavirus, so that identifying the drug treatment options as soon as possible is critical for the response to the 2019-nCoV outbreak. Three general methods, which include existing broad-spectrum antiviral drugs using standard assays, screening of a chemical library containing many existing compounds or databases, and the redevelopment of new specific drugs based on the genome and biophysical understanding of individual coronaviruses, are used to discover the potential antiviral treatment of human pathogen coronavirus. Lopinavir /Ritonavir, Nucleoside analogues, Neuraminidase inhibitors, Remdesivir, peptide (EK1), abidol, RNA synthesis inhibitors (such as TDF, 3TC), anti-inflammatory drugs (such as hormones and other molecules), Chinese traditional medicine, such ShuFengJieDu Capsules and Lianhuaqingwen Capsule, could be the drug treatment options for 2019-nCoV. However, the efficacy and safety of these drugs for 2019- nCoV still need to be further confirmed by clinical experiments.", "qid": 17, "docid": "e5zjrhoq", "rank": 46, "score": 0.856421172618866}, {"content": "Title: Drug treatment options for the 2019-new coronavirus (2019-nCoV). Content: As of January 22, 2020, a total of 571 cases of the 2019-new coronavirus (2019-nCoV) have been reported in 25 provinces (districts and cities) in China. At present, there is no vaccine or antiviral treatment for human and animal coronavirus, so that identifying the drug treatment options as soon as possible is critical for the response to the 2019-nCoV outbreak. Three general methods, which include existing broad-spectrum antiviral drugs using standard assays, screening of a chemical library containing many existing compounds or databases, and the redevelopment of new specific drugs based on the genome and biophysical understanding of individual coronaviruses, are used to discover the potential antiviral treatment of human pathogen coronavirus. Lopinavir /Ritonavir, Nucleoside analogues, Neuraminidase inhibitors, Remdesivir, peptide (EK1), abidol, RNA synthesis inhibitors (such as TDF, 3TC), anti-inflammatory drugs (such as hormones and other molecules), Chinese traditional medicine, such ShuFengJieDu Capsules and Lianhuaqingwen Capsule, could be the drug treatment options for 2019-nCoV. However, the efficacy and safety of these drugs for 2019- nCoV still need to be further confirmed by clinical experiments.", "qid": 17, "docid": "804r5xzd", "rank": 47, "score": 0.856421172618866}, {"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": 17, "docid": "o29773cz", "rank": 48, "score": 0.8543962836265564}, {"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 employed 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 hydroxychloroquine, 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 experimental 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 virus. This also stresses the urgent need for the scientific community to devote its efforts to find other more specific antiviral strategies.", "qid": 17, "docid": "h450b2l5", "rank": 49, "score": 0.8540431261062622}, {"content": "Title: A SYSTEMATIC ANALYSIS OF THE TIME COURSE TO DEVELOP TREATMENTS FOR COVID-19 Content: ABSTRACT Background. The spread of COVID-19 from Wuhan in China throughout the world has been alamingly rapid. Epidemiologic techniques succeeded in containing the disease in China, but efforts were not as successful in the rest of the world, particularly the United States where there have been 1,592, 599 cases with 95,863 deaths as of May 25, 2020. Projections are for continued new infections and deaths if no effective treatments can be activated over the next six months.. We performed a systematic review to determine the potential time course of development of treatments and vaccines focusing on availability in the last half of 2020. Methods. Our search was performed during the week of May 17, 2020. Publications: We reviewed up to date information from several sources to identify potential treatments for COVID-19: We used the Reagan-Udall Expanded Access Navigator COVID-19 Treatment Hub to track the efforts of companies to develop treatments. We then used the results to search for publications on pubmed.gov and on MedRxiv, the preprint server. We further used a targeted Google search to find announcements of trial results. Clinical Trials: We searched for all investigational trials involving potential treatments using several different sources: (A) covid-trials.org, then validated results on (B) clinicaltrials.gov and the (C) World Health Organization's International Clinical Trials Registry Platform (WHO ICTRP). We focused on trials which were completed or currently recruiting for patients, reasoning that the timeline to arrive at treatments by the end of the year would require completion within the next 6 months. We excluded studies which were clearly observational, with no randomization, control or comparison group. We furtherset a cutoff of 100 for numbers of subjects since smaller trial size could lack statistical power to establish superiority of the intervention over the control condition. Results. Published Data: We found 19 publications reporting findings on 6 classes of agents. There were 9 publications related to hydroxychloroquine (HCQ), three on lopanovir/ritonavir (LPV/R) (one of which was combined with interferon beta-1),three on remdesivir, two on favipiravir, one on mepaluzamab, and one on tocilizumab. Ten publications reported randomized controlled trials, the rest were retrospective observational. Only one publication touched on outpatient management, the rest on hospitalized patients. Clinical Trials: We found 409 trials meeting our minimum requirement of 100 subjects which were recruiting or completed. The WHO has launched the Solidarity megatrial performed in over 100 countries actively comparing HCQ, lopanovir/ritonavir (LPV/R) alone and in combination with interferon beta-1, and remdesivir. That trial is scheduled to complete enrollment in the first quarter of 2021. In addition, we found 46 trials of HCQ, 11 trials of LPV/R and 8 trials of interferons. There were 18 ongoing trials of antiviral agents, 24 immune modulator trials, 9 vaccine trials, and 62 trials of other agents.We excluded a large number of trials of Chinese traditional medications, reasoning that there was insufficient clinical experience with these agents outside China to offer these treatments to the rest of the world. Forty four trials were hoping to complete enrollment by the end of the second quarter of 2020. Of these, only 9 were conducted on outpatients. A few vaccine trials are hoping to complete Phase 3 enrollment by the end of the third quarter, but a prolonged follow-up of patients will likely be required. Conclusion. Several treatments for severe disease in hospitalized patients have now been granted emergency authorization. However, the disease is propagated primarily by infected ambulatory individuals. There are only a few randomized controlled studies in outpatients which can be expected to yield results in time to impact on the continuing spread of the epidemic in 2020. It will be necessary for public health authorities to make hard decisions with limited data. The choices will be hardest in dealing with potential early release of vaccines. Keywords: Coronavirus, COVID-19, SARS-Cov-2, remdesivir, hydroxychloroquine", "qid": 17, "docid": "y9rqr1h8", "rank": 50, "score": 0.8538186550140381}, {"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": 0.8537789583206177}, {"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": 17, "docid": "okrpa7k7", "rank": 52, "score": 0.8532766699790955}, {"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": 17, "docid": "m95bmi9t", "rank": 53, "score": 0.8524332046508789}, {"content": "Title: Emergence of novel coronavirus and progress toward treatment and vaccine Content: In late December 2019, a group of patients was observed with pneumonia\u2010like symptoms that were linked with a wet market in Wuhan, China. The patients were found to have a novel coronavirus genetically related to a bat coronavirus that was termed SARS\u2010CoV\u20102. The virus gradually spread worldwide and was declared a pandemic by WHO. Scientists have started trials on potential preventive and treatment options. Currently, there is no specific approved treatment for SARS\u2010CoV\u20102, and various clinical trials are underway to explore better treatments. Some previously approved antiviral and other drugs have shown some in vitro activity. Here we summarize the fight against this novel coronavirus with particular focus on the different treatment options and clinical trials exploring treatment as well as work done toward development of vaccines.", "qid": 17, "docid": "3mpymd8a", "rank": 54, "score": 0.8521896600723267}, {"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": 55, "score": 0.8520333766937256}, {"content": "Title: Antiviral therapy in management of COVID-19: a systematic review on current evidence Content: Background: The purpose of the current systematic review is to evaluate the efficacy of antiviral therapies in treatment of COVID-19 In addition, clinical trials on the efficacy of antiviral therapies in the management of Severe Acute Respiratory Syndrome coronavirus (SARS-Cov) or Middle East Respiratory Syndrome coronavirus (MERS-CoV) have also been reviewed, in order to identify potential treatment options for COVID-19 Method: An extensive search was performed in Medline, Embase, Scopus, Web of Science and CENTRAL databases until the end of March 15, 2020 Two independent researchers performed the screening, and finally the related studies were included Results: Only one clinical trial on the efficacy of antiviral therapy in management of COVID-19 was found The results depicted that adding Lopinavir-Ritonavir to the standard treatment regimen of patients with severe COVID-19 has no benefits Moreover, 21 case-series and case-report studies reported the prescription of antiviral agents in COVID-19, none of which can be used to determine the efficacy of antiviral therapies in confronting COVID-19 In addition, no clinical trials were found to be performed on the efficacy of antiviral agents in the management of SARS-CoV and MERS-CoV Conclusion: The current evidence impede researchers from proposing an appropriate antiviral therapy against COVID-19, making the current situation a serious concern for international organizations such as World Health Organization (WHO) In the time of the current pandemic and future epidemics, organizations such as WHO should pursue more proactive actions and plan well-designed clinical trials so that their results can be used in managing future epidemics", "qid": 17, "docid": "be3udel6", "rank": 56, "score": 0.8519717454910278}, {"content": "Title: Operational protocol for donation of anti\u2010COVID\u201019 convalescent plasma in Italy Content: Coronavirus Disease 19 (COVID-19) represents a public health threat worldwide and Italy at the present time is considered the epicenter of this severe infection in the western world. Unfortunately, no standardized therapy does exist for COVID-19 and a number of investigational drugs for use in patients with life-threatening COVID-19 infections have been tried. One investigational treatment being explored for COVID-19 involves the use of convalescent plasma collected from recovered COVID-19 patients.", "qid": 17, "docid": "9yoqwrdi", "rank": 57, "score": 0.8519272804260254}, {"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": 58, "score": 0.8515973687171936}, {"content": "Title: Clinical trial analysis of 2019\u2010nCoV therapy registered in China Content: So far, there is a lack of effective drugs for the new coronavirus pneumonia. With more and more patients diagnosed, China has carried out more than 100 clinical studies of new coronavirus infection, including antiviral drugs, antimalarial drugs, glucocorticoids, plasma therapy, virus vaccine, and other Western drugs, while Chinese medicine research accounted for half of the studies. Most of the trials were initiated by investigators and the study period would last for 1 to 11 months. The primary endpoints included symptom improvement and virus nucleic acid turning negative, but the optimal endpoint has not been determined. Although the final results of studies will take a long time to complete, the interim research data may provide some help for the current urgent demand for drug treatment. Compared with that of during SARS period in 2003, China has the stronger capability to carry out clinical trials of new drugs in emergency period.", "qid": 17, "docid": "o8j17zzs", "rank": 59, "score": 0.851457953453064}, {"content": "Title: Clinical trial analysis of 2019-nCoV therapy registered in China Content: So far, there is a lack of effective drugs for the new coronavirus pneumonia. With more and more patients diagnosed, China has carried out more than 100 clinical studies of new coronavirus infection, including antiviral drugs, antimalarial drugs, glucocorticoids, plasma therapy, virus vaccine, and other Western drugs, while Chinese medicine research accounted for half of the studies. Most of the trials were initiated by investigators and the study period would last for 1 to 11 months. The primary endpoints included symptom improvement and virus nucleic acid turning negative, but the optimal endpoint has not been determined. Although the final results of studies will take a long time to complete, the interim research data may provide some help for the current urgent demand for drug treatment. Compared with that of during SARS period in 2003, China has the stronger capability to carry out clinical trials of new drugs in emergency period.", "qid": 17, "docid": "g7rjtlht", "rank": 60, "score": 0.851457953453064}, {"content": "Title: COVID\u201019 and toxicity from potential treatments: Panacea or poison Content: Since December 2019, coronavirus disease (COVID\u201019) has been increasingly spreading from its origin in Wuhan, China to many countries around the world eventuating in morbidity and mortality affecting millions of people. This pandemic has proven to be a challenge given that there is no immediate cure, no vaccine is currently available and medications or treatments being used are still undergoing clinical trials. There have already been examples of self\u2010medication and overdose. Clearly, there is a need to further define the efficacy of treatments used in the management of COVID\u201019. This evidence needs to be backed by large randomised\u2010controlled clinical trials. In the meantime, there will no doubt be further off\u2010label use of these medications by patients and practitioners and possibly related toxicity.", "qid": 17, "docid": "z7ajsf2r", "rank": 61, "score": 0.8507643342018127}, {"content": "Title: COVID-19 treatment by repurposing drugs until the vaccine is in sight Content: Corona virus disease (COVID-19) has created pandemic in the world as declared by WHO on March 12, 2020. It is a viral disease caused by SARS-CoV 2 virus and has affected large populations in over 120 countries. There is no specific treatment available and management is empirical. Until such time that an effective vaccine is available for COVID-19 viral infection, one can repurpose known therapeutic drug molecules such as angiotensin receptor 2 blocker, a commonly used antihypertensive drug, to control COVID-19 virus from gaining entry into the host cell by blocking the angiotensin receptor. Clinical trials should also be undertaken to use statins, which are lipid-lowering drugs but have anti-inflammatory and immunomodulatory properties to prevent acute lung injury in COVID-19 infection.", "qid": 17, "docid": "f5vtticw", "rank": 62, "score": 0.8507153987884521}, {"content": "Title: Ventricular Arrhythmia Risk Based on Ethnicity in COVID-19 Patients on Hydroxychloroquine and Azithromycin Combination: Viewpoint Content: There are many reports available now, which are mostly observational or registry trial outcomes having varied results on coronavirus 2019 (COVID-19) patients put on hydroxychloroquine and azithromycin combination. Some are showing increased in-hospital mortality and ventricular arrhythmia increase, while some are showing overall benefit with significant viral RNA load reduction. Everyday things are getting more complicated with the publication of these different outcomes. This needs to be addressed.", "qid": 17, "docid": "ndbko8rf", "rank": 63, "score": 0.8506173491477966}, {"content": "Title: Interim Guidelines on Antiviral Therapy for COVID-19 Content: Since the first case was reported in Wuhan, Hubei Province, China on December 12, 2019, Coronavirus disease 2019 (COVID-19) has spread widely to other countries since January 2020. As of April 16, 2020, 10635 confirmed cases have been reported, with 230 deaths in Korea. COVID-19 patients may be asymptomatic or show various clinical manifestations, including acute symptoms such as fever, fatigue, sore throat; pneumonia presenting as acute respiratory distress syndrome; and multiple organ failure. As COVID-19 has such varied clinical manifestations and case fatality rates, no standard antiviral therapy regimen has been established other than supportive therapy. In the present guideline, we aim to introduce potentially helpful antiviral and other drug therapies based on in vivo and in vitro research and clinical experiences from many countries.", "qid": 17, "docid": "oayjeens", "rank": 64, "score": 0.8505864143371582}, {"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": 65, "score": 0.8505221605300903}, {"content": "Title: [Farmakoter\u00e1pi\u00e1s lehetos\u00e9gek SARS-CoV-2-fertoz\u00e9s/COVID\u00ad19-betegs\u00e9g eset\u00e9n]/ Pharmacological options in treating SASR-CoV-2 infection/COVID-19 Content: There is currently no proven effective therapy for COVID-19. Here we discuss the drugs most investigated for the treatment of the disease. All the listed therapies are experimental at this stage. However, due to the severe healthcare effects of the pandemic and the potentially fatal outcome of COVID-19 patients treated in the intensive care units, their off-label use should none-the-less be considered. Orv Hetil. 2020; 161(17): 685\u00ad688.", "qid": 17, "docid": "ql3fvmrs", "rank": 66, "score": 0.8502259254455566}, {"content": "Title: Clinical Trials for COVID-19: Can we Better Use the Short Window of Opportunity? Content: The scientific community has risen to the coronavirus disease 2019 (COVID-19) challenge, coming up with an impressive list of candidate drugs and vaccines targeting an array of pharmacological and immunological mechanisms. Yet, generating clinical evidence of efficacy and safety of these candidate treatments may be frustrated by the absence of comprehensive trial coordination mechanisms. Many small stand-alone trials and observational studies of single-agent interventions are currently running or in planning; many of these will likely not deliver robust results that could support regulatory and patient-level treatment decisions. In this paper, we discuss actions that all stakeholders in the clinical trial ecosystem need to take to ensure that the window of opportunity during this pandemic will not shut, both for patients in need of treatment and for researchers to conduct decision-relevant clinical trials.", "qid": 17, "docid": "fz6eumik", "rank": 67, "score": 0.8501049280166626}, {"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": 68, "score": 0.8499176502227783}, {"content": "Title: Emerging pharmacotherapies for COVID-19 Content: Novel Corona-virus Disease 2019 (nCOVID 19) is caused by a novel virulent corona virus and leads to potentially fatal virulent pneumonia and severe respiratory distress syndrome. It was initially declared as public health emergency if international concern by WHO followed by Pandemic on 12(th) March 2020. As of 10(th) April 2020, more than 1.5 million people are affected globally with around 95000 deaths. Vaccines for this deadly virus are currently under development and many drugs used for other indications have been repurposed and investigated for prophylaxis and treatment of COVID 19. As per SOLIDARITY trial by WHO, some of the most promising candidates include chloroquine phosphate and hydroxychloroquine which are anti-malarial medications, Remdesivir, Lopinavir-Ritonavir combination with or without interferon which are anti-HIV drugs and convalescent plasma therapy. The current evidence of efficacy and ongoing research has been elaborated in the article. Besides, there has been evidence regarding inflammatory pathogenesis of this virus leading to cytokine storm in susceptible individuals. Thus, anti-proinflammatory cytokine drugs like Anakinra and Tocilizumab are undergoing multiple trials and some results are encouraging. Similarly, use of anti-inflammatory cytokines like IL-37 and IL-38 is hypothesised to be useful and is under research. The situation is still evolving and hence there is yet no definitive therapy but to conclude the use of repurposed medications can be a boon till a definitive therapy and vaccines are developed.", "qid": 17, "docid": "q6px4r3j", "rank": 69, "score": 0.8498888611793518}, {"content": "Title: [Pharmacotherapeutic options for SARS-CoV-2 infection / COVID-19]. Content: There is currently no proven effective therapy for COVID-19. Without wishing to be exhaustive, the drugs most studied in this regard are presented below. Each of the listed therapeutic options is considered experimental at this stage. However, given the severe public health implications of the epidemic and the potentially fatal outcome of COVID-19 patients treated in the intensive care unit, their use 'off-label' should be considered. Orv Hetil. 2020; 161 (17): 685-688.", "qid": 17, "docid": "rmm7fdhg", "rank": 70, "score": 0.8488239049911499}, {"content": "Title: Emerging pharmacotherapies for COVID-19 Content: Novel Corona-virus Disease 2019 (nCOVID 19) is caused by a novel virulent corona virus and leads to potentially fatal virulent pneumonia and severe respiratory distress syndrome. It was initially declared as public health emergency if international concern by WHO followed by Pandemic on 12th March 2020. As of 10th April 2020, more than 1.5 million people are affected globally with around 95,000 deaths. Vaccines for this deadly virus are currently under development and many drugs used for other indications have been repurposed and investigated for prophylaxis and treatment of COVID 19. As per SOLIDARITY trial by WHO, some of the most promising candidates include chloroquine phosphate and hydroxychloroquine which are anti-malarial medications, Remdesivir, Lopinavir-Ritonavir combination with or without interferon which are anti-HIV drugs and convalescent plasma therapy. The current evidence of efficacy and ongoing research has been elaborated in the article. Besides, there has been evidence regarding inflammatory pathogenesis of this virus leading to cytokine storm in susceptible individuals. Thus, anti-proinflammatory cytokine drugs like Anakinra and Tocilizumab are undergoing multiple trials and some results are encouraging. Similarly, use of anti-inflammatory cytokines like IL-37 and IL-38 is hypothesised to be useful and is under research. The situation is still evolving and hence there is yet no definitive therapy but to conclude the use of repurposed medications can be a boon till a definitive therapy and vaccines are developed.", "qid": 17, "docid": "ydbp79wa", "rank": 71, "score": 0.8483670353889465}, {"content": "Title: Systematic review of the efficacy and safety of antiretroviral drugs against SARS, MERS or COVID-19: initial assessment Content: INTRODUCTION: Several antiretroviral drugs are being considered for the treatment of COVID-19, the disease caused by a newly identified coronavirus, (SARS-CoV-2). We systematically reviewed the clinical outcomes of using antiretroviral drugs for the prevention and treatment of coronaviruses and planned clinical trials. METHODS: Three databases were screened from inception to 30 March 2020 for studies reporting clinical outcomes of patients with SARS, MERS or COVID-19 treated with antiretrovirals. RESULTS: From an initial screen of 433 titles, two randomized trials and 24 observational studies provided clinical outcome data on the use of antiretroviral drugs; most studies reported outcomes using LPV/r as treatment. Of the 21 observational studies reporting treatment outcomes, there were three studies among patients with SARS, six studies among patients with MERS and 12 studies among patients with COVID-19. In one randomized trial 99 patients with severe COVID-19 illness were randomized to receive LPV/r (400/100 mg twice a day) and 100 patients to standard of care for 14 days: LPV/r was not associated with a statistically significant difference in time to clinical improvement, although LPV/r given within 12 days of symptoms was associated with shorter time to clinical improvement; 28 day mortality was numerically lower in the LPV/r group (14/99) compared to the control group (25/100), but this difference was not statistically significant. The second trial found no benefit. The certainty of the evidence for the randomized trials was low. In the observational studies 3 out of 361 patients who received LPV/r died; the certainty of evidence was very low. Three studies reported a possible protective effect of LPV/r as post-exposure prophylaxis. Again, the certainty of the evidence was very low due to uncertainty due to limited sample size. CONCLUSIONS: On the basis of the available evidence it is uncertain whether LPV/r and other antiretrovirals improve clinical outcomes or prevent infection among patients at high risk of acquiring COVID-19.", "qid": 17, "docid": "tlrt17m4", "rank": 72, "score": 0.8481288552284241}, {"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": 17, "docid": "fgbilulc", "rank": 73, "score": 0.8480466604232788}, {"content": "Title: Remdesivir for severe acute respiratory syndrome coronavirus 2 causing COVID-19: An evaluation of the evidence Content: The novel coronavirus infection that initially found at the end of 2019 has attracted great attention. So far, the number of infectious cases has increased globally to more than 100 thousand and the outbreak has been defined as a pandemic situation, but there are still no \"specific drug\" available. Relevant reports have pointed out the novel coronavirus has 80% homology with SARS. In the difficulty where new synthesized drug cannot be applied immediately to patients, \"conventional drug in new use\" becomes a feasible solution. The first medication experience of the recovered patients in the US has led remdesivir to be the \"specific drug\". China has also taken immediate action to put remdesivir into clinical trials with the purpose of applying it into clinical therapeutics for Corona Virus Disease 2019 (COVID-19). We started from the structure, immunogenicity, and pathogenesis of coronavirus infections of the novel coronavirus. Further, we analyzed the pharmacological actions and previous trials of remdesivir to identify the feasibility of conducting experiments on COVID-19.", "qid": 17, "docid": "tgtba98u", "rank": 74, "score": 0.8474433422088623}, {"content": "Title: Discovery of the FDA-approved drugs bexarotene, cetilistat, diiodohydroxyquinoline, and abiraterone as potential COVID-19 treatments with a robust two-tier screening system Content: Coronavirus Disease 2019 (COVID-19) caused by the emerging severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) is associated with a crude case fatality rate of about 0.5-10% depending on locality. A few clinically approved drugs, such as remdesivir, chloroquine, hydroxychloroquine, nafamostat, camostat, and ivermectin, exhibited anti-SARS-CoV-2 activity in vitro and/or in a small number of patients. However, their clinical use may be limited by anti-SARS-CoV-2 50% maximal effective concentrations (EC(50)) that exceeded their achievable peak serum concentrations (Cmax), side effects, and/or availability. To find more immediately available COVID-19 antivirals, we established a two-tier drug screening system that combines SARS-CoV-2 enzyme-linked immunosorbent assay and cell viability assay, and applied it to screen a library consisting 1528 FDA-approved drugs. Cetilistat (anti-pancreatic lipase), diiodohydroxyquinoline (anti-parasitic), abiraterone acetate (synthetic androstane steroid), and bexarotene (antineoplastic retinoid) exhibited potent in vitro anti-SARS-CoV-2 activity (EC(50) 1.13-2.01\u00b5M). Bexarotene demonstrated the highest Cmax:EC(50) ratio (1.69) which was higher than those of chloroquine, hydroxychloroquine, and ivermectin. These results demonstrated the efficacy of the two-tier screening system and identified potential COVID-19 treatments which can achieve effective levels if given by inhalation or systemically depending on their pharmacokinetics.", "qid": 17, "docid": "fd5rr87z", "rank": 75, "score": 0.8471066355705261}, {"content": "Title: Characteristics of COVID-19 Clinical Trials in China Based on the Registration Data on ChiCTR and ClinicalTrials.gov Content: Objective: This study aimed to evaluate the fundamental characteristics of coronavirus disease (COVID-19) clinical trials registered in China. Methods: COVID-19 clinical trials registered in China were analyzed from databases on ChiCTR and ClinicalTrials.gov. The study designs, samples, primary end points, and intervention measures were evaluated. Results: In total, 262 intervention clinical trials were retrieved on March 10, 2020. Overall, 181 (69.1%) trials involved two groups, 200 (76.3%) trials were randomized parallel trials, 24 (9.2%) trials were double blind, and 60.3% of trials included &#8804;100 participants. Sixty (22.9%) trials considered symptom improvement as the primary endpoint and 43 (16.4%) trials considered the rate or time at which the subjects became virus-free as the primary endpoint. Of 262 intervention studies, chemical drugs and biological products were studied in 105 (40.1%) intervention studies, of which antiviral drugs accounted for 15.3% and malaria drugs accounted for 8.4% of the studies. Among all trials, 27.9% of the studies used traditional Chinese medicine (TCM), 10.3% used cell therapy, and 5.0% used plasma therapy. Conclusion: This study is the first snapshot of the landscape of COVID-19 clinical trials registered in China and provided the basic features of clinical trial designs for the treatment and prevention of COVID-19 to offer useful information to guide future clinical trials on COVID-19 in other countries.", "qid": 17, "docid": "7izjhyyk", "rank": 76, "score": 0.8470737934112549}, {"content": "Title: Discovery of the FDA-approved drugs bexarotene, cetilistat, diiodohydroxyquinoline, and abiraterone as potential COVID-19 treatments with a robust two-tier screening system Content: Coronavirus Disease 2019 (COVID-19) caused by the emerging severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) is associated with a crude case fatality rate of about 0.5-10 % depending on locality. A few clinically approved drugs, such as remdesivir, chloroquine, hydroxychloroquine, nafamostat, camostat, and ivermectin, exhibited anti-SARS-CoV-2 activity in vitro and/or in a small number of patients. However, their clinical use may be limited by anti-SARS-CoV-2 50 % maximal effective concentrations (EC50) that exceeded their achievable peak serum concentrations (Cmax), side effects, and/or availability. To find more immediately available COVID-19 antivirals, we established a two-tier drug screening system that combines SARS-CoV-2 enzyme-linked immunosorbent assay and cell viability assay, and applied it to screen a library consisting 1528 FDA-approved drugs. Cetilistat (anti-pancreatic lipase), diiodohydroxyquinoline (anti-parasitic), abiraterone acetate (synthetic androstane steroid), and bexarotene (antineoplastic retinoid) exhibited potent in vitro anti-SARS-CoV-2 activity (EC50 1.13-2.01 \u00b5M). Bexarotene demonstrated the highest Cmax:EC50 ratio (1.69) which was higher than those of chloroquine, hydroxychloroquine, and ivermectin. These results demonstrated the efficacy of the two-tier screening system and identified potential COVID-19 treatments which can achieve effective levels if given by inhalation or systemically depending on their pharmacokinetics.", "qid": 17, "docid": "458smf3g", "rank": 77, "score": 0.8470098972320557}, {"content": "Title: Medical Management of COVID-19: Evidence and Experience Content: Coronavirus disease 2019 is caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), and this infectious disease is termed COVID-19 in short. On a global scale, as of June 1, 2020, the World Health Organization (WHO) published statistics of 6,057,853 infected patients and 371,166 deaths worldwide. Despite reported observational data about the experimental use of certain drugs, there is no conclusively proven curative therapy for COVID-19 as of now; however, remdesivir received emergency use authorization (EUA) by the Food and Drug Administration (FDA) recently for use in patients hospitalized with COVID-19. There are several ongoing clinical trials related to the pharmacological choices of therapy for COVID-19 patients; however, drug trials related to observational studies so far have yielded mixed results and therefore have created a sense of confusion among healthcare professionals (HCPs). In this review article, we seek to collate and provide a summary of treatment strategies for COVID-19 patients with a variable degree of illness and discuss pharmacologic and other therapies intended to be used either as experimental medicine/therapy or as part of supportive care in complicated cases of COVID-19.", "qid": 17, "docid": "svnz1ghh", "rank": 78, "score": 0.8467372059822083}, {"content": "Title: Characteristics of COVID-19 Clinical Trials in China Based on the Registration Data on ChiCTR and ClinicalTrials.gov Content: OBJECTIVE: This study aimed to evaluate the fundamental characteristics of coronavirus disease (COVID-19) clinical trials registered in China. METHODS: COVID-19 clinical trials registered in China were analyzed from databases on ChiCTR and ClinicalTrials.gov. The study designs, samples, primary end points, and intervention measures were evaluated. RESULTS: In total, 262 intervention clinical trials were retrieved on March 10, 2020. Overall, 181 (69.1%) trials involved two groups, 200 (76.3%) trials were randomized parallel trials, 24 (9.2%) trials were double blind, and 60.3% of trials included \u2264100 participants. Sixty (22.9%) trials considered symptom improvement as the primary endpoint and 43 (16.4%) trials considered the rate or time at which the subjects became virus-free as the primary endpoint. Of 262 intervention studies, chemical drugs and biological products were studied in 105 (40.1%) intervention studies, of which antiviral drugs accounted for 15.3% and malaria drugs accounted for 8.4% of the studies. Among all trials, 27.9% of the studies used traditional Chinese medicine (TCM), 10.3% used cell therapy, and 5.0% used plasma therapy. CONCLUSION: This study is the first snapshot of the landscape of COVID-19 clinical trials registered in China and provided the basic features of clinical trial designs for the treatment and prevention of COVID-19 to offer useful information to guide future clinical trials on COVID-19 in other countries.", "qid": 17, "docid": "zed7d315", "rank": 79, "score": 0.8466212749481201}, {"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": 80, "score": 0.846544623374939}, {"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": 81, "score": 0.8465445637702942}, {"content": "Title: Potential Antiviral Drugs for SARS-Cov-2 Treatment: Preclinical Findings and Ongoing Clinical Research Content: Severe acute respiratory syndrome coronavirus 2 (SARS-Cov-2), initially termed 2019-new CoV (2019-nCoV), is a novel coronavirus responsible for the severe respiratory illness currently ongoing worldwide from the beginning of December 2019. This beta gene virus, very close to bat coronaviruses (bat-CoV-RaTG13) and bat-SL-CoVZC45, causes a severe disease, similar to those caused by Middle East respiratory syndrome (MERS)-CoV and SARS-CoV viruses, featured by low to moderate mortality rate. Unfortunately, the antiviral drugs commonly used in clinical practice to treat viral infections, are not applicable to SARS-Cov-2 and no vaccine is available. Thus, it is extremely necessary to identify new drugs suitable for the treatment of the 2019-nCoV outbreak. Different preclinical studies conducted on other coronaviruses suggested that promising clinical outcomes for 2019-nCoV should be obtained by using alpha-interferon, chloroquine phosphate, arabinol, remdesivir, lopinavir/ritonavir, and anti-inflammatory drugs. Moreover, clinical trials with these suitable drugs should be performed on patients affected by SARS-Cov-2 to prove their efficacy and safety. Finally, a very promising therapeutic drug, tocilizumab, is discussed; it is currently used to treat patients presenting COVID-19 pneumonia. Herein, we recapitulate these experimental studies to highlight the use of antiviral drugs for the treatment of SARS-Cov-2 disease.", "qid": 17, "docid": "7wbpj88g", "rank": 82, "score": 0.8462632894515991}, {"content": "Title: Potential Antiviral Drugs for SARS-Cov-2 Treatment: Preclinical Findings and Ongoing Clinical Research. Content: Severe acute respiratory syndrome coronavirus 2 (SARS-Cov-2), initially termed 2019-new CoV (2019-nCoV), is a novel coronavirus responsible for the severe respiratory illness currently ongoing worldwide from the beginning of December 2019. This beta gene virus, very close to bat coronaviruses (bat-CoV-RaTG13) and bat-SL-CoVZC45, causes a severe disease, similar to those caused by Middle East respiratory syndrome (MERS)-CoV and SARS-CoV viruses, featured by low to moderate mortality rate. Unfortunately, the antiviral drugs commonly used in clinical practice to treat viral infections, are not applicable to SARS-Cov-2 and no vaccine is available. Thus, it is extremely necessary to identify new drugs suitable for the treatment of the 2019-nCoV outbreak. Different preclinical studies conducted on other coronaviruses suggested that promising clinical outcomes for 2019-nCoV should be obtained by using alpha-interferon, chloroquine phosphate, arabinol, remdesivir, lopinavir/ritonavir, and anti-inflammatory drugs. Moreover, clinical trials with these suitable drugs should be performed on patients affected by SARS-Cov-2 to prove their efficacy and safety. Finally, a very promising therapeutic drug, tocilizumab, is discussed; it is currently used to treat patients presenting COVID-19 pneumonia. Herein, we recapitulate these experimental studies to highlight the use of antiviral drugs for the treatment of SARS-Cov-2 disease.", "qid": 17, "docid": "lav2iavi", "rank": 83, "score": 0.8462632894515991}, {"content": "Title: Evaluation of safety, efficacy, tolerability, and treatment-related outcomes of type I interferons for human coronaviruses (HCoVs) infection in clinical practice: An updated critical systematic review and meta-analysis Content: BACKGROUND: There is no vaccine or specific antiviral treatment for HCoVs infection. The use of type I interferons for coronavirus is still under great debate in clinical practice. MATERIALS AND METHODS: A literature search of all relevant studies published on PubMed, Cochrane library, Web of Science database, Science Direct, Wanfang Data, and China National Knowledge Infrastructure (CNKI) until February 2020 was performed. RESULTS: Of the 1081 identified articles, only 15 studies were included in the final analysis. Comorbidities and delay in diagnosis were significantly associated with case mortality. Type I interferons seem to improve respiratory distress, relieve lung abnormalities, present better saturation, reduce needs for supplemental oxygen support. Type I interferons seem to be well tolerated, and don't increase life threating adverse effects. Data on IFNs in HCoVs are limited, heterogenous and mainly observational. CONCLUSIONS: Current data do not allow making regarding robust commendations for the use of IFNs in HCoVs in general or in specific subtype. But we still recommend type I interferons serving as first-line antivirals in HCoVs infections within local protocols, and interferons may be adopted to the treatments of the SARS-CoV-2 as well. Well-designed large-scale prospective randomized control trials are greatly needed to provide more robust evidence on this topic.", "qid": 17, "docid": "bwld82m2", "rank": 84, "score": 0.8462499380111694}, {"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": 85, "score": 0.8462070226669312}, {"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": 86, "score": 0.8460515737533569}, {"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": 17, "docid": "kc2r034w", "rank": 87, "score": 0.8459807634353638}, {"content": "Title: Drug repurposing clinical trials in the search for life-saving COVID-19 therapies;research targets and methodological and ethical issues Content: Introduction: So far, there is no vaccine, nor are there effective drugs to treat COVID-19, an emerging viral respiratory infection deadlier than influenza Objective: To take a snapshot picture of planned and ongoing clinical research addressing drugs potentially useful for treating SAR-CoV-2 infections Method: A search was conducted (20 April 2020) in an international registry of clinical studies (https://ClinicalTrials gov, US NIH) After excluding observational studies and other interventions that fell outside the scope of this study, 294 research protocols (out of 516 retrieved protocols) were selected for analysis Results: Of 294 included trials, 249 were Randomized Controlled Trials (RCT), 118 of which were double-, triple- or quadruple-blinded studies The interventions (drug therapies) were compared with \"standard-of-care\" (SOC) or with the placebo plus SOC, or yet with presumed \"active\" comparators RCT focused on the primary treatment of the disease (inhibitors of viral replication) or on the therapy for resolution of hyperinflammation in pneumonia/Acute Respiratory Distress Syndrome (ARDS) and thromboembolism associated with SARS-CoV-2 The trials found in the database involve existing antiviral compounds and drugs with multiple modes of antiviral action Antiparasitic drugs, which inhibited viral replication in cell-culture assays, are being tested as well Regarding the adjunctive immunomodulatory, anti-inflammatory and antithrombotic therapies, a number of drugs with distinct pharmacological targets are under investigation in trials enrolling patients with severe COVID-19 Conclusions: Although many clinical studies of drugs for COVID-19 are planned or in progress, only a minority of them are sufficiently large, randomized and placebo-controlled trials with masking and concealment of allocation Owing to methodological limitations, only a few clinical trials found in the registry are likely to yield robust evidence of effectiveness and safety of drugs repurposable for COVID-19", "qid": 17, "docid": "a4oibkt9", "rank": 88, "score": 0.8459203243255615}, {"content": "Title: Evaluation of safety, efficacy, tolerability, and treatment-related outcomes of type I interferons for Human coronaviruses (HCoVs) infection in clinical practice: An updated critical systematic review and meta-analysis Content: BACKGROUND: There is no vaccine or specific antiviral treatment for HCoVs infection. The use of type I interferons for coronavirus is still under great debate in clinical practice. MATERIALS AND METHODS: A literature search of all relevant studies published on PubMed, Cochrane library, Web of Science database, Science Direct, Wanfang Data, and China National Knowledge Infrastructure (CNKI) until February 2020 was performed. RESULTS: Of the 1081 identified articles, only 15 studies were included in the final analysis. Comorbidities and delay in diagnosis were significantly associated with case mortality. Type I interferons seem to improve respiratory distress, relieve lung abnormalities, present better saturation, reduce needs for supplemental oxygen support. Type I interferons seem to be well tolerated, and don\u2019t increase life threating adverse effects. Data on IFNs in HCoVs are limited, heterogenous and mainly observational. CONCLUSIONS: Current data do not allow making regarding robust commendations for the use of IFNs in HCoVs in general or in specific subtype. But we still recommend type I interferons serving as first-line antivirals in HCoVs infections within local protocols, and interferons may be adopted to the treatments of the SARS-CoV-2 as well. Well-designed large-scale prospective randomized control trials are greatly needed to provide more robust evidence on this topic.", "qid": 17, "docid": "6k8196p2", "rank": 89, "score": 0.8458465337753296}, {"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": 17, "docid": "07tdrd4w", "rank": 90, "score": 0.84574294090271}, {"content": "Title: Chloroquine and hydroxychloroquine in the treatment of COVID-19 with or without diabetes: A systematic search and a narrative review with a special reference to India and other developing countries Content: Abstract Background and aims No drugs are currently approved for Coronavirus Disease-2019 (COVID-19), although some have been tried. In view of recent studies and discussion on chloroquine and hydroxychloroquine (HCQ), we aimed to review existing literature and relevant websites regarding these drugs and COVID-19, adverse effects related to drugs, and related guidelines. Aims and methods We systematically searched the PubMed database up till March 21, 2020 and retrieved all the articles published on chloroquine and HCQ and COVID-19. Results Two small human studies have been conducted with both these drugs in COVID-19, and have shown significant improvement in some parameters in patients with COVID-19. Conclusion Considering minimal risk upon use, a long experience of use in other diseases, cost-effectiveness and easy availability across India, we propose that both these drugs are worthy of fast track clinical trial for treatment, and may be carefully considered for clinical use as experimental drugs. Since HCQ has been approved for treatment of diabetes in India, it should be further researched in diabetes and COVID-19, a subgroup where significant mortality has been shown.", "qid": 17, "docid": "41jqgsv0", "rank": 91, "score": 0.8454602956771851}, {"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": 92, "score": 0.8453882932662964}, {"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": 93, "score": 0.8453882932662964}, {"content": "Title: Repurposing Existing Medications for Coronavirus Disease 2019: Protocol for a Rapid and Living Systematic Review Content: BACKGROUND: Coronavirus Disease 2019 (COVID-19) has no known specific treatments. However, there might be in vitro and early clinical data as well as evidence from Severe Acute Respiratory Syndrome and Middle Eastern Respiratory Syndrome that could inform clinicians and researchers. This systematic review aims to create priorities for future research of drugs repurposed for COVID-19. METHODS: This systematic review will include in vitro, animal, and clinical studies evaluating the efficacy of a list of 34 specific compounds and four groups of drugs identified in a previous scoping review. Studies will be identified both from traditional literature databases and pre-print servers. Outcomes assessed will include time to clinical improvement, time to viral clearance, mortality, length of hospital stay, and proportions transferred to the intensive care unit and intubated, respectively. We will use the GRADE methodology to assess the quality of the evidence. DISCUSSION: The challenge posed by COVID-19 requires not just a rapid review of drugs that can be repurposed but also a sustained effort to integrate new evidence into a living systematic review. SYSTEMATIC REVIEW REGISTRATION: PROSPERO 2020 CRD42020175648", "qid": 17, "docid": "g2815zqn", "rank": 94, "score": 0.8453710675239563}, {"content": "Title: [Potential antiviral therapeutics for 2019 Novel Coronavirus]. Content: The recent outbreak of respiratory illness in Wuhan, China is caused by a novel coronavirus, named 2019-nCoV, which is genetically close to a bat-derived coronavirus. 2019-nCoV is categorized as beta genus coronavirus, same as the two other strains-severe acute respiratory syndrome coronavirus (SARS-CoV) and Middle East respiratory syndrome coronavirus (MERS-CoV). Antiviral drugs commonly used in clinical practice, including neuraminidase inhibitors (oseltamivir, paramivir, zanamivir, etc.), ganciclovir, acyclovir and ribavirin, are invalid for 2019-nCoV and not recommended. Drugs are possibly effective for 2019-nCoV include: remdesivir, lopinavir/ritonavir, lopinavir/ritonavir combined with interferon-\u03b2, convalescent plasma, and monoclonal antibodies. But the efficacy and safety of these drugs for 2019-nCoV pneumonia patients need to be assessed by further clinical trials.", "qid": 17, "docid": "fxbiadlv", "rank": 95, "score": 0.845177173614502}, {"content": "Title: [Potential antiviral therapeutics for 2019 Novel Coronavirus]. Content: The recent outbreak of respiratory illness in Wuhan, China is caused by a novel coronavirus, named 2019-nCoV, which is genetically close to a bat-derived coronavirus. 2019-nCoV is categorized as beta genus coronavirus, same as the two other strains - severe acute respiratory syndrome coronavirus (SARS-CoV) and Middle East respiratory syndrome coronavirus (MERS-CoV). Antiviral drugs commonly used in clinical practice, including neuraminidase inhibitors (oseltamivir, paramivir, zanamivir, etc.), ganciclovir, acyclovir and ribavirin, are invalid for 2019-nCoV and not recommended. Drugs are possibly effective for 2019-nCoV include: remdesivir, lopinavir / ritonavir, lopinavir / ritonavir combined with interferon-\u03b2, convalescent plasma, and monoclonal antibodies. But the efficacy and safety of these drugs for 2019-nCoV pneumonia patients need to be assessed by further clinical trials.", "qid": 17, "docid": "fuljgago", "rank": 96, "score": 0.845177173614502}, {"content": "Title: [Potential antiviral therapeutics for 2019 Novel Coronavirus] Content: The recent outbreak of respiratory illness in Wuhan, China is caused by a novel coronavirus, named 2019-nCoV, which is genetically close to a bat-derived coronavirus. 2019-nCoV is categorized as beta genus coronavirus, same as the two other strains - severe acute respiratory syndrome coronavirus (SARS-CoV) and Middle East respiratory syndrome coronavirus (MERS-CoV). Antiviral drugs commonly used in clinical practice, including neuraminidase inhibitors (oseltamivir, paramivir, zanamivir, etc.), ganciclovir, acyclovir and ribavirin, are invalid for 2019-nCoV and not recommended. Drugs are possibly effective for 2019-nCoV include: remdesivir, lopinavir / ritonavir, lopinavir / ritonavir combined with interferon-\u00df, convalescent plasma, and monoclonal antibodies. But the efficacy and safety of these drugs for 2019-nCoV pneumonia patients need to be assessed by further clinical trials.", "qid": 17, "docid": "aqxeyek2", "rank": 97, "score": 0.8451065421104431}, {"content": "Title: Novel Stem Cells and Nucleic Acid-Based Vaccine Trials Against Viral Outbreak: A Systematic Evaluation During COVID-2019 Pandemic Content: The current Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2) outbreak, the cause of coronavirus disease (COVID-19), has influenced health globally. So far, there are no established management options and prophylaxis for those who have been exposed to SARS-CoV-2, and those who develop COVID-19. Documented scientific evidences in similar viral outbreaks in past suggested few therapy regimens. These rather have not shown promising results in management of current pandemic. So, in the current review, we are exploring novel treatment strategies and therapies that are being explored and are in clinical and preclinical stages of research. To explore more about the same, we directed our search towards stem cell based, DNA based, or RNA based vaccines against COVID-19 under development by various universities, institutes or pharmaceutical companies. The current scientific literature and database search were performed by exploring various Trials registry (NIH: https://clinicaltrials.gov/ and https://www.coronavirus.gov) and Chinese clinical trial registry http://www.chictr.org.cn/) and for preclinical trials various University, Institutions, Pharmaceutical companies websites and news bulletins along with google search were checked routinely from 3rd March 2020 to 16 May 2020. The term \u201cStem Cell therapy and COVID-19\u201d, \u201cMesenchymal stem cell and corona 2019 virus\u201d, \u201cDNA Vaccines and COVID-19, RNA Vaccines and COVID-19\u201d and \u201cCell-based therapy with SARS-CoV-2, University/Institutions and COVID-19 research\u201d were used. The vaccine trials (Stem Cells/DNA/RNA) which were cancelled were not included in this review. Similarly, few others like repurposing of drugs, Nano Vaccines, other miscellaneous trials of Herbs, Music therapy etc., were also excluded. In the present review, we have included the various novel therapies like stem cell therapy, DNA or RNA vaccines which are under development and if proven successful may have a lasting impact on the health industry.", "qid": 17, "docid": "ajd9renr", "rank": 98, "score": 0.845038652420044}, {"content": "Title: Immune checkpoint inhibition in the era of COVID-19 Content: The worldwide Coronavirus pandemic continues to result in significant morbidity and mortality, with almost 9 million confirmed cases to date. Approximately 80% of patients have mild disease and do not require hospitalization. A key challenge facing the medical community is predicting which patients are at risk of developing severe disease in order to initiate early supportive treatment and to facilitate enrollment into much needed prospective clinical trials; crucial for developing effective treatment strategies.", "qid": 17, "docid": "f9e24lwh", "rank": 99, "score": 0.8449370265007019}, {"content": "Title: Immune checkpoint inhibition in the era of COVID-19. Content: The worldwide Coronavirus pandemic continues to result in significant morbidity and mortality, with almost 9 million confirmed cases to date. Approximately 80% of patients have mild disease and do not require hospitalization. A key challenge facing the medical community is predicting which patients are at risk of developing severe disease in order to initiate early supportive treatment and to facilitate enrollment into much needed prospective clinical trials; crucial for developing effective treatment strategies.", "qid": 17, "docid": "lc2ybytv", "rank": 100, "score": 0.8449370265007019}]}
{"query": "what are the best masks for preventing infection by Covid-19?", "hits": [{"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": 1, "score": 0.8882578611373901}, {"content": "Title: Comprehensive review of mask utility and challenges during the COVID-19 pandemic. Content: Masks are widely discussed during the course of the ongoing COVID-19 pandemic. Most hospitals have implemented universal masking for their healthcare workers, and the Center for Disease Control currently advises even the general public to wear cloth masks when outdoors. The pertinent need for masks arises from plausible dissemination of the SARS-CoV-2 through close contacts, as well as the possibility of virus transmission from asymptomatic, pre-symptomatic, and mildly symptomatic individuals. Given current global shortages in personal protective equipment, the efficacy of various types of masks: N95 respirators, surgical masks, and cloth masks are researched. To accommodate limited supplies, techniques for extended use, reuse, and sterilization of masks are strategized. However, masks alone may not greatly slow down the COVID-19 pandemic unless they are coupled with adequate social distancing, diligent hand hygiene, and other proven preventive measures.", "qid": 18, "docid": "3ttcfhm3", "rank": 2, "score": 0.8881169557571411}, {"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": 3, "score": 0.8861247301101685}, {"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": 4, "score": 0.883586585521698}, {"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": 5, "score": 0.8807421922683716}, {"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": 6, "score": 0.8775063753128052}, {"content": "Title: Comprehensive review of mask utility and challenges during the COVID-19 pandemic Content: Masks are widely discussed during the course of the ongoing COVID-19 pandemic Most hospitals have implemented universal masking for their healthcare workers, and the Center for Disease Control currently advises even the general public to wear cloth masks when outdoors The pertinent need for masks arises from plausible dissemination of the SARS-CoV-2 through close contacts, as well as the possibility of virus transmission from asymptomatic, pre-symptomatic, and mildly symptomatic individuals Given current global shortages in personal protective equipment, the efficacy of various types of masks: N95 respirators, surgical masks, and cloth masks are researched To accommodate limited supplies, techniques for extended use, reuse, and sterilization of masks are strategized However, masks alone may not greatly slow down the COVID-19 pandemic unless they are coupled with adequate social distancing, diligent hand hygiene, and other proven preventive measures", "qid": 18, "docid": "7qj00qi9", "rank": 7, "score": 0.8757290840148926}, {"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": 8, "score": 0.8752399682998657}, {"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": 9, "score": 0.8752399682998657}, {"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": 10, "score": 0.8750631809234619}, {"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": 11, "score": 0.8746650218963623}, {"content": "Title: The N-95 mask: invaluable ally in the battle against the COVID-19 pandemic Content: The present COVID-19 pandemic, caused by the airborne SARS-CoV-2 virus, has highlighted the vital importance of appropriate personal protective equipment for all exposed health care workers The single most important part of this armor is the N-95 mask With the awareness that the virus is spread by both droplets and through the aerosolized route, the N-95 provides protection that a surgical mask cannot match This timely review looks at the special advantages that an N-95 offers over a surgical mask with specific reference to the COVID-19 epidemic It also emphasizes the crucial importance of ensuring quality masks with a proper fit Finally, with acute scarcities of N-95 masks being reported from hospitals globally, it reviews recent literature which attempts to prolong the life of these masks with extended use, reuse and decontamination of used masks", "qid": 18, "docid": "i1w2snyy", "rank": 12, "score": 0.8735897541046143}, {"content": "Title: Rational use of face mask in a tertiary care hospital setting during COVID-19 pandemic: An observational study Content: Masks play a role in the protection of health-care workers (HCWs) from acquiring respiratory infections, including coronavirus disease 2019 (COVID-19) in health-care settings. This observational study was conducted among 382 HCWs in a tertiary care setting over a period of 1 month. Descriptive analysis was done to assess the rational and recommended use of masks/respirators during COVID-19 pandemic using a structured observation checklist as a survey tool. A total of 374 HCWs were included, 64.9% of whom were using face masks rationally as mentioned per risk area categorization with a predominance of triple-layered mask during all 4 weeks. Overall, 64.1% used masks correctly. Clear guidelines and strategies can help to increase the compliance of HCWs with rational use of face masks.", "qid": 18, "docid": "57zwd3y6", "rank": 13, "score": 0.8734354972839355}, {"content": "Title: Rational use of face mask in a tertiary care hospital setting during COVID-19 pandemic: An observational study. Content: Masks play a role in the protection of health-care workers (HCWs) from acquiring respiratory infections, including coronavirus disease 2019 (COVID-19) in health-care settings. This observational study was conducted among 382 HCWs in a tertiary care setting over a period of 1 month. Descriptive analysis was done to assess the rational and recommended use of masks/respirators during COVID-19 pandemic using a structured observation checklist as a survey tool. A total of 374 HCWs were included, 64.9% of whom were using face masks rationally as mentioned per risk area categorization with a predominance of triple-layered mask during all 4 weeks. Overall, 64.1% used masks correctly. Clear guidelines and strategies can help to increase the compliance of HCWs with rational use of face masks.", "qid": 18, "docid": "t2e4bxsu", "rank": 14, "score": 0.8734354972839355}, {"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": 15, "score": 0.8722549676895142}, {"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": 16, "score": 0.8718831539154053}, {"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": 17, "score": 0.8718831539154053}, {"content": "Title: Cloth Masks May Prevent Transmission of COVID-19: An Evidence-Based, Risk-Based Approach Content: As the COVID-19 pandemic progressed across the world, governments, international agencies, policymakers, and public health officials began recommending widespread use of nonmedical cloth masks to reduce the transmission of SARS-CoV-2. The authors of this article suggest that there is convincing evidence to support this recommendation.", "qid": 18, "docid": "8je46886", "rank": 18, "score": 0.8712455630302429}, {"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": 18, "docid": "iaiosjlu", "rank": 19, "score": 0.86902916431427}, {"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": 18, "docid": "6tod4abn", "rank": 20, "score": 0.86902916431427}, {"content": "Title: Strategy of using personal protective equipment during aerosol generating medical procedures with COVID-19 Content: \u2022 Compared the effectiveness and cost-effectiveness between masks and respirators for the COVID-19 transmission; \u2022 Discussed the strategy to avoid severe nosocomial infection through aerosol-generating medical procedures; \u2022 Suggestions for healthcare workers to choose proper personal protective equipment.", "qid": 18, "docid": "62pnddks", "rank": 21, "score": 0.867233157157898}, {"content": "Title: Disposable masks: Disinfection and sterilization for reuse, and non-certified manufacturing, in the face of shortages during the COVID-19 pandemic Content: The COVID-19 pandemic is posing a huge global health threat. To deal with this problem, in addition to research and work in the medical field, the main health measures being taken in the workplace and at home involve the establishment of safety protocols, which include distance measures, hygiene and the use of personal protective equipment, such as masks, etc. The WHO still does not recommend the use of masks for the general population. However, their successful use in China, South Korea and the Czech Republic has encouraged their widespread use, and the shortage that already existed. This has caused that companies and individuals are looking at the best way to reuse them, and to manufacture, homemade or not, of non-certified masks. This paper is based on two objectives: to consult the scientific literature to identify the main strategies for disinfecting them, and to determine the effectiveness of non-certified disposable masks. A rapid review has been conducted in which the main publications and other information available online have been analyzed. Results showed that the most promising methods are those that use hydrogen peroxide vapor, ultraviolet radiation, moist heat, dry heat and ozone gas. Soapy water, alcohol, bleach immersion, ethylene oxide, ionizing radiation, microwave, high temperature, autoclave or steam are not fully recommended. Regarding the effectiveness of surgical masks compared to PPE, the former have been seen to be slightly less effective than PPE. As for other types of masks the effectiveness of homemade or non-certified masks is very low.", "qid": 18, "docid": "lncsfohg", "rank": 22, "score": 0.8666300773620605}, {"content": "Title: How to Produce Cheap and Easy Custom-Made Sterilizable Filtering Facepiece 2/3 Masks for Healthcare Providers During Pandemic COVID-19 Emergency Content: On January 8, 2020, a novel coronavirus was officially announced as the causative pathogen of coronavirus disease (COVID-19) by the Chinese Center for Disease Control and Prevention.On February 26, COVID-19 has been recognized in 34 countries, with a total of 80,239 laboratory-confirmed patients and 2700 deaths.Protecting healthcare workers from infectious hazards is paramount to ensuring their safety in delivering health care.In addition, being able to protect healthcare workers, constituting the front-line response against high-threat respiratory pathogens, such as severe acute respiratory syndrome coronavirus 2, is important for reducing secondary transmission in healthcare-associated outbreaks.Authors present a simple, reliable, and cheap protocol to produce a custom-made sterilizable filtering facepiece 2/3 masks for healthcare providers during pandemic COVID-19 emergency.", "qid": 18, "docid": "2w05l8r6", "rank": 23, "score": 0.8664097785949707}, {"content": "Title: How to Produce Cheap and Easy Custom-Made Sterilizable Filtering Facepiece 2/3 Masks for Healthcare Providers During Pandemic COVID-19 Emergency. Content: On January 8, 2020, a novel coronavirus was officially announced as the causative pathogen of coronavirus disease (COVID-19) by the Chinese Center for Disease Control and Prevention.On February 26, COVID-19 has been recognized in 34 countries, with a total of 80,239 laboratory-confirmed patients and 2700 deaths.Protecting healthcare workers from infectious hazards is paramount to ensuring their safety in delivering health care.In addition, being able to protect healthcare workers, constituting the front-line response against high-threat respiratory pathogens, such as severe acute respiratory syndrome coronavirus 2, is important for reducing secondary transmission in healthcare-associated outbreaks.Authors present a simple, reliable, and cheap protocol to produce a custom-made sterilizable filtering facepiece 2/3 masks for healthcare providers during pandemic COVID-19 emergency.", "qid": 18, "docid": "y5dalgsz", "rank": 24, "score": 0.8664097785949707}, {"content": "Title: Who is wearing a mask? Gender-, age-, and location-related differences during the COVID-19 pandemic Content: Masks are an effective tool in combatting the spread of COVID-19 but wearing them remains controversial and has not been studied in the United States. To understand the demographics of mask wearers in the US, we observed shoppers (n = 5517) entering retail stores. 41.5% of the observed sample wore a mask. The odds of an individual wearing a mask increased significantly with age, and was also 1.5x greater for females than males. Additionally, the odds of observing a mask on an urban or suburban shopper were ~4x that for rural areas. Thus, gender, age, and location factor into whether American shoppers wear a mask or face covering. Regardless, all demographics wore masks at substantially lesser rates than required to stop the spread of COVID-19.", "qid": 18, "docid": "f4uh73j7", "rank": 25, "score": 0.8661091327667236}, {"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": 18, "docid": "sjenehbl", "rank": 26, "score": 0.8655074834823608}, {"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": 27, "score": 0.8650702238082886}, {"content": "Title: High Filtration Efficiency Face Masks made from Sterilization Wraps Content: COVID-19 pandemic has spawned the need for mass production of N-95 respirators. We used Sterilization Wraps to produce face masks which maintained 93% particle capture efficacy post sterilization. This ubiquitously available material could be explored for production of high quality face masks at a cost less than 30 US cents.", "qid": 18, "docid": "m6cxelu5", "rank": 28, "score": 0.8650070428848267}, {"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": 29, "score": 0.864040732383728}, {"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": 30, "score": 0.8627601861953735}, {"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": 31, "score": 0.8627601861953735}, {"content": "Title: Efficacy of face mask in preventing respiratory virus transmission: a systematic review and meta-analysis Content: Background: Conflicting recommendations exist related to whether masks have a protective effect on the spread of respiratory viruses. Methods: The Preferred Reporting Items for Systematic Reviews and Meta-Analysis (PRISMA) statement was consulted to report this systematic review. Relevant articles were retrieved from PubMed, Web of Science, ScienceDirect, Cochrane Library, and Chinese National Knowledge Infrastructure (CNKI), VIP (Chinese) database. Results: A total of 21 studies met our inclusion criteria. Meta-analyses suggest that mask use provided a significant protective effect (OR = 0.35 and 95% CI = 0.24-0.51). Use of masks by healthcare workers (HCWs) and non-healthcare workers (Non-HCWs) can reduce the risk of respiratory virus infection by 80% (OR = 0.20, 95% CI = 0.11-0.37) and 47% (OR = 0.53, 95% CI = 0.36-0.79). The protective effect of wearing masks in Asia (OR = 0.31) appeared to be higher than that of Western countries (OR = 0.45). Masks had a protective effect against influenza viruses (OR = 0.55), SARS (OR = 0.26), and SARS-CoV-2 (OR = 0.04). In the subgroups based on different study designs, protective effects of wearing mask were significant in cluster randomized trials, case-control studies and retrospective studies. Conclusions: This study adds additional evidence of the enhanced protective value of masks, we stress that the use masks serve as an adjunctive method regarding the COVID-19 outbreak.", "qid": 18, "docid": "ropgq7tr", "rank": 32, "score": 0.8623217344284058}, {"content": "Title: Study of Air Curtain in Context of Individual Protection from Exposure to Coronavirus (SARS-CoV-2) Contained in Cough-Generated Fluid Particles Content: The ongoing respiratory COVID-19 pandemic has heavily impacted the social and private lives of the majority of the global population. This infection is primarily transmitted via virus-laden fluid particles (i.e., droplets and aerosols) that are formed in the respiratory tract of infected individuals and expelled from the mouth in the course of breathing, talking, coughing, and sneezing. To mitigate the risk of virus transmission, in many places of the world, the public has been asked or even obliged to use face covers. It is plausible that in the years ahead we will see the use of face masks, face shields and respirators become a normal practice in our life. However, wearing face covers is uncomfortable in some situations, like, for example, in summer heat, while staying on beaches or at hotel swimming pools, doing exercises in gyms, etc. Also, most types of face cover become contaminated with time and need to be periodically replaced or disinfected. These nuisances are caused by the fact that face covers are based on material barriers, which prevent inward and outward propagation of aerosol and droplets containing the pathogen. Applying well established gas-particle flow formalism, we study a non-material based protection barrier created by a flow of well directed down stream of air across the front of the open face. The~protection is driven by dragging virus-laden particles inside the width of the air flow and hence, as a consequence, displacing them away from their primary trajectories. The study, shows that such, potentially portable, air curtains can effectively provide both inward and outward protection and serve as an effective personal protective equipment (PPE) mitigating human to human transmission of virus infection like COVID-19.", "qid": 18, "docid": "4zrwxcwv", "rank": 33, "score": 0.8621463775634766}, {"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": 18, "docid": "f9syysdw", "rank": 34, "score": 0.8616966605186462}, {"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": 18, "docid": "fpps1ux6", "rank": 35, "score": 0.8615188598632812}, {"content": "Title: Efficacy of face mask in preventing respiratory virus transmission: A systematic review and meta-analysis Content: BACKGROUND: Conflicting recommendations exist related to whether masks have a protective effect on the spread of respiratory viruses. METHODS: The Preferred Reporting Items for Systematic Reviews and Meta-Analysis (PRISMA) statement was consulted to report this systematic review. Relevant articles were retrieved from PubMed, Web of Science, ScienceDirect, Cochrane Library, and Chinese National Knowledge Infrastructure (CNKI), VIP (Chinese) database. RESULTS: A total of 21 studies met our inclusion criteria. Meta-analyses suggest that mask use provided a significant protective effect (OR = 0.35 and 95% CI = 0.24-0.51). Use of masks by healthcare workers (HCWs) and non-healthcare workers (Non-HCWs) can reduce the risk of respiratory virus infection by 80% (OR = 0.20, 95% CI = 0.11-0.37) and 47% (OR = 0.53, 95% CI = 0.36-0.79). The protective effect of wearing masks in Asia (OR = 0.31) appeared to be higher than that of Western countries (OR = 0.45). Masks had a protective effect against influenza viruses (OR = 0.55), SARS (OR = 0.26), and SARS-CoV-2 (OR = 0.04). In the subgroups based on different study designs, protective effects of wearing mask were significant in cluster randomized trials and observational studies. CONCLUSIONS: This study adds additional evidence of the enhanced protective value of masks, we stress that the use masks serve as an adjunctive method regarding the COVID-19 outbreak.", "qid": 18, "docid": "b4znk2wr", "rank": 36, "score": 0.8614888787269592}, {"content": "Title: Efficacy of face mask in preventing respiratory virus transmission: A systematic review and meta-analysis Content: BACKGROUND: Conflicting recommendations exist related to whether masks have a protective effect on the spread of respiratory viruses. METHODS: The Preferred Reporting Items for Systematic Reviews and Meta-Analysis (PRISMA) statement was consulted to report this systematic review. Relevant articles were retrieved from PubMed, Web of Science, ScienceDirect, Cochrane Library, and Chinese National Knowledge Infrastructure (CNKI), VIP (Chinese) database. RESULTS: A total of 21 studies met our inclusion criteria. Meta-analyses suggest that mask use provided a significant protective effect (OR = 0.35 and 95% CI = 0.24\u20130.51). Use of masks by healthcare workers (HCWs) and non-healthcare workers (Non-HCWs) can reduce the risk of respiratory virus infection by 80% (OR = 0.20, 95% CI = 0.11\u20130.37) and 47% (OR = 0.53, 95% CI = 0.36\u20130.79). The protective effect of wearing masks in Asia (OR = 0.31) appeared to be higher than that of Western countries (OR = 0.45). Masks had a protective effect against influenza viruses (OR = 0.55), SARS (OR = 0.26), and SARS-CoV-2 (OR = 0.04). In the subgroups based on different study designs, protective effects of wearing mask were significant in cluster randomized trials and observational studies. CONCLUSIONS: This study adds additional evidence of the enhanced protective value of masks, we stress that the use masks serve as an adjunctive method regarding the COVID-19 outbreak.", "qid": 18, "docid": "x9sfgtim", "rank": 37, "score": 0.8613176345825195}, {"content": "Title: Decontamination of face masks with steam for mask reuse in fighting the pandemic COVID\u201019: experimental supports Content: The COVID\u201019 pandemic caused by the novel coronavirus SARS\u2010CoV\u20102 has claimed many lives worldwide. Wearing medical masks or N95 masks (namely N95 respirators) can slow the virus spread and reduce the infection risk. Reuse of these masks can minimize waste, protect the environment, and help to solve the current imminent shortage of masks. Disinfection of used masks is needed for reuse of them with safety, but improper decontamination can damage the blocking structure of masks. In this study, we demonstrated, using avian coronavirus of infectious bronchitis virus to mimic SARS\u2010CoV\u20102, that medical masks and N95 masks remained their blocking efficacy after being steamed on boiling water even for 2 hours. We also demonstrated that three brands of medical masks blocked over 99% viruses in aerosols. The avian coronavirus was completely inactivated after being steamed for 5 minutes. Together, this study suggested that medical masks are adequate for use on most social occasions, and both medical masks and N95 masks can be reused for a few days with steam decontamination between use. This article is protected by copyright. All rights reserved.", "qid": 18, "docid": "5fq150t1", "rank": 38, "score": 0.8612775802612305}, {"content": "Title: Facial protection for healthcare workers during pandemics: a scoping review Content: BACKGROUND: The coronavirus disease 2019 (COVID-19) pandemic has led to personal protective equipment (PPE) shortages, requiring mask reuse or improvisation. We provide a review of medical-grade facial protection (surgical masks, N95 respirators and face shields) for healthcare workers, the safety and efficacy of decontamination methods, and the utility of alternative strategies in emergency shortages or resource-scarce settings. METHODS: We conducted a scoping review of PubMed and grey literature related to facial protection and potential adaptation strategies in the setting of PPE shortages (January 2000 to March 2020). Limitations included few COVID-19-specific studies and exclusion of non-English language articles. We conducted a narrative synthesis of the evidence based on relevant healthcare settings to increase practical utility in decision-making. RESULTS: We retrieved 5462 peer-reviewed articles and 41 grey literature records. In total, we included 67 records which met inclusion criteria. Compared with surgical masks, N95 respirators perform better in laboratory testing, may provide superior protection in inpatient settings and perform equivalently in outpatient settings. Surgical mask and N95 respirator conservation strategies include extended use, reuse or decontamination, but these strategies may result in inferior protection. Limited evidence suggests that reused and improvised masks should be used when medical-grade protection is unavailable. CONCLUSION: The COVID-19 pandemic has led to critical shortages of medical-grade PPE. Alternative forms of facial protection offer inferior protection. More robust evidence is required on different types of medical-grade facial protection. As research on COVID-19 advances, investigators should continue to examine the impact on alternatives of medical-grade facial protection.", "qid": 18, "docid": "quwwani8", "rank": 39, "score": 0.8607625365257263}, {"content": "Title: Face mask use in the general population and optimal resource allocation during the COVID-19 pandemic Content: The ongoing novel coronavirus disease (COVID-19) pandemic has rapidly spread in early 2020, causing tens of thousands of deaths, over a million cases and widespread socioeconomic disruption. With no vaccine available and numerous national healthcare systems reaching or exceeding capacity, interventions to limit transmission are urgently needed. While there is broad agreement that travel restrictions and closure of non-essential businesses and schools are beneficial in limiting local and regional spread, recommendations around the use of face masks for the general population are less consistent internationally. In this study, we examined the role of face masks in mitigating the spread of COVID-19 in the general population, using epidemic models to estimate the total reduction of infections and deaths under various scenarios. In particular, we examined the optimal deployment of face masks when resources are limited, and explored a range of supply and demand dynamics. We found that face masks, even with a limited protective effect, can reduce infections and deaths, and can delay the peak time of the epidemic. We consistently found that a random distribution of masks in the population was a suboptimal strategy when resources were limited. Prioritizing coverage among the elderly was more beneficial, while allocating a proportion of available resources for diagnosed infected cases provided further mitigation under a range of scenarios. In summary, face mask use, particularly for a pathogen with relatively common asymptomatic carriage, can effectively provide some mitigation of transmission, while balancing provision between vulnerable healthy persons and symptomatic persons can optimize mitigation efforts when resources are limited.", "qid": 18, "docid": "qdamvwxl", "rank": 40, "score": 0.8602904081344604}, {"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": 18, "docid": "6n5gnow1", "rank": 41, "score": 0.8600316047668457}, {"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": 18, "docid": "vjg2auh7", "rank": 42, "score": 0.8596975803375244}, {"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": 18, "docid": "gey0nidn", "rank": 43, "score": 0.8596975803375244}, {"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": 44, "score": 0.8594222068786621}, {"content": "Title: A cloth mask for under-resourced healthcare settings in the COVID19 pandemic Content: INTRODUCTION: COVID19 pandemic poses a global threat, with many unknowns. The potential for resource limited countries to suffer huge mortality is of major concern. Prevention and risk reduction strategies are paramount in the current absence of effective treatment or a vaccine. There is a global shortage of personal protective equipment. AIMS: This short paper describes the rationale for and development of a cloth homemade mask and has a step by step video. RESULTS: The template is reproducible around the world and is both washable and cheap. CONCLUSION: This article describes a simple way to make a cloth mask, suitable if medical masks are not available.", "qid": 18, "docid": "vgqvgz21", "rank": 45, "score": 0.8593308925628662}, {"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": 18, "docid": "sqr11fpv", "rank": 46, "score": 0.8592574000358582}, {"content": "Title: Examining the protection efficacy of face shields against cough aerosol droplets using water sensitive papers Content: Simple plastic face shields have many advantages compared to regular medical masks. They are easily cleaned for reuse and comfortable to wear. In light of the spreading COVID-19 pandemic, the potential of face shields as a substitution for medical masks, as a recommendation to the general population, was tested. Testing the efficacy of the protective equipment utilized a cough simulator that was carefully tuned to replicate human cough in terms of droplet size distribution and outlet velocity. The tested protective equipment was worn on a manikin head simulating human breathing. An Aerodynamic Particle Sizer (APS) was used to analyze the concentration and size distribution of small particles that reach the manikin head respiration pathways. Additionally, Water sensitive papers were taped over and under the tested protective equipment, and were subsequently photographed and analyzed. For droplets larger than 3m by diameter, the efficiency of shields to block cough droplets was found to be comparable to that of regular medical masks, with enhanced protection on face parts the mask does not cover. Additionally, for finer particles, of the order 0.3 to few microns, a shield was found to perform even better, blocking about 10 times more fine particles than the medical mask. This implies that for the general population that is not intendedly exposed to confirmed infected individuals, recommending the use of face shields as an alternative to medical masks should be considered.", "qid": 18, "docid": "5b9jytph", "rank": 47, "score": 0.8592163920402527}, {"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": 48, "score": 0.859060525894165}, {"content": "Title: The use of exhaled nitric oxide and peak expiratory flow to demonstrate improved breathability and antimicrobial properties of novel face mask made with sustainable filter paper and Folium Plectranthii amboinicii oil: additional option for mask shortage during COVID-19 pandemic Content: BACKGROUND: Medical face masks are integral personal protective equipment against infectious airborne disease and become scarce during epidemic outbreaks such as COVID-19. A novel, sustainably manufactured face mask with antimicrobial and anti-inflammatory properties from oil of Folium Plectranthii amboinicii can be an effective alternative to internationally sold masks. METHODS: This prospective, randomized study assigned subjects (n=67) to either conventional surgical face mask or Lamdong Medical College (LMC) face mask for three hours. Fractional concentration of nitric oxide in exhaled breath (FE(NO)) and peak expiratory flow (PEF) was measured before and after mask use. Subjective reporting on respiratory symptoms was also analyzed. Masks were then incubated and analyzed for microorganism growth. RESULTS: Subjects assigned the LMC mask had a lowered FE(NO) (p<0.05) compared to conventional face masks after mask wearing. Subjects with LMC mask use reported higher comfortability (p<0.05), breathability (p<0.05), and lower allergy symptoms (p<0.05). The LMC mask has visually less microorganism growth in the cultured medium, measured by sterile ring radius. CONCLUSIONS: The LMC face mask is a renewably manufactured personal protective tool with antibacterial capacity that can serve as an effective alternative to internationally sold surgical face mask during shortage of mask due to COVID-19.", "qid": 18, "docid": "gocycb7u", "rank": 49, "score": 0.8588384389877319}, {"content": "Title: Assessment of Fabric Masks as Alternatives to Standard Surgical Masks in Terms of Particle Filtration Efficiency Content: In response to the critical shortage of medical masks resulting from the COVID-19 pandemic, large portions of the population are mobilizing to produce cloth masks using locally-sourced fabrics, however the efficacy of these masks as a means of protecting the wearer from airborne particles carrying virus is not well known. Further, existing protocols are designed for testing the fit and performance N95 respirators and tight-fitting facemasks rather than the relatively more loose-fitting surgical mask style most cloth masks follow. In this study tools and methods typically used to assess tight-fitting facemasks were modified to assess the efficacy of community-produced fabric and commercially-produced surgical masks in terms of protecting the wearer from airborne particles that may be carrying virus. Two TSI PortaCount (model 8028) instruments were operated concurrently to collect particle counts (particles/cm^3) in size range 0.02 to >1 um from ambient air and air just inside the breathing zone of the mask (1 measurement per second, evaluation period of 1 minute per test). Percent particle removal was determined for ten home-made, fabric masks of different designs, with and without filter layers, as well as three commercially-produced surgical-type masks. N95 masks were used to validate the method, and a 3M model 1826 surgical mask was used as a baseline for comparison of other masks of this style. Home-made masks worn as designed always had lower particle removal rates than the 3M masks, achieving between 38% and 96% of this baseline. As has been previously observed by Cooper et al. (1983), adding a layer of nylon stocking over the masks minimized the flow of air around the edges of the masks and improved particle filtration efficiency for all masks, including all commercial products tested. Use of a nylon stocking overlayer brought the particle filtration efficiency for five of the ten fabric masks above the 3M surgical mask baseline. This rapid testing method (<2 hours per mask design) provides a holistic evaluation of mask particle removal efficacy (material, design, and fit), and use of this method for testing a wider range of mask materials and designs will provide the public and health care providers with information needed to optimize health protection given resources at hand.", "qid": 18, "docid": "mnjy6bq2", "rank": 50, "score": 0.8586863279342651}, {"content": "Title: Extended use of face masks during the COVID-19 pandemic - Thermal conditioning and spray-on surface disinfection Content: The current COVID-19 pandemic has resulted in globally constrained supplies for face masks and personal protective equipment (PPE). Production capacity is limited in many countries and the future course of the pandemic will likely continue with shortages for high quality masks and PPE in the foreseeable future. Hence, expectations are that mask reuse, extended wear and similar approaches will enhance the availability of personal protective measures. Repeated thermal disinfection could be an important option and likely easier implemented in some situations, at least on the small scale, than UV illumination, irradiation or hydrogen peroxide vapor exposure. An overview on thermal responses and ongoing filtration performance of multiple face mask types is provided. Most masks have adequate material properties to survive a few cycles (i.e. 30 min disinfection steps) of thermal exposure in the 75 \u00b0C regime. Some are more easily affected, as seen by the fusing of plastic liner or warping, given that preferred conditioning temperatures are near the softening point for some of the plastics and fibers used in these masks. Hence adequate temperature control is equally important. As guidance, disinfectants sprayed via dilute solutions maintain a surface presence over extended time at 25 and 37 \u00b0C. Some spray-on alcohol-based solutions containing disinfectants were gently applied to the top surface of masks. Neither moderate thermal aging (less than 24 h at 80 and 95 \u00b0C) nor gentle application of surface disinfectant sprays resulted in measurable loss of mask filter performance. Subject to bio-medical concurrence (additional checks for virus kill efficiency) and the use of low risk non-toxic disinfectants, such strategies, either individually or combined, by offering additional anti-viral properties or short term refreshing, may complement reuse options of professional masks or the now ubiquitous custom-made face masks with their often unknown filtration effectiveness.", "qid": 18, "docid": "77tww0a8", "rank": 51, "score": 0.8586071729660034}, {"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": 18, "docid": "akffx93g", "rank": 52, "score": 0.857877254486084}, {"content": "Title: St George's COVID shield for use by ENT surgeons performing tracheostomies Content: Healthcare workers are at increased risk of exposure to COVID-19. The majority of cases are acquired through inhalation of infected respiratory particles, contamination with infected surfaces or whilst performing aerosol-generating procedures. Basic infection prevention measures are essential to protect healthcare workers from contracting the disease when managing patients; consequently global demand for personal protective equipment (PPE) has exceeded supply in many regions. We present a novel, innovative polycarbonate shield designed for ENT clinicians performing tracheostomies. Clinical investigations using the shield demonstrated a sixteen-fold decrease in the number of particles detected at the position of the operating surgeon when the shield was used (particle size 0.3m; with shield 27,000 versus 439,000 without shield). The shield, used with appropriate PPE, could therefore help to minimise exposure to aerosol generated particles such as during tracheostomies on patients with COVID-19.", "qid": 18, "docid": "05t60u3p", "rank": 53, "score": 0.8574920296669006}, {"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": 54, "score": 0.8571330308914185}, {"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": 18, "docid": "uep2tfnu", "rank": 55, "score": 0.8568824529647827}, {"content": "Title: Facemasks and similar barriers to prevent respiratory illness such as COVID-19: A rapid systematic review Content: The current pandemic of COVID-19 has lead to conflicting opinions on whether wearing facemasks outside of health care facilities protects against the infection. To better understand the value of wearing facemasks we undertook a rapid systematic review of existing scientific evidence about development of respiratory illness, linked to use of facemasks in community settings. METHODS: We included all study designs. There were 31 eligible studies (including 12 RCTs). Narrative synthesis and random-effects meta-analysis of attack rates for primary and secondary prevention in 28 studies were performed. Results were reported by design, setting and type of face barrier in primary prevention, and by who wore the facemask (index patient or well contacts) in secondary prevention trials. The preferred outcome was influenza-like illness (ILI) but similar outcomes were pooled with ILI when ILI was unavailable. GRADE quality assessment was based on RCTs with support from observational studies. RESULTS: Where specific information was available, most studies reported about use of medical grade (surgical paper masks). In 3 RCTs, wearing a facemask may very slightly reduce the odds of developing ILI/respiratory symptoms, by around 6% (OR 0.94, 95% CI 0.75 to 1.19, I2 29%, low certainty evidence). Greater effectiveness was suggested by observational studies. When both house-mates and an infected household member wore facemasks the odds of further household members becoming ill may be modestly reduced by around 19% (OR 0.81, 95%CI 0.48 to 1.37, I 2 45%, 5 RCTs, low certainty evidence). The protective effect was very small if only the well person(OR 0.93, 95% CI 0.68 to 1.28, I2 11%, 2 RCTs, low uncertainty evidence) or the infected person wore the facemask (very low certainty evidence). DISCUSSION: Based on the RCTs we would conclude that wearing facemasks can be very slightly protective against primary infection from casual community contact, and modestly protective against household infections when both infected and uninfected members wear facemasks. However, the RCTs often suffered from poor compliance and controls using facemasks. Across observational studies the evidence in favour of wearing facemasks was stronger. We expect RCTs to under-estimate the protective effect and observational studies to exaggerate it. The evidence is not sufficiently strong to support widespread use of facemasks as a protective measure against COVID-19. However, there is enough evidence to support the use of facemasks for short periods of time by particularly vulnerable individuals when in transient higher risk situations. Further high quality trials are needed to assess when wearing a facemask in the community is most likely to be protective.", "qid": 18, "docid": "844229sb", "rank": 56, "score": 0.8567056655883789}, {"content": "Title: Role of respirators in controlling the spread of novel coronavirus (COVID-19) amongst dental healthcare providers: a review Content: During the ongoing COVID-19 pandemic, healthcare professionals are at the forefront of managing the highly infectious coronavirus. As the most common route of transmission is via aerosols and droplet inhalation, it is critical for healthcare workers to have the correct personal protective equipment (PPE) including gowns, masks and goggles. Surgical masks are not effective in preventing the influenza and SARS, so they are unlikely to be able to resist contaminated aerosols from entering the respiratory system. Therefore, it is vital to use respirators which have been proven to offer better protection against droplets, aerosols and fluid penetration and which form a tight seal around the mouth and nose. Various types of respirators are used in healthcare settings, such as half-mask filtering facepiece respirators (FFRs) and powered air-purifying respirators (PAPRs). The most commonly used FFR is the N95 disposable respirator, which is tight fitting and has a 95% or above particle filtering efficiency for a median particle size of 0.3 \u00b5m. This review discusses respirators, their purpose, types, clinical efficiency and proper donning and doffing techniques.", "qid": 18, "docid": "gprvoecp", "rank": 57, "score": 0.8566672801971436}, {"content": "Title: Decontamination of surgical face masks and N95 respirators by dry heat pasteurization for one hour at 70\u00b0C Content: BACKGROUND: The need for protective masks greatly exceeds their global supply during the current COVID-19 pandemic. METHODS: We optimized the temperature used in the dry heat pasteurization method to destroy pathogens and decontaminate masks while retaining their filtering capacity. RESULTS: The current study showed that dry heat at both 60\u00b0C and 70\u00b0C for 1 hour could successfully kill 6 species of respiratory bacteria and one fungi species, and inactivate the H1N1 indicator virus. After being heated at 70\u00b0C for 1, 2, and 3 hours, the N95 respirators and surgical face masks showed no changes in their shape and components. The filtering efficiency of bacterial aerosol for N95 respirators were 98%, 98%, and 97% after being heated for 1, 2, and 3 hour, respectively, all of which were over the 95% efficiency required and similar to the value before being heated (99%). The filtering efficiency for surgical face masks was 97%, 97%, and 96% for 1, 2, and 3 hours of heating, respectively, all of which were also similar to the value before being heated (97%). CONCLUSIONS: This method can be used at home and can significantly resolve the current shortage of masks.", "qid": 18, "docid": "047asp3a", "rank": 58, "score": 0.8560153841972351}, {"content": "Title: Pretreated household materials carry similar filtration protection against pathogens when compared with surgical masks Content: OBJECTIVE: The past 4 months, the emergence and spread of novel 2019 SARS-Cov-2 (COVID-19) has led to a global pandemic which is rapidly depleting supplies of personal protective equipment worldwide. There are currently over 1.6 million confirmed cases of COVID-19 worldwide which has resulted in more the 100,000 deaths. As these numbers grow daily, hospitals are being forced to reuse surgical masks in hopes of conserving their dwindling supply. Since COVID-19 will most likely have effects that last for many months, our nationwide shortage of masks poses a long term issue that must be addressed immediately. METHODS: Based on a previous study by Quan et al., a salt-based soaking strategy has been reported to enhance the filtration ability of surgical masks. We propose a similar soaking process which uses materials widely available in anyone's household. We tested this method of pretreating a variety of materials with a salt-based solution by a droplet test using fluorescently stained nanoparticles similar in size to the COVID-19 virus. RESULTS: In this study, we found that paper towels and surgical masks pretreated with the salt-based solution showed a noticeable increase in filtration of nanoparticles similar in size to the COVID-19 virus. We also show that the TWEEN20 used by Quan et al. is not a critical component for the solution, and using salt alone in solution still provides a dramatically increased level of protection. CONCLUSIONS: We believe this method will allow for healthcare workers to create a disposable added layer of protection to their surgical masks, N95s, or homemade masks by using household available products. Adoption of this method may play an essential role in ensuring the safety of healthcare workers during the COVID-19 pandemic and any pandemics that may arise in the future.", "qid": 18, "docid": "8t0eks8g", "rank": 59, "score": 0.8559187650680542}, {"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": 60, "score": 0.8556086421012878}, {"content": "Title: Can N95 respirators be reused after disinfection? And for how many times? Content: The Coronavirus Disease 2019 (COVID-19) pandemic has led to a major shortage of N95 respirators, which protect healthcare professionals and the public who may come into contact with the virus. It is necessary to determine the conditions that would allow the safe reuse respirators and personal protection in this crisis. We found that heating (<100 {degrees}C) under various humidities (up to 100% RH at 75 {degrees}C) and ultraviolet (UV) irradiation were the most promising candidates for mask reuse in the modern hospital infrastructure (up to 20 cycles), when tested on a fabric with particle filtration efficiency [\u2265]95%. Treatments involving certain liquids and vapors may require caution, as steam, alcohol, and bleach all led to degradation in filtration efficiency, leaving the user vulnerable to viral aerosols.", "qid": 18, "docid": "dm1wkpnv", "rank": 61, "score": 0.8554219007492065}, {"content": "Title: Can wearing face masks in public affect transmission route and viral load in COVID-19? Content: The mandatory face mask wearing was implemented in the Czech Republic and Slovakia shortly after the COVID-19 outbreak in Central Europe. So far, the number of COVID-19-associated deaths per 100,000 individuals is far lower in these countries as compared with other neighbouring or close countries. The use of face masks in public may not protect the general public from contracting the virus, however, presumptively decreases the viral load and contributes to a favourable clinical outcome in COVID-19 disease. A certain time is required for antigen-specific T cells and B cells to fully develop. Obligatory face mask wearing in public favours the virus transmission through oral mucosa and/or conjunctival epithelium, which enables the adaptive immune responses to evolve. In the case of inhalation of high loads of SARS-CoV-2, the time for the development of fully protective adaptive immune responses seems to be insufficient. Then, a less specific and more damaging innate immune response prevails.", "qid": 18, "docid": "p93u753c", "rank": 62, "score": 0.8553491234779358}, {"content": "Title: Decontamination of Surgical Face Masks and N95 Respirators by Dry Heat Pasteurization for One Hour at 70\u00b0C Content: BACKGROUND: The need for protective masks greatly exceeds their global supply during the current COVID-19 pandemic. METHODS: We optimized the temperature used in the dry heat pasteurization method to destroy pathogens and decontaminate masks while retaining their filtering capacity. RESULTS: The current study showed that dry heat at both 60\u00b0C and 70\u00b0C for one hour could successfully kill six species of respiratory bacteria and one fungi species, and inactivate the H1N1 indicator virus. After being heated at 70\u00b0C for 1 h, 2 h, and 3 h, the N95 respirators and surgical face masks showed no changes in their shape and components. The filtering efficiency of bacterial aerosol for N95 respirators were 98%, 98%, and 97% after being heated for 1 h, 2 h, and 3 h, respectively, all of which were over the 95% efficiency required and similar to the value before being heated (99%). The filtering efficiency for surgical face masks was 97%, 97%, and 96% for 1 h, 2 h, and 3 h of heating, respectively, all of which were also similar to the value before being heated (97%). CONCLUSIONS: This method can be used at home and can resolve the current shortage of masks.", "qid": 18, "docid": "w4q75grn", "rank": 63, "score": 0.8552160263061523}, {"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": 64, "score": 0.8549039363861084}, {"content": "Title: Mascarillas como equipo de protecci\u00f3n individual durante la pandemia de Covid-19: C\u00f3mo, cu\u00e1ndo y cu\u00e1les deben utilizarse Content: Abstract Background and objective: In the COVID-19 pandemic, the demand of masks has been increased by health professionals and the general population. In this context, it is necessary to summarize the features and indications of the different types of masks. Patients or Materials and methods: To consult and to compile the different recommendations disseminated by prestigious institutions such as the World Health Organization, the European Center for Disease Prevention, the Center for Evidence-Based Medicine, or the Ministry of Health of the Government of Spain has been reviewed. Results: The institutions consulted recommend reserving FFP respirators for healthcare workers, especially when carrying out aerosol-generating procedures (AGPs) (minimum FFP2 protection) and consider some reutilization systems during times of scarcity. The use of surgical masks is recommended to professionals who do not perform AGPs and to the symptomatic population but exist variations in its indications intended for the general healthy population. Conclusions: In the context of shortage of personal protective equipment due to the COVID -19 pandemic, a prioritization and rationalization of the use of each type of mask should be established according to the user and the activity performed.", "qid": 18, "docid": "gmofvknn", "rank": 65, "score": 0.8548989295959473}, {"content": "Title: The scientific rationale for the use of simple masks or improvised facial coverings to trap exhaled aerosols and possibly reduce the breathborne spread of COVID-19 Content: The medical community agrees that breathborne infectious materials can be spread with exhaled aerosols and that asymptomatic people, i.e., those showing no symptoms, could be unknowingly infectious. With the current worldwide pandemic of the respiratory coronavirus disease 2019 (COVID-19), various health bodies and governments are recommending that the population wear some form of mask or improvised facial covers while out in public in an effort to reduce the spread of disease . The general concept is that more accessible masks or mask-like materials (scarves, bandanas, etc.) could serve to reduce the amount of infectious aerosol from infected people, and reduce the viral load in the environment. This editorial addresses the underlying scientific rationale that such inexpensive or improvised could indeed serve to reduce the emissions of infectious aerosol by the mechanism of surface adhesion and particle kinetics in addition to the filtration effect.", "qid": 18, "docid": "m17j5u0y", "rank": 66, "score": 0.8546542525291443}, {"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": 67, "score": 0.8542802333831787}, {"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": 68, "score": 0.8538830876350403}, {"content": "Title: Medical masks and Respirators for the Protection of Healthcare Workers from SARS-CoV-2 and other viruses Content: The use of medical masks and respirators as personal protective equipment is pivotal to reducing the level of biological hazard to which healthcare workers are exposed during the outbreak of highly diffusible pathogens, such as the recent novel coronavirus SARS-CoV-2. Unfortunately, during this pandemic, supplies are rapidly running out worldwide, with potential consequences for the rate of occupational infections. Also, knowledge about specific characteristics of respirators is of utmost importance to select the proper type according to the clinical setting. A wide variety of literature is available on the topic, but mostly based on Influenza viruses infection models. Clinical evidence on the use of respirators is poor and interest in the topic has not been constant over time. A better understanding of SARS-CoV-2 transmission is needed, together with high-quality clinical data on the use of respirators or alternative devices. Moreover, healthcare workers, regardless of their level of experience, should receive specific training. This review aims to summarize the available evidence on the use of medical masks and respirators in the context of viral infections, especially the current coronavirus disease 2019 (COVID-19).", "qid": 18, "docid": "uuau3n7s", "rank": 69, "score": 0.8536458611488342}, {"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": 18, "docid": "oyxxji7r", "rank": 70, "score": 0.8535317182540894}, {"content": "Title: Mask is the possible key for self\u2010isolation in COVID\u201019 pandemic Content: Ma's research shows N95 masks, medical masks, even homemade masks could block at least 90% of the virus in aerosols(1). This study puts the debate on whether the public wear masks back on the table. Recently Science interviewed Dr. Gao, director\u2010general of Chinese Center for Disease Control and Prevention (CDC). This article is protected by copyright. All rights reserved.", "qid": 18, "docid": "p5hljkkm", "rank": 71, "score": 0.8534339666366577}, {"content": "Title: Modifying a Full-Face Snorkel Mask to Meet N95 Respirator Standards for Use With Coronavirus Disease 2019 Patients Content: We evaluated a full-face snorkel mask with an airway circuit filter to protect health care providers against airborne pathogens. First, a quantified N95 fit test was performed using aerosolized saline. Second, cardiorespiratory variables (heart rate, peripheral oxygen saturation, end-tidal carbon dioxide tension, and inspired fraction of carbon dioxide) were measured at rest and during moderate exercise. The modified mask passed the United States Occupational Safety and Health Administration (OSHA) N95 respirator (N95) fit test requirements with a fit factor of 142. Neither hypercapnia nor hypoxemia occurred. This modified mask has the potential to protect providers who care for patients with coronavirus disease 2019 (COVID-19).", "qid": 18, "docid": "ps1uds4d", "rank": 72, "score": 0.8531593084335327}, {"content": "Title: Medical masks and Respirators for the Protection of Healthcare Workers from SARS-CoV-2 and other viruses Content: Abstract The use of medical masks and respirators as personal protective equipment is pivotal to reducing the level of biological hazard to which healthcare workers are exposed during the outbreak of highly diffusible pathogens, such as the recent novel coronavirus SARS-CoV-2. Unfortunately, during this pandemic, supplies are rapidly running out worldwide, with potential consequences for the rate of occupational infections. Also, knowledge about specific characteristics of respirators is of utmost importance to select the proper type according to the clinical setting. A wide variety of literature is available on the topic, but mostly based on Influenza viruses infection models. Clinical evidence on the use of respirators is poor and interest in the topic has not been constant over time. A better understanding of SARS-CoV-2 transmission is needed, together with high-quality clinical data on the use of respirators or alternative devices. Moreover, healthcare workers, regardless of their level of experience, should receive specific training. This review aims to summarize the available evidence on the use of medical masks and respirators in the context of viral infections, especially the current coronavirus disease 2019 (COVID-19).", "qid": 18, "docid": "86rb6hov", "rank": 73, "score": 0.8531311750411987}, {"content": "Title: How Efficient Can Non-Professional MasksSuppress COVID-19 Pandemic? Content: The coronavirus disease 2019 (COVID-19) pandemic is caused by the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), which can be transmitted via respiratory secretions. Since there are currently no specific therapeutics or vaccines available against the SARS-CoV-2, the commen nonpharmaceutical interventions (NPIs) are still the main measures to curb the COVID-19 epidemic. Face mask wearing is one important measure to suppress the pandemic. In order to know how efficient is face mask wearing in reducing the pandemic even with low efficiency non-professional face masks, we exploit physical abstraction to model the non-professional face masks made from cotton woven fabrics and characterize them by a parameter virus penetration rate (VPR){gamma}. Monte Carlo simulations exhibit that the effective reproduction number R of COVID-19 or similar pandemics can be approximately reduced by factor {gamma}4 with respect to the basic reproduction number R0,if the face masks with 70% <{gamma}< 90% are universally applied for the entire network. Furthermore, thought experiments and practical exploitation examples in country-level and city-level are enumerated and discussed to support our discovery in this study and indicate that the outbreak of a COVID-19 like pandemic can be even suppressed by the low efficiency non-professional face masks.", "qid": 18, "docid": "1yf1ae1d", "rank": 74, "score": 0.8529508113861084}, {"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": 75, "score": 0.8528863191604614}, {"content": "Title: Is the fit of N95 facial masks effected by disinfection? A study of heat and UV disinfection methods using the OSHA protocol fit test. Content: The current COVID-19 pandemic has highlighted global supply chain shortcomings in the US hospital delivery system, most notably personal protective equipment (PPE) and COVID-19 is found on these masks ~ 7 days. Recent work from our group has shown two promising disinfection methods for N95 facial masks, dry heat (hot air (75C, 30 min) and UVGI which is UVGI 254 nm, 8W, 30 min. Using N95 five models of N95 masks from three different manufacturers we determined the following: 1) Hot air treated N95 masks applied over 5 cycles did not degrade the fit of masks (1.5% change in fit factor, p = .67), 2) UVGI treated N95 masks applied over 10 cycles were significantly degraded in fit and did not pass quantitative fit testing using OSHA testing protocols on a human model (-77.4% change in fit factor, p = .0002).", "qid": 18, "docid": "kpnckxhh", "rank": 76, "score": 0.8528749942779541}, {"content": "Title: Effect of various decontamination procedures on disposable N95 mask integrity and SARS-CoV-2 infectivity Content: The COVID-19 pandemic has created a high demand on personal protective equipment, including disposable N95 masks. Given the need for mask reuse, we tested the feasibility of vaporized hydrogen peroxide (VHP), ultraviolet light (UV), and ethanol decontamination strategies on N95 mask integrity and the ability to remove the infectious potential of SARS-CoV-2. FIT test data showed functional degradation by both ethanol and UV decontamination to different degrees. VHP treated masks showed no significant change in function after two treatments. We also report a single SARS-CoV-2 virucidal experiment using Vero E6 cell infection. We hope our data will guide further research for evidenced-based decisions for disposable N95 mask reuse and help protect caregivers from SARS-CoV-2 and other pathogens.", "qid": 18, "docid": "tq9kjozt", "rank": 77, "score": 0.8527739644050598}, {"content": "Title: Evaluation of Protection Level, Respiratory Safety, and Practical Aspects of Commercially Available Snorkel Masks as Personal Protection Devices Against Aerosolized Contaminants and SARS-CoV2 Content: Introduction: The \"Severe Acute Respiratory Syndrome Coronavirus 2\u00e2\u0080\u00b3 (SARS-CoV2) pandemic has led to a worldwide shortage of personal protection devices (PPD) for medical and paramedical personnel. Adaptation of commercially available snorkel masks to serve as full face masks has been proposed. Even not formally approved as PPD, they are publicized on social media as suitable for this use. Concerns about actual protection levels and risk of carbon dioxide (CO2) accumulation while wearing them for extended periods made us perform a systematic testing of various brands, in order to verify whether they are as safe and effective as claimed. Methods: A 'fit' test was performed, analogous to gas mask testing. Respiratory safety was evaluated by measuring end-tidal CO2 and oxygen saturation while wearing the masks in rest and during physical exercise. Masks were tested with 3D adaptors to mount regular bacterial-viral ventilator filters when available, or with snorkel openings covered with N95/FFP2 cloth. Results: Modified masks performed reasonably well on the fit test, comparable to regular N95/FFP2 masks. Not all ventilator filters are equally protective. For all masks, a small initial increase in end-tidal CO2 was noted, remaining within physiological limits. 3D printed adaptors are safer, have more flexibility and reliability than makeshift adaptations. Conclusions: These masks can offer benefit as a substitute for complete protective gear as they are easier to don and remove and offer full-face protection. They may be more comfortable to wear for extended periods. Proper selection of mask size, fit testing, quality of 3D printed parts, and choice of filter are important.", "qid": 18, "docid": "kwp0g1gl", "rank": 78, "score": 0.8525599241256714}, {"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": 79, "score": 0.8524923920631409}, {"content": "Title: Decontamination of face masks with steam for mask reuse in fighting the pandemic COVID-19: Experimental supports Content: The coronavirus disease 2019 pandemic caused by the novel coronavirus SARS-CoV-2 (severe acute respiratory syndrome coronavirus 2) has claimed many lives worldwide. Wearing medical masks (MMs) or N95 masks ([N95Ms] namely N95 respirators) can slow the virus spread and reduce the infection risk. Reuse of these masks can minimize waste, protect the environment, and help solve the current imminent shortage of masks. Disinfection of used masks is needed for their reuse with safety, but improper decontamination can damage the blocking structure of masks. In this study, we demonstrated using the avian coronavirus of infectious bronchitis virus to mimic SARS-CoV-2 that MMs and N95Ms retained their blocking efficacy even after being steamed on boiling water for 2 hours. We also demonstrated that three brands of MMs blocked over 99% viruses in aerosols. The avian coronavirus was completely inactivated after being steamed for 5 minutes. Altogether, this study suggested that MMs are adequate for use on most social occasions and both MMs and N95Ms can be reused for a few days with steam decontamination between use.", "qid": 18, "docid": "tx7en3rg", "rank": 80, "score": 0.8523352146148682}, {"content": "Title: Importance of face masks for COVID-19 \u2013 a call for effective public education Content: Considerable debates about the general community use of face masks for protection against COVID-19 stemmed out from differing views taken by health authorities. Misconceptions and stigmatization towards the use of face masks may hinder the containment of the COVID-19 pandemic. We address this previous debate by analyzing the advice on the community use of masks across different credible health authorities: countries that promoted the use of masks acknowledged that masks are effective, but also explained the importance of their proper use along with other hygiene measures. In contrast, authorities that recommended against the community use of masks mainly cited shortage of supplies, the argument that the public do not have the adequate skills to wear them, or that wearing masks might reduce compliance with other important behaviors. We suggest promoting effective behavioral changes in personal protective measures by teaching microbiological knowledge instead of just listing out the \u201cdos-and-don\u2019ts\u201d.", "qid": 18, "docid": "p2ufydgs", "rank": 81, "score": 0.851941704750061}, {"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": 18, "docid": "kqlra788", "rank": 82, "score": 0.851891279220581}, {"content": "Title: Evaluation of Protection Level, Respiratory Safety, and Practical Aspects of Commercially Available Snorkel Masks as Personal Protection Devices Against Aerosolized Contaminants and SARS-CoV2 Content: Introduction: The \u201cSevere Acute Respiratory Syndrome Coronavirus 2\u2033 (SARS-CoV2) pandemic has led to a worldwide shortage of personal protection devices (PPD) for medical and paramedical personnel. Adaptation of commercially available snorkel masks to serve as full face masks has been proposed. Even not formally approved as PPD, they are publicized on social media as suitable for this use. Concerns about actual protection levels and risk of carbon dioxide (CO(2)) accumulation while wearing them for extended periods made us perform a systematic testing of various brands, in order to verify whether they are as safe and effective as claimed. Methods: A \u2018fit\u2019 test was performed, analogous to gas mask testing. Respiratory safety was evaluated by measuring end-tidal CO(2) and oxygen saturation while wearing the masks in rest and during physical exercise. Masks were tested with 3D adaptors to mount regular bacterial-viral ventilator filters when available, or with snorkel openings covered with N95/FFP2 cloth. Results: Modified masks performed reasonably well on the fit test, comparable to regular N95/FFP2 masks. Not all ventilator filters are equally protective. For all masks, a small initial increase in end-tidal CO(2) was noted, remaining within physiological limits. 3D printed adaptors are safer, have more flexibility and reliability than makeshift adaptations. Conclusions: These masks can offer benefit as a substitute for complete protective gear as they are easier to don and remove and offer full-face protection. They may be more comfortable to wear for extended periods. Proper selection of mask size, fit testing, quality of 3D printed parts, and choice of filter are important.", "qid": 18, "docid": "avmri968", "rank": 83, "score": 0.8517391085624695}, {"content": "Title: Heat inactivating and reusing of virus-contaminated disposable medical mask Content: As the prevalence of COVID-19 in all the area of China and continuous spread to many other countries, it is in urgent need of medical mask for community people. We have reported a simple method to inactivate artificially influenza virus-contaminated medical mask without affecting the filterability of mask by heating with hair dryer for 30min. In this study, we extended our studies to optimize our protocols and evaluate the filterability of mask after several-rounds of heat treatment. We found that baking at 70 for 30min almost completely inactivated virus as hair dryer treatment for 30min described before. One-round of heat treatment with hair dryer for 30min or baking at 70 for 30min did not affect filterability of mask whilst two-rounds of treatment slightly but significantly reduced filterability of mask. Thus, heating with hair dryer for 30min or baking at 70 for 30min can inactive contaminated medical mask and the treated mask can be reused at least once.", "qid": 18, "docid": "xrjbtr0n", "rank": 84, "score": 0.8514982461929321}, {"content": "Title: Strategies for the reuse of N95 and N99 respiratory masks during the COVID-19 pandemic Content: The COVID-19 pandemic presents a strain of unprecedented scale on health systems around the world. In order to reliably protect medical personnel, and thus to contain the spread of the pandemic, it is essential to provide N95 or N99 (European FFP2 or FFP3) respiratory masks (FFRs). Such masks are currently in extreme shortage: To guarantee their supply sufficiently and for all cases, it would absolutely necessary to reuse them. In recent years, the scientific literature has laid out various possibilities to disinfect the FFRs for their reuse several times. We identify the most promising disinfection methods for the current critical situation (internationally) and project further methods and modifications beyond these.", "qid": 18, "docid": "hwvb979y", "rank": 85, "score": 0.8512561321258545}, {"content": "Title: Pretreated household materials carry similar filtration protection against pathogens when compared with surgical masks Content: The past 4 months, the emergence and spread of novel 2019 SARS-Cov-2 (COVID-19) has led to a global pandemic which is rapidly depleting supplies of personal protective equipment worldwide. There are currently over 1.6 million confirmed cases of COVID-19 worldwide which has resulted in more the 100,000 deaths. As these numbers grow daily, hospitals are being forced to reuse surgical masks in hopes of conserving their dwindling supply. Since COVID-19 will most likely have effects that last for many months, our nationwide shortage of masks poses a long term issue that must be addressed immediately. Based on a previous study by Quan et al., a salt-based soaking strategy has been reported to enhance the filtration ability of surgical masks. We propose a similar soaking process which uses materials widely available in anyone's household. We tested this method of pretreating a variety of materials with a salt-based solution by a droplet test using fluorescently stained nanoparticles similar in size to the COVID-19 virus. Our results show that this filter significantly reduces the amount of penetration of these particles. This will allow for healthcare workers to create a disposable added layer of protection to their surgical masks, N95s, or homemade masks by using household available products.", "qid": 18, "docid": "28enxc5h", "rank": 86, "score": 0.850838303565979}, {"content": "Title: Off-the-shelf barrier for emergency intubation in the cardiac catheterization laboratory during the coronavirus disease 2019 (COVID-19) pandemic Content: With the spread of SARS-CoV-2, it is expected that cases of acute coronary syndrome in the setting of coronavirus disease 2019 (COVID-19) develop. As expensive and sophisticated protection devices are not widely available, we have been working on a simple, off-the-shelf protection device for endotracheal intubation of potentially infected patients. For this purpose, we used a large transparent plastic bag (such as the sterile protective cover of the lead glass shield) for protection from airborne infections. The cover is moved over the patient's head from cranial to caudal, covering the catheter table including the torso with no need for patient mobilization. The intubation is done conventionally under direct visual control.", "qid": 18, "docid": "q4uo2l73", "rank": 87, "score": 0.8505080938339233}, {"content": "Title: Importance of face masks for COVID-19 - a call for effective public education Content: Considerable debates about the general community use of face masks for protection against COVID-19 stemmed out from differing views taken by health authorities. Misconceptions and stigmatization towards the use of face masks may hinder the containment of the COVID-19 pandemic. We address this previous debate by analyzing the advice on the community use of masks across different credible health authorities: countries that promoted the use of masks acknowledged that masks are effective, but also explained the importance of their proper use along with other hygiene measures. In contrast, authorities that recommended against the community use of masks mainly cited shortage of supplies, the argument that the public do not have the adequate skills to wear them, or that wearing masks might reduce compliance with other important behaviors. We suggest promoting effective behavioral changes in personal protective measures by teaching microbiological knowledge instead of just listing out the \"dos-and-don'ts\".", "qid": 18, "docid": "wee1133a", "rank": 88, "score": 0.8503275513648987}, {"content": "Title: [Management and prevention of common skin problems during epidemic prevention and control of COVID-19] Content: In the ongoing fight against the epidemic of COVID-19, the medical staff has been under tremendous pressure. Wearing the protective equipment (masks, goggles, and protective screens) with a poor breathability for a long time causes various skin problems, such as allergies, excessive skin hydration, local mechanical injuries, and even secondary infections. In addition, in a closed environment, compression and friction aggravate skin reactions, which may compromise duty performance of the medical staff. It is therefore essential to provide timely treatment opinions and prevention methods for common skin problems. We also give suggestions concerning the preparation of medical kit for skin protection in the epidemic area.", "qid": 18, "docid": "c7lt52b4", "rank": 89, "score": 0.8502802848815918}, {"content": "Title: [Management and prevention of common skin problems during epidemic prevention and control of COVID-19]. Content: In the ongoing fight against the epidemic of COVID-19, the medical staff has been under tremendous pressure. Wearing the protective equipment (masks, goggles, and protective screens) with a poor breathability for a long time causes various skin problems, such as allergies, excessive skin hydration, local mechanical injuries, and even secondary infections. In addition, in a closed environment, compression and friction aggravate skin reactions, which may compromise duty performance of the medical staff. It is therefore essential to provide timely treatment opinions and prevention methods for common skin problems. We also give suggestions concerning the preparation of medical kit for skin protection in the epidemic area.", "qid": 18, "docid": "8zn56jem", "rank": 90, "score": 0.8502802848815918}, {"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": 91, "score": 0.8500109910964966}, {"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": 92, "score": 0.8499375581741333}, {"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": "ckqdh4pg", "rank": 93, "score": 0.8498930335044861}, {"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": 94, "score": 0.8498930335044861}, {"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": 95, "score": 0.8497316837310791}, {"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": 96, "score": 0.8497316837310791}, {"content": "Title: Progress and Perspective of Antiviral Protective Material Content: Public health events caused by viruses pose a significant risk to humans worldwide. From December 2019 till now, the rampant novel 2019 coronavirus (SAR-CoV-2) has hugely impacted China and over world. Regarding a commendable means of protection, mask technology is relatively mature, though most of the masks cannot effectively resist the viral infections. The key material of the mask is a non-woven material, which makes the barrier of virus through filtration. Due to the lack of the ability to kill the viruses, masks are prone to cross-infection and become an additional source of infection after being discarded. If the filteration and antiviral effects can be simultaneously integrated into the mask, it will be more effcient, work for a longer time and create less difficulty in post-treatment. This mini-review presents the advances in antiviral materials, different mechanisms of their activity, and their potential applications in personal protective fabrics. Furthermore, the article addresses the future challenges and directions of mask technology.", "qid": 18, "docid": "18crkfzj", "rank": 97, "score": 0.8496557474136353}, {"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": 98, "score": 0.8491231203079224}, {"content": "Title: Reply to Zhang et al.: Slowing the rate of spread of COVID-19 Content: Zhang et al. (2020) reported that mandating face coverings in public is necessary to decrease the rate of new COVID-19 infections. We present a counterexample that disproves this finding. We agree with Zhang et al. that masks can be an important element in reducing virus transmission and that widespread use may be essential for returning to full activity. However, their analysis neglects the potential importance of physical distancing for limiting COVID-19 transmission by misattributing its effect to mask requirements. A full suite of epidemiological tools is necessary in these challenging times.", "qid": 18, "docid": "8t8psk46", "rank": 99, "score": 0.8487100601196289}, {"content": "Title: Off-the-shelf barrier for emergency intubation in the cardiac catheterization laboratory during the coronavirus disease 2019 (COVID-19) pandemic Content: With the spread of SARS-CoV-2, it is expected that cases of acute coronary syndrome in the setting of coronavirus disease 2019 (COVID-19) develop. As expensive and sophisticated protection devices are not widely available, we have been working on a simple, off-the-shelf protection device for endotracheal intubation of potentially infected patients. For this purpose, we used a large transparent plastic bag (such as the sterile protective cover of the lead glass shield) for protection from airborne infections. The cover is moved over the patient's head from cranial to caudal, covering the catheter table including the torso with no need for patient mobilization. The intubation is done conventionally under direct visual control. ELECTRONIC SUPPLEMENTARY MATERIAL: The online version of this article (10.1007/s00392-020-01696-9) contains supplementary material, which is available to authorized users.", "qid": 18, "docid": "f690f30n", "rank": 100, "score": 0.8486189246177673}]}
{"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": 0.8830397725105286}, {"content": "Title: Efficient inactivation of SARS-CoV-2 by WHO-recommended hand rub formulations and alcohols Content: The recent emergence of Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) causing COVID-19 is a major burden for health care systems worldwide. It is important to address if the current infection control instructions based on active ingredients are sufficient. We therefore determined the virucidal activity of two alcohol-based hand rub solutions for hand disinfection recommended by the World Health Organization (WHO), as well as commercially available alcohols. Efficient SARS-CoV-2 inactivation was demonstrated for all tested alcohol-based disinfectants. These findings show the successful inactivation of SARS-CoV-2 for the first time and provide confidence in its use for the control of COVID-19. Importance The current COVID-19 outbreak puts a huge burden on the world\u2019s health care systems. Without effective therapeutics or vaccines being available, effective hygiene measure are of utmost importance to prevent viral spreading. It is therefore crucial to evaluate current infection control strategies against SARS-CoV-2. We show the inactivation of the novel coronavirus for the first time and endorse the importance of disinfectant-based hand hygiene to reduce SARS-CoV-2 transmission.", "qid": 19, "docid": "c1n994j6", "rank": 2, "score": 0.8642857074737549}, {"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": 3, "score": 0.8549113273620605}, {"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": 4, "score": 0.8516136407852173}, {"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": 5, "score": 0.8514662981033325}, {"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": 19, "docid": "r1oqwdkz", "rank": 6, "score": 0.8507401943206787}, {"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": 7, "score": 0.8490647673606873}, {"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": 19, "docid": "6wxjm7m0", "rank": 8, "score": 0.8489896655082703}, {"content": "Title: Inanimate surfaces as potential source of 2019-nCoV spread and their disinfection with biocidal agents Content: The WHO has declared COVID-19 illness a global health concern which is caused by 2019-nCoV, causing severe respiratory tract infections in humans. Transmissibility among individual to individual have been reported through droplets and probably also via contaminated surfaces and hands. Human coronaviruses can persist on inanimate surfaces such as plastic, glass, fibers and metals up to nine days. 2019-nCoV remains infectious in air for 3 h and on inanimate surfaces such as cardboard, copper, plastic and steel up to 24, 4, 72 and 48 h respectively. Disinfectant activity of various biocidal agents against coronaviruses like ethanol (62\u201371%), sodium hypochlorite (0.1%) and hydrogen peroxide (0.5%) can be regarded effective against 2019-nCoV as well. As no vaccine and antiviral therapies have been discovered for 2019-nCoV, prevention of further spread will viable option to control the ongoing and future outbreaks.", "qid": 19, "docid": "esvutpel", "rank": 9, "score": 0.8463492393493652}, {"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": 10, "score": 0.8458174467086792}, {"content": "Title: Inactivation of Severe Acute Respiratory Syndrome Coronavirus 2 by WHO-Recommended Hand Rub Formulations and Alcohols Content: Infection control instructions call for use of alcohol-based hand rub solutions to inactivate severe acute respiratory syndrome coronavirus 2. We determined the virucidal activity of World Health Organization\u2013recommended hand rub formulations, at full strength and multiple dilutions, and of the active ingredients. All disinfectants demonstrated efficient virus inactivation.", "qid": 19, "docid": "b0nkhsvv", "rank": 11, "score": 0.844629168510437}, {"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": 12, "score": 0.8445156216621399}, {"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": 13, "score": 0.8436678051948547}, {"content": "Title: The importance of the minimum dosage necessary for UVC decontamination of N95 respirators during the COVID\u201019 pandemic Content: The World Health Organization (WHO) recently released a press report highlighting the severe shortage of personal protective equipment (PPE) that is endangering healthcare workers worldwide during the COVID-19 pandemic.1 To meet this urgent need, healthcare institutions across the world have begun to utilize the germicidal properties of ultraviolet C (UVC) to decontaminate N95 respirators so that they can be reused.2 It is clearly crucial that the dose of UVC delivered is sufficient to kill any viable SARS-CoV-2, the causative virus of the COVID-19 pandemic, that may be present on the respirators.", "qid": 19, "docid": "hmdq2g3u", "rank": 14, "score": 0.8422199487686157}, {"content": "Title: Inactivation of Severe Acute Respiratory Syndrome Coronavirus 2 by WHO-Recommended Hand Rub Formulations and Alcohols Content: Infection control instructions call for use of alcohol-based hand rub solutions to inactivate severe acute respiratory syndrome coronavirus 2. We determined the virucidal activity of World Health Organization-recommended hand rub formulations, at full strength and multiple dilutions, and of the active ingredients. All disinfectants demonstrated efficient virus inactivation.", "qid": 19, "docid": "1v8wwn0d", "rank": 15, "score": 0.8413817286491394}, {"content": "Title: Fight Against COVID-19: ARCI\u2019s Technologies for Disinfection Content: COVID-19 (SARS-CoV-2) is causing a huge concern to the global population due to its highly contagious properties. The SARS-CoV-2 is a new variant in the coronavirus family. The world is focussing on several methods to battle against this novel corona virus, including control of its spread. In this context, ARCI has quickly made efforts to develop disinfection systems including a UVC-based disinfection trolley, honeycomb air heater and a fogging chamber using UVC germicidal lamps, dry heat sterilization and HOCl-based chemical disinfectant to provide rapid and effective inactivation of microorganisms causing the pandemic. These systems have been successfully deployed at different hospitals for their validation.", "qid": 19, "docid": "bq6ogxyq", "rank": 16, "score": 0.8412779569625854}, {"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": 17, "score": 0.8409467935562134}, {"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": 18, "score": 0.8407099843025208}, {"content": "Title: Potential role of inanimate surfaces for the spread of coronaviruses and their inactivation with disinfectant agents Content: Summary The novel human coronavirus SARS-CoV-2 has become a global health concern causing severe respiratory tract infections in humans. Human-to-human transmissions have been described, probably via droplets but possibly also via contaminated hands or surfaces. In a recent review on the persistence of human and veterinary coronaviruses on inanimate surfaces it was shown that human coronaviruses such as Severe Acute Respiratory Syndrome (SARS) coronavirus, Middle East Respiratory Syndrome (MERS) coronavirus or endemic human coronaviruses (HCoV) can persist on inanimate surfaces like metal, glass or plastic for up to 9 days. Some disinfectant agents effectively reduce coronavirus infectivity within 1 minute such 62%\u201371% ethanol, 0.5% hydrogen peroxide or 0.1% sodium hypochlorite. Other compounds such as 0.05%\u20130.2% benzalkonium chloride or 0.02% chlorhexidine digluconate are less effective. An effective surface disinfection may help to ensure an early containment and prevention of further viral spread.", "qid": 19, "docid": "80dfqjql", "rank": 19, "score": 0.8406636714935303}, {"content": "Title: Efficacy of a novel iodine complex solution, CupriDyne, in inactivating SARS-CoV-2 Content: The coronavirus known as SARS-CoV-2, which causes COVID-19 disease, is presently responsible for a global pandemic wherein more than 3.5 million people have been infected and more than 250,000 killed to-date. There is currently no vaccine for COVID-19, leaving governments and public health agencies with little defense against the virus aside from advising or enforcing best practices for virus transmission prevention, which include hand-washing, physical distancing, use of face covers, and use of effective disinfectants. In this study, a novel iodine complex called CupriDyne\u00ae was assessed for its ability to inactivate SARS-CoV-2. CupriDyne was shown to be effective in inactivating the virus in a time-dependent manner, reducing virus titers by 99% (2 logs) after 30 minutes, and reducing virus titers to below the detection limit after 60 minutes. The novel iodine complex tested herein offers a safe and gentle alternative to conventional disinfectants for use on indoor and outdoor surfaces.", "qid": 19, "docid": "d8xtacyj", "rank": 20, "score": 0.8399397730827332}, {"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": 21, "score": 0.8391023874282837}, {"content": "Title: Covid-19 and the N95 respirator shortage: Closing the gap Content: Due to extreme shortages of personal protective equipment caused by the COVID-19 pandemic, many healthcare workers will be forced to recycle protective masks intended for disposal after a single use. We propose investigating the use of ultraviolet germicidal irradiation to sterilize masks of SARS-CoV-2 for safer reuse.", "qid": 19, "docid": "1vav13al", "rank": 22, "score": 0.8390096426010132}, {"content": "Title: Hand Hygiene Among Health Care Workers During COVID-19 Pandemic: Challenges and Recommendations Content: In-hospital transmission is one of the main routes of the 2019 novel coronavirus (SARS-CoV-2) spreading among health care workers (HCWs) who are the frontline fighters. However, coming into contact with COVID-19-positive patients is unavoidable. Therefore, hand hygiene is of utmost importance for the prevention of COVID-19 among HCWs. This purpose can be achieved by applying alcohol-based hand rubs, washing hands properly with soap and water, and applying other antiseptic agents. Nevertheless, regular hand hygiene could also be challenging, because water, detergents, and disinfectants may predispose HCWs to hand dermatitis. The current article reviews the risk factors for the development of hand dermatitis, with further focus on the most common agents used among HCWs. In addition, the risk of occupational hand dermatitis for each agent is evaluated to increase awareness of this common condition. Finally, some recommendations are discussed to reduce the effect of hand dermatitis on HCWs.", "qid": 19, "docid": "odfssrr6", "rank": 23, "score": 0.8387244343757629}, {"content": "Title: Hand Hygiene Among Health Care Workers During COVID-19 Pandemic: Challenges and Recommendations. Content: In-hospital transmission is one of the main routes of the 2019 novel coronavirus (SARS-CoV-2) spreading among health care workers (HCWs) who are the frontline fighters. However, coming into contact with COVID-19-positive patients is unavoidable. Therefore, hand hygiene is of utmost importance for the prevention of COVID-19 among HCWs. This purpose can be achieved by applying alcohol-based hand rubs, washing hands properly with soap and water, and applying other antiseptic agents. Nevertheless, regular hand hygiene could also be challenging, because water, detergents, and disinfectants may predispose HCWs to hand dermatitis. The current article reviews the risk factors for the development of hand dermatitis, with further focus on the most common agents used among HCWs. In addition, the risk of occupational hand dermatitis for each agent is evaluated to increase awareness of this common condition. Finally, some recommendations are discussed to reduce the effect of hand dermatitis on HCWs.", "qid": 19, "docid": "ji5pqh47", "rank": 24, "score": 0.8387244343757629}, {"content": "Title: Coronavirus Disease 2019: A Comprehensive Review of Etiology, Pathogenesis, Diagnosis, and Ongoing Clinical Trials Content: Coronavirus disease 2019 (COVID-19) is an acute respiratory viral infection caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). The disease outbreak started in China in late December 2019 and quickly spread to the rest of the world, resulting in a pandemic. The incidence of cases is increasing every day, affecting millions of people around the globe and resulting in a public health emergency. Furthermore, disease management has been challenging for the clinicians and other medical personnel in terms of treatment options and availability of personal protective equipment. The off-label use of drugs such as hydroxychloroquine and emergency use authorization of remdesivir can hopefully help the clinicians while treating critically ill patients. The use of convalescent serum has also shown some interim benefit until a definitive treatment and preventive options are uncovered, such as vaccines and other effective treatment regimens.", "qid": 19, "docid": "au5akuop", "rank": 25, "score": 0.8370052576065063}, {"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": 26, "score": 0.8362581729888916}, {"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": 27, "score": 0.8361763954162598}, {"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": 28, "score": 0.8361719846725464}, {"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": 29, "score": 0.8361719846725464}, {"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": 30, "score": 0.8360168933868408}, {"content": "Title: Using effective hand hygiene practice to prevent and control infection Content: Decontamination using hand hygiene remains one of the most important and effective methods for reducing healthcare-associated infections and cross-infection between patients. In 1860, Florence Nightingale wrote that nurses should wash their hands frequently throughout the day, demonstrating an early awareness of the effectiveness of this simple procedure. The COVID-19 pandemic has demonstrated that effectively applied hand hygiene is a vital intervention that can be used to prevent the spread of disease. This article details the correct procedure required for effective hand hygiene and emphasises the need for nurses to keep up to date with evidence-based guidelines. The article also outlines the differences between hand decontamination using alcohol-based hand gels and soap and water, and the complex factors that can interfere with effective hand hygiene compliance.", "qid": 19, "docid": "k5lz7ql7", "rank": 31, "score": 0.8360038995742798}, {"content": "Title: Using effective hand hygiene practice to prevent and control infection. Content: Decontamination using hand hygiene remains one of the most important and effective methods for reducing healthcare-associated infections and cross-infection between patients. In 1860, Florence Nightingale wrote that nurses should wash their hands frequently throughout the day, demonstrating an early awareness of the effectiveness of this simple procedure. The COVID-19 pandemic has demonstrated that effectively applied hand hygiene is a vital intervention that can be used to prevent the spread of disease. This article details the correct procedure required for effective hand hygiene and emphasises the need for nurses to keep up to date with evidence-based guidelines. The article also outlines the differences between hand decontamination using alcohol-based hand gels and soap and water, and the complex factors that can interfere with effective hand hygiene compliance.", "qid": 19, "docid": "4jx0oq65", "rank": 32, "score": 0.8360038995742798}, {"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": 33, "score": 0.8358485102653503}, {"content": "Title: Surfactant-based prophylaxis and therapy against COVID-19: A possibility Content: Hand hygiene by washing with soap and water is recommended for the prevention of COVID-19 spread. Soaps and detergents are explained to act by damaging viral spike glycoproteins (peplomers) or by washing out the virus through entrapment in the micelles. Technically, soaps come under a functional category of molecules known as surfactants. Surfactants are widely used in pharmaceutical formulations as excipients. We wonder why surfactants are still not tried for prophylaxis or therapy against COVID-19? That too when many of them have proven antiviral properties. Moreover, lung surfactants have already shown benefits in respiratory viral infections. Therefore, we postulate that surfactant-based prophylaxis and therapy would be promising. We believe that our hypothesis would stimulate debate or new research exploring the possibility of surfactant-based prophylaxis and therapy against COVID-19. The success of a surfactant-based technique would save the world from any such pandemic in the future too.", "qid": 19, "docid": "mtq8kubd", "rank": 34, "score": 0.8353443145751953}, {"content": "Title: Surfactant-based prophylaxis and therapy against COVID-19: a possibility Content: Hand hygiene by washing with soap and water is recommended for the prevention of COVID-19 spread. Soaps and detergents are explained to act by damaging viral spike glycoproteins (peplomers) or by washing out the virus through entrapment in the micelles. Technically, soaps come under a functional category of molecules known as surfactants. Surfactants are widely used in pharmaceutical formulations as excipients. We wonder why surfactants are still not tried for prophylaxis or therapy against COVID-19. That too when many of them have proven antiviral properties. Moreover, lung surfactants have already shown benefits in respiratory viral infections. Therefore, we postulate that surfactant-based prophylaxis and therapy would be promising. We believe that our hypothesis would stimulate debate or new research exploring the possibility of surfactant-based prophylaxis and therapy against COVID-19. The success of a surfactant-based technique would save the world from any such pandemic in the future too.", "qid": 19, "docid": "ud4rh1a8", "rank": 35, "score": 0.8350668549537659}, {"content": "Title: Effect of various decontamination procedures on disposable N95 mask integrity and SARS-CoV-2 infectivity Content: The COVID-19 pandemic has created a high demand on personal protective equipment, including disposable N95 masks. Given the need for mask reuse, we tested the feasibility of vaporized hydrogen peroxide (VHP), ultraviolet light (UV), and ethanol decontamination strategies on N95 mask integrity and the ability to remove the infectious potential of SARS-CoV-2. FIT test data showed functional degradation by both ethanol and UV decontamination to different degrees. VHP treated masks showed no significant change in function after two treatments. We also report a single SARS-CoV-2 virucidal experiment using Vero E6 cell infection. We hope our data will guide further research for evidenced-based decisions for disposable N95 mask reuse and help protect caregivers from SARS-CoV-2 and other pathogens.", "qid": 19, "docid": "tq9kjozt", "rank": 36, "score": 0.8344658613204956}, {"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": 37, "score": 0.8342326283454895}, {"content": "Title: COVID-19: Prevention and control measures in community Content: On January 30, 2020, the WHO declared the COVID-19 outbreak a public health emergency of international concern and, in March 2020, began to characterize it as a pandemic in order to emphasize the gravity of the situation and urge all countries to take action in detecting infection and preventing spread. Unfortunately, there is no medication that has been approved by the FDA, gone through controlled studies and demonstrated an effect on the virus for this global pandemic. Although there are cures for illnesses and developments made by leaps and bounds in our day, the strongest and most effective weapon that society has against this virus that is affecting not just health but also economics, politics, and social order, is the prevention of its spread. The main points in preventing the spread in society are hand hygiene, social distancing and quarantine. With increased testing capacity, detecting more COVID-19 positive patients in the community will also enable the reduction of secondary cases with stricter quarantine rules.", "qid": 19, "docid": "x7yugjzj", "rank": 38, "score": 0.8331286907196045}, {"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": 39, "score": 0.833000659942627}, {"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": 40, "score": 0.8328326940536499}, {"content": "Title: Operational protocol for donation of anti\u2010COVID\u201019 convalescent plasma in Italy Content: Coronavirus Disease 19 (COVID-19) represents a public health threat worldwide and Italy at the present time is considered the epicenter of this severe infection in the western world. Unfortunately, no standardized therapy does exist for COVID-19 and a number of investigational drugs for use in patients with life-threatening COVID-19 infections have been tried. One investigational treatment being explored for COVID-19 involves the use of convalescent plasma collected from recovered COVID-19 patients.", "qid": 19, "docid": "9yoqwrdi", "rank": 41, "score": 0.8323336839675903}, {"content": "Title: Rapid inactivation of SARS-CoV-2 with Deep-UV LED irradiation Content: The spread of novel coronavirus disease 2019 (COVID-19) infections worldwide has raised concerns about the prevention and control of SARS-CoV-2. Devices that rapidly inactivate viruses can reduce the chance of infection through aerosols and contact transmission. This in vitro study demonstrated that irradiation with a deep ultraviolet light-emitting diode (DUV-LED) of 280 \u00b15 nm wavelength rapidly inactivates SARS-CoV-2 obtained from a COVID-19 patient. Development of devices equipped with DUV-LED is expected to prevent virus invasion through the air and after touching contaminated objects.", "qid": 19, "docid": "49e7o9aw", "rank": 42, "score": 0.8322525024414062}, {"content": "Title: Application of Biosafety Principles in Laboratory Analysis of Clinical Samples from Patients with COVID-19 Content: COVID-19 poses a great challenge to clinical and diagnostic services around the world. The need of biosafety practices can never be emphasised more than under current circumstances. The four pillars of biosafety namely, leadership, standard operating procedures, personal protective equipment (PPE) and engineering controls must be employed for effective and safe practices in the clinical setting in general and laboratory settings in particular. Risk assessment must be carried out before meeting up the diagnostic challenge for COVID-19 and essential biorisk management measures are required to be taken. In our resource-poor settings, we need to adapt safe but cost-effective and improvised solutions to ensure safe handling of clinical samples from COVID-19 patients in the laboratories. The correct use of PPE and their suitable alternatives are available for selection and use. Disinfection of the lab areas and safe disposal of the clinical samples from such patients is also of paramount importance.", "qid": 19, "docid": "8h4adfqi", "rank": 43, "score": 0.830101490020752}, {"content": "Title: Application of Biosafety Principles in Laboratory Analysis of Clinical Samples from Patients with COVID-19. Content: COVID-19 poses a great challenge to clinical and diagnostic services around the world. The need of biosafety practices can never be emphasised more than under current circumstances. The four pillars of biosafety namely, leadership, standard operating procedures, personal protective equipment (PPE) and engineering controls must be employed for effective and safe practices in the clinical setting in general and laboratory settings in particular. Risk assessment must be carried out before meeting up the diagnostic challenge for COVID-19 and essential biorisk management measures are required to be taken. In our resource-poor settings, we need to adapt safe but cost-effective and improvised solutions to ensure safe handling of clinical samples from COVID-19 patients in the laboratories. The correct use of PPE and their suitable alternatives are available for selection and use. Disinfection of the lab areas and safe disposal of the clinical samples from such patients is also of paramount importance.", "qid": 19, "docid": "7z2cq8gq", "rank": 44, "score": 0.830101490020752}, {"content": "Title: COVID-19 Global Pandemic Planning: Decontamination and Reuse Processes for N95 Respirators Content: Coronavirus disease 2019 (COVID-19) is an illness caused by a novel coronavirus, severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). The disease was first identified as a cluster of respiratory illness in Wuhan City, Hubei Province, China in December 2019, and has rapidly spread across the globe to greater than 200 countries. Healthcare providers are at an increased risk for contracting the disease due to occupational exposure and require appropriate personal protective equipment (PPE), including N95 respirators. The rapid worldwide spread of high numbers of COVID-19 cases has facilitated the need for a substantial supply of PPE that is largely unavailable in many settings, thereby creating critical shortages. Creative solutions for the decontamination and safe reuse of PPE to protect our frontline healthcare personnel are essential. Here, we describe the development of a process that began in late February 2020 for selecting and implementing the use of hydrogen peroxide vapor (HPV) as viable method to reprocess N95 respirators. Since pre-existing HPV decontamination chambers were not available, we optimized the sterilization process in an operating room after experiencing initial challenges in other environments. Details are provided about the prioritization and implementation of processes for collection and storage, pre-processing, HPV decontamination, and post-processing of filtering facepiece respirators (FFRs). Important lessons learned from this experience include, developing an adequate reserve of PPE for effective reprocessing and distribution, and identifying a suitable location with optimal environmental controls (i.e., operating room). Collectively, information presented here provides a framework for other institutions considering decontamination procedures for N95 respirators.", "qid": 19, "docid": "arivuags", "rank": 45, "score": 0.8280956149101257}, {"content": "Title: Biosafety measures for preventing infection from COVID-19 in clinical laboratories: IFCC Taskforce Recommendations Content: Coronavirus disease 2019 (COVID-19) is the third coronavirus outbreak that has emerged in the past 20 years, after severe acute respiratory syndrome (SARS) and Middle East respiratory syndrome (MERS). One important aspect, highlighted by many global health organizations, is that this novel coronavirus outbreak may be especially hazardous to healthcare personnel, including laboratory professionals. Therefore, the aim of this document, prepared by the COVID-19 taskforce of the International Federation of Clinical Chemistry and Laboratory Medicine (IFCC), is to provide a set of recommendations, adapted from official documents of international and national health agencies, on biosafety measures for routine clinical chemistry laboratories that operate at biosafety levels 1 (BSL-1; work with agents posing minimal threat to laboratory workers) and 2 (BSL-2; work with agents associated with human disease which pose moderate hazard). We believe that the interim measures proposed in this document for best practice will help minimazing the risk of developing COVID-19 while working in clinical laboratories.", "qid": 19, "docid": "qyc49fyp", "rank": 46, "score": 0.8263435363769531}, {"content": "Title: Biosafety measures for preventing infection from COVID-19 in clinical laboratories: IFCC Taskforce Recommendations. Content: Coronavirus disease 2019 (COVID-19) is the third coronavirus outbreak that has emerged in the past 20 years, after severe acute respiratory syndrome (SARS) and Middle East respiratory syndrome (MERS). One important aspect, highlighted by many global health organizations, is that this novel coronavirus outbreak may be especially hazardous to healthcare personnel, including laboratory professionals. Therefore, the aim of this document, prepared by the COVID-19 taskforce of the International Federation of Clinical Chemistry and Laboratory Medicine (IFCC), is to provide a set of recommendations, adapted from official documents of international and national health agencies, on biosafety measures for routine clinical chemistry laboratories that operate at biosafety levels 1 (BSL-1; work with agents posing minimal threat to laboratory workers) and 2 (BSL-2; work with agents associated with human disease which pose moderate hazard). We believe that the interim measures proposed in this document for best practice will help minimazing the risk of developing COVID-19 while working in clinical laboratories.", "qid": 19, "docid": "bt80vw8h", "rank": 47, "score": 0.8263435363769531}, {"content": "Title: Pharmacotherapy for reducing saliva and droplet production in airborne procedures may help to decrease the COVID-19 transmission: A hypothesis Content: The pandemic of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) has affected health care service practices worldwide. Therefore, a global reaction to prepare health care systems is mandatory. Preventing the transmission of this virus during medical and dental procedures producing airborne particles and droplets, could be considered as one of the main venues in prevention of Coronavirus disease 2019 (COVID-19) transmission in health care facilities. To the best of our knowledge, no intervention has been approved for this purpose, so the major suggestion in this regard is using personal preventive equipment (PPE) and similar measures as well as other sanitizing practices. Since we do not know how long we should face this universal issue, using antecedent pharmacotherapies for reducing oral-respiratory secretions to combat this virus might play a role in this regard. Given that currently there is no definitive cure for COVID-19, so we hypothesize that, considering drug solutions to reduce saliva and droplet production may be helpful in controlling Coronavirus spread during aerosol and respiratory droplet producing procedures.", "qid": 19, "docid": "shfuj6ma", "rank": 48, "score": 0.8263157606124878}, {"content": "Title: Pharmacotherapy for reducing saliva and droplet production in airborne procedures may help to decrease the COVID-19 transmission: A hypothesis. Content: The pandemic of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) has affected health care service practices worldwide. Therefore, a global reaction to prepare health care systems is mandatory. Preventing the transmission of this virus during medical and dental procedures producing airborne particles and droplets, could be considered as one of the main venues in prevention of Coronavirus disease 2019 (COVID-19) transmission in health care facilities. To the best of our knowledge, no intervention has been approved for this purpose, so the major suggestion in this regard is using personal preventive equipment (PPE) and similar measures as well as other sanitizing practices. Since we do not know how long we should face this universal issue, using antecedent pharmacotherapies for reducing oral-respiratory secretions to combat this virus might play a role in this regard. Given that currently there is no definitive cure for COVID-19, so we hypothesize that, considering drug solutions to reduce saliva and droplet production may be helpful in controlling Coronavirus spread during aerosol and respiratory droplet producing procedures.", "qid": 19, "docid": "o03xzbih", "rank": 49, "score": 0.8263157606124878}, {"content": "Title: Disinfection of corona virus in histopathology laboratories Content: Severe acute respiratory syndrome (SARS CoV-2/COVID-19) is a highly contagious and deadly disease caused by a virus belonging to the coronaviridae family. Researchers working in histopathology laboratories, dealing with morbid samples, are particularly vulnerable to infection unless they have very strong immunity. Hence, a proper precautionary protocol is required for the safety of the laboratory staff. The current review highlights the biological and physical agents that can be used to inactivate the virus and disinfect the surrounding environment in the laboratory.", "qid": 19, "docid": "e87jj1g4", "rank": 50, "score": 0.8261828422546387}, {"content": "Title: Review on the global epidemiological situation and the efficacy of chloroquine and hydroxychloroquine for the treatment of COVID-19 Content: Covid-19 disease is caused by SARS-CoV-2, a virus belonging to the coronavirus family. Covid-19 is so new that there is currently no specific vaccine or treatment. Clinical trials are currently underway. In vitro tests are also being conducted to assess the efficacy of chloroquine and hydroxychloroquine for the treatment of this epidemic, which is considered a pandemic by the WHO. We note that the content of this review is dated. The information it contains is subject to change and modification as the epidemic progresses.", "qid": 19, "docid": "wbkn7yjh", "rank": 51, "score": 0.8258247971534729}, {"content": "Title: Vaporized H2O2 decontamination against surrogate viruses for the reuse of N95 respirators in the COVID-19 emergency Content: Decontamination of N95 respirators has become critical to alleviate PPE shortages for healthcare workers in the current COVID-19 emergency. The factors that are considered for the effective reuse of these masks are the fit, filter efficiency and decontamination/disinfection level both for SARS-CoV-2, which is the causative virus for COVID-19, and for other organisms of concern in the hospital environment such as Staphylococcus aureus or Clostridium difficile. In its guidance entitled 'Recommendations for Sponsors Requesting EUAs for Decontamination and Bioburden Reduction Systems for Surgical Masks and Respirators During the Coronavirus Disease 2019 (COVID19) Public Health Emergency' (May 2020)[1], the FDA recommends a 6-log10 reduction in either the most resistant bacterial spores for the system or in a mycobacterium species to authorize the use of a decontamination method of N95 respirators for single or multiple users. While the goal is primarily inactivation against SARS-CoV-2, testing of decontamination methods against the virus may not always be available. For decontamination methods considered for only single users, the recommendation is a 6-log10 reduction in the infective virus concentration of 3 non-enveloped viruses or in the concentration of two Gram (+) and two Gram (-) bacteria. Based on these recommendations, we explored the efficacy of vaporized H2O2 (VHP) treatment of N95 respirators against surrogate viruses covering a wide range of disinfection resistance for emergency decontamination and reuse to alleviate PPE shortages for healthcare workers in the COVID-19 emergency.", "qid": 19, "docid": "z22gaapb", "rank": 52, "score": 0.8256101608276367}, {"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": 53, "score": 0.8254088759422302}, {"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": 54, "score": 0.8254088759422302}, {"content": "Title: COVID-19-associated shortage of alcohol-based hand rubs, face masks, medical gloves and gowns - proposal for a risk-adapted approach to ensure patient and healthcare worker safety Content: The COVID-19 pandemic has caused a huge demand of alcohol-based hand rubs, medical gloves, face masks and gowns in healthcare and from the public. More and more hospitals face a serious shortage of these articles. We propose a risk-adapted approach to ensure adequate patient and healthcare worker safety for as long as possible.", "qid": 19, "docid": "dxx0ihcy", "rank": 55, "score": 0.82435542345047}, {"content": "Title: Novel Coronavirus COVID-19: Current Evidence and Evolving Strategies Content: COVID-19 is a global pandemic that has currently infected &gt;300,000 globally. Fever and cough are the most common symptoms of the disease, and it is important to remember that the virus can even be transmitted by individuals who test positive for the disease but do not have any symptoms. Currently reported mortality rates vary because of the rapid spread of the disease and different approaches to calculating this estimate, but it is clear that the risk of death is associated with age and the presence of underlying conditions. Risk mitigation techniques (i.e., hand washing, social distancing, and self-isolation) have already been emphasized across major news outlets. It is essential that we continue these practices, as the outbreak is currently expected to last for many more months and we must be mindful of the lessons learned from past pandemics to prevent a second wave from occurring.", "qid": 19, "docid": "3ateeei3", "rank": 56, "score": 0.8238723278045654}, {"content": "Title: How to reduce the likelihood of coronavirus-19 (CoV-19 or SARS-CoV-2) infection and lung inflammation mediated by IL-1 Content: SARS-CoV-2, also referred to as CoV-19, is an RNA virus which can cause severe acute respiratory diseases (COVID-19), with serious infection of the lower respiratory tract followed by bronchitis, pneumonia and fibrosis. The severity of the disease depends on the efficiency of the immune system which, if it is weak, cannot stem the infection and its symptoms. The new CoV-19 spreads in the population at a rate of 0.8-3% more than normal flu and mostly affects men, since immune genes are more expressed on the X chromosome. If CoV-19 would spread with a higher incidence rate (over 10%), and affect the people who live in closed communities such as islands, it would cause many more deaths. Moreover, people from the poorest classes are most at risk because of lack of health care and should be given more assistance by the competent authorities. To avoid the aggravation of CoV-19 infection, and the collapse of the health system, individuals should remain at home in quarantine for a period of approximately one month in order to limit viral transmission. In the case of a pandemic, the severe shortage of respirators and protective clothing, due to the enormous demand and insufficient production, could lead the CoV-19 to kill a large number of individuals. At present, there is no drug capable of treating CoV-19 flu, the only therapeutic remedies are those aimed at the side effects caused by the virus, such as inflammation and pulmonary fibrosis, recognized as the first causes of death. One of the COVID-19 treatments involves inhaling a mixture of gaseous hydrogen and oxygen, obtaining better results than with oxygen alone. It was also noted that individuals vaccinated for viral and/or bacterial infectious diseases were less likely to become infected. In addition, germicidal UV radiation \"breaks down\" the oxygen O2 which then aggregate into O3 (ozone) molecules creating the ozone layer, capable of inhibiting viral replication and improving lung respiration. All these precautions should be taken into consideration to lower the risk of infection by CoV-19. New anti-viral therapies with new drugs should also be taken into consideration. For example, microbes are known to bind TLR, inducing IL-1, a pleiotropic cytokine, highly inflammatory, mediator of fever and fibrosis. Therefore, drugs that suppress IL-1 or IL-1R, also used for the treatment of rheumatoid arthritis are to be taken into consideration to treat COVID-19. We strongly believe that all these devices described above can lead to greater survival and. therefore, reduction in mortality in patients infected with CoV-19.", "qid": 19, "docid": "g5rf10n5", "rank": 57, "score": 0.8235608339309692}, {"content": "Title: How to reduce the likelihood of coronavirus-19 (CoV-19 or SARS-CoV-2) infection and lung inflammation mediated by IL-1. Content: SARS-CoV-2, also referred to as CoV-19, is an RNA virus which can cause severe acute respiratory diseases (COVID-19), with serious infection of the lower respiratory tract followed by bronchitis, pneumonia and fibrosis. The severity of the disease depends on the efficiency of the immune system which, if it is weak, cannot stem the infection and its symptoms. The new CoV-19 spreads in the population at a rate of 0.8-3% more than normal flu and mostly affects men, since immune genes are more expressed on the X chromosome. If CoV-19 would spread with a higher incidence rate (over 10%), and affect the people who live in closed communities such as islands, it would cause many more deaths. Moreover, people from the poorest classes are most at risk because of lack of health care and should be given more assistance by the competent authorities. To avoid the aggravation of CoV-19 infection, and the collapse of the health system, individuals should remain at home in quarantine for a period of approximately one month in order to limit viral transmission. In the case of a pandemic, the severe shortage of respirators and protective clothing, due to the enormous demand and insufficient production, could lead the CoV-19 to kill a large number of individuals. At present, there is no drug capable of treating CoV-19 flu, the only therapeutic remedies are those aimed at the side effects caused by the virus, such as inflammation and pulmonary fibrosis, recognized as the first causes of death. One of the COVID-19 treatments involves inhaling a mixture of gaseous hydrogen and oxygen, obtaining better results than with oxygen alone. It was also noted that individuals vaccinated for viral and/or bacterial infectious diseases were less likely to become infected. In addition, germicidal UV radiation \"breaks down\" the oxygen O2 which then aggregate into O3 (ozone) molecules creating the ozone layer, capable of inhibiting viral replication and improving lung respiration. All these precautions should be taken into consideration to lower the risk of infection by CoV-19. New anti-viral therapies with new drugs should also be taken into consideration. For example, microbes are known to bind TLR, inducing IL-1, a pleiotropic cytokine, highly inflammatory, mediator of fever and fibrosis. Therefore, drugs that suppress IL-1 or IL-1R, also used for the treatment of rheumatoid arthritis are to be taken into consideration to treat COVID-19. We strongly believe that all these devices described above can lead to greater survival and. therefore, reduction in mortality in patients infected with CoV-19.", "qid": 19, "docid": "uzfzopz5", "rank": 58, "score": 0.8235608339309692}, {"content": "Title: Prevention of exposure to and spread of COVID-19 using air purifiers: challenges and concerns Content: Coronavirus disease 2019 (COVID-19) is now a pandemic. The Korean government has declared a red alert, which is the highest level of the national infectious disease alert system, and the World Health Organization has similarly declared its highest-level pandemic alert (phase 6). The spread of COVID-19 is an unprecedented worldwide public health problem that governments and individuals must work to overcome. Recently, an infection cluster arose in a call center in Seoul. To support call center companies, the Korean Ministry of Employment and Labor has proposed covering the costs of installing partitions and air purifiers, providing hand sanitizers, and supplying masks to prevent droplet and aerosol infections. Air purifiers are expected to be installed on the floor with the exhaust outlets at a higher level, such as the level of the desks or breathing zones of workers. When a worker coughs or releases droplets near a colleague's respiratory system, the droplets may spread throughout the call center via air flow from air purifier. In this fashion, a single infected person can give rise to an infection cluster. Attempts to prevent infection must not lead to new infections, and the installation of air purifiers may cause new problems. Therefore, using air purifiers to control the spread of COVID-19 should be approached with caution.", "qid": 19, "docid": "lsmz786j", "rank": 59, "score": 0.8234114646911621}, {"content": "Title: Practical Guidelines for Collection, Manipulation and Inactivation of SARS-CoV-2 and COVID-19 Clinical Specimens Content: SARS-CoV-2 is a novel coronavirus that causes the acute respiratory disease-Coronavirus disease 2019 (COVID-19)-which has led to a global health crisis. Currently, no prophylactics or therapies exist to control virus spread or mitigate the disease. Thus, the risk of infection for physicians and scientists is high, requiring work to be conducted in Biosafety Level-3 (BSL-3) facilities if virus will be isolated or propagated. However, inactivation of the virus can enable safe handling at a reduced biosafety level, making samples accessible to a diverse array of institutions and investigators. Institutions of all types have an immediate need for guidelines that outline safe collection, handling, and inactivation of samples suspected to contain active virus. Here we provide a practical guide for physicians and researchers wishing to work with materials from patients who are COVID-19 positive or suspected positive. \u00a9 2020 Wiley Periodicals LLC. Basic Protocol 1: Practical guidelines for the safe collection and handling of specimens collected from COVID-19 and suspected COVID-19 patients Basic Protocol 2: Inactivating SARS-CoV-2.", "qid": 19, "docid": "sx4d8h97", "rank": 60, "score": 0.8234043717384338}, {"content": "Title: COVID-19 treatment by repurposing drugs until the vaccine is in sight Content: Corona virus disease (COVID-19) has created pandemic in the world as declared by WHO on March 12, 2020. It is a viral disease caused by SARS-CoV 2 virus and has affected large populations in over 120 countries. There is no specific treatment available and management is empirical. Until such time that an effective vaccine is available for COVID-19 viral infection, one can repurpose known therapeutic drug molecules such as angiotensin receptor 2 blocker, a commonly used antihypertensive drug, to control COVID-19 virus from gaining entry into the host cell by blocking the angiotensin receptor. Clinical trials should also be undertaken to use statins, which are lipid-lowering drugs but have anti-inflammatory and immunomodulatory properties to prevent acute lung injury in COVID-19 infection.", "qid": 19, "docid": "f5vtticw", "rank": 61, "score": 0.8233191967010498}, {"content": "Title: Covid-19 : les soignants entre h\u00e9ro\u00efsation et ostracisation./ [Covid-19: health care workers between heroism and ostracism] Content: Originating in China in November 2019, the wave of infection caused by the new coronavirus Sars-CoV-2 is sweeping across the planet through human contact and fast, global, mass travel. Health professionals on every level are fighting relentlessly against Covid-19, this deadly, invisible yet real enemy. The public, increasingly worried, expect them to protect it against the disease and death. Perceived by most people as a line of defence against the pandemic, health professionals are supported and treated as heroes. Some people howeverfear tthat they may be possible contamination agents.", "qid": 19, "docid": "7u41zswj", "rank": 62, "score": 0.8230253458023071}, {"content": "Title: [Covid-19: health care workers between heroism and ostracism]. Content: Originating in China in November 2019, the wave of infection caused by the new coronavirus Sars-CoV-2 is sweeping across the planet through human contact and fast, global, mass travel. Health professionals on every level are fighting relentlessly against Covid-19, this deadly, invisible yet real enemy. The public, increasingly worried, expect them to protect it against the disease and death. Perceived by most people as a line of defence against the pandemic, health professionals are supported and treated as heroes. Some people howeverfear tthat they may be possible contamination agents.", "qid": 19, "docid": "2l457ism", "rank": 63, "score": 0.8230253458023071}, {"content": "Title: Calcitriol, the active form of vitamin D, is a promising candidate for COVID-19 prophylaxis Content: COVID-19, the disease caused by SARS-CoV-2 (1), was declared a pandemic by the World Health Organization (WHO) in March 2020 (2). While awaiting a vaccine, several antivirals are being used to manage the disease with limited success (3, 4). To expand this arsenal, we screened 4 compound libraries: a United States Food and Drug Administration (FDA) approved drug library, an angiotensin converting enzyme-2 (ACE2) targeted compound library, a flavonoid compound library as well as a natural product library. Of the 121 compounds identified with activity against SARS-CoV-2, 7 were shortlisted for validation. We show for the first time that the active form of Vitamin D, calcitriol, exhibits significant potent activity against SARS-CoV-2. This finding paves the way for consideration of host-directed therapies for ring prophylaxis of contacts of SARS-CoV-2 patients.", "qid": 19, "docid": "sbon3aes", "rank": 64, "score": 0.8228592276573181}, {"content": "Title: Inhaled modified angiotensin converting enzyme 2 (ACE2) as a decoy to mitigate SARS-CoV-2 infection Content: COVID-19 is a new zoonotic disease caused by the SARS-CoV-2 virus Since its emergence in Wuhan City, China, the virus has rapidly spread across the globe causing calamitous health, economic and societal consequences It causes disproportionately severe disease in the elderly and those with co-morbidities, such as hypertension and diabetes There is currently no proven treatment for COVID-19 and a safe and effective vaccine is at least a year away The virus gains access to the respiratory epithelium through cell surface angiotensin converting enzyme 2 (ACE2) The receptor binding domain (RBD) of the virus is unlikely to mutate without loss of pathogenicity and thus represents an attractive target for antiviral treatment Inhaled modified recombinant human ACE2, may bind SARS-CoV-2 and mitigate lung damage This decoy strategy is unlikely to provoke an adverse immune response and may reduce morbidity and mortality in high-risk groups", "qid": 19, "docid": "u6zpwhnd", "rank": 65, "score": 0.8226044178009033}, {"content": "Title: Gastrointestinal effects of an attempt to \u201cdisinfect\u201d from COVID\u201019 Content: In April 2020 during the COVID\u201019 pandemic, a 41\u2010year\u2010old female presented to the emergency department with recurrent vomiting and abdominal pain that had been ongoing on for two days and additional hematemesis for several hours. The past medical history was unremarkable, except for bariatric gastric bypass surgery performed in 2016. During detailed inquiry the patient reported, she had intentionally taken 10 ml of Ethanol\u2010containing hand disinfectant orally per diem for a period of over three weeks in fear of being infected with COVID\u201019. The product had been obtained from a regular pharmacy and had been produced locally according to WHO standards for hand disinfectan. Upper gastrointestinal endoscopy was performed and showed superficial mucosal damage in the oesophagus (Figure 1A), slightly increased mucosal redness in the stomach and severely injured small bowel mucosa with extensive fibrinous exudates (Figure 2A).", "qid": 19, "docid": "t0qtzh02", "rank": 66, "score": 0.8223819732666016}, {"content": "Title: Post-donation COVID-19 identification in blood donors. Content: The coronavirus disease 19 (COVID-19) outbreak, which was characterized as a pandemic on 11 March 2020 by the WHO, started in December 2019 with the emergence of pneumonia cases of unknown cause in Wuhan, Hubei, China [1]. SARS-CoV-2, the causative agent of COVID-19, are enveloped, non-segmented, single stranded positive sense RNA viruses and are classified as a sister clade to the prototype human and bat severe acute respiratory syndrome coronaviruses (SARS-CoVs) of the species Severe acute respiratory syndrome-related coronavirus [2]. So far, no respiratory virus, including SARS-CoV and the Middle East Respiratory Syndrome (MERS)-CoV, has been confirmed as transfusion-transmissible [3,4].", "qid": 19, "docid": "82sc928x", "rank": 67, "score": 0.8223792314529419}, {"content": "Title: Advice regarding COVID\u201019 and use of immunomodulators, in patients with severe dermatological diseases Content: Coronavirus disease 2019 (COVID-19) is the disease caused by the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), as named by the International Committee on Taxonomy of Viruses (ICTV). There is very limited evidence base to formulate specific advice for dermatology patients on immunomodulators with regards to COVID-19. The following is based on expert opinion, taking into account known risks of influenza (a negative sense single-stranded RNA virus) and other, positive-sense single-stranded, RNA virus infections (such as SARS, MERS, and the common cold). An Australia/New Zealand consensus document is in development.", "qid": 19, "docid": "nfjxp783", "rank": 68, "score": 0.8222923278808594}, {"content": "Title: COVID-19 and Cardiovascular Disease Content: Coronavirus disease 2019 (COVID-19) is a global pandemic affecting 185 countries and >3 000 000 patients worldwide as of April 28, 2020. COVID-19 is caused by severe acute respiratory syndrome coronavirus 2, which invades cells through the angiotensin-converting enzyme 2 receptor. Among patients with COVID-19, there is a high prevalence of cardiovascular disease, and >7% of patients experience myocardial injury from the infection (22% of critically ill patients). Although angiotensin-converting enzyme 2 serves as the portal for infection, the role of angiotensin-converting enzyme inhibitors or angiotensin receptor blockers requires further investigation. COVID-19 poses a challenge for heart transplantation, affecting donor selection, immunosuppression, and posttransplant management. There are a number of promising therapies under active investigation to treat and prevent COVID-19.", "qid": 19, "docid": "r6kl7vb0", "rank": 69, "score": 0.8222683668136597}, {"content": "Title: O Efeito da Doen\u00e7a de Coronav\u00edrus 2019 nas Doen\u00e7as Cardiovasculares./ O Efeito da Doen\u00e7a de Coronav\u00edrus 2019 nas Doen\u00e7as Cardiovasculares./ The Effect of Coronavirus Disease 2019 on Cardiovascular Diseases Content: Coronavirus disease 2019 (COVID-19) is a global pandemic affecting the world, seen in more than 1,300,000 patients. COVID-19 acts through the angiotensin-converting enzyme 2 (ACE2) receptor. Cardiovascular comorbidities are more common with COVID-19, and nearly 10% of cases develop myocarditis (22% of critical patients). Further research is needed to continue or discontinue ACE inhibitors and angiotensin receptor blockers, which are essential in hypertension and heart failure in COVID-19. Intensive research is promising for the treatment and prevention of COVID-19.", "qid": 19, "docid": "uzmj8zki", "rank": 70, "score": 0.8221231698989868}, {"content": "Title: The Effect of Coronavirus Disease 2019 on Cardiovascular Diseases. Content: Coronavirus disease 2019 (COVID-19) is a global pandemic affecting the world, seen in more than 1,300,000 patients. COVID-19 acts through the angiotensin-converting enzyme 2 (ACE2) receptor. Cardiovascular comorbidities are more common with COVID-19, and nearly 10% of cases develop myocarditis (22% of critical patients). Further research is needed to continue or discontinue ACE inhibitors and angiotensin receptor blockers, which are essential in hypertension and heart failure in COVID-19. Intensive research is promising for the treatment and prevention of COVID-19.", "qid": 19, "docid": "a30ryzkj", "rank": 71, "score": 0.8221231698989868}, {"content": "Title: Sustainability of Coronavirus on different surfaces Content: COVID-19 is the name of the disease supposedly manifested in December 2019 from Wuhan, because of virus named as SARS-CoV-2. Now this disease has spread to almost all other parts of the world. COVID-19 pandemic has various reasons for its dramatic worldwide increase. Here, we have studied Coronavirus sustainability on various surfaces. Various disinfectants and their roles are discussed from the available literature. The infection capabilities of SARS-CoV-1 and SARS-CoV-2 for different materials are discussed and finally studies infection decay for SARS-CoV-1 and SARS-CoV-2.", "qid": 19, "docid": "9fnpfncr", "rank": 72, "score": 0.82188481092453}, {"content": "Title: COVID-19-associated shortage of alcohol-based hand rubs, face masks, medical gloves and gowns \u2013 proposal for a risk-adapted approach to ensure patient and healthcare worker safety Content: Summary The COVID-19 pandemic has caused a huge demand of alcohol-based hand rubs, medical gloves, face masks and gowns in healthcare and from the public. More and more hospitals face a serious shortage of these articles. We propose a risk-adapted approach to ensure adequate patient and healthcare worker safety for as long as possible.", "qid": 19, "docid": "y5hx6g55", "rank": 73, "score": 0.8217451572418213}, {"content": "Title: Inactivation analysis of SARS-CoV-2 by specimen transport media, nucleic acid extraction reagents, detergents and fixatives Content: The COVID-19 pandemic has necessitated a rapid multi-faceted response by the scientific community, bringing researchers, health officials and industry together to address the ongoing public health emergency. To meet this challenge, participants need an informed approach for working safely with the etiological agent, the novel human coronavirus SARS-CoV-2. Work with infectious SARS-CoV-2 is currently restricted to high-containment laboratories, but material can be handled at a lower containment level after inactivation. Given the wide array of inactivation reagents that are being used in laboratories during this pandemic, it is vital that their effectiveness is thoroughly investigated. Here, we evaluated a total of 23 commercial reagents designed for clinical sample transportation, nucleic acid extraction and virus inactivation for their ability to inactivate SARS-CoV-2, as well as seven other common chemicals including detergents and fixatives. As part of this study, we have also tested five filtration matrices for their effectiveness at removing the cytotoxic elements of each reagent, permitting accurate determination of levels of infectious virus remaining following treatment. In addition to providing critical data informing inactivation methods and risk assessments for diagnostic and research laboratories working with SARS-CoV-2, these data provide a framework for other laboratories to validate their inactivation processes and to guide similar studies for other pathogens.", "qid": 19, "docid": "7vj5x1nv", "rank": 74, "score": 0.8216797113418579}, {"content": "Title: The dissemination of COVID-19: an expectant and preventive role in global health Content: Backgroung: Coronaviruses (CoV) make up a large family of viruses, known since the mid-1960s, which received this name due to the spikes on its surface, which resemble a crown (from the Latin corona). CoV infections can cause everything from a common cold to severe respiratory syndromes, such as severe acute respiratory syndrome (SARS-CoV) and Middle Eastern respiratory syndrome (MERS-CoV).COVID-19 (SARS-CoV2) is a new variant of the coronavirus, and its isolation occurred in China on January 7th, 2020. COVID-19 has stood out with a high impact on public health due to the high number of cases with infection in a short period of time. However, it is possible to observe that 17% of patients confirmed with COVID-19 have severe infections and about 2.5% of these patients die. Current studies have shown that the number of mild and asymptomatic cases may be even greater. Thus, the challenges for controlling unreported cases of patients with mild symptoms that are spreading the virus and interfering with the magnitude and real data of the cases stand out. The transmission of the coronavirus occurs between humans, and it can occur from person to person through the air, through coughing or sneezing, by touching or shaking hands or by contact with contaminated objects or surfaces, followed by contact with the mouth, nose or eyes. Given the fluctuation in the incidence and the lethality rate, it is essential to stand out the precepts of health promotion in search of reorienting hygiene practices, considering that there is validity in health care models, still with a curative approach and the current situation experienced by the world population requires a preventive stance.(AU)", "qid": 19, "docid": "9efi8hf9", "rank": 75, "score": 0.8215625286102295}, {"content": "Title: COVID-19 global pandemic planning: Decontamination and reuse processes for N95 respirators Content: Coronavirus disease 2019 (COVID-19) is an illness caused by a novel coronavirus, severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). The disease was first identified as a cluster of respiratory illness in Wuhan City, Hubei Province, China, in December 2019, and has rapidly spread across the globe to greater than 200 countries. Healthcare providers are at an increased risk for contracting the disease due to occupational exposure and require appropriate personal protective equipment (PPE), including N95 respirators. The rapid worldwide spread of high numbers of COVID-19 cases has facilitated the need for a substantial supply of PPE that is largely unavailable in many settings, thereby creating critical shortages. Creative solutions for the decontamination and safe reuse of PPE to protect our frontline healthcare personnel are essential. Here, we describe the development of a process that began in late February 2020 for selecting and implementing the use of hydrogen peroxide vapor (HPV) as viable method to reprocess N95 respirators. Since pre-existing HPV decontamination chambers were not available, we optimized the sterilization process in an operating room after experiencing initial challenges in other environments. Details are provided about the prioritization and implementation of processes for collection and storage, pre-processing, HPV decontamination, and post-processing of filtering facepiece respirators. Important lessons learned from this experience include, developing an adequate reserve of PPE for effective reprocessing and distribution, and identifying a suitable location with optimal environmental controls (i.e. operating room). Collectively, information presented here provides a framework for other institutions considering decontamination procedures for N95 respirators. IMPACT STATEMENT: There is a critical shortage of personal protective equipment (PPE) around the globe. This article describes the safe collection, storage, and decontamination of N95 respirators using hydrogen peroxide vapor (HPV). This article is unique because it describes the HPV process in an operating room, and is therefore, a deployable method for many healthcare settings. Results presented here offer creative solutions to the current PPE shortage.", "qid": 19, "docid": "md4ilfik", "rank": 76, "score": 0.8214901685714722}, {"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": 19, "docid": "cz3qt5qd", "rank": 77, "score": 0.8213787078857422}, {"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": 78, "score": 0.8212264776229858}, {"content": "Title: COVID\u201019: Infection prevention and control guidance for all ultrasound practitioners Content: The severe acute respiratory syndrome coronavirus (SARS\u2010CoV\u20102), an enveloped virus, is the causative agent of the disease known as COVID\u201019 (coronavirus disease\u20102019). Proper infection prevention and control measures and good hygiene practices are essential to prevent spread of COVID\u201019 and protect both patients and the healthcare worker. These guidelines are relevant to all ultrasound practitioners and provides guidance on cleaning and disinfection of ultrasound equipment, the environment and PPE (protective personal equipment) during the COVID\u201019 outbreak in the Australasian region.", "qid": 19, "docid": "bcb8q6h0", "rank": 79, "score": 0.8209817409515381}, {"content": "Title: Coronaviruses widespread on nonliving surfaces: important questions and promising answers. Content: The world is facing, while writing this review, a global pandemic due to one of the types of the coronaviruses (i.e., COVID-19), which is a new virus. Among the most important reasons for the transmission of infection between humans is the presence of this virus active on the surfaces and materials. Here, we addressed important questions such as do coronaviruses remain active on the inanimate surfaces? Do the types of inanimate surfaces affect the activity of coronaviruses? What are the most suitable ingredients that used to inactivate viruses? This review article addressed many of the works that were done in the previous periods on the survival of many viruses from the coronaviruses family on various surfaces such as steel, glass, plastic, Teflon, ceramic tiles, silicon rubber and stainless steel copper alloys, Al surface, sterile sponges, surgical gloves and sterile latex. The impacts of environmental conditions such as temperature and humidity were presented and discussed. The most important active ingredients that can deactivate viruses on the surfaces were reported here. We hope that these active ingredients will have the same effect on COVID-19.", "qid": 19, "docid": "9xv9t5ba", "rank": 80, "score": 0.8209432363510132}, {"content": "Title: Coronaviruses widespread on nonliving surfaces: important questions and promising answers Content: The world is facing, while writing this review, a global pandemic due to one of the types of the coronaviruses (i.e., COVID-19), which is a new virus. Among the most important reasons for the transmission of infection between humans is the presence of this virus active on the surfaces and materials. Here, we addressed important questions such as do coronaviruses remain active on the inanimate surfaces? Do the types of inanimate surfaces affect the activity of coronaviruses? What are the most suitable ingredients that used to inactivate viruses? This review article addressed many of the works that were done in the previous periods on the survival of many viruses from the coronaviruses family on various surfaces such as steel, glass, plastic, Teflon, ceramic tiles, silicon rubber and stainless steel copper alloys, Al surface, sterile sponges, surgical gloves and sterile latex. The impacts of environmental conditions such as temperature and humidity were presented and discussed. The most important active ingredients that can deactivate viruses on the surfaces were reported here. We hope that these active ingredients will have the same effect on COVID-19.", "qid": 19, "docid": "fxx5vrg0", "rank": 81, "score": 0.8209431171417236}, {"content": "Title: Target Virus or Target Ourselves for COVID-19 Drugs Discovery?-Lessons learned from anti-influenzas virus therapies Content: The COVID-19 pandemic, after it was reported in December 2019, is a highly contagious and now spreading to over 190 countries, causing a severe public health burden. Currently, there is no vaccine or specific drug to treat COVID-19, which is caused by a novel coronavirus, SARS-2-CoV. For this emergency, the FDA has approved Remdesivir and Hydroxychloroquine for treatment of COVID-19 as Emergency Use Authorization. However, even after this pandemic, COVID-19 may still have a chance to come back. Therefore, we need to come out with new strategies for drug discovery for combating COVID-19 in the future.", "qid": 19, "docid": "dblg9wfk", "rank": 82, "score": 0.8207199573516846}, {"content": "Title: Decontamination Methods for Reuse of Filtering Facepiece Respirators Content: Importance: The novel coronavirus disease 2019 (COVID-19) has proven to be highly infectious, putting health care professionals around the world at increased risk. Furthermore, there are widespread shortages of necessary personal protective equipment (PPE) for these individuals. Filtering facepiece respirators, such as the N95 respirator, intended for single use, can be reused in times of need. We explore the evidence for decontamination or sterilization of N95 respirators for health care systems seeking to conserve PPE while maintaining the health of their workforce. Observations: The filtration properties and fit of N95 respirators must be preserved to function adequately over multiple uses. Studies have shown that chemical sterilization using soap and water, alcohols, and bleach render the respirator nonfunctional. Decontamination with microwave heat and high dry heat also result in degradation of respirator material. UV light, steam, low-dry heat, and commercial sterilization methods with ethylene oxide or vaporized hydrogen peroxide appear to be viable options for successful decontamination. Furthermore, since the surface viability of the novel coronavirus is presumed to be 72 hours, rotating N95 respirator use and allowing time decontamination of the respirators is also a reasonable option. We describe a protocol and best practice recommendations for redoffing decontaminated N95 and rotating N95 respirator use. Conclusions and Relevance: COVID-19 presents a high risk for health care professionals, particularly otolaryngologists, owing to the nature of viral transmission, including possible airborne transmission and high viral load in the upper respiratory tract. Proper PPE is effective when used correctly, but in times of scarce resources, institutions may turn to alternative methods of preserving and reusing filtering facepiece respirators. Based on studies conducted on the decontamination of N95 respirators after prior outbreaks, there are several options for institutions to consider for both immediate and large-scale implementation.", "qid": 19, "docid": "8e3fg0o6", "rank": 83, "score": 0.8206785917282104}, {"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": 19, "docid": "g477u9k1", "rank": 84, "score": 0.8203930258750916}, {"content": "Title: Infection control in dental health care during and after the SARS-CoV-2 outbreak Content: COVID-19 is an emerging infectious disease caused by the widespread transmission of the coronavirus SARS-CoV-2. Some of those infected become seriously ill. Others do not show any symptoms, but can still contribute to transmission of the virus. SARS-CoV-2 is excreted in the oral cavity and can be spread via aerosols. Aerosol generating procedures in dental health care can increase the risk of transmission of the virus. Due to the risk of infection of both dental healthcare workers and patients, additional infection control measures for all patients are strongly recommended when providing dental health care. Consideration should be given to which infection control measures are necessary when providing care in both the current situation and in the future.", "qid": 19, "docid": "a401kyv5", "rank": 85, "score": 0.8203226327896118}, {"content": "Title: Prevention of exposure and dispersion of COVID-19 using air purifiers: challenges and concerns Content: The outbreak of COVID-19 is now a pandemic. The Korean government has declared the highest infectious-disease alert as a 'red' and the World Health Organization (WHO) has announced the highest level (Phase 6). Control of COVID-19 is an unprecedented worldwide public health problem that governments and individuals must overcome. Recently, infection cluster occurred in a call center located in Seoul. The Ministry of Employment and Labor has decided to support call center companies use the cost of installing partitions, air purifiers, hand sanitizers and masks to prevent droplet and aerosol infections. Air purifiers are expected to be installed on the floor and exhaust stayed on the higher level such as desk or breathing zone of worker. When a worker coughs or releases droplets near a colleague's respiratory system, the droplets can spread throughout the call center space through the air flow. If there is only one infected person, there is a chance that the infection cluster will increase. Installation of air purifiers may cause new problems, so the control to prevent infection should not lead to a new infection. Therefore, using the air purifier to control the COVID-19 should be approached with caution.", "qid": 19, "docid": "fq1olldq", "rank": 86, "score": 0.8203128576278687}, {"content": "Title: Prevention of exposure and dispersion of COVID-19 using air purifiers: challenges and concerns. Content: The outbreak of COVID-19 is now a pandemic. The Korean government has declared the highest infectious-disease alert as a 'red' and the World Health Organization (WHO) has announced the highest level (Phase 6). Control of COVID-19 is an unprecedented worldwide public health problem that governments and individuals must overcome. Recently, infection cluster occurred in a call center located in Seoul. The Ministry of Employment and Labor has decided to support call center companies use the cost of installing partitions, air purifiers, hand sanitizers and masks to prevent droplet and aerosol infections. Air purifiers are expected to be installed on the floor and exhaust stayed on the higher level such as desk or breathing zone of worker. When a worker coughs or releases droplets near a colleague's respiratory system, the droplets can spread throughout the call center space through the air flow. If there is only one infected person, there is a chance that the infection cluster will increase. Installation of air purifiers may cause new problems, so the control to prevent infection should not lead to a new infection. Therefore, using the air purifier to control the COVID-19 should be approached with caution.", "qid": 19, "docid": "1c5t8fn1", "rank": 87, "score": 0.8203128576278687}, {"content": "Title: Identification of potent and safe antiviral therapeutic candidates against SARS-CoV-2 Content: COVID-19 pandemic has infected millions of people with mortality exceeding 300,000. There is an urgent need to find therapeutic agents that can help clear the virus to prevent the severe disease and death. Identifying effective and safer drugs can provide with more options to treat the COVID-19 infections either alone or in combination. Here we performed a high throughput screen of approximately 1700 US FDA approved compounds to identify novel therapeutic agents that can effectively inhibit replication of coronaviruses including SARS-CoV-2. Our two-step screen first used a human coronavirus strain OC43 to identify compounds with anti-coronaviral activities. The effective compounds were then screened for their effectiveness in inhibiting SARS-CoV-2. These screens have identified 24 anti-SARS-CoV-2 drugs including previously reported compounds such as hydroxychloroquine, amlodipine, arbidol hydrochloride, tilorone 2HCl, dronedarone hydrochloride, and merfloquine hydrochloride. Five of the newly identified drugs had a safety index (cytotoxic/effective concentration) of >600, indicating wide therapeutic window compared to hydroxychloroquine which had safety index of 22 in similar experiments. Mechanistically, five of the effective compounds were found to block SARS-CoV-2 S protein-mediated cell fusion. These FDA approved compounds can provide much needed therapeutic options that we urgently need in the midst of the pandemic.", "qid": 19, "docid": "e9fjo7tl", "rank": 88, "score": 0.8200816512107849}, {"content": "Title: Biocides and Novel Antimicrobial Agents for the Mitigation of Coronaviruses Content: In December, 2019, a highly infectious and rapidly spreading new pneumonia of unknown cause was reported to the Chinese WHO Country Office. A cluster of these cases had appeared in Wuhan, a city in the Hubei Province of China. These infections were found to be caused by a new coronavirus which was given the name \u201c2019 novel coronavirus\u201d (2019-nCoV). It was later renamed \u201csevere acute respiratory syndrome coronavirus 2,\u201d or SARS-CoV-2 by the International Committee on Taxonomy of Viruses on February 11, 2020. It was named SARS-CoV-2 due to its close genetic similarity to the coronavirus which caused the SARS outbreak in 2002 (SARS-CoV-1). The aim of this review is to provide information, primarily to the food industry, regarding a range of biocides effective in eliminating or reducing the presence of coronaviruses from fomites, skin, oral/nasal mucosa, air, and food contact surfaces. As several EPA approved sanitizers against SARS-CoV-2 are commonly used by food processors, these compounds are primarily discussed as much of the industry already has them on site and is familiar with their application and use. Specifically, we focused on the effects of alcohols, povidone iodine, quaternary ammonium compounds, hydrogen peroxide, sodium hypochlorite (NaOCl), peroxyacetic acid (PAA), chlorine dioxide, ozone, ultraviolet light, metals, and plant-based antimicrobials. This review highlights the differences in the resistance or susceptibility of different strains of coronaviruses, or similar viruses, to these antimicrobial agents.", "qid": 19, "docid": "453tnoyr", "rank": 89, "score": 0.8195943832397461}, {"content": "Title: COVID-19 pandemic: Effects and evidence-based recommendations for otolaryngology and head and neck surgery practice Content: The 2019 novel coronavirus disease (COVID-19) is a highly contagious zoonosis produced by SARS-CoV-2 that is spread human-to-human by respiratory secretions. It was declared by the WHO as a public health emergency. The most susceptible populations, needing mechanical ventilation, are the elderly and people with associated comorbidities. There is an important risk of contagion for anesthetists, dentists, head and neck surgeons, maxillofacial surgeons, ophthalmologists, and otolaryngologists. Health workers represent between 3.8% and 20% of the infected population; some 15% will develop severe complaints and among them, many will lose their lives. A large number of patients do not have overt signs and symptoms (fever/respiratory), yet pose a real risk to surgeons (who should know this fact and must therefore apply respiratory protective strategies for all patients they encounter). All interventions that have the potential to aerosolize aerodigestive secretions should be avoided or used only when mandatory. Health workers who are: pregnant, over 55 to 65 years of age, with a history of chronic diseases (uncontrolled hypertension, diabetes mellitus, chronic obstructive pulmonary diseases, and all clinical scenarios where immunosuppression is feasible, including that induced to treat chronic inflammatory conditions and organ transplants) should avoid the clinical attention of a potentially infected patient. Health care facilities should prioritize urgent and emergency visits and procedures until the present condition stabilizes; truly elective care should cease and discussed on a case-by-case basis for patients with cancer. For those who are working with COVID-19 infected patients' isolation is compulsory in the following settings: (a) unprotected close contact with COVID-19 pneumonia patients; (b) onset of fever, cough, shortness of breath, and other symptoms (gastrointestinal complaints, anosmia, and dysgeusia have been reported in a minority of cases). For any care or intervention in the upper aerodigestive tract region, irrespective of the setting and a confirmed diagnosis (eg, rhinoscopy or flexible laryngoscopy in the outpatient setting and tracheostomy or rigid endoscopy under anesthesia), it is strongly recommended that all health care personnel wear personal protective equipment such as N95, gown, cap, eye protection, and gloves. The procedures described are essential in trying to maintain safety of health care workers during COVID-19 pandemic. In particular, otolaryngologists, head and neck, and maxillofacial surgeons are per se exposed to the greatest risk of infection while caring for COVID-19 positive subjects, and their protection should be considered a priority in the present circumstances.", "qid": 19, "docid": "lclpuqvw", "rank": 90, "score": 0.8194488286972046}, {"content": "Title: Novel coronavirus infection: Covid-19/ Yeni Koronavir\u00fcs \u0130nfeksiyonu: COVID-19 Content: Coronaviruses (CoV) are enveloped, single-chain positive RNA viruses constituting a fairly large family. 229E, OC43, NL63 and HKU1 species are common in humans, often causing mild to moderate respiratory infections. On the other hand, new coronaviruses have emerged, causing severe respiratory infection such as \u201csevere acute respiratory syndrome\u201d (SARS) in 2002 and \u201cMiddle East respiratory syndrome\u201d (MERS) in 2012. The most recent coronavirus, SARS-CoV-2, causing COVID-19 disease was identified in 2019. While people of all ages are susceptible to COVID-19 infection, those with underlying chronic diseases and elderly age have increased susceptibility. There is no specific antiviral drug for COVID-19 infection. Therefore, treatment strategy is mostly aimed at supportive treatment and prevention of complications. The main protection measure is to avoid contact with the person infected with COVID-19. Following the identification of COVID-19 disease, it exceeded the region where it was located, the number of cases increased gradually, and intercontinental reports were made. COVID-19 is a highly pathogenic respiratory virus threatening global public health today. In order to eradicate the virus, it is necessary to clarify the source of the virus, to develop specific, effective treatments and a safe vaccine. Effective surveillance and appropriate infection control measures are critical to prevent the spread of the virus.", "qid": 19, "docid": "rly2ydn5", "rank": 91, "score": 0.819345235824585}, {"content": "Title: Tackling COVID-19 Pandemic through Nanocoatings: Confront and Exactitude Content: Abstract After the eruption of the most deadly influenza flu pandemic in 1918, also known as Spanish flu, infected about 500 million people with a death toll of approximately 50 million globally, the second most devastating pandemic flue emerged in December 2019 at Wuhan (Hubei Province) of China. This viral disease caused by a novel coronavirus SARS-COV-2 was named COVID-19 by World Health Organization (WHO). The COVID-19 virus affected 213 countries globally with 5.6 million cases and 353,373 deaths as of May 28, 2020 [1] (Fig. 1). Still, there is no promising solution known to tackle this severe epidemic disease worldwide. Protecting the global population from COVID-19 we must follow three steps \u2013 early detection, monitoring, and treatment. At the same time, it is important to follow WHO guidelines on preventive measures. Many countries have restricted the movement of people completely and lockdown enforced to maintain social distancing. But lockdown alone is insufficient to prevent resurgence, can upend economies and roil society. People need to step out to perform essential tasks and may get exposed to this deadly virus. Learnings from previous outbreaks suggest the usage of nanotechnology as an important avenue to develop antiviral drugs and materials. So, to effectively minimize the acquired infection of COVID-19 in public places like hospitals, transport, schools, worship places, stores, malls, etc. antimicrobial nanocoatings at these places and development of targeted antiviral drugs through capped nanoparticles will be a major effective option to tackle the spread of this disease.", "qid": 19, "docid": "rbemevt2", "rank": 92, "score": 0.8191817402839661}, {"content": "Title: Airborne transmission of SARS-CoV-2: The world should face the reality Content: Hand washing and maintaining social distance are the main measures recommended by the World Health Organization (WHO) to avoid contracting COVID-19. Unfortunately, these measured do not prevent infection by inhalation of small droplets exhaled by an infected person that can travel distance of meters or tens of meters in the air and carry their viral content. Science explains the mechanisms of such transport and there is evidence that this is a significant route of infection in indoor environments. Despite this, no countries or authorities consider airborne spread of COVID-19 in their regulations to prevent infections transmission indoors. It is therefore extremely important, that the national authorities acknowledge the reality that the virus spreads through air, and recommend that adequate control measures be implemented to prevent further spread of the SARS-CoV-2 virus, in particularly removal of the virus-laden droplets from indoor air by ventilation.", "qid": 19, "docid": "q67g8r1b", "rank": 93, "score": 0.8191635012626648}, {"content": "Title: Applied Clinical Pharmacology in a Crisis: Interleukin-6 Axis Blockade and COVID-19 Content: The global pandemic of coronavirus disease 2019 (COVID-19) represents an emergent threat to the public health. Mitigation strategies have been employed to varying effect in many Western nations. Treatment strategies to effectively address COVID-19 and equitably distribute resources are needed, especially in overwhelmed hospitals.", "qid": 19, "docid": "d2cha1wd", "rank": 94, "score": 0.818642795085907}, {"content": "Title: Comparison of In Vitro Inactivation of SARS CoV-2 with Hydrogen Peroxide and Povidone-Iodine Oral Antiseptic Rinses Content: PURPOSE: To evaluate the in vitro inactivation of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) with hydrogen peroxide (H2 O2 ) and povidone-iodine (PVP-I) oral antiseptic rinses at clinically recommended concentrations and contact times. MATERIALS AND METHODS: SARS-CoV-2, USA-WA1/2020 strain virus stock was prepared prior to testing by growing in Vero 76 cells. The culture media for prepared virus stock was minimum essential medium (MEM) with 2% fetal bovine serum (FBS) and 50 \u00b5g/mL gentamicin. Test compounds consisting of PVP-I oral rinse solutions and H2 O2 aqueous solutions were mixed directly with the virus solution so that the final concentration was 50% of the test compound and 50% of the virus solution. Thus PVP-I was tested at concentrations of 0.5%, 1.25% and 1.5%, and H2 O2 was tested at 3% and 1.5% concentrations to represent clinically recommended concentrations. Ethanol and water were evaluated in parallel as standard positive and negative controls. All samples were tested at contact periods of 15 seconds and 30 seconds. Surviving virus from each sample was then quantified by standard end-point dilution assay and the log reduction value of each compound compared to the negative control was calculated. RESULTS: After the 15-second and 30-second contact times, PVP-I oral antiseptic rinse at all 3 concentrations of 0.5%, 1.25% and 1.5% completely inactivated SARS-CoV-2. The H2 O2 solutions at concentrations of 1.5% and 3.0% showed minimal viricidal activity after 15 seconds and 30 seconds of contact time. CONCLUSIONS: SARS-CoV-2 virus was completely inactivated by PVP-I oral antiseptic rinse in vitro, at the lowest concentration of 0.5 % and at the lowest contact time of 15 seconds. Hydrogen peroxide at the recommended oral rinse concentrations of 1.5% and 3.0% was minimally effective as a viricidal agent after contact times as long as 30 seconds. Therefore, preprocedural rinsing with diluted PVP-I in the range of 0.5% to 1.5% may be preferred over hydrogen peroxide during the COVID-19 pandemic. This article is protected by copyright. All rights reserved.", "qid": 19, "docid": "w6w1f9zt", "rank": 95, "score": 0.8184717893600464}, {"content": "Title: Possibility of Disinfection of SARS-CoV-2 (COVID-19) in Human Respiratory Tract by Controlled Ethanol Vapor Inhalation Content: Viruses such as SARS-CoV-2 and Influenza are lipophilic, enveloped viruses, and are relatively easy to inactivate by exposure to alcohols. The envelope mainly consists of the lipid bilayer, taken from the host cells at assembly/budding stage of the viral life cycle. Therefore the constitution of the lipid bilayer should be common in all SARS, MERS and influenza viruses, even after mutations, and thus these closely-related viruses will be disinfected by exposure to ethanol with the same concentration. Existing experimental data indicate that an ethanol concentration of 30~40 v/v% is sufficient to inactivate Influenza-A viruses in solution[1,2,3]. The author suggests that it may be possible to use alcoholic beverages of 16~20 v/v% concentration for this disinfection process, such as Whisky (1:1 hot water dilution) or Japanese Sake, because they are readily available and safe (non-toxic). By inhaling the alcohol vapor at 50~60$^\\circ$C (122~140$^\\circ$F) through the nose for one or two minutes, it will condense on surfaces inside the respiratory tract; mainly in the nasal cavity. The alcohol concentration will be intensified to ~36 v/v% by this process, which is enough to disinfect the corona virus on the mucous membrane. This method also provides more moisture into respiratory tract, and helps to clean the inside of the nasal cavity by stimulating blowing of the nose, and also makes the mucous escalator work actively so that the self-clearing mechanism in the trachea will remove viruses faster. An alternative prompt method is also discussed. We use 40 v/v% whisky or similar alcohol, dripping on a gauze, inhale the vapor slowly at room temperature. This method works well for the front part of the nasal cavity. This is suitable for clinical workers, because they may need to use prompt preventative measures at any time.", "qid": 19, "docid": "k8k5kg4z", "rank": 96, "score": 0.8183743953704834}, {"content": "Title: Detection of SARS-CoV-2 in Exhaled Breath from COVID-19 Patients Ready for Hospital Discharge Content: The COVID-19 pandemic has brought an unprecedented crisis to the global health sector1. When recovering COVID-19 patients are discharged in accordance with throat or nasal swab protocols using reverse transcription polymerase chain reaction (RT-PCR), the potential risk of re-introducing the infection source to humans and the environment must be resolved 2,3,4. Here we show that 20% of COVID-19 patients, who were ready for a hospital discharge based on current guidelines, had SARS-CoV-2 in their exhaled breath (~105 RNA copies/m3). They were estimated to emit about 1400 RNA copies into the air per minute. Although fewer surface swabs (1.3%, N=318) tested positive, medical equipment frequently contacted by healthcare workers and the work shift floor were contaminated by SARS-CoV-2 in four hospitals in Wuhan. All air samples (N=44) appeared negative likely due to the dilution or inactivation through natural ventilation (1.6-3.3 m/s) and applied disinfection. Despite the low risk of cross environmental contamination in the studied hospitals, there is a critical need for strengthening the hospital discharge standards in preventing re-emergence of COVID-19 spread.", "qid": 19, "docid": "tm49ksch", "rank": 97, "score": 0.8183690309524536}, {"content": "Title: Coronavirus et COVID-19 : le point sur une pand\u00e9mie galopante./ [Coronavirus and COVID-19 : focus on a galopping pandemic] Content: The international community is currently facing a pandemic of acute respiratory syndrome caused by a new coronavirus, SARS-CoV-2. This syndrome has been named COVID-19 for CoronaVIrus Disease 2019 by the World Health Organization. The starting point of the epidemic is the city of Wuhan (China), where the virus is said to have been transmitted from animals to humans before inter-human transmission. This is the third epidemic caused by a coronavirus after those of severe acute respiratory syndrome (SARS) in 2003 and Middle East respiratory syndrome (MERS) started in 2012. COVID-19 has rapidly spread to China and is currently spreading all over the world. The infection mainly affects patients over 40 years of age and mortality is increased in the presence of comorbidities. Children are pauci- or asymptomatic. The diagnosis is most often based on the detection of the viral genome in the nasopharynx by molecular biology methods. In the absence of specific anti-viral molecules, treatment is currently mainly symptomatic. It is clear that the COVID-19 pandemic is more difficult to control than what the first data suggested. The key strategy to SARS-CoV-2 is to limit its transmission. Preventive measures are mainly based on the application of adequate hand hygiene measures and disinfection of the environment, as well as measures of social distance aimed at limiting contacts in the population and protecting populations at risk.", "qid": 19, "docid": "xpf9mec6", "rank": 98, "score": 0.8181192874908447}, {"content": "Title: [Coronavirus and COVID-19 : focus on a galopping pandemic]. Content: The international community is currently facing a pandemic of acute respiratory syndrome caused by a new coronavirus, SARS-CoV-2. This syndrome has been named COVID-19 for CoronaVIrus Disease 2019 by the World Health Organization. The starting point of the epidemic is the city of Wuhan (China), where the virus is said to have been transmitted from animals to humans before inter-human transmission. This is the third epidemic caused by a coronavirus after those of severe acute respiratory syndrome (SARS) in 2003 and Middle East respiratory syndrome (MERS) started in 2012. COVID-19 has rapidly spread to China and is currently spreading all over the world. The infection mainly affects patients over 40 years of age and mortality is increased in the presence of comorbidities. Children are pauci- or asymptomatic. The diagnosis is most often based on the detection of the viral genome in the nasopharynx by molecular biology methods. In the absence of specific anti-viral molecules, treatment is currently mainly symptomatic. It is clear that the COVID-19 pandemic is more difficult to control than what the first data suggested. The key strategy to SARS-CoV-2 is to limit its transmission. Preventive measures are mainly based on the application of adequate hand hygiene measures and disinfection of the environment, as well as measures of social distance aimed at limiting contacts in the population and protecting populations at risk.", "qid": 19, "docid": "7nhnds83", "rank": 99, "score": 0.8181192874908447}, {"content": "Title: Is hydroxychloroquine beneficial for COVID-19 patients? Content: The outbreak of coronavirus disease 2019 (COVID-19) caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) was first reported in December 2019. As similar cases rapidly emerged around the world(1\u20133), the World Health Organization (WHO) declared a public health emergency of international concern on January 30, 2020 and pronounced the rapidly spreading coronavirus outbreak as a pandemic on March 11, 2020(4). The virus has reached almost all countries of the globe. As of June 3, 2020, the accumulated confirmed cases reached 6,479,405 with more than 383,013 deaths worldwide. The urgent and emergency care of COVID-19 patients calls for effective drugs, in addition to the beneficial effects of remdesivir(5), to control the disease and halt the pandemic.", "qid": 19, "docid": "hqkrer9m", "rank": 100, "score": 0.8181055784225464}]}
{"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": 0.8877884149551392}, {"content": "Title: Concerns related to COVID\u201019 pandemic among patients with inflammatory bowel disease and its influence on patient management Content: A novel coronavirus, currently identified as COVID-19, was recently defined as the cause of a cluster of patients with pneumonia of unknown origin that was initially reported from Wuhan, Hubei province, People's Republic of China.", "qid": 1, "docid": "47pszpgp", "rank": 2, "score": 0.8847236633300781}, {"content": "Title: [Editorial] Possibility of transmission through dogs being a contributing factor to the extreme Covid\u00ad19 outbreak in North Italy Content: Covid\u00ad19 origin and transmission to humans. Covid\u00ad19 infection began in Wuhan (Hubei, China) in December, 2019. Although to date it is considered that Covid\u00ad19 originates from bats (96.2% overall genome sequence identity) (1), the type of intermediate animals that caused the transmission to humans remains unknown (2-4). Zhou et al (1) mentioned that 'Direct contact with intermediate host animals or consumption of wild animals was suspected to be the main route of SARS\u00adCoV\u00ad2 transmission. However, the source(s) and transmission routine(s) of SARS\u00adCoV\u00ad2 remain elusive' (1).", "qid": 1, "docid": "jwxt4ygt", "rank": 3, "score": 0.8841727375984192}, {"content": "Title: Possibility of transmission through dogs being a contributing factor to the extreme Covid-19 outbreak in North Italy Content: Covid\u201119 origin and transmission to humans. Covid\u201119 infection began in Wuhan (Hubei, China) in December, 2019. Although to date it is considered that Covid\u201119 originates from bats (96.2% overall genome sequence identity) (1), the type of intermediate animals that caused the transmission to humans remains unknown (2-4). Zhou et al (1) mentioned that 'Direct contact with intermediate host animals or consumption of wild animals was suspected to be the main route of SARS\u2011CoV\u20112 transmission. However, the source(s) and transmission routine(s) of SARS\u2011CoV\u20112 remain elusive' (1).", "qid": 1, "docid": "k9lcpjyo", "rank": 4, "score": 0.8840075731277466}, {"content": "Title: Pangolins Harbor SARS-CoV-2-Related Coronaviruses Content: The pandemic of coronavirus disease 2019 (COVID-19) caused by SARS-CoV-2 has posed a severe threat to global public health. Yet, the origin of SARS-CoV-2 remains mysterious. Several recent studies (e.g., Lam et al ., Xiao et al .) identified SARS-CoV-2-related viruses in pangolins, providing novel insights into the evolution and diversity of SARS-CoV-2-related viruses.", "qid": 1, "docid": "k9yus2sv", "rank": 5, "score": 0.8799269199371338}, {"content": "Title: Pangolins Harbor SARS-CoV-2-Related Coronaviruses Content: The pandemic of coronavirus disease 2019 (COVID-19) caused by SARS-CoV-2 has posed a severe threat to global public health. Yet, the origin of SARS-CoV-2 remains mysterious. Several recent studies (e.g., Lam et al.,Xiao et al.) identified SARS-CoV-2-related viruses in pangolins, providing novel insights into the evolution and diversity of SARS-CoV-2-related viruses.", "qid": 1, "docid": "pfv7q4v6", "rank": 6, "score": 0.8799269199371338}, {"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": 7, "score": 0.8775320649147034}, {"content": "Title: Projection of COVID-19 Pandemic in Uganda Content: COVID-19 (Corona Virus) is caused by Severe Acute Respiratory Syndrome Corona Virus 2 (SARS-COV-2). The virus that was first discovered in China Wuhan Province about 3 months ago (first cases were reported in Wuhan on December 31st, 2019) has spread world wide. The six (6) top countries (excluding China) most affected so far include; USA, Italy, Spain, Germany, France, and Iran. With Italy showing the highest death toll. In Uganda where it was discovered on 19/3/2020 with one (01) case has just in nine (9) days, increased to thirty (30) infected individuals. This model is a wake-up call over the rate at which COVID-19 is likely to spread throughout the country. Thus it is a guide for policymakers and planners to benchmark on for solutions to this deadly virus.", "qid": 1, "docid": "co4ckyp9", "rank": 8, "score": 0.8766061663627625}, {"content": "Title: Genetic diversity and evolution of SARS-CoV-2 Content: COVID-19 is a viral respiratory illness caused by a new coronavirus called SARS-CoV-2. The World Health Organization declared the SARS-CoV-2 outbreak a global public health emergency. We performed genetic analyses of eighty-six complete or near-complete genomes of SARS-CoV-2 and revealed many mutations and deletions on coding and non-coding regions. These observations provided evidence of the genetic diversity and rapid evolution of this novel coronavirus.", "qid": 1, "docid": "can1e8ro", "rank": 9, "score": 0.8731384873390198}, {"content": "Title: Zoonotic origins of human coronavirus 2019 (HCoV-19 / SARS-CoV-2): why is this work important? Content: The ongoing pandemic of coronavirus disease 2019 (COVID-19), caused by infection with human coronavirus 2019 (HCoV-19 / SARS-CoV-2 / 2019-nCoV), is a global threat to the human population. Here, we briefly summarize the available data for the zoonotic origins of HCoV-19, with reference to the other two epidemics of highly virulent coronaviruses, SARS-CoV and MERS-CoV, which cause severe pneumonia in humans. We propose to intensify future efforts for tracing the origins of HCoV-19, which is a very important scientific question for the control and prevention of the pandemic.", "qid": 1, "docid": "75773gwg", "rank": 10, "score": 0.8708015084266663}, {"content": "Title: Genetic diversity and evolution of SARS-CoV-2 Content: Abstract COVID-19 is a viral respiratory illness caused by a new coronavirus called SARS-CoV-2. The World Health Organization declared the SARS-CoV-2 outbreak a global public health emergency. We performed genetic analyses of eighty-six complete or near-complete genomes of SARS-CoV-2 and revealed many mutations and deletions on coding and non-coding regions. These observations provided evidence of the genetic diversity and rapid evolution of this novel coronavirus.", "qid": 1, "docid": "0nh58odf", "rank": 11, "score": 0.8682237267494202}, {"content": "Title: Severe acute respiratory syndrome-coronavirus 2 and novel coronavirus disease 2019: An extraordinary pandemic Content: COVID-19 has emerged as one of the most significant illnesses of the current century. It is caused by severe acute respiratory syndrome coronavirus 2. The world was initially viewing it as a localized outbreak in Wuhan city of China; however, it started spreading quickly to other parts of the world. Globally, half-hearted containment measures and a false sense of safety against this novel coronavirus led to the dissemination of disease. Currently, no effective therapy or vaccine is available to manage this illness. After learning a huge lesson, global efforts would hopefully lead to effective control of this pandemic.", "qid": 1, "docid": "i8opdley", "rank": 12, "score": 0.8671082258224487}, {"content": "Title: Post-donation COVID-19 identification in blood donors. Content: The coronavirus disease 19 (COVID-19) outbreak, which was characterized as a pandemic on 11 March 2020 by the WHO, started in December 2019 with the emergence of pneumonia cases of unknown cause in Wuhan, Hubei, China [1]. SARS-CoV-2, the causative agent of COVID-19, are enveloped, non-segmented, single stranded positive sense RNA viruses and are classified as a sister clade to the prototype human and bat severe acute respiratory syndrome coronaviruses (SARS-CoVs) of the species Severe acute respiratory syndrome-related coronavirus [2]. So far, no respiratory virus, including SARS-CoV and the Middle East Respiratory Syndrome (MERS)-CoV, has been confirmed as transfusion-transmissible [3,4].", "qid": 1, "docid": "82sc928x", "rank": 13, "score": 0.8660715222358704}, {"content": "Title: Endotheliitis and Endothelial Dysfunction in Patients with COVID-19: Its Role in Thrombosis and Adverse Outcomes. Content: Coronavirus disease 2019 (COVID-19) is a contagious disease caused by severe acute respiratory syndrome coronavirus-2 (SARS-CoV2), emerging in Wuhan, China and developing into a pandemic with rapidly emerging cardiovascular manifestations [...].", "qid": 1, "docid": "25613kd3", "rank": 14, "score": 0.86358642578125}, {"content": "Title: Novel Coronavirus disease 2019 (COVID-19): new challenges and new responsibilities in developing countries Content: Novel coronavirus disease 2019 (COVID-19) is caused by the SARS-CoV-2 virus, which belongs to the genus Coronaviridae with its high mutation rate. From the current perspective, we discuss the current status of COVID-19, new challenges, and potential interventions to control the pandemic in developing counties such as Pakistan.", "qid": 1, "docid": "ig5kb9ke", "rank": 15, "score": 0.8628097772598267}, {"content": "Title: Novel Coronavirus disease 2019 (COVID-19): new challenges and new responsibilities in developing countries. Content: Novel coronavirus disease 2019 (COVID-19) is caused by the SARS-CoV-2 virus, which belongs to the genus Coronaviridae with its high mutation rate. From the current perspective, we discuss the current status of COVID-19, new challenges, and potential interventions to control the pandemic in developing counties such as Pakistan.", "qid": 1, "docid": "8uvj7krx", "rank": 16, "score": 0.8628097772598267}, {"content": "Title: To alert coinfection of COVID-19 and dengue virus in developing countries in the dengue-endemic area Content: Coronavirus disease 2019 (CoVID-19) is a new outbreak infectious disease caused by SARS-CoV-2, which was originated from Wuhan in China and has now spread to the whole world. At the meantime, dengue was endemic in the Southeast Asia and South America, and a part of the patients shared the same symptoms, so, we write this paper to alert the clinicians to distinguish these two diseases.", "qid": 1, "docid": "0oiq44gl", "rank": 17, "score": 0.858208417892456}, {"content": "Title: Statistical investigation of relationship between spread of coronavirus disease (COVID-19) and environmental factors based on study of four mostly affected places of China and five mostly affected places of Italy Content: COVID-19 is a new type of coronavirus disease which is caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). It originated in China in the month of December 2019 and quickly started to spread within the country. On 31st December 2019, it was first reported to country office of World Health Organization (WHO) in China. Since then, it has spread to most of the countries around the globe. However, there has been a recent rise in trend in believing that it would go away during summer days, which has not yet been properly investigated. In this paper, relationship of daily number of confirmed cases of COVID-19 with three environmental factors, viz. maximum relative humidity (RH_max), maximum temperature (T_max) and highest wind speed (WS_max), considering the incubation period, have been investigated statistically, for four of the most affected places of China, viz. Beijing, Chongqing, Shanghai, Wuhan and five of the most affected places of Italy, viz. Bergamo, Cremona, Lodi, Milano. It has been found that the relationship with maximum relative humidity and highest wind is mostly negligible, whereas relationship with maximum temperature is ranging between negligible to moderate.", "qid": 1, "docid": "4ay3hsi7", "rank": 18, "score": 0.8581587076187134}, {"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": 1, "docid": "828ubhzi", "rank": 19, "score": 0.8580327033996582}, {"content": "Title: Multi-Center Evaluation of the Cepheid Xpert Xpress SARS-CoV-2 Assay for the Detection of SARS-CoV-2 in Oropharyngeal Swab Specimens Content: The coronavirus disease 2019 (COVID-19), caused by severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2) is a global health concern that has spread worldwide since December 2019 (1-4). .", "qid": 1, "docid": "vwxk5bqb", "rank": 20, "score": 0.8570945262908936}, {"content": "Title: Genetic evolution analysis of 2019 novel coronavirus and coronavirus from other species Content: The Corona Virus Disease 2019 (COVID-19) caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) is a Public Health Emergency of International Concern. However, so far, there are still controversies about the source of the virus and its intermediate host. Here, we found the novel coronavirus was closely related to coronaviruses derived from five wild animals, including Paguma larvata, Paradoxurus hermaphroditus, Civet, Aselliscus stoliczkanus and Rhinolophus sinicus, and was in the same branch of the phylogenetic tree. However, genome and ORF1a homology show that the virus is not the same coronavirus as the coronavirus derived from these five animals, whereas the virus has the highest homology with Bat coronavirus isolate RaTG13.", "qid": 1, "docid": "zxudiyj4", "rank": 21, "score": 0.856958270072937}, {"content": "Title: Genomic surveillance of SARS-CoV-2 in Thailand reveals mixed imported populations, a local lineage expansion and a virus with truncated ORF7a Content: Coronavirus Disease 2019 (COVID-19) is a global public health threat. Genomic surveillance of SARS-CoV-2 was implemented during March 2020 at a major diagnostic hub in Bangkok, Thailand. Several virus lineages supposedly originated in many countries were found, and a Thai-specific lineage, designated A/Thai-1, has expanded to be predominant in Thailand. A virus sample in the SARS-CoV-2 A/Thai-1 lineage contains a frame-shift deletion at ORF7a, encoding a putative host antagonizing factor of the virus.", "qid": 1, "docid": "ok4ah1r7", "rank": 22, "score": 0.8568675518035889}, {"content": "Title: COVID-19: laboratory diagnosis for clinicians. An updating article Content: COVID-19 (coronavirus disease 2019) is an infectious disease caused by the new coronavirus associated with severe acute respiratory syndrome 2 (SARS-CoV-2) Coronaviridae comprises a large family, of which at least seven members are known to cause respiratory diseases in humans Coronaviruses have the ability to infect virtually all major groups of animals and, eventually, can infect humans SARS-CoV-2 is the third coronavirus to cross the species barrier and infect humans This virus was identified in an outbreak of pneumonia cases in Wuhan city, Hubei province, China, in December 2019 Its entire genome is inscribed on a single strand of ribonucleic acid Some proteins present on the surface of the virus act as facilitators for its entry into host cells, while others, apparently, are related to its pathogenesis Coronaviruses are responsible for respiratory infections in humans and some animals The infection is often mild to moderate in intensity, but some coronaviruses may cause serious illnesses, such as severe acute respiratory syndrome (SARS), which occurred in 2002, and the Middle East respiratory syndrome (MERS) Coronaviruses can activate an excessive and unregulated immune response, which may promote SARS development Although the lungs are one of the target organs, the hypoxia mechanism is systemic and other organs begin to suffer both through lack of oxygen and through deregulation of inflammation control mechanisms", "qid": 1, "docid": "8685l1n9", "rank": 23, "score": 0.8562003374099731}, {"content": "Title: Papa Giovanni XXIII Bergamo Hospital at the time of the COVID-19 outbreak: letter from the warfront. Content: In early December 2019, the 2019 novel coronavirus (COVID-19) was identified as the agent responsible for the first pneumonia cases of unknown origin in Wuhan, the capital of the Hubei region in China. The virus has been identified as a novel enveloped RNA betacoronavirus2 , that has been promptly named SARS-CoV-2 (severe acute respiratory syndrome coronavirus 2). The World Health Organization (WHO), on January 12, 2020 declared the COVID-19 a public health emergency of international concern. On March 11, the WHO made the assessment that COVID-19 can be characterized as a pandemic.", "qid": 1, "docid": "d11cj86k", "rank": 24, "score": 0.8555176258087158}, {"content": "Title: Covid-19 outbreak and perspective in morocco Content: Coronavirus disease 2019 (COVID-19) is a respiratory illness that can spread from person to person. The virus that causes COVID-19 is a novel coronavirus that was first identified during an investigation into an outbreak in Wuhan, China and rapidly spread across the world to become the first pandemic caused by a coronavirus. As of 26 March 2020, there are 275 cases affected by COVID-19 announced by the Moroccan government, and it possible to limit the spread of this serious disease, with the cooperation of all the citizens in respect of the measures of containment and individual protection. Also, with the announce yesterday by the Moroccan government of the authorization of use of chloroquine in treatment of COVID-19 pneumonia, COVID-19 will be soon eradicated from Morocco and hopefully from all over the world.", "qid": 1, "docid": "8yr41aa8", "rank": 25, "score": 0.8544992208480835}, {"content": "Title: Novel Coronavirus COVID-19 Strike on Arab Countries and Territories: A Situation Report I Content: The novel Coronavirus (COVID-19) is an infectious disease caused by a new virus called COVID-19 or 2019-nCoV that first identified in Wuhan, China. The disease causes respiratory illness (such as the flu) with other symptoms such as a cough, fever, and in more severe cases, difficulty breathing. This new Coronavirus seems to be very infectious and has spread quickly and globally. In this work, information about COVID-19 is provided and the situation in Arab countries and territories regarding the COVID-19 strike is presented. The next few weeks main expectations is also given.", "qid": 1, "docid": "9fngwsh3", "rank": 26, "score": 0.8544636368751526}, {"content": "Title: The recent challenges of highly contagious COVID-19; causing respiratory infections: symptoms, diagnosis, transmission, possible vaccines, animal models and immunotherapy Content: COVID-19 is highly contagious pathogenic viral infection initiated from Wuhan seafood wholesale market of China on December 2019 and spread rapidly around the whole world due to onward transmission. This recent outbreak of novel coronavirus (CoV) was believed to be originated from bats and causing respiratory infections such as common cold, dry cough, fever, headache, dyspnea, pneumonia and finally Severe Acute Respiratory Syndrome (SARS) in humans. For this widespread zoonotic virus, human-to-human transmission has resulted in nearly 83 lakh cases in 213 countries and territories with 4,50,686 deaths as on 19th June 2020. This review presents a report on the origin, transmission, symptoms, diagnosis, possible vaccines, animal models and immunotherapy for this novel virus and will provide ample references for the researchers towards the ongoing development of therapeutic agents and vaccines and also preventing the spread of this disease.", "qid": 1, "docid": "jxbk30gh", "rank": 27, "score": 0.8540793061256409}, {"content": "Title: The recent challenges of highly contagious COVID-19; causing respiratory infections: symptoms, diagnosis, transmission, possible vaccines, animal models and immunotherapy. Content: COVID-19 is highly contagious pathogenic viral infection initiated from Wuhan seafood wholesale market of China on December 2019 and spread rapidly around the whole world due to onward transmission. This recent outbreak of novel coronavirus (CoV) was believed to be originated from bats and causing respiratory infections such as common cold, dry cough, fever, headache, dyspnea, pneumonia and finally Severe Acute Respiratory Syndrome (SARS) in humans. For this widespread zoonotic virus, human-to-human transmission has resulted in nearly 83 lakh cases in 213 countries and territories with 4,50,686 deaths as on 19th June 2020. This review presents a report on the origin, transmission, symptoms, diagnosis, possible vaccines, animal models and immunotherapy for this novel virus and will provide ample references for the researchers towards the ongoing development of therapeutic agents and vaccines and also preventing the spread of this disease.", "qid": 1, "docid": "r2ynbnxx", "rank": 28, "score": 0.8540793061256409}, {"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": 29, "score": 0.8538795709609985}, {"content": "Title: Time Course of COVID-19 Cases in Austria Content: COVID-19 is an infectious disease caused by a novel coronavirus, which first appeared in China in late 2019, and reached pandemic distribution in early 2020. The first major outbreak in Europe occurred in Northern Italy where it spread to neighboring countries, notably to Austria, where skiing resorts served as a main transmission hub. Soon, the Austrian government introduced strict measures to curb the spread of the virus. Using publicly available data, we assessed the efficiency of the governmental measures. We assumed an average incubation period of one week and an average duration of infectivity of 10 days. One week after the introduction of strict measures, the increase in daily new cases was reversed, and the reproduction number dropped. The crude estimates tended to overestimate the reproduction rate in the early phase. Publicly available data provide a first estimate about the effectiveness of public health measures. However, more data are needed for an unbiased assessment.", "qid": 1, "docid": "cfk25vpu", "rank": 30, "score": 0.8527951240539551}, {"content": "Title: COVID-19: Healthy environmental impact for public safety and menaces oil market Content: COVID-19 seems as global emergency, by infectious virus, caused respiratory illness like having symptoms of flue, sickness, headache, and difficulty in breathing. Within months the world has been transformed into new order, thousands of people died and many more are fallen ill due to COVID-19 outbreak. China was the first country to see the outbreak and the first country to control it. However, the disease has broken out in Europe, the Middle East, the United States and other places. The United States has the highest number of cases in the world.", "qid": 1, "docid": "g62tz7b7", "rank": 31, "score": 0.8521913290023804}, {"content": "Title: COVID-19: Healthy environmental impact for public safety and menaces oil market. Content: COVID-19 seems as global emergency, by infectious virus, caused respiratory illness like having symptoms of flue, sickness, headache, and difficulty in breathing. Within months the world has been transformed into new order, thousands of people died and many more are fallen ill due to COVID-19 outbreak. China was the first country to see the outbreak and the first country to control it. However, the disease has broken out in Europe, the Middle East, the United States and other places. The United States has the highest number of cases in the world.", "qid": 1, "docid": "5x4k9b7j", "rank": 32, "score": 0.8521913290023804}, {"content": "Title: Clinical features and outcomes of four HIV patients with COVID\u201019 in Wuhan, China Content: SARS-CoV-2 is the coronavirus that has been identified as the pathogen causing COVID-19.1 Human Immunodeficiency Virus (HIV) attacks the immune system and leads to acquired immune deficiency syndrome (AIDS) in the late stage of disease. Concerns have been raised on HIV as a risk factor for COVID-19. This article is protected by copyright. All rights reserved.", "qid": 1, "docid": "f9gmlkez", "rank": 33, "score": 0.8521747589111328}, {"content": "Title: Distinct characteristics of COVID\u201019 patients with initial rRT\u2010PCR\u2010positive and rRT\u2010PCR\u2010negative results for SARS\u2010CoV\u20102 Content: Since the coronavirus disease 2019 (COVID-19) caused by SARS-CoV-2 (severe acute respiratory syndrome coronavirus 2) first emerged in Wuhan, China in December 2019, the outbreak of COVID-19 epidemic has become an increasingly serious global health concern. Currently, over 150 countries have reported COVID-19 cases, and the situation has progressed to a pandemic associated with substantial morbidity and mortality.1.", "qid": 1, "docid": "hryhgy77", "rank": 34, "score": 0.8521601557731628}, {"content": "Title: World Health Organization declares global emergency: A review of the 2019 novel coronavirus (COVID-19) Content: An unprecedented outbreak of pneumonia of unknown aetiology in Wuhan City, Hubei province in China emerged in December 2019. A novel coronavirus was identified as the causative agent and was subsequently termed COVID-19 by the World Health Organization (WHO). Considered a relative of severe acute respiratory syndrome (SARS) and Middle East respiratory syndrome (MERS), COVID-19 is caused by a betacoronavirus named SARS-CoV-2 that affects the lower respiratory tract and manifests as pneumonia in humans. Despite rigorous global containment and quarantine efforts, the incidence of COVID-19 continues to rise, with 90,870 laboratory-confirmed cases and over 3,000 deaths worldwide. In response to this global outbreak, we summarise the current state of knowledge surrounding COVID-19.", "qid": 1, "docid": "mq4b2rw2", "rank": 35, "score": 0.8517837524414062}, {"content": "Title: SARS-CoV-2 receptor mutation in Egyptian population Content: The Coronavirus disease 2019 (COVID-19) is a respiratory tract infectious disease caused by Severe Acute Respiratory Syndrome coronavirus 2 (SARS-CoV-2). SARS-CoV-2 triggers severe pneumonia leading to acute respiratory distress syndrome and death in severe cases. According to WHO reported, Egypt is among the countries with low confirmed SARS CoV2 infected symptomatic cases and death. We postulate that one of the reasons for this may be due mutations in the viral receptor. Therefore this study was conducted to confirm or reject this postulation.", "qid": 1, "docid": "xirt6efg", "rank": 36, "score": 0.8517320156097412}, {"content": "Title: Is visiting Qom spread CoVID-19 epidemic in the Middle East? Content: The CoVID-19 epidemic started in Wuhan, China and spread to 217 other countries around the world through direct contact with patients, goods transfer, animal transport, and touching unclean surfaces. In the Middle East, the first confirmed case in both Iran and UAE originated from China. A series of infections since those confirmed cases started in the Middle East originated from Qom, Iran, and other Shi'ite holy places. Thereafter, CoVID-19 has been transmitted to other countries in the Middle East. This report aims to trace all of the confirmed cases in the Middle East until March 6, 2020 and their further spread. This report proves that further transmission of CoVID-19 to the Middle East was because of human mobility, besides engaging in different Jewish and Shi'ite religious rites. This report suggests avoiding several religious rites, closing the borders of infected countries, and supporting the infected countries to prevent further transmission.", "qid": 1, "docid": "7h9yjkt3", "rank": 37, "score": 0.851482629776001}, {"content": "Title: Accelerating drug development through repurposed FDA approved drugs for COVID-19: speed is important, not haste Content: A life-threatening, emerging respiratory disease called Coronavirus Disease 2019 (COVID-19) 26 originated in the city of Wuhan in China's Hubei province in December, 2019 and has been classified as 27 an international pandemic by the World Health Organization. .", "qid": 1, "docid": "oekr2d5w", "rank": 38, "score": 0.8507781028747559}, {"content": "Title: Genotype and phenotype of COVID-19: Their roles in pathogenesis Content: COVID-19 is a novel coronavirus with an outbreak of unusual viral pneumonia in Wuhan, China, and then pandemic. Based on its phylogenetic relationships and genomic structures the COVID-19 belongs to genera Betacoronavirus. Human Betacoronaviruses (SARS-CoV-2, SARS-CoV, and MERS-CoV) have many similarities, but also have differences in their genomic and phenotypic structure that can influence their pathogenesis. COVID-19 is containing single-stranded (positive-sense) RNA associated with a nucleoprotein within a capsid comprised of matrix protein. A typical CoV contains at least six ORFs in its genome. All the structural and accessory proteins are translated from the sgRNAs of CoVs. Four main structural proteins are encoded by ORFs 10, 11 on the one-third of the genome near the 3'-terminus. The genetic and phenotypic structure of COVID-19 in pathogenesis is important. This article highlights the most important of these features compared to other Betacoronaviruses.", "qid": 1, "docid": "2gmvx0vp", "rank": 39, "score": 0.8505420684814453}, {"content": "Title: Co-infection with Influenza A and COVID-19 Content: COVID-19, also called severe acute respiratory distress syndrome coronavirus 2 (SARS-CoV-2), originated in Wuhan, China. It has caused significant morbidity and mortality worldwide and has been declared a global pandemic by the WHO. Influenza occurs mainly during the winter, with the burden of disease determined by several factors, including the effectiveness of the vaccine that season, the characteristics of the circulating viruses, and how long the season lasts. We describe the case of a 66-year-old woman who was diagnosed with influenza A and COVID-19 co-infection. LEARNING POINTS: COVID-19 can co-occur with other viral infections. Some of these co-infections have active treatments, while supportive treatment is the mainstay of treatment for others.", "qid": 1, "docid": "9i024s08", "rank": 40, "score": 0.8504045009613037}, {"content": "Title: Estudios de imagen cardiaca en la pandemia COVID-19./ Cardiac imaging studies in the COVID-19 pandemic Content: COVID-19 is an acute respiratory syndrome caused by coronavirus-2 (SARS COV2). The different cardiac imaging methods have issued specific recommendations for the different imaging methods in this pandemic, so it is essential to emphasize the recommendations for carrying out these studies.", "qid": 1, "docid": "11q83ony", "rank": 41, "score": 0.8495824337005615}, {"content": "Title: Cardiac imaging studies in the COVID-19 pandemic. Content: COVID-19 is an acute respiratory syndrome caused by coronavirus-2 (SARS COV2). The different cardiac imaging methods have issued specific recommendations for the different imaging methods in this pandemic, so it is essential to emphasize the recommendations for carrying out these studies.", "qid": 1, "docid": "9vypr79o", "rank": 42, "score": 0.8495824337005615}, {"content": "Title: Predicting COVID-19 distribution in Mexico through a discrete and time-dependent Markov chain and an SIR-like model Content: COVID-19 is an emergent viral infection which rose in December 2019 in a city in the Chinese province of Hubei, Wuhan; the viral aetiology of this infection is now known as COVID-19 virus, which belongs to the Betacoronavirus genus. This virus produces the syndrome of acute respiratory stress that h as been witnessed in other coronaviruses, such as that MERS-CoV in Middle East countries or SARS-CoV which was seen in 2002 and 2003 in China. This virus mediates its entry through its spike (S) proteins interacting with ACE2 receptors in lung epithelial cells, and may promote an inflammatory response by means of inflammasome NLRP3 activation and unfolded protein response (these are possibly consequence of the envelope E protein of COVID-19 virus). Efforts have been made worldwide to prevent further spread of the disease, but in March 2020 the WHO declared it a pandemic emergency and Mexico started to report its first cases. In this paper we attempt to summarize the biological features of the virus and the possible pathophysiological mechanisms of its disease, as well as a stochastic model characterizing the probability distribution of cases in Mexico by states and the estimated number of cases in Mexico through a differential equation model (modified SIR model), thus will we be able to characterize the disease and its course in Mexico in order to display more preparedness and promote more logical actions by both the policy makers as well as the general population.", "qid": 1, "docid": "jlv5llys", "rank": 43, "score": 0.8490408062934875}, {"content": "Title: Estudios de imagen cardiaca en la pandemia COVID-19 Content: COVID-19 is an acute respiratory syndrome caused by coronavirus-2 (SARS COV2) The different cardiac imaging methods have issued specific recommendations for the different imaging methods in this pandemic, so it is essential to emphasize the recommendations for carrying out these studies", "qid": 1, "docid": "rcccwfl8", "rank": 44, "score": 0.8489530086517334}, {"content": "Title: The continued epidemic threat of SARS-CoV-2 and implications for the future of global public health Content: A new coronavirus (CoV) called SARS-CoV-2 emerged in Wuhan, China in December 2019 as the etiological agent of a viral pneumonia called COVID-19. The global spread of SARS-CoV-2 has been so extensive that the WHO declared COVID-19 a pandemic on March 11, 2020. Below, we discuss the emergence of SARS-CoV-2 and provide the historical context, which strongly suggests emerging CoVs provide an immediate threat to global public health and will continue to do so in the future.", "qid": 1, "docid": "deg8ju9a", "rank": 45, "score": 0.8488023281097412}, {"content": "Title: Neuroinfection may contribute to pathophysiology and clinical manifestations of COVID\u201019 Content: The new coronavirus, classified as SARS-CoV-2 that emerged in Hubei province in China, causes a new coronavirus disease, which was termed COVID-19 by WHO on February 11, 2020. COVID-19 claimed almost 19000 lives around the world by March 25, 2020.", "qid": 1, "docid": "lop3va1f", "rank": 46, "score": 0.8485709428787231}, {"content": "Title: COVID-19 in Kenya Content: COVID-19 meaning Coronavirus disease which is severe acute respiratory syndrome Coronavirus 2 (SARS-CoV-2) discovered in the year December 2019 at Wuhan in China after an outbreak an infectious disease causing respiratory illness-pneumonia. SARS-CoV-2 was previously known as 2019 novel Coronavirus disease or 2019-nCov. Kenya has 122 positive cases of COVID-19 as at 4thApril 2020, four deaths and three recoveries as reported by the Government of Kenya.", "qid": 1, "docid": "thvwtf9j", "rank": 47, "score": 0.8485069274902344}, {"content": "Title: COVID\u201019: Herd Immunity and Convalescent Plasma Transfer Therapy Content: Coronavirus disease 2019 (COVID\u201019), caused by Severe Acute Respiratory Syndrome Coronavirus 2 (SARS\u2010CoV\u20102), has spread worldwide triggering a pandemic. Its first case was reported in Wuhan, the capital of China's Hubei province, and since then it has spread across world becoming one of the worst pandemics in the history of mankind(1). Its basic reproductive number (R(0)) has been determined to be 2\u20103(2). This article is protected by copyright. All rights reserved.", "qid": 1, "docid": "z20zha8t", "rank": 48, "score": 0.8481742739677429}, {"content": "Title: Differential diagnosis of illness in patients under investigation for the novel coronavirus (SARS-CoV-2), Italy, February 2020 Content: A novel coronavirus (SARS-CoV-2) has been identified as the causative pathogen of an ongoing outbreak of respiratory disease, now named COVID-19. Most cases and sustained transmission occurred in China, but travel-associated cases have been reported in other countries, including Europe and Italy. Since the symptoms are similar to other respiratory infections, differential diagnosis in travellers arriving from countries with wide-spread COVID-19 must include other more common infections such as influenza and other respiratory tract diseases.", "qid": 1, "docid": "err1npxf", "rank": 49, "score": 0.8480410575866699}, {"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": 1, "docid": "icwvm7jp", "rank": 50, "score": 0.8479554653167725}, {"content": "Title: Point-of-Care RNA-Based Diagnostic Device for COVID-19 Content: At the end of 2019, the novel coronavirus disease (COVID-19), a fast-spreading respiratory disease caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), was reported in Wuhan, China and has now affected over 123 countries globally [...].", "qid": 1, "docid": "k6j7ukmq", "rank": 51, "score": 0.8475807309150696}, {"content": "Title: Risk Factors of Healthcare Workers with Corona Virus Disease 2019: A Retrospective Cohort Study in a Designated Hospital of Wuhan in China Content: Corona Virus Disease 2019 (COVID-19) originated in Wuhan, China has caused many healthcare workers (HCWs) infected. Seventy-two HCWs manifested with acute respiratory illness were retrospectively enrolled to analyze the risk factors. The high-risk department, longer duty hours, and suboptimal hand hygiene after contacting with patients were linked to COVID-19.", "qid": 1, "docid": "ga5vpakb", "rank": 52, "score": 0.8473858833312988}, {"content": "Title: Genotype and phenotype of COVID-19: Their roles in pathogenesis Content: Abstract COVID-19 is a novel coronavirus with an outbreak of unusual viral pneumonia in Wuhan, China, and then pandemic. Based on its phylogenetic relationships and genomic structures the COVID-19 belongs to genera Betacoronavirus. Human Betacoronaviruses (SARS-CoV-2, SARS-CoV, and MERS-CoV) have many similarities, but also have differences in their genomic and phenotypic structure that can influence their pathogenesis. COVID-19 is containing single-stranded (positive-sense) RNA associated with a nucleoprotein within a capsid comprised of matrix protein. A typical CoV contains at least six ORFs in its genome. All the structural and accessory proteins are translated from the sgRNAs of CoVs. Four main structural proteins are encoded by ORFs 10, 11 on the one-third of the genome near the 3\u2032-terminus. The genetic and phenotypic structure of COVID-19 in pathogenesis is important. This article highlights the most important of these features compared to other Betacoronaviruses.", "qid": 1, "docid": "p3gswh23", "rank": 53, "score": 0.847332239151001}, {"content": "Title: Infection risk in a gastroenterological ward during a nosocomial COVID-19 infection event Content: The coronavirus disease (COVID-19) first emerged in Wuhan, China, in December 2019 and rapidly infected a large number of individuals, and disease clusters have spread worldwide. A case of presumably nosocomial COVID-19 was detected in the gastroenterological ward; however, appropriate precautions against contact and droplet prevented a subsequent infection cluster. This article is protected by copyright. All rights reserved.", "qid": 1, "docid": "o6ohwt62", "rank": 54, "score": 0.8472426533699036}, {"content": "Title: Povidone\u2010iodine gargle as a prophylactic intervention to interrupt the transmission of SARS\u2010CoV\u20102 Content: Coronavirus disease 2019 (COVID-19), caused by a novel coronavirus, SARS-COV-2 was declared a Public Health Emergency of International Concern (PHEIC) by the World Health Organization (WHO) in January 2020. Human-to-Human transmission occurs through close contact with an infected person or surfaces that are contaminated with droplets or secretions.", "qid": 1, "docid": "pd78369r", "rank": 55, "score": 0.8469518423080444}, {"content": "Title: Power-law distribution in the number of confirmed COVID-19 cases Content: COVID-19 is an emerging respiratory infectious disease caused by the coronavirus SARS-CoV-2. It was first reported on in early December 2019 in Wuhan, China and within three month spread as a pandemic around the whole globe. Here, we study macro-epidemiological patterns along the time course of the pandemic. We compute the distribution of confirmed COVID-19 cases and deaths for countries worldwide and for counties in the US, and show that both distributions follow a truncated power-law over five orders of magnitude. We are able to explain the origin of this scaling behavior as a dual-scale process: the large-scale spread of the virus between countries and the small-scale accumulation of case numbers within each country. Assuming exponential growth on both scales, the critical exponent of the power-law is determined by the ratio of large-scale to small-scale growth rates. We confirm this theory in numerical simulations in a simple meta-population model, describing the epidemic spread in a network of interconnected countries. Our theory gives a mechanistic explanation why most COVID-19 cases occurred within a few epicenters, at least in the initial phase of the outbreak. Assessing how well a simple dual-scale model predicts the early spread of epidemics, despite the huge contrasts between countries, could help identify critical temporal and spatial scales of response in which to mitigate future epidemic threats.", "qid": 1, "docid": "fs5rx07q", "rank": 56, "score": 0.8466752171516418}, {"content": "Title: Stay Strong: Aboriginal leaders deliver COVID\u201019 health messages Content: COVID-19 caused by Severe Acute Respiratory Syndrome-Coronavirus-2 (SARS-CoV-2) has constituted a pandemic unparalleled in modern history. The spread, case numbers, and socioeconomic consequences have resulted in pandemic control measures attempting to \"flatten the curve\". Australia recorded its first case of COVID-19 on the 25th of January 2020. The federal government responded to the virus spread by escalating human movement controls: during February any person arriving from countries with high rates of infection were expected to quarantine for 14 days in a third country before entering Australia.", "qid": 1, "docid": "0bvdcroc", "rank": 57, "score": 0.8464674949645996}, {"content": "Title: Accelerating drug development through repurposed FDA approved drugs for COVID-19: speed is important, not haste. Content: A life-threatening, emerging respiratory disease called Coronavirus Disease 2019 (COVID-19) 26 originated in the city of Wuhan in China's Hubei province in December, 2019 and has been classified as 27 an international pandemic by the World Health Organization.\u2026.", "qid": 1, "docid": "rjjuda02", "rank": 58, "score": 0.8462401032447815}, {"content": "Title: Transmission and risk factors of OF COVID-19 Content: SARS-CoV-2, the virus that causes COVID-19, is transmitted through respiratory secretions and saliva. The virus can also live for short periods of time (1 to several hours) on fomites such as doorknobs, handrails, and tables. Aerosolization of the virus can occur during procedures including bronchoscopy, endotracheal intubation, and administration of nebulized treatments. Asymptomatic shedding of the virus does occur and may account for up to 60% of cases. Risk factors for a more severe course of COVID-19 include age 65 and older, living in a nursing home or long term care facility, chronic lung disease, and others.", "qid": 1, "docid": "eimqd5b9", "rank": 59, "score": 0.845510721206665}, {"content": "Title: Transmission and risk factors of OF COVID-19. Content: SARS-CoV-2, the virus that causes COVID-19, is transmitted through respiratory secretions and saliva. The virus can also live for short periods of time (1 to several hours) on fomites such as doorknobs, handrails, and tables. Aerosolization of the virus can occur during procedures including bronchoscopy, endotracheal intubation, and administration of nebulized treatments. Asymptomatic shedding of the virus does occur and may account for up to 60% of cases. Risk factors for a more severe course of COVID-19 include age 65 and older, living in a nursing home or long term care facility, chronic lung disease, and others.", "qid": 1, "docid": "l1nvnvkg", "rank": 60, "score": 0.845510721206665}, {"content": "Title: Multi-Center Evaluation of the Cepheid Xpert Xpress SARS-CoV-2 Assay for the Detection of SARS-CoV-2 in Oropharyngeal Swab Specimens. Content: The coronavirus disease 2019 (COVID-19), caused by severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2) is a global health concern that has spread worldwide since December 2019 (1-4).\u2026.", "qid": 1, "docid": "9990qwnn", "rank": 61, "score": 0.8453783392906189}, {"content": "Title: World Health Organization declares global emergency: A review of the 2019 novel coronavirus (COVID-19) Content: Abstract An unprecedented outbreak of pneumonia of unknown aetiology in Wuhan City, Hubei province in China emerged in December 2019. A novel coronavirus was identified as the causative agent and was subsequently termed COVID-19 by the World Health Organization (WHO). Considered a relative of severe acute respiratory syndrome (SARS) and Middle East respiratory syndrome (MERS), COVID-19 is caused by a betacoronavirus named SARS-CoV-2 that affects the lower respiratory tract and manifests as pneumonia in humans. Despite rigorous global containment and quarantine efforts, the incidence of COVID-19 continues to rise, with 90,870 laboratory-confirmed cases and over 3,000 deaths worldwide. In response to this global outbreak, we summarise the current state of knowledge surrounding COVID-19.", "qid": 1, "docid": "iudq5jdu", "rank": 62, "score": 0.8453111052513123}, {"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": 63, "score": 0.8452868461608887}, {"content": "Title: COVID-19: A New Virus as a Potential Rapidly Spreading in the Worldwide Content: Covid-19 is a novel virus with high affinity to spread in the community In December 2019, it was first identified in Wuhan, China The symptoms are non-specific, so fever, cough, dyspnea, are prominent features Respiratory failure and mortality have also been reported The most common lung CT scan findings are bilateral ground glass opacities", "qid": 1, "docid": "0em5sf3g", "rank": 64, "score": 0.8452121615409851}, {"content": "Title: Review on the global epidemiological situation and the efficacy of chloroquine and hydroxychloroquine for the treatment of COVID-19 Content: Covid-19 disease is caused by SARS-CoV-2, a virus belonging to the coronavirus family. Covid-19 is so new that there is currently no specific vaccine or treatment. Clinical trials are currently underway. In vitro tests are also being conducted to assess the efficacy of chloroquine and hydroxychloroquine for the treatment of this epidemic, which is considered a pandemic by the WHO. We note that the content of this review is dated. The information it contains is subject to change and modification as the epidemic progresses.", "qid": 1, "docid": "wbkn7yjh", "rank": 65, "score": 0.8449633121490479}, {"content": "Title: First cases of coronavirus disease 2019 (COVID-19) in the WHO European Region, 24 January to 21 February 2020 Content: A cluster of pneumonia of unknown origin was identified in Wuhan, China, in December 2019 [1] On 12 January 2020, Chinese authorities shared the sequence of a novel coronavirus termed severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) isolated from some clustered cases [2] Since then, the disease caused by SARS-CoV-2 has been named coronavirus disease 2019 (COVID-19) As at 21 February 2020, the virus had spread rapidly mostly within China but also to 28 other countries, including in the World Health Organization (WHO) European Region [3-5] Here we describe the epidemiology of the first cases of COVID-19 in this region, excluding cases reported in the United Kingdom (UK), as at 21 February 2020 The study includes a comparison between cases detected among travellers from China and cases whose infection was acquired due to subsequent local transmission %R doi:https://doi org/10 2807/1560-7917 ES 2020 25 9 2000178", "qid": 1, "docid": "7nla9aji", "rank": 66, "score": 0.8446764945983887}, {"content": "Title: An Introduction to COVID-19 Content: A novel coronavirus (CoV) named \u20182019-nCoV\u2019 or \u20182019 novel coronavirus\u2019 or \u2018COVID-19\u2019 by the World Health Organization (WHO) is in charge of the current outbreak of pneumonia that began at the beginning of December 2019 near in Wuhan City, Hubei Province, China [1\u20134]. COVID-19 is a pathogenic virus. From the phylogenetic analysis carried out with obtainable full genome sequences, bats occur to be the COVID-19 virus reservoir, but the intermediate host(s) has not been detected till now.", "qid": 1, "docid": "8kqhvxlz", "rank": 67, "score": 0.8446397185325623}, {"content": "Title: [Etiology of epidemic outbreaks COVID-19 on Wuhan, Hubei province, Chinese People Republic associated with 2019-nCoV (Nidovirales, Coronaviridae, Coronavirinae, Betacoronavirus, Subgenus Sarbecovirus): lessons of SARS-CoV outbreak.] Content: Results of analysis of phylogenetic, virological, epidemiological, ecological, clinical data of COVID-19 outbreaks in Wuhan, China (PRC) in comparison with SARS-2002 and MERS-2012 outbreaks allow to conclude: - the etiological agent of COVID-19 is coronavirus (2019-CoV), phylogenetically close to the SARS-CoV, isolated from human, and SARS-related viruses isolated from bats (SARS-related bat CoV viruses). These viruses belong to the Sarbecovirus subgenus, Betacoronavirus genus, Orthocoronavirinae subfamily, Coronaviridae family (Cornidovirinea: Nidovirales). COVID-19 is a variant of SARS-2002 and is different from MERS-2012 outbreak, which were caused by coronavirus belonged to the subgenus Merbecovirus of the same genus; - according to the results of phylogenetic analysis of 35 different betacoronaviruses, isolated from human and from wild animals in 2002-2019, the natural source of COVID-19 and SARS-CoV (2002) is bats of Rhinolophus genus (Rhinolophidae) and, probably, some species of other genera. An additional reservoir of the virus could be an intermediate animal species (snakes, civet, hedgehogs, badgers, etc.) that are infected by eating of infected bats. SARS-like coronaviruses circulated in bats in the interepidemic period (2003-2019); - seasonal coronaviruses (subgenus Duvinacovirus, Alphacoronavirus) are currently circulating (November 2019 - January 2020) in the European part of Russia, Urals, Siberia and the Far East of Russia, along with the influenza viruses A(H1N1)pdm09, A(H3N2), and \u00d0\u0092, as well as six other respiratory viruses (HPIV, HAdV, HRSV, HRV, HBoV, and HMPV).", "qid": 1, "docid": "wt9j5mvd", "rank": 68, "score": 0.8444969654083252}, {"content": "Title: [Etiology of epidemic outbreaks COVID-19 on Wuhan, Hubei province, Chinese People Republic associated with 2019-nCoV (Nidovirales, Coronaviridae, Coronavirinae, Betacoronavirus, Subgenus Sarbecovirus): lessons of SARS-CoV outbreak.] Content: Results of analysis of phylogenetic, virological, epidemiological, ecological, clinical data of COVID-19 outbreaks in Wuhan, China (PRC) in comparison with SARS-2002 and MERS-2012 outbreaks allow to conclude: - the etiological agent of COVID-19 is coronavirus (2019-CoV), phylogenetically close to the SARS-CoV, isolated from human, and SARS-related viruses isolated from bats (SARS-related bat CoV viruses). These viruses belong to the Sarbecovirus subgenus, Betacoronavirus genus, Orthocoronavirinae subfamily, Coronaviridae family (Cornidovirinea: Nidovirales). COVID-19 is a variant of SARS-2002 and is different from MERS-2012 outbreak, which were caused by coronavirus belonged to the subgenus Merbecovirus of the same genus; - according to the results of phylogenetic analysis of 35 different betacoronaviruses, isolated from human and from wild animals in 2002-2019, the natural source of COVID-19 and SARS-CoV (2002) is bats of Rhinolophus genus (Rhinolophidae) and, probably, some species of other genera. An additional reservoir of the virus could be an intermediate animal species (snakes, civet, hedgehogs, badgers, etc.) that are infected by eating of infected bats. SARS-like coronaviruses circulated in bats in the interepidemic period (2003-2019); - seasonal coronaviruses (subgenus Duvinacovirus, Alphacoronavirus) are currently circulating (November 2019 - January 2020) in the European part of Russia, Urals, Siberia and the Far East of Russia, along with the influenza viruses A(H1N1)pdm09, A(H3N2), and \u0412, as well as six other respiratory viruses (HPIV, HAdV, HRSV, HRV, HBoV, and HMPV).", "qid": 1, "docid": "vcfljekt", "rank": 69, "score": 0.8444693088531494}, {"content": "Title: Proteome Organization of COVID-19: Illustrating Targets for Vaccine Development Content: 'COVID-19' the recent virulent viral infection had influenced the lives of millions globally leading to both loss of life, economic and financial crisis Coronavirus belongs to family coronaviridae with four genus viz alpha/beta and gamma-coronavirus, infecting both aves and mammals The SARS-Cov-2 emerged in Wuhan, China in Dec, 2019 and since then had spread to 213 countries Its origin is debatable with both natural origin and conspiracy theory providing no conclusive evidences Coronavirus have '+'ive RNA and encodes for 29 proteins, which carries out its life cycle including infection and disease progression The study of its proteome organization could illustrate the proteins which act as the key molecular players in the infection cycle of the virus These proteins can also act as important drug targets in combating COVID-19 infection Majority of the drugs have been formulated in order to act as agonist to spike proteins inhibiting infection by binding to ACE2 receptors Proteome analysis has also revealed the critical mutated proteins that are responsible for COVID-19 pathogenesis and virulence mRNA based vaccines (mRNA-1273, BNT162) also targets these spike proteins Although DNA vaccine has also been attempted using RDT, but the high rate of mutation associated with COVID-19 have made such vaccines ineffective even before use Thus evolutionarily conserved proteins have been the best candidature for vaccine development Similarly phylogenetic analysis of its proteins could help us to understand the evolutionary pattern of COVID-19 It could be used to develop a predictable model for such pathogenic infections, preparing ourselves to take preventive action against its reoccurrence", "qid": 1, "docid": "69ldtdik", "rank": 70, "score": 0.8443556427955627}, {"content": "Title: Dual Challenge of Cancer and COVID-19: Impact on Health Care and Socioeconomic Systems in Asia Pacific Content: Coronavirus or COVID-19 is caused by severe acute respiratory syndrome coronavirus 2. The COVID-19 pandemic has resulted in social and economic disruption throughout the entire world. Each country is being challenged. Although much of the world's focus has been on the rapid spread in Italy, Spain, and the United States, the potential impact on the world's poor, a majority of whom are living in Asia, could be devastating. Asia has the world's most densely populated cities, and its developing countries are facing challenges in their socioeconomic and health care systems. COVID-19 is quickly overwhelming the fragile and overstretched health systems of low- and low- to middle-income countries. With its aging population having chronic diseases and the growing burden of cancer, Asia is facing the dual challenge of controlling the spread of COVID-19 and at the same time providing and maintaining cancer care.", "qid": 1, "docid": "sv700gnq", "rank": 71, "score": 0.8434535264968872}, {"content": "Title: Dual Challenge of Cancer and COVID-19: Impact on Health Care and Socioeconomic Systems in Asia Pacific. Content: Coronavirus or COVID-19 is caused by severe acute respiratory syndrome coronavirus 2. The COVID-19 pandemic has resulted in social and economic disruption throughout the entire world. Each country is being challenged. Although much of the world's focus has been on the rapid spread in Italy, Spain, and the United States, the potential impact on the world's poor, a majority of whom are living in Asia, could be devastating. Asia has the world's most densely populated cities, and its developing countries are facing challenges in their socioeconomic and health care systems. COVID-19 is quickly overwhelming the fragile and overstretched health systems of low- and low- to middle-income countries. With its aging population having chronic diseases and the growing burden of cancer, Asia is facing the dual challenge of controlling the spread of COVID-19 and at the same time providing and maintaining cancer care.", "qid": 1, "docid": "v0g12cne", "rank": 72, "score": 0.8434535264968872}, {"content": "Title: Liver transplantation in an ICU dominated by COVID-19 Content: The Letter from D'Antiga L about concerns of transplanting patients in the context of COVID19 pandemic is very interesting [1]. COVID-19 designates the infection caused by the SARS-Cov2 virus. This illness originated in December, 2019, in Wuhan, China. Since then, it has been identified in more than 150 countries. The first case of COVID-19 in Portugal was notified in March 02, 2020.", "qid": 1, "docid": "8a6flxl6", "rank": 73, "score": 0.8432620763778687}, {"content": "Title: Liver transplantation in an ICU dominated by COVID-19. Content: The Letter from D'Antiga L about concerns of transplanting patients in the context of COVID19 pandemic is very interesting [1]. COVID-19 designates the infection caused by the SARS-Cov2 virus. This illness originated in December, 2019, in Wuhan, China. Since then, it has been identified in more than 150 countries. The first case of COVID-19 in Portugal was notified in March 02, 2020.", "qid": 1, "docid": "6ck2ntid", "rank": 74, "score": 0.8432620763778687}, {"content": "Title: Advice regarding COVID\u201019 and use of immunomodulators, in patients with severe dermatological diseases Content: Coronavirus disease 2019 (COVID-19) is the disease caused by the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), as named by the International Committee on Taxonomy of Viruses (ICTV). There is very limited evidence base to formulate specific advice for dermatology patients on immunomodulators with regards to COVID-19. The following is based on expert opinion, taking into account known risks of influenza (a negative sense single-stranded RNA virus) and other, positive-sense single-stranded, RNA virus infections (such as SARS, MERS, and the common cold). An Australia/New Zealand consensus document is in development.", "qid": 1, "docid": "nfjxp783", "rank": 75, "score": 0.8425729870796204}, {"content": "Title: How did SARS-CoV-19 spread in India from Italy, Iran and China? Genetic surveillance of early cases and virus demography Content: SARS-CoV-19 after emerging from Wuhan, drastically devastated all sectors of human life by crushing down the global economy and increased psychological burden on public, government, and healthcare professionals. We manifested by analyzing 35 early coronavirus cases of India, that virus introduction in India, occurred from Italy, Iran and China and population demography apparently revealed a rapid population expansion after the outbreak with a present steady growth. We depicted nucleotide substitutions in structural genes, drove for the adaptive selection and plead for sequencing more genomes to facilitate identification of new emerged mutants, genetic evolution and disease transmission caused by coronavirus.", "qid": 1, "docid": "royn4uum", "rank": 76, "score": 0.8424575328826904}, {"content": "Title: COVID-19: A Risk Assessment Perspective Content: [Image: see text] COVID-19 is a newly emerging viral respiratory disease first identified in Wuhan, China, in December 2019. The disease is caused by the coronavirus SARS-CoV-2, which is related to the viruses that cause SARS and MERS. While the case fatality ratio for COVID-19 (5%) is far lower than that for SARS (11%) and MERS (34%), COVID-19 is spreading relatively uncontrolled at this time across the globe. In contrast, SARS appears to be contained, and MERS is controlled. This paper will explore why COVID-19 is able to progress to a global pandemic that affects our daily lives to an extent not known in recent history. The COVID-19 outbreak and spread will be examined based on the current literature, using a researcher\u2019s perspective of risk assessment and risk mitigation; this approach will be related to public health.", "qid": 1, "docid": "ip16lh2a", "rank": 77, "score": 0.8423922657966614}, {"content": "Title: The Rheumatologist's Role in Covid-19. Content: The novel coronavirus (SARS-CoV-2) pandemic has spread rapidly throughout the planet. It is believed to have originated in the Wuhan province of China, but this highly contagious respiratory virus has spread to over 140 countries on 6 continents as of mid-March 2020 according to the World Health Organization (WHO). Worldwide, there have been over 164,000 cases identified and over 6,500 deaths attributed to the viral infection. As of March 15, 2020, there are over 3,700 confirmed cases and 68 deaths ascribed to Covid-19 (the disease caused by SARS-CoV-2) in the United States [https://www.livescience.com/coronavirus-updates-unitedstates.html].", "qid": 1, "docid": "8m7l0uid", "rank": 78, "score": 0.8423035144805908}, {"content": "Title: A case series of chest imaging manifestation of COVID-19 Content: Coronavirus disease 2019 (COVID-19) is caused by a infection with severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) [1]. It started in Wuhan, China, in December 2019, after which quickly spread to many other countries around the world. Chest radiography (CXR) and computed tomography (CT) play key roles in managment and diagnosis of COVID-19. In this case series we are presenting three patients with predominant left-sided changes caused by COVID-19 infection.", "qid": 1, "docid": "c2bdmgj7", "rank": 79, "score": 0.8421299457550049}, {"content": "Title: Higher prevalence of asymptomatic or mild COVID\u201019 in children, claims and clues Content: The current pandemic of COVID-19 has generated many challenging questions for the scientific community, ranging from queries about the origin of the virus to its pathogenesis and clinical management. This article is protected by copyright. All rights reserved.", "qid": 1, "docid": "n15i01tn", "rank": 80, "score": 0.8420342803001404}, {"content": "Title: Decoding the evolution and transmissions of the novel pneumonia coronavirus (SARS-CoV-2 / HCoV-19) using whole genomic data Content: The outbreak of COVID-19 started in mid-December 2019 in Wuhan, China. Up to 29 February 2020, SARS-CoV-2 (HCoV-19 / 2019-nCoV) had infected more than 85 000 people in the world. In this study, we used 93 complete genomes of SARS-CoV-2 from the GISAID EpiFlu(TM) database to investigate the evolution and human-to-human transmissions of SARS-CoV-2 in the first two months of the outbreak. We constructed haplotypes of the SARS-CoV-2 genomes, performed phylogenomic analyses and estimated the potential population size changes of the virus. The date of population expansion was calculated based on the expansion parameter tau (\u03c4) using the formula t=\u03c4/2u. A total of 120 substitution sites with 119 codons, including 79 non-synonymous and 40 synonymous substitutions, were found in eight coding-regions in the SARS-CoV-2 genomes. Forty non-synonymous substitutions are potentially associated with virus adaptation. No combinations were detected. The 58 haplotypes (31 found in samples from China and 31 from outside China) were identified in 93 viral genomes under study and could be classified into five groups. By applying the reported bat coronavirus genome (bat-RaTG13-CoV) as the outgroup, we found that haplotypes H13 and H38 might be considered as ancestral haplotypes, and later H1 was derived from the intermediate haplotype H3. The population size of the SARS-CoV-2 was estimated to have undergone a recent expansion on 06 January 2020, and an early expansion on 08 December 2019. Furthermore, phyloepidemiologic approaches have recovered specific directions of human-to-human transmissions and the potential sources for international infected cases.", "qid": 1, "docid": "127c5bve", "rank": 81, "score": 0.8413275480270386}, {"content": "Title: Deaths in healthcare workers due to COVID\u201019: the need for robust data and analysis Content: The novel coronavirus SARS-CoV-2 has rapidly spread across the world from its origin in Wuhan, China in late 2019. The resultant disease (COVID-19) has placed an enormous burden on healthcare systems because of the high transmission rates, prevalence of severe disease and mortality [1]. The risk of viral transmission to healthcare workers has been a concern since the start of the outbreak and the first person to raise concerns about the illness to the international community was Dr Li Wen-Liang, an ophthalmologist in Wuhan who sadly died of the disease that he likely contracted whilst at work [2].", "qid": 1, "docid": "2po918ec", "rank": 82, "score": 0.8411485552787781}, {"content": "Title: Emergence of Institutional Antithrombotic Protocols for Coronavirus 2019 Content: The coronavirus infection (COVID\u201019), first identified in December 2019 in Wuhan, China, is a major public health crisis with new infections increasing exponentially worldwide. COVID\u201019 is an acute infectious disease caused by the severe acute respiratory syndrome coronavirus 2 (SARS\u2010CoV2) and has contributed to significant morbidity and mortality, including the development of coagulopathy. Similar thrombotic and thromboembolic events have occurred during other viral outbreaks, including severe acute respiratory syndrome (SARS), Middle Eastern respiratory syndrome (MERS\u2010CoV), and influenza A H1N1.", "qid": 1, "docid": "rux6rku0", "rank": 83, "score": 0.8409210443496704}, {"content": "Title: COVID-19: A series of important recent clinical and laboratory reports in immunology and pathogenesis of SARS-CoV-2 infection and care of allergy patients Content: The \"coronavirus disease 2019 (COVID-19)\" outbreak was first reported in December 2019 (China). Since then, this disease has rapidly spread across the globe and in March 2020 the World Health Organization (WHO) declared the COVID-19 pandemic.1 Since the outbreak was first announced, our journal has extensively focused on the clinical features, outcomes, diagnosis, immunology, and pathogenesis of COVID-19 and its infectious agent severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2).", "qid": 1, "docid": "svqzqztq", "rank": 84, "score": 0.8407433032989502}, {"content": "Title: SARS-CoV-2 and COVID-19: The most important research questions Content: Coronavirus disease 2019 (COVID-19) caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) is an ongoing global health emergency. Here we highlight nine most important research questions concerning virus transmission, asymptomatic and presymptomatic virus shedding, diagnosis, treatment, vaccine development, origin of virus and viral pathogenesis.", "qid": 1, "docid": "hfkzu18p", "rank": 85, "score": 0.8407068848609924}, {"content": "Title: Olfactory and Gustatory Dysfunction in Coronavirus Disease 19 (COVID-19) Content: Coronavirus-disease-2019 (COVID-19) caused by the severe-acute-respiratory-syndrome-coronavirus-2 (SARS-CoV-2) shows a rapid spread over-the-world. Given scarce resources, non-laboratory diagnostics is crucial. In this cross-sectional study, two-thirds of European patients with polymerase chain reaction confirmed COVID-19 reported olfactory and gustatory dysfunction, indicating the significance of this history in the early diagnostics.", "qid": 1, "docid": "ct67dmgg", "rank": 86, "score": 0.8405206203460693}, {"content": "Title: The newly emerged COVID-19 disease: a systemic review Content: Coronaviruses are large family-RNA viruses that belong to the order Nidovirales, family Coronaviridae, subfamily Coronavirinae. The novel COVID-19 infection, caused by a beta coronavirus called SARS-CoV-2, is a new outbreak that has been emerged in Wuhan, China in December 2019. The most common symptoms of COVID-19 are fever, cough, and dyspnea. As per the March 12, 2020, WHO report, more than 125,048 confirmed COVID-19 cases and over 4613 deaths have been identified in more than 117 countries. It is now regarded as a pandemic that seriously spread and attack the world. The primary means of transmission is person to person through droplets that occurred during coughing or sneezing, through personal contact (shaking hands), or by touching contaminated objects. So far, there is no effective therapy and vaccine available against this novel virus and therefore, only supportive care is used as the mainstay of management of patients with COVID-19. The mortality rate of COVID-19 is considerable. This work aimed to provide insight on the newly emerged COVID-19, in the hope to gain a better understanding on the general overview, epidemiology, transmission, clinical features, diagnosis, treatment, and clinical outcomes as well as the prevention and control of COVID-19.", "qid": 1, "docid": "uboe5ui7", "rank": 87, "score": 0.8405187129974365}, {"content": "Title: Decoding the evolution and transmissions of the novel pneumonia coronavirus (SARS-CoV-2 / HCoV-19) using whole genomic data Content: The outbreak of COVID-19 started in mid-December 2019 in Wuhan, China. Up to 29 February 2020, SARS-CoV-2 (HCoV-19 / 2019-nCoV) had infected more than 85 000 people in the world. In this study, we used 93 complete genomes of SARS-CoV-2 from the GISAID EpiFlu TM database to investigate the evolution and human-to-human transmissions of SARS-CoV-2 in the first two months of the outbreak. We constructed haplotypes of the SARS-CoV-2 genomes, performed phylogenomic analyses and estimated the potential population size changes of the virus. The date of population expansion was calculated based on the expansion parameter tau ( &#964;) using the formula t= &#964;/2 u. A total of 120 substitution sites with 119 codons, including 79 non-synonymous and 40 synonymous substitutions, were found in eight coding-regions in the SARS-CoV-2 genomes. Forty non-synonymous substitutions are potentially associated with virus adaptation. No combinations were detected. The 58 haplotypes (31 found in samples from China and 31 from outside China) were identified in 93 viral genomes under study and could be classified into five groups. By applying the reported bat coronavirus genome (bat-RaTG13-CoV) as the outgroup, we found that haplotypes H13 and H38 might be considered as ancestral haplotypes, and later H1 was derived from the intermediate haplotype H3. The population size of the SARS-CoV-2 was estimated to have undergone a recent expansion on 06 January 2020, and an early expansion on 08 December 2019. Furthermore, phyloepidemiologic approaches have recovered specific directions of human-to-human transmissions and the potential sources for international infected cases.", "qid": 1, "docid": "gy78e87y", "rank": 88, "score": 0.8403645753860474}, {"content": "Title: SARS-CoV-2 detection in patients with influenza-like illness Content: Coronavirus disease 2019 (COVID-19), caused by the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), was first reported in Wuhan, Hubei Province, China in late December 2019. We re-analysed 640 throat swabs collected from patients in Wuhan with influenza-like-illness from 6 October 2019 to 21 January 2020 and found that 9 of the 640 throat swabs were positive for SARS-CoV-2 RNA by quantitative PCR, suggesting community transmission of SARS-CoV2 in Wuhan in early January 2020.", "qid": 1, "docid": "m2vfn83n", "rank": 89, "score": 0.8403370380401611}, {"content": "Title: SARS-CoV-2 detection in patients with influenza-like illness. Content: Coronavirus disease 2019 (COVID-19), caused by the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), was first reported in Wuhan, Hubei Province, China in late December 2019. We re-analysed 640 throat swabs collected from patients in Wuhan with influenza-like-illness from 6 October 2019 to 21 January 2020 and found that 9 of the 640 throat swabs were positive for SARS-CoV-2 RNA by quantitative PCR, suggesting community transmission of SARS-CoV2 in Wuhan in early January 2020.", "qid": 1, "docid": "ctddjm8r", "rank": 90, "score": 0.8403370380401611}, {"content": "Title: Genomic Epidemiology of SARS-CoV-2 in Guangdong Province, China Content: Coronavirus disease 2019 (COVID-19) is caused by SARS-CoV-2 infection 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 because of 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, because the number of cases imported from other countries has increased.", "qid": 1, "docid": "zfj3tglm", "rank": 91, "score": 0.8399481773376465}, {"content": "Title: The Indian perspective of COVID-19 outbreak Content: The emerging infection of COVID-19 was initiated from Wuhan, China, have been spread to more than 210 countries around the globe including India. The clinical symptoms of COVID-19 are very similar to other respiratory viruses. The number of laboratory-confirmed cases and associated deaths are increasing regularly in various parts of the World. Seven coronaviruses (229E, NL63, OC43, HKU1, SARS, MERS and, COVID-19) can naturally infect human beings. Out of these four (229E-CoV, NL63-CoV, OC43-CoV, HKU1-CoV) are responsible for mild upper respiratory infections, while SARS-CoV, MERS-CoV, and COVID-19 are well known for their high mortality. Few mild strains of coronaviruses are circulating in India but there is no evidence of SARS and MERS outbreaks. The COVID-19 is an emerging viral infection responsible for pandemics. Fortunately, the mortality of COVID-19 is low as compared with SARS and MERS, the majority of its cases are recovered. The death toll of COVID-19 is high even after its low mortality because COVID-19 causes a pandemic while SARS-CoV and MERS-CoV cause epidemics only. COVID-19 influenced the large segments of the world population, which led to a public health emergency of international concern, putting all health organizations on high alert. COVID-19 is the first coronavirus after Spanish Flu 1918\u20131919, who has extremely influenced the health system, economy, and psychology of India. The present study review is on the general continent, virology, pathogenesis, global epidemiology, clinical presentation, diagnosis, treatment and control of COVID-19 with the reference to India.", "qid": 1, "docid": "bzvdkxu9", "rank": 92, "score": 0.8399126529693604}, {"content": "Title: Innate Immune Signaling and Proteolytic Pathways in the Resolution or Exacerbation of SARS-CoV-2 in Covid-19: Key Therapeutic Targets? Content: COVID-19 is caused by the Severe Acute Respiratory Syndrome (SARS) coronavirus (Cov)-2, an enveloped virus with a positive-polarity, single-stranded RNA genome. The initial outbreak of the pandemic began in December 2019, and it is affecting the human health of the global community. In common with previous pandemics (Influenza H1N1 and SARS-CoV) and the epidemics of Middle east respiratory syndrome (MERS)-CoV, CoVs target bronchial and alveolar epithelial cells. Virus protein ligands (e.g., haemagglutinin or trimeric spike glycoprotein for Influenza and CoV, respectively) interact with cellular receptors, such as (depending on the virus) either sialic acids, Dipeptidyl peptidase 4 (DPP4), or angiotensin-converting enzyme 2 (ACE2). Host proteases, e.g., cathepsins, furin, or members of the type II transmembrane serine proteases (TTSP) family, such as Transmembrane protease serine 2 (TMPRSS2), are involved in virus entry by proteolytically activating virus ligands. Also involved are Toll Like Receptor (TLR) family members, which upregulate anti-viral and pro-inflammatory mediators [interleukin (IL)-6 and IL-8 and type I and type III Interferons among others], through the activation of Nuclear Factor (NF)-kB. When these events (virus cellular entry and innate immune responses) are uncontrolled, a deleterious systemic response is sometimes encountered in infected patients, leading to the well-described \"cytokine storm\" and an ensuing multiple organ failure promoted by a downregulation of dendritic cell, macrophage, and T-cell function. We aim to describe how the lung and systemic host innate immune responses affect survival either positively, through downregulating initial viral load, or negatively, by triggering uncontrolled inflammation. An emphasis will be put on host cellular signaling pathways and proteases involved with a view on tackling these therapeutically.", "qid": 1, "docid": "ls88uo78", "rank": 93, "score": 0.8397681713104248}, {"content": "Title: COVID-19: The first documented coronavirus pandemic in history Content: The novel human coronavirus disease COVID-19 has become the fifth documented pandemic since the 1918 flu pandemic. COVID-19 was first reported in Wuhan, China, and subsequently spread worldwide. The coronavirus was officially named severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) by the International Committee on Taxonomy of Viruses based on phylogenetic analysis. SARS-CoV-2 is believed to be a spillover of an animal coronavirus and later adapted the ability of human-to-human transmission. Because the virus is highly contagious, it rapidly spreads and continuously evolves in the human population. In this review article, we discuss the basic properties, potential origin, and evolution of the novel human coronavirus. These factors may be critical for studies of pathogenicity, antiviral designs, and vaccine development against the virus.", "qid": 1, "docid": "3fiz0tqy", "rank": 94, "score": 0.8395903706550598}, {"content": "Title: Pandemia COVID-19, la nueva emergencia sanitaria de preocupaci\u00f3n internacional: una revisi\u00f3n./ [Pandemic COVID-19, the new health emergency of international concern: a review] Content: In late December 2019, some cases of atypical pneumonia, at that time of unknown origin, were reported in Wuhan, China. Days later, the etiologic agent was identified as a new coronavirus. This new coronavirus was called SARS-CoV-2 and the disease it produces was named COVID-19. The origin of this new virus is presumed zoonotic, with bats being its probable vector. Due to the rapid number of infections and deaths that occurred first in China and later around the world, the infection of this virus quickly went from being an isolated outbreak in a Chinese region to becoming a health emergency of international concern and later, a pandemic. The purpose of this review is to study the most relevant and current information on the pathogen, as well as epidemiology, pathology, clinical features, transmission, prevention, and treatment of the disease.", "qid": 1, "docid": "x3sb1o4u", "rank": 95, "score": 0.8395804762840271}, {"content": "Title: The Indian perspective of COVID-19 outbreak Content: The emerging infection of COVID-19 was initiated from Wuhan, China, have been spread to more than 210 countries around the globe including India. The clinical symptoms of COVID-19 are very similar to other respiratory viruses. The number of laboratory-confirmed cases and associated deaths are increasing regularly in various parts of the World. Seven coronaviruses (229E, NL63, OC43, HKU1, SARS, MERS and, COVID-19) can naturally infect human beings. Out of these four (229E-CoV, NL63-CoV, OC43-CoV, HKU1-CoV) are responsible for mild upper respiratory infections, while SARS-CoV, MERS-CoV, and COVID-19 are well known for their high mortality. Few mild strains of coronaviruses are circulating in India but there is no evidence of SARS and MERS outbreaks. The COVID-19 is an emerging viral infection responsible for pandemics. Fortunately, the mortality of COVID-19 is low as compared with SARS and MERS, the majority of its cases are recovered. The death toll of COVID-19 is high even after its low mortality because COVID-19 causes a pandemic while SARS-CoV and MERS-CoV cause epidemics only. COVID-19 influenced the large segments of the world population, which led to a public health emergency of international concern, putting all health organizations on high alert. COVID-19 is the first coronavirus after Spanish Flu 1918-1919, who has extremely influenced the health system, economy, and psychology of India. The present study review is on the general continent, virology, pathogenesis, global epidemiology, clinical presentation, diagnosis, treatment and control of COVID-19 with the reference to India.", "qid": 1, "docid": "i3xfyapo", "rank": 96, "score": 0.8395563364028931}, {"content": "Title: Characterizing the transmission and identifying the control strategy for COVID-19 through epidemiological modeling Content: The outbreak of the novel coronavirus disease, COVID-19, originating from Wuhan, China in early December, has infected more than 70,000 people in China and other countries and has caused more than 2,000 deaths. As the disease continues to spread, the biomedical society urgently began identifying effective approaches to prevent further outbreaks. Through rigorous epidemiological analysis, we characterized the fast transmission of COVID-19 with a basic reproductive number 5.6 and proved a sole zoonotic source to originate in Wuhan. No changes in transmission have been noted across generations. By evaluating different control strategies through predictive modeling and Monte carlo simulations, a comprehensive quarantine in hospitals and quarantine stations has been found to be the most effective approach. Government action to immediately enforce this quarantine is highly recommended.", "qid": 1, "docid": "rr7r7ef0", "rank": 97, "score": 0.8394874334335327}, {"content": "Title: Active Monitoring of Persons Exposed to Patients with Confirmed COVID-19 - United States, January-February 2020. Content: In December 2019, an outbreak of coronavirus disease 2019 (COVID-19), caused by the virus SARS-CoV-2, began in Wuhan, China (1). The disease spread widely in China, and, as of February 26, 2020, COVID-19 cases had been identified in 36 other countries and territories, including the United States. Person-to-person transmission has been widely documented, and a limited number of countries have reported sustained person-to-person spread.* On January 20, state and local health departments in the United States, in collaboration with teams deployed from CDC, began identifying and monitoring all persons considered to have had close contact\u2020 with patients with confirmed COVID-19 (2). The aims of these efforts were to ensure rapid evaluation and care of patients, limit further transmission, and better understand risk factors for transmission.", "qid": 1, "docid": "mvm1t0y7", "rank": 98, "score": 0.8392691612243652}, {"content": "Title: HRS/EHRA/APHRS/LAHRS/ACC/AHA worldwide practice update for telehealth and arrhythmia monitoring during and after a pandemic Content: Coronavirus disease 2019 (COVID\u201019), caused by the severe acute respiratory syndrome coronavirus 2 (SARS\u2010CoV\u20102), started in the city of Wuhan late in 2019. Within a few months, the disease spread toward all parts of the world and was declared a pandemic on March 11, 2020. The current health care dilemma worldwide is how to sustain the capacity for quality services not only for those suffering from COVID\u201019 but also for non\u2010COVID\u201019 patients, all while protecting physicians, nurses, and other allied health care workers.", "qid": 1, "docid": "5fif117n", "rank": 99, "score": 0.8388413190841675}, {"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": 100, "score": 0.8385347723960876}]}
{"query": "how does the coronavirus respond to changes in the weather", "hits": [{"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": 1, "score": 0.8361380100250244}, {"content": "Title: Rhinoviruses and coronaviruses - virological aspects of their role in causing colds in man. Content: Rhinoviruses are picornaviruses that cause colds. They are naturally temperature sensitive and highly adapted to grow in respiratory epithelium. Coronaviruses are structurally quite different, being enveloped viruses but are also adapted to grow in respiratory epithelium and also cause colds.", "qid": 2, "docid": "8hau76g7", "rank": 2, "score": 0.8319908380508423}, {"content": "Title: Susceptible supply limits the role of climate in the COVID-19 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 of climate-dependence based on known coronavirus biology. We find that while variations in humidity may be important for endemic infections, during the pandemic stage of an emerging pathogen such as SARS-CoV-2 climate may drive only modest changes to pandemic size and duration. Our results suggest that, in the absence of effective control measures, significant cases in the coming months are likely to occur in more humid (warmer) climates, irrespective of the climate-dependence of transmission and that summer temperatures will not substantially limit pandemic growth.", "qid": 2, "docid": "zxx7tikz", "rank": 3, "score": 0.8301243782043457}, {"content": "Title: Mechanisms of severe acute respiratory syndrome pathogenesis and innate immunomodulation. Content: The modulation of the immune response is a common practice of many highly pathogenic viruses. The emergence of the highly pathogenic coronavirus severe acute respiratory virus (SARS-CoV) serves as a robust model system to elucidate the virus-host interactions that mediate severe end-stage lung disease in humans and animals. Coronaviruses encode the largest positive-sense RNA genome of approximately 30 kb, encode a variety of replicase and accessory open reading frames that are structurally unique, and encode novel enzymatic functions among RNA viruses. These viruses have broad or specific host ranges, suggesting the possibility of novel strategies for targeting and regulating host innate immune responses following virus infection. Using SARS-CoV as a model, we review the current literature on the ability of coronaviruses to interact with and modify the host intracellular environment during infection. These studies are revealing a rich set of novel viral proteins that engage, modify, and/or disrupt host cell signaling and nuclear import machinery for the benefit of virus replication.", "qid": 2, "docid": "ildyxrce", "rank": 4, "score": 0.8278341293334961}, {"content": "Title: The most eagerly awaited summer of the Anthropocene: A perspective of SARS-CoV-2 decay and seasonal change Content: To date, the world perhaps has never waited for the summer so impatiently in the entire Anthropocene, owing to the debate whether increasing temperature and humidity will decrease the environmental endurance of SARS-CoV-2. We present the perspective on the seasonal change on SARS-CoV-2 decay and COVID-19 spread. Our arguments are based on: i) structural similarity of coronavirus with several enteric viruses, and its vulnerability; ii) reports related to decay of those similar transmissible gastroenteritis viruses (TGEV) like norovirus and iii) improvement in the human immunity during summer with respect to winter. We present reasons why we can be optimistic about the slowdown of corona in the upcoming summer.", "qid": 2, "docid": "9v83g7dj", "rank": 5, "score": 0.8265992999076843}, {"content": "Title: Murine encephalitis caused by HCoV-OC43, a human coronavirus with broad species specificity, is partly immune-mediated Content: Abstract The human coronavirus HCoV-OC43 causes a significant fraction of upper respiratory tract infections. Most coronaviruses show a strong species specificity, although the SARS-Coronavirus crossed species from palm civet cats to infect humans. Similarly, HCoV-OC43, likely a member of the same coronavirus group as SARS-CoV, readily crossed the species barrier as evidenced by its rapid adaptation to the murine brain [McIntosh, K., Becker, W.B., Chanock, R.M., 1967. Growth in suckling-mouse brain of \u201cIBV-like\u201d viruses from patients with upper respiratory tract disease. Proc Natl Acad Sci U.S.A. 58, 2268\u201373]. Herein, we investigated two consequences of this plasticity in species tropism. First, we showed that HCoV-OC43 was able to infect cells from a large number of mammalian species. Second, we showed that virus that was passed exclusively in suckling mouse brains was highly virulent and caused a uniformly fatal encephalitis in adult mice. The surface glycoprotein is a major virulence factor in most coronavirus infections. We identified three changes in the HCoV-OC43 surface glycoprotein that correlated with enhanced neurovirulence in mice; these were located in the domain of the protein responsible for binding to host cells. These data suggest that some coronaviruses, including HCoV-OC43 and SARS-CoV, readily adapt to growth in cells from heterologous species. This adaptability has facilitated the isolation of HCoV-OC43 viral variants with markedly differing abilities to infect animals and tissue culture cells.", "qid": 2, "docid": "vuvgi8xx", "rank": 6, "score": 0.8248934745788574}, {"content": "Title: The most eagerly awaited summer of the Anthropocene: A perspective of SARS-CoV-2 decay and seasonal change Content: Abstract To date, the world perhaps has never waited for the summer so impatiently in the entire Anthropocene, owing to the debate whether increasing temperature and humidity will decrease the environmental endurance of SARS-CoV-2. We present the perspective on the seasonal change on SARS-CoV-2 decay and COVID-19 spread. Our arguments are based on: i) structural similarity of coronavirus with several enteric viruses, and its vulnerability; ii) reports related to decay of those similar transmissible gastroenteritis viruses (TGEV) like norovirus and iii) improvement in the human immunity during summer with respect to winter. We present reasons why we can be optimistic about the slowdown of corona in the upcoming summer.", "qid": 2, "docid": "6exmxw6r", "rank": 7, "score": 0.8243225812911987}, {"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": 2, "docid": "ig0rnbqb", "rank": 8, "score": 0.8226049542427063}, {"content": "Title: Environmental concern regarding the effect of humidity and temperature on 2019-nCoV survival: fact or fiction Content: The new coronavirus, called 2019-nCoV, is a new type of virus that was first identified in Wuhan, China, in December 2019. Environmental conditions necessary for survival and spread of 2019-nCoV are somewhat transparent but unlike animal coronaviruses. We are poorly aware of their survival in environment and precise factors of their transmission. Countries located in east and west of globe did not have a significant impact on prevalence of disease among communities, and on the other hand, north and south have provided a model for relative prediction of disease outbreaks. The 2019-nCoV can survive for up to 9 days at 25 \u00b0C, and if this temperature rises to 30 \u00b0C, its lifespan will be shorter. The 2019-nCoV is sensitive to humidity, and lifespan of viruses in 50% humidity is longer than that of 30%. Also, temperature and humidity are important factors influencing the COVID-19 mortality rate and may facilitate 2019-nCoV transmission. Thus, considering the available and recent evidence, it seems that low temperatures, as well as dry and unventilated air, may affect stability and transmissibility of 2019-nCoV.", "qid": 2, "docid": "zqsfw75p", "rank": 9, "score": 0.8192165493965149}, {"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": 10, "score": 0.818303108215332}, {"content": "Title: Roles of meteorological conditions in COVID-19 transmission on a worldwide scale Content: The novel coronavirus (SARS-CoV-2/ 2019-nCoV) identified in Wuhan, China, in December 2019 has caused great damage to public health and economy worldwide with over 140,000 infected cases up to date. Previous research has suggested an involvement of meteorological conditions in the spread of droplet-mediated viral diseases, such as influenza. However, as for the recent novel coronavirus, few studies have discussed systematically about the role of daily weather in the epidemic transmission of the virus. Here, we examine the relationships of meteorological variables with the severity of the outbreak on a worldwide scale. The confirmed case counts, which indicates the severity of COVID-19 spread, and four meteorological variables, i.e., air temperature, relative humidity, wind speed, and visibility, were collected daily between January 20 and March 11 (52 days) for 430 cities and districts all over China, 21 cities/ provinces in Italy, 21 cities/ provinces in Japan, and 51 other countries around the world. Four different time delays of weather (on the day, 3 days ago, 7 days ago, and 14 days ago) as to the epidemic situation were taken for modeling and we finally chose the weather two weeks ago to model against the daily epidemic situation as its correlated with the outbreak best. Taken Chinese cities as a discovery dataset, it was suggested that temperature, wind speed, and relative humidity combined together could best predict the epidemic situation. The meteorological model could well predict the outbreak around the world with a high correlation (r2>0.6) with the real data. Using this model, we further predicted the possible epidemic situation in the future 12 days in several high-latitude cities with potential outbreak. This model could provide more information for government's future decisions on COVID-19 outbreak control.", "qid": 2, "docid": "3svnvozz", "rank": 11, "score": 0.8181617259979248}, {"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": 12, "score": 0.8173902630805969}, {"content": "Title: Regulation of Stress Responses and Translational Control by Coronavirus Content: Similar to other viruses, coronavirus infection triggers cellular stress responses in infected host cells. The close association of coronavirus replication with the endoplasmic reticulum (ER) results in the ER stress responses, which impose a challenge to the viruses. Viruses, in turn, have come up with various mechanisms to block or subvert these responses. One of the ER stress responses is inhibition of the global protein synthesis to reduce the amount of unfolded proteins inside the ER lumen. Viruses have evolved the capacity to overcome the protein translation shutoff to ensure viral protein production. Here, we review the strategies exploited by coronavirus to modulate cellular stress response pathways. The involvement of coronavirus-induced stress responses and translational control in viral pathogenesis will also be briefly discussed.", "qid": 2, "docid": "vj3wk150", "rank": 13, "score": 0.8173344135284424}, {"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": 14, "score": 0.8167304992675781}, {"content": "Title: Grundlagen der Replikation und der Immunologie von SARS-CoV-2 Content: Coronaviruses are a genetically highly variable family of viruses that infect vertebrates and have succeeded in infecting humans many times by overcoming the species barrier. The severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), which initially appeared in China at the end of 2019, exhibits a high infectivity and pathogenicity compared to other coronaviruses. As the viral coat and other viral components are recognized as being foreign by the immune system, this can lead to initial symptoms, which are induced by the very efficiently working immune defense system via the respiratory epithelium. During severe courses a systemically expressed proinflammatory cytokine storm and subsequent changes in the coagulation and complement systems can occur. Virus-specific antibodies, the long-term expression of which is ensured by the formation of B memory cell clones, generate a specific immune response that is also detectable in blood (seroconversion). Specifically effective cytotoxic CD8+ T\u2011cell populations are also formed, which recognize viral epitopes as pathogen-specific patterns in combination with MHC presentation on the cell surface of virus-infected cells and destroy these cells. At the current point in time it is unclear how regular, robust and durable this immune status is constructed. Experiences with other coronavirus infections (SARS and Middle East respiratory syndrome, MERS) indicate that the immunity could persist for several years. Based on animal experiments, already acquired data on other coronavirus types and plausibility assumptions, it can be assumed that seroconverted patients have an immunity of limited duration and only a very low risk of reinfection. Knowledge of the molecular mechanisms of viral cycles and immunity is an important prerequisite for the development of vaccination strategies and development of effective drugs.", "qid": 2, "docid": "neq2vqym", "rank": 15, "score": 0.8164240121841431}, {"content": "Title: Human Coronaviruses: Insights into Environmental Resistance and Its Influence on the Development of New Antiseptic Strategies Content: The Coronaviridae family, an enveloped RNA virus family, and, more particularly, human coronaviruses (HCoV), were historically known to be responsible for a large portion of common colds and other upper respiratory tract infections. HCoV are now known to be involved in more serious respiratory diseases, i.e. bronchitis, bronchiolitis or pneumonia, especially in young children and neonates, elderly people and immunosuppressed patients. They have also been involved in nosocomial viral infections. In 2002\u20132003, the outbreak of severe acute respiratory syndrome (SARS), due to a newly discovered coronavirus, the SARS-associated coronavirus (SARS-CoV); led to a new awareness of the medical importance of the Coronaviridae family. This pathogen, responsible for an emerging disease in humans, with high risk of fatal outcome; underline the pressing need for new approaches to the management of the infection, and primarily to its prevention. Another interesting feature of coronaviruses is their potential environmental resistance, despite the accepted fragility of enveloped viruses. Indeed, several studies have described the ability of HCoVs (i.e. HCoV 229E, HCoV OC43 (also known as betacoronavirus 1), NL63, HKU1 or SARS-CoV) to survive in different environmental conditions (e.g. temperature and humidity), on different supports found in hospital settings such as aluminum, sterile sponges or latex surgical gloves or in biological fluids. Finally, taking into account the persisting lack of specific antiviral treatments (there is, in fact, no specific treatment available to fight coronaviruses infections), the Coronaviridae specificities (i.e. pathogenicity, potential environmental resistance) make them a challenging model for the development of efficient means of prevention, as an adapted antisepsis-disinfection, to prevent the environmental spread of such infective agents. This review will summarize current knowledge on the capacity of human coronaviruses to survive in the environment and the efficacy of well-known antiseptic-disinfectants against them, with particular focus on the development of new methodologies to evaluate the activity of new antiseptic-disinfectants on viruses.", "qid": 2, "docid": "bp6st31f", "rank": 16, "score": 0.8159891366958618}, {"content": "Title: Chapter Two Coronavirus Spike Protein and Tropism Changes Content: Abstract Coronaviruses (CoVs) have a remarkable potential to change tropism. This is particularly illustrated over the last 15 years by the emergence of two zoonotic CoVs, the severe acute respiratory syndrome (SARS)- and Middle East respiratory syndrome (MERS)-CoV. Due to their inherent genetic variability, it is inevitable that new cross-species transmission events of these enveloped, positive-stranded RNA viruses will occur. Research into these medical and veterinary important pathogens\u2014sparked by the SARS and MERS outbreaks\u2014revealed important principles of inter- and intraspecies tropism changes. The primary determinant of CoV tropism is the viral spike (S) entry protein. Trimers of the S glycoproteins on the virion surface accommodate binding to a cell surface receptor and fusion of the viral and cellular membrane. Recently, high-resolution structures of two CoV S proteins have been elucidated by single-particle cryo-electron microscopy. Using this new structural insight, we review the changes in the S protein that relate to changes in virus tropism. Different concepts underlie these tropism changes at the cellular, tissue, and host species level, including the promiscuity or adaptability of S proteins to orthologous receptors, alterations in the proteolytic cleavage activation as well as changes in the S protein metastability. A thorough understanding of the key role of the S protein in CoV entry is critical to further our understanding of virus cross-species transmission and pathogenesis and for development of intervention strategies.", "qid": 2, "docid": "yd77xfg2", "rank": 17, "score": 0.8157960176467896}, {"content": "Title: Innate Immunity in Coronavirus Infection ;\u0432\u0440\u043e\u0436\u0434\u0435\u043d\u043d\u044b\u0439 \u0418\u043c\u043c\u0443\u043d\u0438\u0442\u0435\u0442 \u041f\u0440\u0438 \u041a\u043e\u0440\u043e\u043d\u0430\u0432\u0438\u0440\u0443\u0441\u043d\u043e\u0439 \u0418\u043d\u0444\u0435\u043a\u0446\u0438\u0438 Content: Coronaviruses (CoVs) comprise a polymorphic group of respiratory viruses causing acute inflammatory diseases in domestic and agricultural animals (chicken, pig, buffalo, cat, dog) Until recently, this infection in humans was mainly observed during the autumn-winter period and characterized by a mild, often asymptomatic, course The situation changed dramatically in 2003, when SARS outbreak caused by pathogenic CoV (SARS-CoV) was recorded in China A decade later, a new CoV outbreak occurred in the form of the Middle East respiratory syndrome (MERS-CoV), whereas in December 2019, SARS-CoV-2 (COVID-19) cases were recorded, which transformed within the first months of 2020 into the pandemic In all three cases, CoV disease led to severe bronchopulmonary lesions, varying from dry, debilitating cough to acute respiratory distress syndrome (ARDS) At the same time, multiple changes in innate immunity were noted most often manifested as a pronounced inflammatory reaction in the lower respiratory tract, featured by damaged type II pneumocytes, apoptosis, hyalinization of alveolar membranes, focal or generalized pulmonary edema Destructive processes in the respiratory tract were accompanied by migration of monocytes/macrophages and granulocyte neutrophils to the inflammatory focus Such events were accompanied by production of pro-inflammatory cytokines, which magnitude could ascend up to a cytokine storm SARS-CoV is characterized by symptoms of secondary immunosuppression, manifested by the late onset of interferon production and activation of NLRP3 inflammasomes \u00e2\u20ac\u201c the key inflammatory factor The reason for such reaction may be accounted for by CoV arsenal containing extensive set of structural and inflammatory proteins exerting pro-inflammatory and immunosuppressive properties Delayed IFN production allowed CoV to replicate actively and freely, and when type I IFN synthesis was eventually triggered, its activity was detrimental and accompanied by an aggravated infection course Thus, SARS can surely be referred to immune-dependent infections with a marked immunopathological component The purpose of this review was to describe some mechanisms underlying formation of innate immune response to infection caused by pathogenic coronaviruses SARS-CoV, MERS-CoV and SARS-CoV-2 (COVID-19) 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\u00d0\u00bf\u00d0\u00be\u00d0\u00bb\u00d0\u00bd\u00d1\u2039\u00d0\u00bc \u00d0\u00be\u00d1\u0081\u00d0\u00bd\u00d0\u00be\u00d0\u00b2\u00d0\u00b0\u00d0\u00bd\u00d0\u00b8\u00d0\u00b5\u00d0\u00bc \u00d0\u00be\u00d1\u201a\u00d0\u00bd\u00d0\u00b5\u00d1\u0081\u00d1\u201a\u00d0\u00b8\u00d0\u00ba \u00d1\u2021\u00d0\u00b8\u00d1\u0081\u00d0\u00bb\u00d1\u0192 \u00d0\u00b8\u00d0\u00bc\u00d0\u00bc\u00d1\u0192\u00d0\u00bd\u00d0\u00be-\u00d0\u00b7\u00d0\u00b0\u00d0\u00b2\u00d0\u00b8\u00d1\u0081\u00d0\u00b8\u00d0\u00bc\u00d1\u2039\u00d1\u2026 \u00d0\u00b8\u00d0\u00bd\u00d1\u201e\u00d0\u00b5\u00d0\u00ba\u00d1\u2020\u00d0\u00b8\u00d0\u00b9 \u00d1\u0081 \u00d0\u00b2\u00d1\u2039\u00d1\u20ac\u00d0\u00b0\u00d0\u00b6\u00d0\u00b5\u00d0\u00bd\u00d0\u00bd\u00d1\u2039\u00d0\u00bc \u00d0\u00b8\u00d0\u00bc\u00d0\u00bc\u00d1\u0192\u00d0\u00bd\u00d0\u00be\u00d0\u00bf\u00d0\u00b0\u00d1\u201a\u00d0\u00be\u00d0\u00bb\u00d0\u00be\u00d0\u00b3\u00d0\u00b8\u00d1\u2021\u00d0\u00b5\u00d1\u0081\u00d0\u00ba\u00d0\u00b8\u00d0\u00bc \u00d0\u00ba\u00d0\u00be\u00d0\u00bc\u00d0\u00bf\u00d0\u00be\u00d0\u00bd\u00d0\u00b5\u00d0\u00bd\u00d1\u201a\u00d0\u00be\u00d0\u00bc \u00d0\u00a6\u00d0\u00b5\u00d0\u00bb\u00d1\u0152 \u00d1\u008d\u00d1\u201a\u00d0\u00be\u00d0\u00b3\u00d0\u00be \u00d0\u00be\u00d0\u00b1\u00d0\u00b7\u00d0\u00be\u00d1\u20ac\u00d0\u00b0 \u00d0\u00be\u00d0\u00bf\u00d0\u00b8\u00d1\u0081\u00d0\u00b0\u00d1\u201a\u00d1\u0152 \u00d0\u00bd\u00d0\u00b5\u00d0\u00ba\u00d0\u00be\u00d1\u201a\u00d0\u00be\u00d1\u20ac\u00d1\u2039\u00d0\u00b5 \u00d0\u00bc\u00d0\u00b5\u00d1\u2026\u00d0\u00b0\u00d0\u00bd\u00d0\u00b8\u00d0\u00b7\u00d0\u00bc\u00d1\u2039 \u00d1\u201e\u00d0\u00be\u00d1\u20ac\u00d0\u00bc\u00d0\u00b8\u00d1\u20ac\u00d0\u00be\u00d0\u00b2\u00d0\u00b0\u00d0\u00bd\u00d0\u00b8\u00d1\u008f \u00d0\u00b2\u00d1\u20ac\u00d0\u00be\u00d0\u00b6\u00d0\u00b4\u00d0\u00b5\u00d0\u00bd\u00d0\u00bd\u00d0\u00be\u00d0\u00b3\u00d0\u00be \u00d0\u00b8\u00d0\u00bc\u00d0\u00bc\u00d1\u0192\u00d0\u00bd\u00d0\u00bd\u00d0\u00be\u00d0\u00b3\u00d0\u00be \u00d0\u00be\u00d1\u201a\u00d0\u00b2\u00d0\u00b5\u00d1\u201a\u00d0\u00b0 \u00d0\u00bd\u00d0\u00b0 \u00d0\u00b8\u00d0\u00bd\u00d1\u201e\u00d0\u00b8\u00d1\u2020\u00d0\u00b8\u00d1\u20ac\u00d0\u00be\u00d0\u00b2\u00d0\u00b0\u00d0\u00bd\u00d0\u00b8\u00d0\u00b5 \u00d0\u00bf\u00d0\u00b0\u00d1\u201a\u00d0\u00be\u00d0\u00b3\u00d0\u00b5\u00d0\u00bd\u00d0\u00bd\u00d1\u2039\u00d0\u00bc\u00d0\u00b8 \u00d0\u00ba\u00d0\u00be\u00d1\u20ac\u00d0\u00be\u00d0\u00bd\u00d0\u00b0\u00d0\u00b2\u00d0\u00b8\u00d1\u20ac\u00d1\u0192\u00d1\u0081\u00d0\u00b0\u00d0\u00bc\u00d0\u00b8: SARS-CoV, MERS-CoV \u00d0\u00b8 CoV-2 (COVID-19)", "qid": 2, "docid": "t1gxo4mw", "rank": 18, "score": 0.8153600096702576}, {"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": 2, "docid": "xkzvzonj", "rank": 19, "score": 0.8151135444641113}, {"content": "Title: Grundlagen der Replikation und der Immunologie von SARS-CoV-2./ [Basic principles of replication and immunology of SARS-CoV-2] Content: Coronaviruses are a genetically highly variable family of viruses that infect vertebrates and have succeeded in infecting humans many times by overcoming the species barrier. The severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), which initially appeared in China at the end of 2019, exhibits a high infectivity and pathogenicity compared to other coronaviruses. As the viral coat and other viral components are recognized as being foreign by the immune system, this can lead to initial symptoms, which are induced by the very efficiently working immune defense system via the respiratory epithelium. During severe courses a systemically expressed proinflammatory cytokine storm and subsequent changes in the coagulation and complement systems can occur. Virus-specific antibodies, the long-term expression of which is ensured by the formation of B memory cell clones, generate a specific immune response that is also detectable in blood (seroconversion). Specifically effective cytotoxic CD8+ T\u00adcell populations are also formed, which recognize viral epitopes as pathogen-specific patterns in combination with MHC presentation on the cell surface of virus-infected cells and destroy these cells. At the current point in time it is unclear how regular, robust and durable this immune status is constructed. Experiences with other coronavirus infections (SARS and Middle East respiratory syndrome, MERS) indicate that the immunity could persist for several years. Based on animal experiments, already acquired data on other coronavirus types and plausibility assumptions, it can be assumed that seroconverted patients have an immunity of limited duration and only a very low risk of reinfection. Knowledge of the molecular mechanisms of viral cycles and immunity is an important prerequisite for the development of vaccination strategies and development of effective drugs.", "qid": 2, "docid": "r6y70to9", "rank": 20, "score": 0.8151012659072876}, {"content": "Title: Innate immunity in coronavirus infection/ \u0412\u0420\u041e\u0416\u0414\u0415\u041d\u041d\u042b\u0419 \u0418\u041c\u041c\u0423\u041d\u0418\u0422\u0415\u0422 \u041f\u0420\u0418 \u041a\u041e\u0420\u041e\u041d\u0410\u0412\u0418\u0420\u0423\u0421\u041d\u041e\u0419 \u0418\u041d\u0424\u0415\u041a\u0426\u0418\u0418 Content: Coronaviruses (CoVs) comprise a polymorphic group of respiratory viruses causing acute inflammatory diseases in domestic and agricultural animals (chicken, pig, buffalo, cat, dog). Until recently, this infection in humans was mainly observed during the autumn-winter period and characterized by a mild, often asymptomatic, course. The situation changed dramatically in 2003, when SARS outbreak caused by pathogenic CoV (SARS-CoV) was recorded in China. A decade later, a new CoV outbreak occurred in the form of the Middle East respiratory syndrome (MERS-CoV), whereas in December 2019, SARS-CoV-2 (COVID-19) cases were recorded, which transformed within the first months of 2020 into the pandemic. In all three cases, CoV disease led to severe bronchopulmonary lesions, varying from dry, debilitating cough to acute respiratory distress syndrome (ARDS). At the same time, multiple changes in innate immunity were noted most often manifested as a pronounced inflammatory reaction in the lower respiratory tract, featured by damaged type II pneumocytes, apoptosis, hyalinization of alveolar membranes, focal or generalized pulmonary edema. Destructive processes in the respiratory tract were accompanied by migration of monocytes/macrophages and granulocyte neutrophils to the inflammatory focus. Such events were accompanied by production of pro-inflammatory cytokines, which magnitude could ascend up to a cytokine storm. SARS-CoV is characterized by symptoms of secondary immunosuppression, manifested by the late onset of interferon production and activation of NLRP3 inflammasomes \u2013 the key inflammatory factor. The reason for such reaction may be accounted for by CoV arsenal containing extensive set of structural and non-structural proteins exerting pro-inflammatory and immunosuppressive properties. Delayed IFN production allowed CoV to replicate actively and freely, and when type I IFN synthesis was eventually triggered, its activity was detrimental and accompanied by an aggravated infection course. Thus, SARS can surely be referred to immune-dependent infections with a marked immunopathological component. The purpose of this review was to describe some mechanisms underlying formation of innate immune response to infection caused by pathogenic coronaviruses SARS-CoV, MERS-CoV and SARS-CoV-2 (COVID-19).", "qid": 2, "docid": "977afhj8", "rank": 21, "score": 0.8140145540237427}, {"content": "Title: [Bats, viruses and humans: coronaviruses on the rise?]. Content: The outbreak of the SARS coronavirus in 2002/2003 and the recent disease cases with a new human coronavirus (originally designated EMC-CoV, recently renamed MERS-CoV) have put the focus onto the virus family Coronaviridae. Both viruses appeared to have managed to jump over the species barrier from a bat reservoir to the human population. Bats are considered to serve as a natural reservoir for coronaviruses infecting mammals. An important factor for crossing the species-barrier is the adaptation to a new receptor on cells of the new host species. During evolution coronaviruses have developed a large diversity of binding specificities demonstrating the high flexibility of the coronaviral spike protein, which is responsible for binding to target cells.", "qid": 2, "docid": "uw25s2mc", "rank": 22, "score": 0.8131146430969238}, {"content": "Title: Will the COVID-19 pandemic slow down in the Northern hemisphere by the onset of summer? An epidemiological hypothesis Content: The COVID-19 pandemic has affected most countries of the world. As corona viruses are highly prevalent in the cold season, the question remains whether or not the pandemic will improve with increasing temperatures in the Northern hemisphere. We use data from a primary care registry of almost 15,000 patients over 20 years to retrieve information on viral respiratory infection outbreaks. Our analysis suggests that the severity of the pandemic will be softened by the seasonal change to summer.", "qid": 2, "docid": "iztm1z6g", "rank": 23, "score": 0.8129724264144897}, {"content": "Title: Distinct Roles for Sialoside and Protein Receptors in Coronavirus Infection Content: Coronaviruses (CoVs) are common human and animal pathogens that can transmit zoonotically and cause severe respiratory disease syndromes. CoV infection requires spike proteins, which bind viruses to host cell receptors and catalyze virus-cell membrane fusion. Several CoV strains have spike proteins with two receptor-binding domains, an S1A that engages host sialic acids and an S1B that recognizes host transmembrane proteins. As this bivalent binding may enable broad zoonotic CoV infection, we aimed to identify roles for each receptor in distinct infection stages. Focusing on two betacoronaviruses, murine JHM-CoV and human Middle East respiratory syndrome coronavirus (MERS-CoV), we found that virus particle binding to cells was mediated by sialic acids; however, the transmembrane protein receptors were required for a subsequent virus infection. These results favored a two-step process in which viruses first adhere to sialic acids and then require subsequent engagement with protein receptors during infectious cell entry. However, sialic acids sufficiently facilitated the later stages of virus spread through cell-cell membrane fusion, without requiring protein receptors. This virus spread in the absence of the prototype protein receptors was increased by adaptive S1A mutations. Overall, these findings reveal roles for sialic acids in virus-cell binding, viral spike protein-directed cell-cell fusion, and resultant spread of CoV infections.IMPORTANCE CoVs can transmit from animals to humans to cause serious disease. This zoonotic transmission uses spike proteins, which bind CoVs to cells with two receptor-binding domains. Here, we identified the roles for the two binding processes in the CoV infection process. Binding to sialic acids promoted infection and also supported the intercellular expansion of CoV infections through syncytial development. Adaptive mutations in the sialic acid-binding spike domains increased the intercellular expansion process. These findings raise the possibility that the lectin-like properties of many CoVs contribute to facile zoonotic transmission and intercellular spread within infected organisms.", "qid": 2, "docid": "9ul4682l", "rank": 24, "score": 0.8118469715118408}, {"content": "Title: Meteorological impacts on the incidence of COVID-19 in the U.S. Content: Since the World Health Organization has declared the current outbreak of the novel coronavirus (COVID-19) a global pandemic, some have been anticipating that the mitigation could happen in the summer like seasonal influenza, while medical solutions are still in a slow progress. Experimental studies have revealed a few evidences that coronavirus decayed quickly under the exposure of heat and humidity. This study aims to carry out an epidemiological investigation to establish the association between meteorological factors and COVID-19 in high risk areas of the United States (U.S.). We analyzed daily new confirmed cases of COVID-19 and seven meteorological measures in top 50 U.S. counties with the most accumulative confirmed cases from March 22, 2020 to April 22, 2020. Our analyses indicate that each meteorological factor and COVID-19 more likely have a nonlinear association rather than a linear association over the wide ranges of temperature, relative humidity, and precipitation observed. Average temperature, minimum relative humidity, and precipitation were better predictors to address the meteorological impact on COVID-19. By including all the three meteorological factors in the same model with their lagged effects up to 3 days, the overall impact of the average temperature on COVID-19 was found to peak at 68.45 \u00b0F and decrease at higher degrees, though the overall relative risk percentage (RR %) reduction did not become significantly negative up to 85 \u00b0F. There was a generally downward trend of RR % with the increase of minimum relative humidity; nonetheless, the trend reversed when the minimum relative humidity exceeded 91.42%. The overall RR % of COVID-19 climbed to the highest level of 232.07% (95% confidence interval = 199.77, 267.85) with 1.60 inches of precipitation, and then started to decrease. When precipitation exceeded 1.85 inches, its impact on COVID-19 became significantly negative. Our findings alert people to better have self-protection during the pandemic rather than expecting that the natural environment can curb coronavirus for human beings.", "qid": 2, "docid": "miyvn7vd", "rank": 25, "score": 0.8116405606269836}, {"content": "Title: The role of absolute humidity on transmission rates of the COVID-19 outbreak Content: A novel coronavirus (COVID-19) was identified in Wuhan, Hubei Province, China, in December 2019 and has caused over 40,000 cases worldwide to date. Previous studies have supported an epidemiological hypothesis that cold and dry (low absolute humidity) environments facilitate the survival and spread of droplet-mediated viral diseases, and warm and humid (high absolute humidity) environments see attenuated viral transmission (i.e., influenza). However, the role of absolute humidity in transmission of COVID-19 has not yet been established. Here, we examine province-level variability of the basic reproductive numbers of COVID-19 across China and find that changes in weather alone (i.e., increase of temperature and humidity as spring and summer months arrive in the North Hemisphere) will not necessarily lead to declines in COVID-19 case counts without the implementation of extensive public health interventions.", "qid": 2, "docid": "zvngy7zz", "rank": 26, "score": 0.8110262751579285}, {"content": "Title: CORONAVIRUS VIRULENCE GENES WITH MAIN FOCUS ON SARS-CoV ENVELOPE GENE Content: Coronavirus (CoV) infection is usually detected by cellular sensors, which trigger the activation of the innate immune system. Nevertheless, CoVs have evolved viral proteins that target different signaling pathways to counteract innate immune responses. Some CoV proteins act as antagonists of interferon (IFN) by inhibiting IFN production or signaling, aspects that are briefly addressed in this review. After CoV infection, potent cytokines relevant in controlling virus infections and priming adaptive immune responses are also generated. However, an uncontrolled induction of these proinflammatory cytokines can lead to pathogenesis and disease severity as described for SARS-CoV and MERS-CoV. The cellular pathways mediated by interferon regulatory factor (IRF)-3 and 7, activating transcription factor (ATF)-2/jun, activator protein (AP)-1, nuclear factor kappa-light-chain-enhancer of activated B cells (NF-\u03baB), and nuclear factor of activated T cells (NF-AT), are the main drivers of the inflammatory response triggered after viral infections, with NF-\u03baB pathway the most frequently activated. Key CoV proteins involved in the regulation of these pathways and the proinflammatory immune response are revisited in this manuscript. It has been shown that the envelope (E) protein plays a variable role in CoV morphogenesis, depending on the CoV genus, being absolutely essential in some cases (genus \u03b1 CoVs such as TGEV, and genus \u03b2 CoVs such as MERS-CoV), but not in others (genus \u03b2 CoVs such as MHV or SARS-CoV). A comprehensive accumulation of data has shown that the relatively small E protein elicits a strong influence on the interaction of SARS-CoV with the host. In fact, after infection with viruses in which this protein has been deleted, increased cellular stress and unfolded protein responses, apoptosis, and augmented host immune responses were observed. In contrast, the presence of E protein activated a pathogenic inflammatory response that may cause death in animal models and in humans. The modification or deletion of different motifs within E protein, including the transmembrane domain that harbors an ion channel activity, small sequences within the middle region of the carboxy-terminus of E protein, and its most carboxy-terminal end, which contains a PDZ domain-binding motif (PBM) is sufficient to attenuate the virus. Interestingly, a comprehensive collection of SARS-CoVs in which these motifs have been modified elicited full and long-term protection even in old mice, making those deletion mutants promising vaccine candidates. These data indicate that despite its small size, E protein drastically influences the replication of CoVs and their pathogenicity. Although E protein is not essential for CoV genome replication or subgenomic mRNA synthesis, it affects virus morphogenesis, budding, assembly, intracellular trafficking, and virulence. In fact, E protein is responsible in a significant proportion of the inflammasome activation and the associated inflammation elicited by SARS-CoV in the lung parenchyma. This exacerbated inflammation causes edema accumulation leading to acute respiratory distress syndrome (ARDS) and, frequently, to the death of infected animal models or human patients.", "qid": 2, "docid": "jm1mf6g1", "rank": 27, "score": 0.8108867406845093}, {"content": "Title: Biochemical aspects of coronavirus replication and virus-host interaction. Content: Infection by different coronaviruses (CoVs) causes alterations in the transcriptional and translational patterns, cell cycle, cytoskeleton, and apoptosis pathways of the host cells. In addition, CoV infection may cause inflammation, alter immune and stress responses, and modify the coagulation pathways. The balance between the up- and downregulated genes could explain the pathogenesis caused by these viruses. We review specific aspects of CoV-host interactions. CoV genome replication takes place in the cytoplasm in a membrane-protected microenvironment and may control the cell machinery by locating some of their proteins in the host cell nucleus. CoVs initiate translation by cap-dependent and cap-independent mechanisms. CoV transcription involves a discontinuous RNA synthesis (template switching) during the extension of a negative copy of the subgenomic mRNAs. The requirement for base-pairing during transcription has been formally demonstrated in arteriviruses and CoVs. CoV N proteins have RNA chaperone activity that may help initiate template switching. Both viral and cellular proteins are required for replication and transcription, and the role of selected proteins is addressed.", "qid": 2, "docid": "jxqngqei", "rank": 28, "score": 0.8103726506233215}, {"content": "Title: Subversion of host stress granules by coronaviruses: Potential roles of \u03c0-rich disordered domains of viral nucleocapsids Content: Coronavirus nucleocapsids (CoV N's) play both structural and non-structural roles in viral life-cycle. Here, we propose a mechanism for host stress granule (SG) subversion by CoV N proteins. We posit that disordered domains of CoV N's can engage in &#960;-&#960; intermolecular fuzzy interactions with host SG proteins and are crucial to the viral hijacking of host machineries. This article is protected by copyright. All rights reserved.", "qid": 2, "docid": "un8mj98n", "rank": 29, "score": 0.8100822567939758}, {"content": "Title: Parallel problems Content: Our fight against climate change offers useful lessons for tackling the coronavirus", "qid": 2, "docid": "1ckrnxom", "rank": 30, "score": 0.809725821018219}, {"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": 2, "docid": "ac0whd9v", "rank": 31, "score": 0.8094443082809448}, {"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": 2, "docid": "28sgnyh1", "rank": 32, "score": 0.8094443082809448}, {"content": "Title: Climatic-niche evolution of SARS CoV-2 Content: Adaptation of species to new environments is governed by natural selection that discriminates among genetic variations and favors survival of the fittest. Here, we propose climate plays an important role in the evolution of SARS CoV-2 and the spread of COVID-19 all over the world which was previously not known. To understand the climatic factors responsible for shaping the molecular determinants of the novel coronavirus, genotyping SARS CoV-2 across different latitudes and Koppen\u2019s climate is imperative. It seems this virus follows inverse latitudinal biodiversity gradient due to its preference towards Koppen\u2019s temperate (C) and cold climate (D). Our molecular phylogenetic analysis revealed division of 176 SARS CoV-2 strains into two variant groups, G1 and G2, well defined by four mutations. Initially, SARS CoV-2 was restricted to a \u201chumid-subtropical\u201d (Cfa) climate of southeast China, which soon spread all over the world having C climate. Genomic information superimposed on global Koppen\u2019s climate map elucidates that the gradation \u201chumid-subtropical\u201d (Cfa) and \u201cmarine-temperate\u201d (Cfb) to \u201chumid-continental\u201d (Dfa-Dfb) climate drives the evolution of G1 into G2 variant group. It seems an early infection in Europe and USA is due to the dominance of C climate. Russia and North America were infected through linkage of C to D climate and South America from C to A climate. Our study elucidates viruses are sensitive to climate and combined genomic and climatic studies provide crucial information about the pathogenesis and natural spreading pathways during a pandemic which will enable us to take pre-emptive precautionary measures in such outbreaks. Graphical Abstract In Brief The authors elucidate adaptation of SARS CoV-2 to different climates by studying phylogenetics and the distribution of strains on Koppen\u2019s climate map. Highlights SARS CoV-2 follows inverse latitudinal gradient. Phylogenetic network divides SARS CoV-2 strains into two variant groups, G1 and G2. G1 strains is restricted to Koppen\u2019s \u201ctemperate\u201d climate (mainly Cfa-Cfb). G2 strains has evolved from G1 to sustain in \u201chumid-continental\u201d (Dfa-Dfb) and \u201ctropical-savannah\u201d (Aw) climate.", "qid": 2, "docid": "niq3hosc", "rank": 33, "score": 0.8090518712997437}, {"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": 2, "docid": "3p2dl8yf", "rank": 34, "score": 0.8088233470916748}, {"content": "Title: Distinct Roles for Sialoside and Protein Receptors in Coronavirus Infection Content: Coronaviruses (CoVs) are common human and animal pathogens that can transmit zoonotically and cause severe respiratory disease syndromes. CoV infection requires spike proteins, which bind viruses to host cell receptors and catalyze virus-cell membrane fusion. Several CoV strains have spike proteins with two receptor-binding domains, an S1A that engages host sialic acids and an S1B that recognizes host transmembrane proteins. As this bivalent binding may enable broad zoonotic CoV infection, we aimed to identify roles for each receptor in distinct infection stages. Focusing on two betacoronaviruses, murine JHM-CoV and human Middle East respiratory syndrome coronavirus (MERS-CoV), we found that virus particle binding to cells was mediated by sialic acids; however, the transmembrane protein receptors were required for a subsequent virus infection. These results favored a two-step process in which viruses first adhere to sialic acids and then require subsequent engagement with protein receptors during infectious cell entry. However, sialic acids sufficiently facilitated the later stages of virus spread through cell-cell membrane fusion, without requiring protein receptors. This virus spread in the absence of the prototype protein receptors was increased by adaptive S1A mutations. Overall, these findings reveal roles for sialic acids in virus-cell binding, viral spike protein-directed cell-cell fusion, and resultant spread of CoV infections.", "qid": 2, "docid": "1mowsbjy", "rank": 35, "score": 0.8087341785430908}, {"content": "Title: Coronavirus, as a source of pandemic pathogens Content: The coronavirus and the influenza virus have similarities and differences. In order to comprehensively compare them, their genome sequencing data were examined by principal component analysis. Variations in coronavirus were smaller than those in a subclass of the influenza virus. In addition, differences among coronaviruses in a variety of hosts were small. These characteristics may have facilitated the infection of different hosts. Although many of the coronaviruses were more conservative, those repeatedly found among humans showed annual changes. If SARS-CoV-2 changes its genome like the Influenza H type, it will repeatedly spread every few years. In addition, the coronavirus family has many other candidates for subsequent pandemics. One Sentence Summary The genome data of coronavirus were compared to influenza virus, to investigate its spreading mechanism and future status. Coronavirus would repeatedly spread every few years. In addition, the coronavirus family has many other candidates for subsequent pandemics.", "qid": 2, "docid": "431ksdno", "rank": 36, "score": 0.8087151646614075}, {"content": "Title: Seasonality and uncertainty in COVID-19 growth rates Content: The virus causing COVID-19 has spread rapidly worldwide and threatens millions of lives. It remains unknown if summer weather will reduce its continued spread, thereby alleviating strains on hospitals and providing time for vaccine development. Early insights from laboratory studies of related coronaviruses predicted that COVID-19 would decline at higher temperatures, humidity, and ultraviolet light. Using current, fine-scaled weather data and global reports of infection we developed a model that explained 36% of variation in early growth rates before intervention, with 17% based on weather or demography and 19% based on country-specific effects. We found that ultraviolet light was most strongly associated with lower COVID-19 growth rates. Projections suggest that, in the absence of intervention, COVID-19 will decrease temporarily during summer, rebound by autumn, and peak next winter. However, uncertainty remains high and the probability of a weekly doubling rate remained >20% throughout the summer in the absence of control. Consequently, aggressive policy interventions will likely be needed in spite of seasonal trends.", "qid": 2, "docid": "0vlzwksu", "rank": 37, "score": 0.8079515099525452}, {"content": "Title: Association between ambient temperature and COVID-19 infection in 122 cities from China Content: BACKGROUND: Coronavirus disease 2019 (COVID-19) has become a severe public health problem globally. Both epidemiological and laboratory studies have shown that ambient temperature could affect the transmission and survival of coronaviruses. This study aimed to determine whether the temperature is an essential factor in the infection caused by this novel coronavirus. METHODS: Daily confirmed cases and meteorological factors in 122 cities were collected between January 23, 2020, to February 29, 2020. A generalized additive model (GAM) was applied to explore the nonlinear relationship between mean temperature and COVID-19 confirmed cases. We also used a piecewise linear regression to determine the relationship in detail. RESULTS: The exposure-response curves suggested that the relationship between mean temperature and COVID-19 confirmed cases was approximately linear in the range of <3 \u00b0C and became flat above 3 \u00b0C. When mean temperature (lag0-14) was below 3 \u00b0C, each 1 \u00b0C rise was associated with a 4.861% (95% CI: 3.209-6.513) increase in the daily number of COVID-19 confirmed cases. These findings were robust in our sensitivity analyses. CONCLUSIONS: Our results indicate that mean temperature has a positive linear relationship with the number of COVID-19 cases with a threshold of 3 \u00b0C. There is no evidence supporting that case counts of COVID-19 could decline when the weather becomes warmer, which provides useful implications for policymakers and the public.", "qid": 2, "docid": "y1rlk8th", "rank": 38, "score": 0.8077900409698486}, {"content": "Title: Lessons for COVID-19 immunity from other coronavirus infections Content: Abstract A key goal to controlling COVID-19 is developing an effective vaccine. Development of a vaccine requires knowledge of what constitutes a protective immune response and also features that might be pathogenic. Protective and pathogenic aspects of the response to SARS-CoV-2 are not well understood, partly because the virus has infected humans for only 6 months. However, insight into coronavirus immunity can be informed by previous studies of immune responses to non-human coronaviruses, to common cold coronaviruses, and to SARS-CoV and MERS-CoV. Here we review the literature describing these responses and discuss their relevance to the SARS-CoV-2 immune response.", "qid": 2, "docid": "s6v4bgev", "rank": 39, "score": 0.8076943159103394}, {"content": "Title: Mathematical modeling of interaction between innate and adaptive immune responses in COVID-19 and implications for viral pathogenesis Content: We have applied mathematical modeling to investigate the infections of the ongoing coronavirus disease-2019 (COVID-19) pandemic caused by SARS-CoV-2 virus. We first validated our model using the well-studied influenza viruses and then compared the pathogenesis processes between the two viruses. The interaction between host innate and adaptive immune responses was found to be a potential cause for the higher severity and mortality in COVID-19 patients. Specifically, the timing mismatch between the two immune responses has a major impact on disease progression. The adaptive immune response of the COVID-19 patients is more likely to come before the peak of viral load, while the opposite is true for influenza patients. This difference in timing causes delayed depletion of vulnerable epithelial cells in the lungs in COVID-19 patients while enhancing viral clearance in influenza patients. Stronger adaptive immunity in COVID-19 patients can potentially lead to longer recovery time and more severe secondary complications. Based on our analysis, delaying the onset of adaptive immune responses during the early phase of infections may be a potential treatment option for high-risk COVID-19 patients. Suppressing the adaptive immune response temporarily and avoiding its interference with the innate immune response may allow the innate immunity to more efficiently clear the virus.", "qid": 2, "docid": "u2qaqrao", "rank": 40, "score": 0.8075600862503052}, {"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": 2, "docid": "528p64iu", "rank": 41, "score": 0.8063125014305115}, {"content": "Title: Mouse hepatitis coronavirus A59 nucleocapsid protein is a type I interferon antagonist. Content: The recent emergence of several new coronaviruses, including the etiological cause of severe acute respiratory syndrome, has significantly increased the importance of understanding virus-host cell interactions of this virus family. We used mouse hepatitis virus (MHV) A59 as a model to gain insight into how coronaviruses affect the type I alpha/beta interferon (IFN) system. We demonstrate that MHV is resistant to type I IFN. Protein kinase R (PKR) and the alpha subunit of eukaryotic translation initiation factor are not phosphorylated in infected cells. The RNase L activity associated with 2',5'-oligoadenylate synthetase is not activated or is blocked, since cellular RNA is not degraded. These results are consistent with lack of protein translation shutoff early following infection. We used a well-established recombinant vaccinia virus (VV)-based expression system that lacks the viral IFN antagonist E3L to screen viral genes for their ability to rescue the IFN sensitivity of the mutant. The nucleocapsid (N) gene rescued VVDeltaE3L from IFN sensitivity. N gene expression prevents cellular RNA degradation and partially rescues the dramatic translation shutoff characteristic of the VVDeltaE3L virus. However, it does not prevent PKR phosphorylation. The results indicate that the MHV N protein is a type I IFN antagonist that likely plays a role in circumventing the innate immune response.", "qid": 2, "docid": "yl60pb6n", "rank": 42, "score": 0.8061445355415344}, {"content": "Title: Estimated Inactivation of Coronaviruses by Solar Radiation With Special Reference to COVID-19 Content: Using a model developed for estimating solar inactivation of viruses of biodefense concerns, we calculated the expected inactivation of SARS-CoV-2 virus, cause of COVID-19 pandemic, by artificial UVC and by solar ultraviolet radiation in several cities of the world during different times of the year. The UV sensitivity estimated here for SARS-CoV-2 is compared with those reported for other ssRNA viruses, including influenza A virus. The results indicate that SARS-CoV-2 aerosolized from infected patients and deposited on surfaces could remain infectious outdoors for considerable time during the winter in many temperate-zone cities, with continued risk for re-aerosolization and human infection. Conversely, the presented data indicate that SARS-CoV-2 should be inactivated relatively fast (faster than influenza A) during summer in many populous cities of the world, indicating that sunlight should have a role in the occurrence, spread rate, and duration of coronavirus pandemics.", "qid": 2, "docid": "7emv2bao", "rank": 43, "score": 0.805164635181427}, {"content": "Title: A contemporary review on pathogenesis and immunity of COVID-19 infection Content: Emerging of the COVID-19 pandemic has raised interests in the field of biology and pathogenesis of coronaviruses; including interactions between host immune reactions specific, and viral factors. Deep knowledge about the interaction between coronaviruses and the host factors could be useful to provide a better support for the disease sufferers and be advantageous for managing and treatment of the lung infection caused by the virus. At this study, we reviewed the updated information on the pathogenesis of the COVID-19 and the immune responses toward it, with a special focus on structure, genetics, and viral accessory proteins, viral replication, viral receptors, the human immune reactions, cytopathic effects, and host-related factors.", "qid": 2, "docid": "owby50fr", "rank": 44, "score": 0.8049863576889038}, {"content": "Title: Association between ambient temperature and COVID-19 infection in 122 cities from China Content: Abstract Background Coronavirus disease 2019 (COVID-19) has become a severe public health problem globally. Both epidemiological and laboratory studies have shown that ambient temperature could affect the transmission and survival of coronaviruses. This study aimed to determine whether the temperature is an essential factor in the infection caused by this novel coronavirus. Methods Daily confirmed cases and meteorological factors in 122 cities were collected between January 23, 2020, to February 29, 2020. A generalized additive model (GAM) was applied to explore the nonlinear relationship between mean temperature and COVID-19 confirmed cases. We also used a piecewise linear regression to determine the relationship in detail. Results The exposure-response curves suggested that the relationship between mean temperature and COVID-19 confirmed cases was approximately linear in the range of <3 \u00b0C and became flat above 3 \u00b0C. When mean temperature (lag0\u201314) was below 3 \u00b0C, each 1 \u00b0C rise was associated with a 4.861% (95% CI: 3.209\u20136.513) increase in the daily number of COVID-19 confirmed cases. These findings were robust in our sensitivity analyses. Conclusions Our results indicate that mean temperature has a positive linear relationship with the number of COVID-19 cases with a threshold of 3 \u00b0C. There is no evidence supporting that case counts of COVID-19 could decline when the weather becomes warmer, which provides useful implications for policymakers and the public.", "qid": 2, "docid": "u19e9j2w", "rank": 45, "score": 0.8048983812332153}, {"content": "Title: To sense or not to sense viral RNA\u2014essentials of coronavirus innate immune evasion Content: An essential function of innate immunity is to distinguish self from non-self and receptors have evolved to specifically recognize viral components and initiate the expression of antiviral proteins to restrict viral replication. Coronaviruses are RNA viruses that replicate in the host cytoplasm and evade innate immune sensing in most cell types, either passively by hiding their viral signatures and limiting exposure to sensors or actively, by encoding viral antagonists to counteract the effects of interferons. Since many cytoplasmic viruses exploit similar mechanisms of innate immune evasion, mechanistic insight into the direct interplay between viral RNA, viral RNA-processing enzymes, cellular sensors and antiviral proteins will be highly relevant to develop novel antiviral targets and to restrict important animal and human infections.", "qid": 2, "docid": "u8b5sccq", "rank": 46, "score": 0.8048830032348633}, {"content": "Title: Coronavirus-induced ER stress response and its involvement in regulation of coronavirus\u2013host interactions Content: Abstract Coronavirus replication is structurally and functionally associated with the endoplasmic reticulum (ER), a major site of protein synthesis, folding, modification and sorting in the eukaryotic cells. Disturbance of ER homeostasis may occur under various physiological or pathological conditions. In response to the ER stress, signaling pathways of the unfolded protein response (UPR) are activated. UPR is mediated by three ER transmembrane sensors, namely the PKR-like ER protein kinase (PERK), the inositol-requiring protein 1 (IRE1) and the activating transcriptional factor 6 (ATF6). UPR facilitates adaptation to ER stress by reversible translation attenuation, enhancement of ER protein folding capacity and activation of ER-associated degradation (ERAD). In cells under prolonged and irremediable ER stress, UPR can also trigger apoptotic cell death. Accumulating evidence has shown that coronavirus infection causes ER stress and induces UPR in the infected cells. UPR is closely associated with a number of major signaling pathways, including autophagy, apoptosis, the mitogen-activated protein (MAP) kinase pathways, innate immunity and pro-inflammatory response. Therefore, studies on the UPR are pivotal in elucidating the complicated issue of coronavirus-host interaction. In this paper, we present the up-to-date knowledge on coronavirus-induced UPR and discuss its potential involvement in regulation of innate immunity and apoptosis.", "qid": 2, "docid": "msnhtzck", "rank": 47, "score": 0.8046643733978271}, {"content": "Title: Coronavirus Endoribonuclease and Deubiquitinating Interferon Antagonists Differentially Modulate the Host Response during Replication in Macrophages Content: Coronaviruses (CoVs) encode multiple interferon (IFN) antagonists that modulate the host response to virus replication. Here, we evaluated the host transcriptional response to infection with murine coronaviruses encoding independent mutations in one of two different viral antagonists, the deubiquitinase (DUB) within nonstructural protein 3 or the endoribonuclease (EndoU) within nonstructural protein 15. We used transcriptomics approaches to compare the scope and kinetics of the host response to the wild-type (WT), DUBmut, and EndoUmut viruses in infected macrophages. We found that the EndoUmut virus activates a focused response that predominantly involves type I interferons and interferon-related genes, whereas the WT and DUBmut viruses more broadly stimulate upregulation of over 2,800 genes, including networks associated with activating the unfolded protein response (UPR) and the proinflammatory response 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 inactivating a dominant viral antagonist, the coronavirus endoribonuclease, dramatically alters the host response in macrophages.IMPORTANCE Macrophages are an important cell type during coronavirus infections because they \"notice\" the infection and respond by inducing type I interferons, which limits virus replication. In turn, coronaviruses encode proteins that mitigate the cell's ability to signal an interferon response. Here, we evaluated the host macrophage response to two independent mutant coronaviruses, one with 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-related genes. In contrast, wild-type virus and the DUBmut virus elicited a more limited interferon response and ultimately activated over 2,800 genes, including players in the unfolded protein response and proinflammatory pathways associated with progression of significant disease. This study reveals that EndoU activity substantially contributes to the ability of coronaviruses to evade the host innate response and to replicate in macrophages.", "qid": 2, "docid": "9y7ebe8v", "rank": 48, "score": 0.8045287132263184}, {"content": "Title: Estimated Inactivation of Coronaviruses by Solar Radiation With Special Reference to COVID-19 Content: Using a model developed for estimating solar inactivation of viruses of biodefense concerns, we calculated the expected inactivation of SARS-CoV-2 virus, cause of COVID-19 pandemic, by artificial UVC and by solar ultraviolet radiation in several cities of the world during different times of the year. The UV sensitivity estimated here for SARS-CoV-2 is compared with those reported for other ssRNA viruses, including influenza A virus. The results indicate that SARS-CoV-2 aerosolized from infected patients and deposited on surfaces could remain infectious outdoors for considerable time during the winter in many temperate-zone cities, with continued risk for re-aerosolization and human infection. Conversely, the presented data indicate that SARS-CoV-2 should be inactivated relatively fast (faster than influenza A) during summer in many populous cities of the world, indicating that sunlight should have a role in the occurrence, spread rate and duration of coronavirus pandemics.", "qid": 2, "docid": "4xijeti6", "rank": 49, "score": 0.8044084310531616}, {"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": 2, "docid": "ll76vrr3", "rank": 50, "score": 0.8043442964553833}, {"content": "Title: [Advances in recently identified coronaviruses]. Content: Coronaviruses are a large family of viruses which include viruses that cause the common cold and severe acute respiratory syndrome (SARS) in humans and other diseases in animals. There are considerable genetic diversities within coronaviruses due to their wide rang hosts and their special gene replication and transcription mechanisms. During this process, gene recombinations often occur, resulting in novel subtype or coronavirus emerge constantly. Of note are SARS-like-CoVs and novel HCoV-EMC identified in 2012. This minireview summarized major advances of recently identified coronaviruses, focusing on the genome structures and interspecies jumping mechanism of coronavirus.", "qid": 2, "docid": "xfnpzovi", "rank": 51, "score": 0.8041131496429443}, {"content": "Title: UV light influences covid-19 activity through big data: trade offs between northern subtropical, tropical, and southern subtropical countries Content: UV (ultraviolet) light is an important factor should be considered to predict coronavirus epidemic growth pace. UV is different from weather temperature since UV is electromagnetic wavelength from 10 nm to 400 nm in size, shorter than of visible lights. For some people, UV light can lead to cancer from unprotected sun exposure, however, for tropical people, which have been used to live in such condition, have resisted from negative effect high UV index. Moreover, UV has the capability to inactivate virus. This conclusion has been discussed deeply with biological experts. Although UV light has the ability to inactivate viruses, it may be meaningless in areas with high air pollution where UV light turns into heat.", "qid": 2, "docid": "odbi4yvz", "rank": 52, "score": 0.803945779800415}, {"content": "Title: Coronavirus infection modulates the unfolded protein response and mediates sustained translational repression. Content: During coronavirus replication, viral proteins induce the formation of endoplasmic reticulum (ER)-derived double-membrane vesicles for RNA synthesis, and viral structural proteins assemble virions at the ER-Golgi intermediate compartment. We hypothesized that the association and intense utilization of the ER during viral replication would induce the cellular unfolded protein response (UPR), a signal transduction cascade that acts to modulate translation, membrane biosynthesis, and the levels of ER chaperones. Here, we report that infection by the murine coronavirus mouse hepatitis virus (MHV) triggers the proximal UPR transducers, as revealed by monitoring the IRE1-mediated splicing of XBP-1 mRNA and the cleavage of ATF6alpha. However, we detected minimal downstream induction of UPR target genes, including ERdj4, ER degradation-enhancing alpha-mannosidase-like protein, and p58(IPK), or expression of UPR reporter constructs. Translation initiation factor eIF2alpha is highly phosphorylated during MHV infection, and translation of cellular mRNAs is attenuated. Furthermore, we found that the critical homeostasis regulator GADD34, which recruits protein phosphatase 1 to dephosphorylate eIF2alpha during the recovery phase of the UPR, is not expressed during MHV infection. These results suggest that MHV modifies the UPR by impeding the induction of UPR-responsive genes, thereby favoring a sustained shutdown of the synthesis of host cell proteins while the translation of viral proteins escalates. The role of this modified response and its potential relevance to viral mechanisms for the evasion of innate defense signaling pathways during coronavirus replication are discussed.", "qid": 2, "docid": "0l8mt6a7", "rank": 53, "score": 0.8035913705825806}, {"content": "Title: Decoding the global outbreak of COVID-19: the nature is behind the scene Content: The sudden emergence of SARS-CoV-2 causing the global pandemic is a major public health concern. Though the virus is considered as a novel entity, it is not a completely new member. It is just a new version of previously emerged human SARS corona virus. The rapid evolving nature by changing host body environment and extreme environmental stability, collectively makes SARS-CoV-2 into an extremely virulent genetic variant. The evolution of the virus has been occurred by the continuous process of molecular genetic manipulation, through mutation, deletion and genetic recombinationevents. Different host body environment acts as the supportive system for the pathogen which creates extreme selective pressure. By the process of genetic evolution the pathogen developes new characters. Then the new version of the virus has been naturally selected by susceptible human host and adapt itself inside the host body causing deadly effect. Moreover, extreme environmental stability helps in the process of viral survival outside the host and its transmission. Thus both the host body or internal environment and the external environment performs equally as a source, responsible for shaping the genetic evolution of the SARS-CoV-2 towards theCOVID-19 disease fitness in nature in a pandemic form.", "qid": 2, "docid": "gq3965se", "rank": 54, "score": 0.8035383224487305}, {"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": 2, "docid": "jxsj3lg6", "rank": 55, "score": 0.8034104108810425}, {"content": "Title: SARS-CoV-2\u2013A Tough Opponent for the Immune System Content: Coronaviruses recently returned with a new one, SARS-CoV-2, related to a potentially severe respiratory disease-called the coronavirus disease (COVID-19). Research shows that the SARS-CoV-2 can be clustered with the Bat SARS-like coronavirus. Bats possess an additional, innate ability for antiviral defense, and, on the other hand, the potential to go hand-in-hand with the virus to generate variability. Besides the high potential of the novel coronavirus in compromising the respiratory system, its rapid transmission and ability to engage many hosts in severe forms of infections or immunopathological complications make it a tough opponent for the immune system. The interactions between SARS-CoV2 and the host immune system result in unleashing tremendous amounts of cytokines, and these cytokines make a storm that would determine the outcome (recovery or death) of the lungs of the patient.", "qid": 2, "docid": "703febui", "rank": 56, "score": 0.8034086227416992}, {"content": "Title: SARS-CoV-2-A Tough Opponent for the Immune System Content: Coronaviruses recently returned with a new one, SARS-CoV-2, related to a potentially severe respiratory disease-called the coronavirus disease (COVID-19). Research shows that the SARS-CoV-2 can be clustered with the Bat SARS-like coronavirus. Bats possess an additional, innate ability for antiviral defense, and, on the other hand, the potential to go hand-in-hand with the virus to generate variability. Besides the high potential of the novel coronavirus in compromising the respiratory system, its rapid transmission and ability to engage many hosts in severe forms of infections or immunopathological complications make it a tough opponent for the immune system. The interactions between SARS-CoV2 and the host immune system result in unleashing tremendous amounts of cytokines, and these cytokines make a storm that would determine the outcome (recovery or death) of the lungs of the patient.", "qid": 2, "docid": "4lm663f1", "rank": 57, "score": 0.8034086227416992}, {"content": "Title: Endoplasmic reticulum as a potential therapeutic target for covid-19 infection management? Content: In December 2019, many pneumonia cases with unidentified sources appeared in Wuhan, Hubei, China, with clinical symptoms like viral pneumonia. Deep sequencing analysis of samples from lower respiratory tract revealed a novel coronavirus, called 2019 novel coronavirus (2019-nCoV). Currently there is a rapid global spread. World Health Organization declare the disease a pandemic condition. The pathologic source of this disease was a new RNA virus from Coronaviridae family, which was named COVID-19. SARS-CoV-2 entry starts with the binding of the spike glycoprotein expressed on the viral envelope to ACE2 on the alveolar surface followed by clathrin-dependent endocytosis of the SARS-CoV-2 and ACE2 complex. SARS-CoV-2 enters the cells through endocytosis process, which is possibly facilitated, via a pH dependent endosomal cysteine protease cathepsins. Once inside the cells, SARS-CoV-2 exploits the endogenous transcriptional machinery of alveolar cells to replicate and spread through the entire lung. Endosomal acidic pH for SARS-CoV-2 processing and internalization is critical. After entering the cells, it possibly activates or hijack many intracellular pathways in favor of its replication. In the current opinion article, we will explain the possible involvement of unfolded protein response as a cellular stress response to the SARS-CoV-2 infection.", "qid": 2, "docid": "38alpn2v", "rank": 58, "score": 0.8033456802368164}, {"content": "Title: Cell Host Response to Infection with Novel Human Coronavirus EMC Predicts Potential Antivirals and Important Differences with SARS Coronavirus Content: A novel human coronavirus (HCoV-EMC) was recently identified in the Middle East as the causative agent of a severe acute respiratory syndrome (SARS) resembling the illness caused by SARS coronavirus (SARS-CoV). Although derived from the CoV family, the two viruses are genetically distinct and do not use the same receptor. Here, we investigated whether HCoV-EMC and SARS-CoV induce similar or distinct host responses after infection of a human lung epithelial cell line. HCoV-EMC was able to replicate as efficiently as SARS-CoV in Calu-3 cells and similarly induced minimal transcriptomic changes before 12 h postinfection. Later in infection, HCoV-EMC induced a massive dysregulation of the host transcriptome, to a much greater extent than SARS-CoV. Both viruses induced a similar activation of pattern recognition receptors and the interleukin 17 (IL-17) pathway, but HCoV-EMC specifically down-regulated the expression of several genes within the antigen presentation pathway, including both type I and II major histocompatibility complex (MHC) genes. This could have an important impact on the ability of the host to mount an adaptive host response. A unique set of 207 genes was dysregulated early and permanently throughout infection with HCoV-EMC, and was used in a computational screen to predict potential antiviral compounds, including kinase inhibitors and glucocorticoids. Overall, HCoV-EMC and SARS-CoV elicit distinct host gene expression responses, which might impact in vivo pathogenesis and could orient therapeutic strategies against that emergent virus.", "qid": 2, "docid": "9ux181xg", "rank": 59, "score": 0.8032609224319458}, {"content": "Title: Coronavirus genomes carry the signatures of their habitats Content: Coronaviruses such as SARS-CoV-2 regularly infect host tissues that express antiviral proteins (AVPs) in abundance. Understanding how they evolve to adapt or evade host immune responses is important in the effort to control the spread of COVID-19. Two AVPs that may shape viral genomes are the zinc finger antiviral protein (ZAP) and the apolipoprotein B mRNA-editing enzyme-catalytic polypeptide-like 3 protein (APOBEC3). The former binds to CpG dinucleotides to facilitate the degradation of viral transcripts while the latter deaminates C into U residues leading to dysfunctional transcripts. We tested the hypothesis that both APOBEC3 and ZAP may act as primary selective pressures that shape the genome of an infecting coronavirus by considering a comprehensive number of publicly available genomes for seven coronaviruses (SARS-CoV-2, SARS-CoV, MERS, Bovine CoV, Murine MHV, Porcine HEV, and Canine CoV). We show that coronaviruses that regularly infect tissues with abundant AVPs have CpG-deficient and U-rich genomes; whereas viruses that do not infect tissues with abundant AVPs do not share these sequence hallmarks. In SARS-CoV-2, CpG is most deficient in the S protein region to evaded ZAP-mediated antiviral defense during cell entry. Furthermore, over four months of SARS-CoV-2 evolutionary history, we observed a marked increase in C to U substitutions in the 5\u2019 UTR and ORF1ab regions. This suggests that the two regions could be under constant C to U deamination by APOBEC3. The evolutionary pressures exerted by host immune systems onto viral genomes may motivate novel strategies for SARS-CoV-2 vaccine development.", "qid": 2, "docid": "qj7coqfr", "rank": 60, "score": 0.8032525777816772}, {"content": "Title: Blood single cell immune profiling reveals the interferon-MAPK pathway mediated adaptive immune response for COVID-19 Content: The coronavirus disease 2019 (COVID-19) outbreak is an ongoing global health emergence, but the pathogenesis remains unclear. We revealed blood cell immune response profiles using 5' mRNA, TCR and BCR V(D)J transcriptome analysis with single-cell resolution. Data from 134,620 PBMCs and 83,387 TCR and 12,601 BCR clones was obtained, and 56 blood cell subtypes and 23 new cell marker genes were identified from 16 participants. The number of specific subtypes of immune cells changed significantly when compared patients with controls. Activation of the interferon-MAPK pathway is the major defense mechanism, but MAPK transcription signaling is inhibited in cured patients. TCR and BCR V(D)J recombination is highly diverse in generating different antibodies against SARS-CoV-2. Therefore, the interferon-MAPK pathway and TCR- and BCR-produced antibodies play important roles in the COVID-19 immune response. Immune deficiency or immune over-response may result in the condition of patients with COVID-19 becoming critical or severe.", "qid": 2, "docid": "2okcuviq", "rank": 61, "score": 0.8031445741653442}, {"content": "Title: Revisi\u00f3n narrativa sobre la respuesta inmunitaria frente a coronavirus: descripci\u00f3n general, aplicabilidad para SARS-COV-2 e implicaciones terap\u00e9uticas./ [Narrative review of the immune response against coronavirus: An overview, applicability for SARS-COV-2, and therapeutic implications] Content: The new coronavirus (SARS-CoV-2) that causes a severe acute respiratory syndrome emerges 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-CoV-2 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 its applicability to SARS-CoV-2. 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": 2, "docid": "voqzmze6", "rank": 62, "score": 0.803076446056366}, {"content": "Title: Is COVID-19 receiving ADE from other coronaviruses? Content: One of the most perplexing questions regarding the current COVID-19 coronavirus epidemic is the discrepancy between the severity of cases observed in the Hubei province of China and those occurring elsewhere in the world. One possible answer is antibody dependent enhancement (ADE) of SARS-CoV-2 due to prior exposure to other coronaviruses. ADE modulates the immune response and can elicit sustained inflammation, lymphopenia, and/or cytokine storm, one or all of which have been documented in severe cases and deaths. ADE also requires prior exposure to similar antigenic epitopes, presumably circulating in local viruses, making it a possible explanation for the observed geographic limitation of severe cases and deaths.", "qid": 2, "docid": "fjxspb7b", "rank": 63, "score": 0.8030743598937988}, {"content": "Title: Mechanisms of Coronavirus Cell Entry Mediated by the Viral Spike Protein Content: Coronaviruses are enveloped positive-stranded RNA viruses that replicate in the cytoplasm. To deliver their nucleocapsid into the host cell, they rely on the fusion of their envelope with the host cell membrane. The spike glycoprotein (S) mediates virus entry and is a primary determinant of cell tropism and pathogenesis. It is classified as a class I fusion protein, and is responsible for binding to the receptor on the host cell as well as mediating the fusion of host and viral membranes\u2014A process driven by major conformational changes of the S protein. This review discusses coronavirus entry mechanisms focusing on the different triggers used by coronaviruses to initiate the conformational change of the S protein: receptor binding, low pH exposure and proteolytic activation. We also highlight commonalities between coronavirus S proteins and other class I viral fusion proteins, as well as distinctive features that confer distinct tropism, pathogenicity and host interspecies transmission characteristics to coronaviruses.", "qid": 2, "docid": "dkxi8mgw", "rank": 64, "score": 0.8029528856277466}, {"content": "Title: Mathematical modeling of interaction between innate and adaptive immune responses in COVID\u201019 and implications for viral pathogenesis Content: We have applied mathematical modeling to investigate the infections of the ongoing coronavirus disease\u20102019 (COVID\u201019) pandemic caused by SARS\u2010CoV\u20102 virus. We first validated our model using the well\u2010studied influenza viruses and then compared the pathogenesis processes between the two viruses. The interaction between host innate and adaptive immune responses was found to be a potential cause for the higher severity and mortality in COVID\u201019 patients. Specifically, the timing mismatch between the two immune responses has a major impact on disease progression. The adaptive immune response of the COVID\u201019 patients is more likely to come before the peak of viral load, while the opposite is true for influenza patients. This difference in timing causes delayed depletion of vulnerable epithelial cells in the lungs in COVID\u201019 patients while enhancing viral clearance in influenza patients. Stronger adaptive immunity in COVID\u201019 patients can potentially lead to longer recovery time and more severe secondary complications. Based on our analysis, delaying the onset of adaptive immune responses during the early phase of infections may be a potential treatment option for high\u2010risk COVID\u201019 patients. Suppressing the adaptive immune response temporarily and avoiding its interference with the innate immune response may allow the innate immunity to more efficiently clear the virus.", "qid": 2, "docid": "2s1npse5", "rank": 65, "score": 0.8027611970901489}, {"content": "Title: SARS-CoV-2 launches a unique transcriptional signature from in vitro, ex vivo, and in vivo systems Content: One of the greatest threats to humanity is the emergence of a pandemic virus. Among those with the greatest potential for such an event include influenza viruses and coronaviruses. In the last century alone, we have observed four major influenza A virus pandemics as well as the emergence of three highly pathogenic coronaviruses including SARS-CoV-2, the causative agent of the ongoing COVID-19 pandemic. As no effective antiviral treatments or vaccines are presently available against SARS-CoV-2, it is important to understand the host response to this virus as this may guide the efforts in development towards novel therapeutics. Here, we offer the first in-depth characterization of the host transcriptional response to SARS-CoV-2 and other respiratory infections through in vitro, ex vivo, and in vivo model systems. Our data demonstrate the each virus elicits both core antiviral components as well as unique transcriptional footprints. Compared to the response to influenza A virus and respiratory syncytial virus, SARS-CoV-2 elicits a muted response that lacks robust induction of a subset of cytokines including the Type I and Type III interferons as well as a numerous chemokines. Taken together, these data suggest that the unique transcriptional signature of this virus may be responsible for the development of COVID-19.", "qid": 2, "docid": "ahpkmffy", "rank": 66, "score": 0.8027087450027466}, {"content": "Title: Innate Immune Signaling and Proteolytic Pathways in the Resolution or Exacerbation of SARS-CoV-2 in Covid-19: Key Therapeutic Targets? Content: COVID-19 is caused by the Severe Acute Respiratory Syndrome (SARS) coronavirus (Cov)-2, an enveloped virus with a positive-polarity, single-stranded RNA genome. The initial outbreak of the pandemic began in December 2019, and it is affecting the human health of the global community. In common with previous pandemics (Influenza H1N1 and SARS-CoV) and the epidemics of Middle east respiratory syndrome (MERS)-CoV, CoVs target bronchial and alveolar epithelial cells. Virus protein ligands (e.g., haemagglutinin or trimeric spike glycoprotein for Influenza and CoV, respectively) interact with cellular receptors, such as (depending on the virus) either sialic acids, Dipeptidyl peptidase 4 (DPP4), or angiotensin-converting enzyme 2 (ACE2). Host proteases, e.g., cathepsins, furin, or members of the type II transmembrane serine proteases (TTSP) family, such as Transmembrane protease serine 2 (TMPRSS2), are involved in virus entry by proteolytically activating virus ligands. Also involved are Toll Like Receptor (TLR) family members, which upregulate anti-viral and pro-inflammatory mediators [interleukin (IL)-6 and IL-8 and type I and type III Interferons among others], through the activation of Nuclear Factor (NF)-kB. When these events (virus cellular entry and innate immune responses) are uncontrolled, a deleterious systemic response is sometimes encountered in infected patients, leading to the well-described \"cytokine storm\" and an ensuing multiple organ failure promoted by a downregulation of dendritic cell, macrophage, and T-cell function. We aim to describe how the lung and systemic host innate immune responses affect survival either positively, through downregulating initial viral load, or negatively, by triggering uncontrolled inflammation. An emphasis will be put on host cellular signaling pathways and proteases involved with a view on tackling these therapeutically.", "qid": 2, "docid": "ls88uo78", "rank": 67, "score": 0.8026010990142822}, {"content": "Title: Sub-continental Atmosphere and Inherent Immune System may have Impact on Novel Corona Virus' 2019 (nCovid-19) Prevalence in South East Asia Content: Pandemic enveloped RNA Novel Corona Virus' 2019 (SARS-CoV-2) appears as a beating reed which induce overwhelming outbreak all over the world since November 2019 to till date. Inherent Immunity developed by traditional food habit, exposure to various antigens and vitamin D induced sunlight exposure. Meteorological parameters are the important factors which influencing the severe acute respiratory syndrome (SARS) like infectious disease. Aim of this review to enhance our knowledge and explore the association among build up immunity, weather parameters and Corona virus disease (COVID-19) death. In this review we emphasize role of meteorological factor included degree of sun exposure and effect of temperature on enveloped lipid bi-layer structure of Novel corona virus. These meteorological factors and inherent immunity may have impact on SARS-CoV-2 incidence among South East Asian including Bangladeshi. In summary, this study suggests that temperature-humidity variation, inherent immunity and lower life expectancy of South East Asia may be important.", "qid": 2, "docid": "p8p6e72k", "rank": 68, "score": 0.8020818829536438}, {"content": "Title: Sub-continental Atmosphere and Inherent Immune System may have Impact on Novel Corona Virus' 2019 (nCovid-19) Prevalence in South East Asia. Content: Pandemic enveloped RNA Novel Corona Virus' 2019 (SARS-CoV-2) appears as a beating reed which induce overwhelming outbreak all over the world since November 2019 to till date. Inherent Immunity developed by traditional food habit, exposure to various antigens and vitamin D induced sunlight exposure. Meteorological parameters are the important factors which influencing the severe acute respiratory syndrome (SARS) like infectious disease. Aim of this review to enhance our knowledge and explore the association among build up immunity, weather parameters and Corona virus disease (COVID-19) death. In this review we emphasize role of meteorological factor included degree of sun exposure and effect of temperature on enveloped lipid bi-layer structure of Novel corona virus. These meteorological factors and inherent immunity may have impact on SARS-CoV-2 incidence among South East Asian including Bangladeshi. In summary, this study suggests that temperature-humidity variation, inherent immunity and lower life expectancy of South East Asia may be important.", "qid": 2, "docid": "ww1rgcds", "rank": 69, "score": 0.802081823348999}, {"content": "Title: Coronavirus neurovirulence correlates with the ability of the virus to induce proinflammatory cytokine signals from astrocytes and microglia. Content: The molecular and cellular basis of coronavirus neurovirulence is poorly understood. Since neurovirulence may be determined at the early stages of infection of the central nervous system (CNS), we hypothesize that it may depend on the ability of the virus to induce proinflammatory signals from brain cells for the recruitment of blood-derived inflammatory cells. To test this hypothesis, we studied the interaction between coronaviruses (mouse hepatitis virus) of different neurovirulences with primary cell cultures of brain immune cells (astrocytes and microglia) and mouse tissues. We found that the level of neurovirulence of the virus correlates with its differential ability to induce proinflammatory cytokines (interleukin 12 [IL-12] p40, tumor necrosis factor alpha, IL-6, IL-15, and IL-1beta) in astrocytes and microglia and in mouse brains and spinal cords. These findings suggest that coronavirus neurovirulence may depend on a novel discriminatory ability of astrocytes and microglia to induce a proinflammatory response in the CNS.", "qid": 2, "docid": "1nb08be3", "rank": 70, "score": 0.8020343780517578}, {"content": "Title: A single amino acid mutation in the spike protein of coronavirus infectious bronchitis virus hampers its maturation and incorporation into virions at the nonpermissive temperature Content: Abstract The spike (S) glycoprotein of coronavirus is responsible for receptor binding and membrane fusion. A number of variants with deletions and mutations in the S protein have been isolated from naturally and persistently infected animals and tissue cultures. Here, we report the emergence and isolation of two temperature sensitive (ts) mutants and a revertant in the process of cold-adaptation of coronavirus infectious bronchitis virus (IBV) to a monkey kidney cell line. The complete sequences of wild type (wt) virus, two ts mutants, and the revertant were compared and variations linked to phenotypes were mapped. A single amino acid reversion (L294-to-Q) in the S protein is sufficient to abrogate the ts phenotype. Interestingly, unlike wt virus, the revertant grows well at and below 32 \u00b0C, the permissive temperature, as it carries other mutations in multiple genes that might be associated with the cold-adaptation phenotype. If the two ts mutants were allowed to enter cells at 32 \u00b0C, the S protein was synthesized, core-glycosylated and at least partially modified at 40 \u00b0C. However, compared with wt virus and the revertant, no infectious particles of these ts mutants were assembled and released from the ts mutant-infected cells at 40 \u00b0C. Evidence presented demonstrated that the Q294-to-L294 mutation, located at a highly conserved domain of the S1 subunit, might hamper processing of the S protein to a matured 180-kDa, endo-glycosidase H-resistant glycoprotein and the translocation of the protein to the cell surface. Consequently, some essential functions of the S protein, including mediation of cell-to-cell fusion and its incorporation into virions, were completely abolished.", "qid": 2, "docid": "krb1eidw", "rank": 71, "score": 0.8019989132881165}, {"content": "Title: Coronavirus immunogens Content: Abstract Coronaviruses (CV) infect a variety of livestock, poultry and companion animals. They belong to at least five antigenic groups. CV cause localized infections of the respiratory and/or intestinal tracts, with the exception of feline infectious peritonitis virus (FIVP) and hemagglutinating encephalomyelitis (HEV) which cause systemic infections. The enteropathogenic CV infect the villous enterocytes resulting in villous atrophy leading to malabsorptive diarrhea. Several CV (bovine CV-BCV, porcine respiratory CV-PRCV, infectious bronchitis virus-IBV) cause respiratory disease. Current evidence indicates that protection against enteric and respiratory CV infections is mediated by passive or active immunity at the primary site of CV replication. Maternal vaccination approaches to induce passive immunity include the use of inactivated and modified live viral vaccines. Modified live viruses and a Ts mutant CV (FIPV) are also used as oral or intranasal vaccines to induce active mucosal immunity. The success of these vaccines in the field is often compromised by a number of potential problems. Coronaviruses are spherical, enveloped viruses, ranging from 80\u2013160 nm in diameter and containing a positive-stranded RNA genome. They possess prominent surface spikes and some species display a fringe of smaller surface projections believed to be the hemagglutinin (HE). Coronaviruses possess 3 to 4 structural proteins: the spike (S) glycoprotein (150\u2013200 kDa), the integral membrane glycoprotein (M; 20\u201330 kDa) and the nucleocapsid phosphoprotein (N; 43\u201350 kDa). A subset of CV (BCV, HEV, turkey CV) possess a third glycoprotein on the virion surface, the HE (60\u201365 kDa). These proteins can be quantitated using pooled monoclonal antibodies (mAb) to distinct epitopes of each protein in ELISA. Most research has focused on the S protein as a candidate antigen for CV vaccines since it induces virus neutralizing (VN) antibodies. However the HE protein stimulates the production of VN and HE inhibiting antibodies and the M protein induces antibodies that neutralize virus in the presence of complement. Attempts to correlate in vitro VN antibody activity with in vivo protection have shown that the passive transfer of VN mAb to the S or HE protein conferred passive protection against CV challenge in some studies, but not others. Additional research has implicated a possible role for other CV proteins in immunity. Studies of mAb to the M protein of transmissible gastroenteritis (TGEV) have provided evidence for a direct role of the M protein in the induction of \u03b1IFN by porcine blood leukocytes. The potential significance of this phenomenon to immunity to TGEV is unclear. Similarly, studies of IBV have suggested that determinants recognized by T cells reside on the N protein and these determinants may be shared among heterologous strains of IBV, resulting in the induction of cross-protection. Thus epitopes on the N protein may be important for induction of cell mediated immunity (CMI). CMI may play an important role in protection of cats against FIPV, since induction of circulating antibodies to the S protein of FIPV contributes to disease pathogenesis by the induction of immune complexes and antibody dependent enhancement of the infectivity of FIPV for macrophages. An increased understanding of antibody and CMI responses following natural CV infections in animals is needed to identify the antigens and epitopes that induce protective immune responses. The expression of CV structural protein genes in various vectors will provide the recombinant proteins needed for future immunogenicity studies in the host species. Furthermore, live rDNA vectors that replicate in the gut and express coronavirus genes may provide a new generation of coronavirus vaccines.", "qid": 2, "docid": "k406jf98", "rank": 72, "score": 0.8019779920578003}, {"content": "Title: Coronavirus Endoribonuclease and Deubiquitinating Interferon Antagonists Differentially Modulate the Host Response during Replication in Macrophages Content: Coronaviruses (CoVs) encode multiple interferon (IFN) antagonists that modulate the host response to virus replication. Here, we evaluated the host transcriptional response to infection with murine coronaviruses encoding independent mutations in one of two different viral antagonists, the deubiquitinase (DUB) within nonstructural protein 3 or the endoribonuclease (EndoU) within nonstructural protein 15. We used transcriptomics approaches to compare the scope and kinetics of the host response to the wild-type (WT), DUBmut, and EndoUmut viruses in infected macrophages. We found that the EndoUmut virus activates a focused response that predominantly involves type I interferons and interferon-related genes, whereas the WT and DUBmut viruses more broadly stimulate upregulation of over 2,800 genes, including networks associated with activating the unfolded protein response (UPR) and the proinflammatory response 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 inactivating a dominant viral antagonist, the coronavirus endoribonuclease, dramatically alters the host response in macrophages. IMPORTANCE Macrophages are an important cell type during coronavirus infections because they \u201cnotice\u201d the infection and respond by inducing type I interferons, which limits virus replication. In turn, coronaviruses encode proteins that mitigate the cell\u2019s ability to signal an interferon response. Here, we evaluated the host macrophage response to two independent mutant coronaviruses, one with 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-related genes. In contrast, wild-type virus and the DUBmut virus elicited a more limited interferon response and ultimately activated over 2,800 genes, including players in the unfolded protein response and proinflammatory pathways associated with progression of significant disease. This study reveals that EndoU activity substantially contributes to the ability of coronaviruses to evade the host innate response and to replicate in macrophages.", "qid": 2, "docid": "k38jssr0", "rank": 73, "score": 0.8019751310348511}, {"content": "Title: The Effects of Temperature and Relative Humidity on the Viability of the SARS Coronavirus Content: The main route of transmission of SARS CoV infection is presumed to be respiratory droplets. However the virus is also detectable in other body fluids and excreta. The stability of the virus at different temperatures and relative humidity on smooth surfaces were studied. The dried virus on smooth surfaces retained its viability for over 5 days at temperatures of 22\u201325\u00b0C and relative humidity of 40\u201350%, that is, typical air-conditioned environments. However, virus viability was rapidly lost (>3 log(10)) at higher temperatures and higher relative humidity (e.g., 38\u00b0C, and relative humidity of >95%). The better stability of SARS coronavirus at low temperature and low humidity environment may facilitate its transmission in community in subtropical area (such as Hong Kong) during the spring and in air-conditioned environments. It may also explain why some Asian countries in tropical area (such as Malaysia, Indonesia or Thailand) with high temperature and high relative humidity environment did not have major community outbreaks of SARS.", "qid": 2, "docid": "x3b6j5d0", "rank": 74, "score": 0.8015694618225098}, {"content": "Title: Evidence that higher temperatures are associated with lower incidence of COVID-19 in pandemic state, cumulative cases reported up to March 27, 2020 Content: Seasonal temperature variation may impact the trajectories of COVID-19 in different global regions. Cumulative data reported by the World Health Organization, for dates up to March 27, 20201, show association between COVID-19 incidence and regions at or above 30\u00b0 latitude. Historic climate data also show significant reduction of case rates with mean maximum temperature above approximately 22.5 degrees Celsius. Variance at the local level, however, could not be well explained by geography and temperature. These preliminary findings support continued countermeasures and study of SARS-CoV-2/COVID-19 transmission rates by temperature and humidity.", "qid": 2, "docid": "g26to20g", "rank": 75, "score": 0.8015569448471069}, {"content": "Title: Mouse hepatitis virus nsp14 exoribonuclease activity is required for resistance to innate immunity Content: Coronaviruses (CoV) are positive-sense RNA viruses that infect numerous mammalian and avian species and are capable of causing severe and lethal disease in humans. CoVs encode several innate immune antagonists that interact with the host innate immune response to facilitate efficient viral replication. CoV non-structural protein 14 (nsp14) encodes 3'-to-5' exoribonuclease activity (ExoN), which performs a proofreading function and is required for high-fidelity replication. Outside of the order Nidovirales, arenaviruses are the only RNA viruses that encode an ExoN, which functions to degrade dsRNA replication intermediates. In this study, we tested the hypothesis that CoV ExoN may also function to antagonize the innate immune response. We demonstrate that viruses lacking ExoN activity [ExoN(-)] are sensitive to cellular pretreatment with interferon beta (IFN-\u03b2) in a dose-dependent manner. In addition, ExoN(-) virus replication was attenuated in wild-type bone marrow-derived macrophages (BMMs) and partially restored in interferon alpha/beta receptor deficient (IFNAR-/-) BMMs. ExoN(-) virus replication did not result in IFN-\u03b2 gene expression, and in the presence of an IFN-\u03b2-mediated antiviral state, ExoN(-) viral RNA levels were not substantially reduced relative to untreated. However, ExoN(-) virus generated from IFN-\u03b2 pretreated cells had reduced specific infectivity and decreased relative fitness, suggesting that ExoN(-) virus generated during an antiviral state is less viable to establish a subsequent infection. Overall, our data suggest MHV ExoN activity is required for resistance to the innate immune response and antiviral mechanisms affecting the viral RNA sequence and/or an RNA modification act on viruses lacking ExoN activity.", "qid": 2, "docid": "p3b4yk5d", "rank": 76, "score": 0.8015539646148682}, {"content": "Title: Molecular mechanism of evolution and human infection with the novel coronavirus (2019-nCoV) Content: Since December, 2019, an outbreak of pneumonia caused by the new coronavirus (2019-nCoV) has hit the city of Wuhan in the Hubei Province. With the continuous development of the epidemic, it has become a national public health crisis and calls for urgent antiviral treatments or vaccines. The spike protein on the coronavirus envelope is critical for host cell infection and virus vitality. Previous studies showed that 2019-nCoV is highly homologous to human SARS-CoV and attaches host cells though the binding of the spike receptor binding domain (RBD) domain to the angiotensin-converting enzyme II (ACE2). However, the molecular mechanisms of 2019-nCoV binding to human ACE2 and evolution of 2019-nCoV remain unclear. In this study, we have extensively studied the RBD-ACE2 complex, spike protein, and free RBD systems of 2019-nCoV and SARS-CoV using protein-protein docking and molecular dynamics (MD) simulations. It was shown that the RBD-ACE2 binding free energy for 2019-nCoV is significantly lower than that for SARS-CoV, which is consistent with the fact that 2019-nCoV is much more infectious than SARS-CoV. In addition, the spike protein of 2019-nCoV shows a significantly lower free energy than that of SARS-CoV, suggesting that 2019-nCoV is more stable and able to survive a higher temperature than SARS-CoV. This may also provide insights into the evolution of 2019-nCoV because SARS-like coronaviruses are thought to have originated in bats that are known to have a higher body-temperature than humans. It was also revealed that the RBD of 2019-nCoV is much more flexible especially near the binding site and thus will have a higher entropy penalty upon binding ACE2, compared to the RBD of SARS-CoV. That means that 2019-nCoV will be much more temperature-sensitive in terms of human infection than SARS-CoV. With the rising temperature, 2019-nCoV is expected to decrease its infection ability much faster than SARS-CoV, and get controlled more easily. The present findings are expected to be helpful for the disease prevention and control as well as drug and vaccine development of 2019-nCoV.", "qid": 2, "docid": "hicqy5sj", "rank": 77, "score": 0.8015326261520386}, {"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": 2, "docid": "rq5nqm92", "rank": 78, "score": 0.801384449005127}, {"content": "Title: Vascular skin symptoms in COVID-19: a french observational study Content: Coronavirus 19 (COVID-19) was declared as a pandemic viral infection by the World Health organization on March 11th 2020. Usual clinical manifestations of COVID-19 infection include fever, fatigue, myalgia, headache, diarrhea, dry cough, dyspnea that may lead to acute respiratory distress syndrome and death (1). Skin symptoms of COVID-19 have been poorly described but may include erythematous rash, urticaria and chicken pox like lesions (2-7). Angiotensin-converting enzyme 2 (ACE2) is a cellular receptor for COVID-19.", "qid": 2, "docid": "vp5xj8m5", "rank": 79, "score": 0.8013733625411987}, {"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": 2, "docid": "r7ahl9gd", "rank": 80, "score": 0.80134117603302}, {"content": "Title: SARS-CoV-2 mortality in blacks and temperature-sensitivity to an angiotensin-2 receptor blocker Content: Tropical climates provoke adaptations in skin pigmentation and in mechanisms controlling the volume, salt-content and pressure of body fluids. For many whose distant ancestors moved to temperate climes, these adaptations proved harmful: pigmentation decreased by natural selection and susceptibility to hypertension emerged. Now an added risk is lung inflammation from coronavirus that may be furthered by innate immune differences. Hypertension and coronavirus have in common angiotensin converting enzyme 2 (ACE2), which decreases blood pressure and mediates virus entry. In keeping with less detailed studies, a long-term case-report shows that decreased blood pressure induced by blocking a primary angiotensin receptor is supplemented, above critical blocker dosage, by a further temperature-dependent fall, likely mediated by ACE2 and secondary angiotensin receptors. Temperature-dependence suggests a linkage with tropical heritage and an influence of blockers on the progress of coronavirus infections. Positive therapeutic results should result from negation of host pro-inflammatory effects mediated by the primary angiotensin receptor and concomitant promotion of countervailing anti-inflammatory effects mediated by ACE2 through other receptors. These effects may involve components of the lectin complement pathway. Black vulnerability, more likely based on physiological than on socioeconomic differences, provides an important clue that may guide treatments.", "qid": 2, "docid": "2sdqehyw", "rank": 81, "score": 0.8011821508407593}, {"content": "Title: As We Went to Press: COVID-19 Continues to Spread Content: Updates on the coronavirus.", "qid": 2, "docid": "7t976vq8", "rank": 82, "score": 0.8010879755020142}, {"content": "Title: As We Went to Press: COVID-19 Continues to Spread. Content: Updates on the coronavirus.", "qid": 2, "docid": "sb1n3fra", "rank": 83, "score": 0.8010879755020142}, {"content": "Title: Is COVID-19 receiving ADE from other coronaviruses? Content: Abstract One of the most perplexing questions regarding the current COVID-19 coronavirus epidemic is the discrepancy between the severity of cases observed in the Hubei province of China and those occurring elsewhere in the world. One possible answer is antibody dependent enhancement (ADE) of SARS-CoV-2 due to prior exposure to other coronaviruses. ADE modulates the immune response and can elicit sustained inflammation, lymphopenia, and/or cytokine storm, one or all of which have been documented in severe cases and deaths. ADE also requires prior exposure to similar antigenic epitopes, presumably circulating in local viruses, making it a possible explanation for the observed geographic limitation of severe cases and deaths.", "qid": 2, "docid": "ctd9sutv", "rank": 84, "score": 0.8010812997817993}, {"content": "Title: Innate Immune Signaling and Proteolytic Pathways in the Resolution or Exacerbation of SARS-CoV-2 in Covid-19: Key Therapeutic Targets? Content: COVID-19 is caused by the Severe Acute Respiratory Syndrome (SARS) coronavirus (Cov)-2, an enveloped virus with a positive-polarity, single-stranded RNA genome. The initial outbreak of the pandemic began in December 2019, and it is affecting the human health of the global community. In common with previous pandemics (Influenza H1N1 and SARS-CoV) and the epidemics of Middle east respiratory syndrome (MERS)-CoV, CoVs target bronchial and alveolar epithelial cells. Virus protein ligands (e.g., haemagglutinin or trimeric spike glycoprotein for Influenza and CoV, respectively) interact with cellular receptors, such as (depending on the virus) either sialic acids, Dipeptidyl peptidase 4 (DPP4), or angiotensin-converting enzyme 2 (ACE2). Host proteases, e.g., cathepsins, furin, or members of the type II transmembrane serine proteases (TTSP) family, such as Transmembrane protease serine 2 (TMPRSS2), are involved in virus entry by proteolytically activating virus ligands. Also involved are Toll Like Receptor (TLR) family members, which upregulate anti-viral and pro-inflammatory mediators [interleukin (IL)-6 and IL-8 and type I and type III Interferons among others], through the activation of Nuclear Factor (NF)-kB. When these events (virus cellular entry and innate immune responses) are uncontrolled, a deleterious systemic response is sometimes encountered in infected patients, leading to the well-described \u201ccytokine storm\u201d and an ensuing multiple organ failure promoted by a downregulation of dendritic cell, macrophage, and T-cell function. We aim to describe how the lung and systemic host innate immune responses affect survival either positively, through downregulating initial viral load, or negatively, by triggering uncontrolled inflammation. An emphasis will be put on host cellular signaling pathways and proteases involved with a view on tackling these therapeutically.", "qid": 2, "docid": "5gz2dotn", "rank": 85, "score": 0.8010420799255371}, {"content": "Title: Is There a Role for Environmental and Metabolic Factors Predisposing to Severe COVID-19? Content: The severe acute respiratory syndrome-coronavirus-2 (SARS-CoV-2) pandemic affects people around the world. However, there have been striking differences in the number of infected individuals and deaths in different countries. Particularly, within Central Europe in countries that are similar in ethnicity, age, and medical standards and have performed similar steps of containment, such differences in mortality rates remain inexplicable. We suggest to consider and explore environmental factors to explain these intriguing variations. Countries like Northern Italy, France, Spain, and UK have suffered from 5 times more deaths from the corona virus infection than neighboring countries like Germany, Switzerland, Austria, and Denmark related to the size of their respective populations. There is a striking correlation between the level of environmental pollutants including pesticides, dioxins, and air pollution such as NO2 known to affect immune function and healthy metabolism with the rate of mortality in COVID-19 pandemic in these European countries. There is also a correlation with the use of chlorination of drinking water in these regions. In addition to the improvement of environmental protective programs, there are possibilities to lower the blood levels of these pollutants by therapeutic apheresis. Furthermore, therapeutic apheresis might be an effective method to improve metabolic inflammation, altered vascular perfusion, and neurodegeneration observed as long-term complications of COVID-19 disease.", "qid": 2, "docid": "wrmu94g3", "rank": 86, "score": 0.8008238077163696}, {"content": "Title: Temperature Decreases Spread Parameters of the New Covid-19 Case Dynamics Content: (1) Background: The virulence of coronavirus diseases due to viruses like SARS-CoV or MERS-CoV decreases in humid and hot weather. The putative temperature dependence of infectivity by the new coronavirus SARS-CoV-2 or covid-19 has a high predictive medical interest. (2) Methods: External temperature and new covid-19 cases in 21 countries and in the French administrative regions were collected from public data. Associations between epidemiological parameters of the new case dynamics and temperature were examined using an ARIMA model. (3) Results: We show that, in the first stages of the epidemic, the velocity of contagion decreases with country- or region-wise temperature. (4) Conclusions: Results indicate that high temperatures diminish initial contagion rates, but seasonal temperature effects at later stages of the epidemy remain questionable. Confinement policies and other eviction rules should account for climatological heterogeneities, in order to adapt the public health decisions to possible geographic or seasonal gradients.", "qid": 2, "docid": "03s9spbi", "rank": 87, "score": 0.8003302812576294}, {"content": "Title: Coronavirus Spike Protein Inhibits Host Cell Translation by Interaction with eIF3f Content: In response to viral infection, the expression of numerous host genes, including predominantly a number of proinflammatory cytokines and chemokines, is usually up-regulated at both transcriptional and translational levels. It was noted that in cells infected with coronavirus, transcription and translation of some of these genes were differentially induced. Drastic induction of their expression at the transcriptional level was observed in cells infected with coronavirus. However, induction of the same genes at the translational level was usually found to be minimal to moderate. To investigate the underlying mechanisms, yeast two-hybrid screen was carried out using SARS-CoV proteins as baits, revealing that a subunit of the eukaryotic initiation factor 3 (eIF3), eIF3f, may interact with the N-terminal region of the SARS-CoV spike (S) protein. This interaction was subsequently confirmed by co-immunoprecipitation and immunofluorescent staining. Meanwhile, parallel experiments confirmed that eIF3f could also interact with the S protein of another coronavirus, the avian coronavirus infectious bronchitis virus (IBV). These interactions led to the inhibition of translation of a reporter gene in both in vitro expression system and intact cells. Interestingly, IBV-infected cells stably expressing a Flag-tagged eIF3f showed much higher translation of IL-6 and IL-8, suggesting that the interaction between coronavirus S protein and eIF3f plays a functional role in controlling the expression of host genes, especially genes that are induced during coronavirus infection cycles. This study reveals a novel mechanism exploited by coronavirus to regulate viral pathogenesis.", "qid": 2, "docid": "gstpi4mw", "rank": 88, "score": 0.8002274632453918}, {"content": "Title: Anomalous atmospheric circulation favored the spread of COVID-19 in Europe Content: The current pandemic caused by the coronavirus SARS-CoV-2 is having negative health, social and economic consequences worldwide. In Europe, the pandemic started to develop strongly at the end of February and beginning of March 2020. It has subsequently spread over the continent, with special virulence in northern Italy and inland Spain. In this study we show that an unusual persistent anticyclonic situation prevailing in southwestern Europe during February 2020 (i.e. anomalously strong positive phase of the North Atlantic and Arctic Oscillations) could have resulted in favorable conditions, in terms of air temperature and humidity, in Italy and Spain for a quicker spread of the virus compared with the rest of the European countries. It seems plausible that the strong atmospheric stability and associated dry conditions that dominated in these regions may have favored the virus's propagation, by short-range droplet transmission as well as likely by long-range aerosol (airborne) transmission.", "qid": 2, "docid": "frlc6694", "rank": 89, "score": 0.7998483180999756}, {"content": "Title: Subversion of host stress granules by coronaviruses: Potential roles of \u03c0\u2010rich disordered domains of viral nucleocapsids Content: Coronavirus nucleocapsids (CoV N's) play both structural and non\u2010structural roles in viral life\u2010cycle. Here, we propose a mechanism for host stress granule (SG) subversion by CoV N proteins. We posit that disordered domains of CoV N's can engage in \u03c0\u2010\u03c0 intermolecular fuzzy interactions with host SG proteins and are crucial to the viral hijacking of host machineries. This article is protected by copyright. All rights reserved.", "qid": 2, "docid": "e4mve8ja", "rank": 90, "score": 0.7997455596923828}, {"content": "Title: Effect of Temperature on the Transmission of COVID-19: A Machine Learning Case Study in Spain Content: The novel coronavirus (COVID-19) has already spread to almost every country in the world and has infected over 3 million people. To understand the transmission mechanism of this highly contagious virus, it is necessary to study the potential factors, including meteorological conditions. Here, we present a machine learning approach to study the effect of temperature, humidity and wind speed on the number of infected people in the three most populous autonomous communities in Spain. We find that there is a moderate inverse correlation between temperature and the daily number of infections. This correlation manifests for temperatures recorded up to 6 days before the onset, which corresponds well to the known mean incubation period of COVID-19. We also show that the correlation for humidity and wind speed is not significant.", "qid": 2, "docid": "r9yrr45q", "rank": 91, "score": 0.7995675802230835}, {"content": "Title: Childbirth, Puerperium and Abortion Care Protocol during the COVID-19 Pandemic. Content: The new coronavirus (severe acute respiratory syndrome-related coronavirus 2, SARS-CoV-2) is a virus that causes a potentially serious respiratory disease that has spread in several countries, reaching humans in all age groups, including pregnant women. The purpose of this protocol is to provide technical and scientific support to Brazilian obstetricians regarding childbirth, postpartum and abortion care during the pandemic.", "qid": 2, "docid": "moh63x6z", "rank": 92, "score": 0.7992905378341675}, {"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": 2, "docid": "lqdgvsaq", "rank": 93, "score": 0.7991733551025391}, {"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": 2, "docid": "vslevssr", "rank": 94, "score": 0.7991733551025391}, {"content": "Title: The intensity of COVID-19 outbreaks is modulated by variation in SARS-CoV-2 free-living survival and environmental transmission Content: COVID-19 has circled the globe, rapidly expanding into a pandemic within a matter of weeks. While early studies revealed important features of SARS-CoV-2 transmission, the role of variation in free-living virus survival in modulating the dynamics of outbreaks remains unclear. Using an empirically determined understanding of SARS-CoV-2 natural history and detailed, country-level case data, we elucidate how variation in free-living virus survival influences key features of COVID-19 epidemics. Our findings suggest that COVID-19\u2019s basic reproductive number ([Formula: see text]) and other key signatures of outbreak intensity are defined by transmission between infected individuals and the environment. Summarizing, we propose that variation in environmental transmission may explain observed differences in disease dynamics from setting to setting, and can inform public health interventions.", "qid": 2, "docid": "dspux26k", "rank": 95, "score": 0.7990667223930359}, {"content": "Title: The NF-\u03baB-dependent and -independent transcriptome and chromatin landscapes of human coronavirus 229E-infected cells Content: Coronavirus replication takes place in the host cell cytoplasm and triggers inflammatory gene expression by poorly characterized mechanisms. To obtain more insight into the signals and molecular events that coordinate global host responses in the nucleus of coronavirus-infected cells, first, transcriptome dynamics was studied in human coronavirus 229E (HCoV-229E)-infected A549 and HuH7 cells, respectively, revealing a core signature of upregulated genes in these cells. Compared to treatment with the prototypical inflammatory cytokine interleukin(IL)-1, HCoV-229E replication was found to attenuate the inducible activity of the transcription factor (TF) NF-\u03baB and to restrict the nuclear concentration of NF-\u03baB subunits by (i) an unusual mechanism involving partial degradation of IKK\u03b2, NEMO and I\u03baB\u03b1 and (ii) upregulation of TNFAIP3 (A20), although constitutive IKK activity and basal TNFAIP3 expression levels were shown to be required for efficient virus replication. Second, we characterized actively transcribed genomic regions and enhancers in HCoV-229E-infected cells and systematically correlated the genome-wide gene expression changes with the recruitment of Ser5-phosphorylated RNA polymerase II and prototypical histone modifications (H3K9ac, H3K36ac, H4K5ac, H3K27ac, H3K4me1). The data revealed that, in HCoV-infected (but not IL-1-treated) cells, an extensive set of genes was activated without inducible p65 NF-\u03baB being recruited. Furthermore, both HCoV-229E replication and IL-1 were shown to upregulate a small set of genes encoding immunomodulatory factors that bind p65 at promoters and require IKK\u03b2 activity and p65 for expression. Also, HCoV-229E and IL-1 activated a common set of 440 p65-bound enhancers that differed from another 992 HCoV-229E-specific enhancer regions by distinct TF-binding motif combinations. Taken together, the study shows that cytoplasmic RNA viruses fine-tune NF-\u03baB signaling at multiple levels and profoundly reprogram the host cellular chromatin landscape, thereby orchestrating the timely coordinated expression of genes involved in multiple signaling, immunoregulatory and metabolic processes.", "qid": 2, "docid": "2haiwiop", "rank": 96, "score": 0.7988455295562744}, {"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": 97, "score": 0.7988187074661255}, {"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": 2, "docid": "nacxjt2f", "rank": 98, "score": 0.7988169193267822}, {"content": "Title: Differential stepwise evolution of SARS coronavirus functional proteins in different host species Content: BACKGROUND: SARS coronavirus (SARS-CoV) was identified as the etiological agent of SARS, and extensive investigations indicated that it originated from an animal source (probably bats) and was recently introduced into the human population via wildlife animals from wet markets in southern China. Previous studies revealed that the spike (S) protein of SARS had experienced adaptive evolution, but whether other functional proteins of SARS have undergone adaptive evolution is not known. RESULTS: We employed several methods to investigate selective pressure among different SARS-CoV groups representing different epidemic periods and hosts. Our results suggest that most functional proteins of SARS-CoV have experienced a stepwise adaptive evolutionary pathway. Similar to previous studies, the spike protein underwent strong positive selection in the early and middle phases, and became stabilized in the late phase. In addition, the replicase experienced positive selection only in human patients, whereas assembly proteins experienced positive selection mainly in the middle and late phases. No positive selection was found in any proteins of bat SARS-like-CoV. Furthermore, specific amino acid sites that may be the targets of positive selection in each group are identified. CONCLUSION: This extensive evolutionary analysis revealed the stepwise evolution of different functional proteins of SARS-CoVs at different epidemic stages and different hosts. These results support the hypothesis that SARS-CoV originated from bats and that the spill over into civets and humans were more recent events.", "qid": 2, "docid": "i5hkucrn", "rank": 99, "score": 0.798717737197876}, {"content": "Title: Virus Adaptation by Manipulation of Host's Gene Expression Content: Viruses adapt to their hosts by evading defense mechanisms and taking over cellular metabolism for their own benefit. Alterations in cell metabolism as well as side-effects of antiviral responses contribute to symptoms development and virulence. Sometimes, a virus may spill over from its usual host species into a novel one, where usually will fail to successfully infect and further transmit to new host. However, in some cases, the virus transmits and persists after fixing beneficial mutations that allow for a better exploitation of the new host. This situation would represent a case for a new emerging virus. Here we report results from an evolution experiment in which a plant virus was allowed to infect and evolve on a na\u00efve host. After 17 serial passages, the viral genome has accumulated only five changes, three of which were non-synonymous. An amino acid substitution in the viral VPg protein was responsible for the appearance of symptoms, whereas one substitution in the viral P3 protein the epistatically contributed to exacerbate severity. DNA microarray analyses show that the evolved and ancestral viruses affect the global patterns of host gene expression in radically different ways. A major difference is that genes involved in stress and pathogen response are not activated upon infection with the evolved virus, suggesting that selection has favored viral strategies to escape from host defenses.", "qid": 2, "docid": "3ib99gup", "rank": 100, "score": 0.7985146045684814}]}
{"query": "will SARS-CoV2 infected people develop immunity? Is cross protection possible?", "hits": [{"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": 1, "score": 0.8784176111221313}, {"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": 2, "score": 0.8707402944564819}, {"content": "Title: SARS-CoV-2 infection protects against rechallenge in rhesus macaques Content: An understanding of protective immunity to SARS-CoV-2 is critical for vaccine and public health strategies aimed at ending the global COVID-19 pandemic. A key unanswered question is whether infection with SARS-CoV-2 results in protective immunity against re-exposure. We developed a rhesus macaque model of SARS-CoV-2 infection and observed that macaques had high viral loads in the upper and lower respiratory tract, humoral and cellular immune responses, and pathologic evidence of viral pneumonia. Following initial viral clearance, animals were rechallenged with SARS-CoV-2 and showed 5 log10 reductions in median viral loads in bronchoalveolar lavage and nasal mucosa compared with primary infection. Anamnestic immune responses following rechallenge suggested that protection was mediated by immunologic control. These data show that SARS-CoV-2 infection induced protective immunity against re-exposure in nonhuman primates.", "qid": 3, "docid": "t3sjv4hv", "rank": 3, "score": 0.8666390776634216}, {"content": "Title: SARS-CoV-2 infection protects against rechallenge in rhesus macaques Content: An understanding of protective immunity to SARS-CoV-2 is critical for vaccine and public health strategies aimed at ending the global COVID-19 pandemic. A key unanswered question is whether infection with SARS-CoV-2 results in protective immunity against re-exposure. We developed a rhesus macaque model of SARS-CoV-2 infection and observed that macaques had high viral loads in the upper and lower respiratory tract, humoral and cellular immune responses, and pathologic evidence of viral pneumonia. Following initial viral clearance, animals were rechallenged with SARS-CoV-2 and showed 5 log(10) reductions in median viral loads in bronchoalveolar lavage and nasal mucosa compared with primary infection. Anamnestic immune responses following rechallenge suggested that protection was mediated by immunologic control. These data show that SARS-CoV-2 infection induced protective immunity against re-exposure in nonhuman primates.", "qid": 3, "docid": "car394ou", "rank": 4, "score": 0.8661542534828186}, {"content": "Title: Children's vaccines do not induce cross reactivity against SARS-CoV. Content: In contrast with adults, children infected by severe acute respiratory syndrome-corona virus (SARS-CoV) develop milder clinical symptoms. Because of this, it is speculated that children vaccinated with various childhood vaccines might develop cross immunity against SARS-CoV. Antisera and T cells from mice immunised with various vaccines were used to determine whether they developed cross reactivity against SARS-CoV. The results showed no marked cross reactivity against SARS-CoV, which implies that the reduced symptoms among children infected by SARS-CoV may be caused by other factors.", "qid": 3, "docid": "eo4ehcjv", "rank": 5, "score": 0.8658335208892822}, {"content": "Title: Seropr\u00e4valenz und SARS-CoV-2-Testung in Gesundheitsberufen./ [Seroprevalence and SARS-CoV-2 testing in healthcare occupations] Content: The SARS-CoV\u00ad2 causes a disease spectrum that includes asymptomatic and mildly symptomatic infections with subclinical manifestations but which can nevertheless still be potentially contagious. Evidence from SARS-CoV\u00ad2 infected macaque monkeys and from studies with seasonal coronaviruses suggests that the infection is likely to produce an immunity that is protective for a certain period of time. Available test methods enable a high degree of reliability, e.g. if high-quality serological methods are combined. Although individual test results have to be interpreted with caution, serosurveillance in a tertiary eye care center and large eye research institute can reduce anxiety and provide clarity regarding the actual number of (unreported) SARS-CoV\u00ad2 infections.", "qid": 3, "docid": "rlpe6tpm", "rank": 6, "score": 0.8651522397994995}, {"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": 7, "score": 0.8650558590888977}, {"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": 3, "docid": "dptgg05n", "rank": 8, "score": 0.8648175597190857}, {"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": 9, "score": 0.8640625476837158}, {"content": "Title: Immune Responses to SARS-CoV, MERS-CoV and SARS-CoV-2 Content: The world has given an outbreak alarm in the last two decades, with different members of the coronavirus family infecting people at different times. The spread of the SARS-CoV-2 virus, which last appeared in December 2019 in China and spread rapidly to all over the world, has led the scientific world to studies on these viruses. While scientists are trying to develop vaccines or drugs against the virus, the body's immune response to the virus is emerged the biggest guide. In this review, we aimed to provide a good view on immune strategies by comparing immunological responses to SARS-CoV-2 disease among other members of the family, SARS-CoV and MERS-CoV. In the near future, it may contribute to vaccine or drug studies to be developed on immune intervention.", "qid": 3, "docid": "chaa3swx", "rank": 10, "score": 0.8631606101989746}, {"content": "Title: Immune Responses to SARS-CoV, MERS-CoV and SARS-CoV-2. Content: The world has given an outbreak alarm in the last two decades, with different members of the coronavirus family infecting people at different times. The spread of the SARS-CoV-2 virus, which last appeared in December 2019 in China and spread rapidly to all over the world, has led the scientific world to studies on these viruses. While scientists are trying to develop vaccines or drugs against the virus, the body's immune response to the virus is emerged the biggest guide. In this review, we aimed to provide a good view on immune strategies by comparing immunological responses to SARS-CoV-2 disease among other members of the family, SARS-CoV and MERS-CoV. In the near future, it may contribute to vaccine or drug studies to be developed on immune intervention.", "qid": 3, "docid": "v155jl20", "rank": 11, "score": 0.8631604909896851}, {"content": "Title: Universal coronavirus vaccines: the time to start is now Content: The continued explosive spread of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) despite aggressive public health measures has triggered an unprecedented international vaccine effort. However, correlates of protection, which can help guide intelligent vaccine design, are not known for SARS-CoV-2. Research on influenza immunity and vaccine development may provide valuable lessons for coronavirus efforts, especially considering similarities in rapid evolutionary potential. The apparent inevitability of future novel coronavirus outbreaks must prompt work on a universal coronavirus vaccine.", "qid": 3, "docid": "yrrz7oef", "rank": 12, "score": 0.8627628087997437}, {"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": 3, "docid": "fzdmcahf", "rank": 13, "score": 0.8621779084205627}, {"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": 3, "docid": "ipw96f03", "rank": 14, "score": 0.8621452450752258}, {"content": "Title: Seropr\u00e4valenz und SARS-CoV-2-Testung in Gesundheitsberufen Content: The SARS-CoV\u20112 causes a disease spectrum that includes asymptomatic and mildly symptomatic infections with subclinical manifestations but which can nevertheless still be potentially contagious. Evidence from SARS-CoV\u20112 infected macaque monkeys and from studies with seasonal coronaviruses suggests that the infection is likely to produce an immunity that is protective for a certain period of time. Available test methods enable a high degree of reliability, e.g. if high-quality serological methods are combined. Although individual test results have to be interpreted with caution, serosurveillance in a tertiary eye care center and large eye research institute can reduce anxiety and provide clarity regarding the actual number of (unreported) SARS-CoV\u20112 infections.", "qid": 3, "docid": "u4sy1sjr", "rank": 15, "score": 0.8615311980247498}, {"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": 16, "score": 0.8614306449890137}, {"content": "Title: Trained Immunity: a Tool for Reducing Susceptibility to and the Severity of SARS-CoV-2 Infection Content: SARS-CoV-2 infection is mild in the majority of individuals but progresses into severe pneumonia in a small proportion of patients. The increased susceptibility to severe disease in the elderly and individuals with co-morbidities argues for an initial defect in anti-viral host defense mechanisms. Long-term boosting of innate immune responses, also termed \"trained immunity,\" by certain live vaccines (BCG, oral polio vaccine, measles) induces heterologous protection against infections through epigenetic, transcriptional, and functional reprogramming of innate immune cells. We propose that induction of trained immunity by whole-microorganism vaccines may represent an important tool for reducing susceptibility to and severity of SARS-CoV-2.", "qid": 3, "docid": "g5ovvjc6", "rank": 17, "score": 0.8603847026824951}, {"content": "Title: Evidence Supporting Transmission of Severe Acute Respiratory Syndrome Coronavirus 2 While Presymptomatic or Asymptomatic Content: Recent epidemiologic, virologic, and modeling reports support the possibility of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) transmission from persons who are presymptomatic (SARS-CoV-2 detected before symptom onset) or asymptomatic (SARS-CoV-2 detected but symptoms never develop). SARS-CoV-2 transmission in the absence of symptoms reinforces the value of measures that prevent the spread of SARS-CoV-2 by infected persons who may not exhibit illness despite being infectious. Critical knowledge gaps include the relative incidence of asymptomatic and symptomatic SARS-CoV-2 infection, the public health interventions that prevent asymptomatic transmission, and the question of whether asymptomatic SARS-CoV-2 infection confers protective immunity.", "qid": 3, "docid": "g12i1jig", "rank": 18, "score": 0.8603606224060059}, {"content": "Title: Updated thoughts on SARS-CoV-2 and coronavirus therapies, fighting and surviving Content: From late December 2019 a new human-adapted coronavirus, SARS-CoV-2, was observed and isolated in clustered patients in Wuhan, China. It has been proved to be able to transmit human-to-human and cause pneumonia, leading to about 2% fatality. Its genome characteristics, immune responses and related potential treatments, such as chemical drugs, serum transfusion and vaccines including DNA vaccines, are discussed in this review for a brief summary.", "qid": 3, "docid": "a1nc5k51", "rank": 19, "score": 0.8600667715072632}, {"content": "Title: Can an effective SARS-CoV-2 vaccine be developed for the older population? Content: The emergence of SARS-CoV-2 and its inordinately rapid spread is posing severe challenges to the wellbeing of millions of people worldwide, health care systems and the global economy. While many younger people experience no or mild symptoms on infection, older adults are highly susceptible to life-threatening respiratory and systemic conditions which demand a full understanding and leveraging of knowledge of the differences between immunity in young and old people. Consequently, we welcome papers addressing any issues relevant to immunity and ageing in the context of SARS-CoV-2, and will endeavour to fast-track peer-review. We aim to provide a platform exclusively for discussions of individual and age differences in susceptibility and immune responses to COVID caused by SARS-CoV-2 infection and how to prevent or reduce severity of disease in older adults.", "qid": 3, "docid": "fi1ldwe8", "rank": 20, "score": 0.859636664390564}, {"content": "Title: The SARS-CoV-2 Coronavirus and the COVID-19 Outbreak Content: The SARS-CoV-2, a newly identified \u00df-coronavirus, is the causative agent of the third large-scale pandemic from the last two decades. The outbreak started in December 2019 in Wuhan City, Hubei province in China. The patients presented clinical symptoms of dry cough, fever, dyspnea, and bilateral lung infiltrates on imaging. By February 2020, The World Health Organization (WHO) named the disease as Coronavirus Disease 2019 (COVID-19). The Coronavirus Study Group (CSG) of the International Committee on Taxonomy of Viruses (ICTV) recognized and designated this virus as severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). The SARS-CoV-2 uses the same host receptor, angiotensin-converting enzyme 2 (ACE2), used by SARS-CoV to infect humans. One hypothesis of SARSCoV-2 origin indicates that it is likely that bats serve as reservoir hosts for SARSCoV-2, being the intermediate host not yet determined. The predominant route of transmission of SARS-CoV-2 is from human to human. As of May 10th 2020, the number of worldwide confirmed COVID-19 cases is over 4 million, while the number of global deaths is around 279.000 people. The United States of America (USA) has the highest number of COVID-19 cases with over 1.3 million cases followed by Spain, Italy, United Kingdom, Russia, France and Germany with over 223.000, 218.000, 215.000, 209.000, 176.000, and 171.000 cases, respectively.", "qid": 3, "docid": "7re3jgya", "rank": 21, "score": 0.8583029508590698}, {"content": "Title: Long-term and herd immunity against SARS-CoV-2: implications from current and past knowledge Content: Effective herd immunity against SARS-CoV-2 will be determined on many factors: the percentage of the immune population, the length and effectiveness of the immune response and the stability of the viral epitopes. The required percentage of immune individuals has been estimated to be 50\u201366% of the population which, given the current infection rates, will take long to be achieved. Furthermore, data from SARS-CoV suggest that the duration of immunity may not be sufficiently significant, while the immunity response against SARS-CoV-2 may not be efficiently effective in all patients, as relapses have already been reported. In addition, the development of mutant strains, which has already been documented, can cause the reemergence of the epidemic. In conclusion, the development of an effective vaccine is an urgent necessity, as long-term natural immunity to SARS-CoV-2 may not be sufficient for the control of the current and future outbreaks.", "qid": 3, "docid": "6jr3z9wx", "rank": 22, "score": 0.8576704263687134}, {"content": "Title: Long-term and herd immunity against SARS-CoV-2: implications from current and past knowledge Content: Effective herd immunity against SARS-CoV-2 will be determined on many factors: the percentage of the immune population, the length and effectiveness of the immune response and the stability of the viral epitopes. The required percentage of immune individuals has been estimated to be 50-66% of the population which, given the current infection rates, will take long to be achieved. Furthermore, data from SARS-CoV suggest that the duration of immunity may not be sufficiently significant, while the immunity response against SARS-CoV-2 may not be efficiently effective in all patients, as relapses have already been reported. In addition, the development of mutant strains, which has already been documented, can cause the reemergence of the epidemic. In conclusion, the development of an effective vaccine is an urgent necessity, as long-term natural immunity to SARS-CoV-2 may not be sufficient for the control of the current and future outbreaks.", "qid": 3, "docid": "pcyscqux", "rank": 23, "score": 0.857024073600769}, {"content": "Title: The SARS-CoV-2 Coronavirus and the COVID-19 Outbreak. Content: The SARS-CoV-2, a newly identified \u03b2-coronavirus, is the causative agent of the third large-scale pandemic from the last two decades. The outbreak started in December 2019 in Wuhan City, Hubei province in China. The patients presented clinical symptoms of dry cough, fever, dyspnea, and bilateral lung infiltrates on imaging. By February 2020, The World Health Organization (WHO) named the disease as Coronavirus Disease 2019 (COVID-19). The Coronavirus Study Group (CSG) of the International Committee on Taxonomy of Viruses (ICTV) recognized and designated this virus as severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). The SARS-CoV-2 uses the same host receptor, angiotensin-converting enzyme 2 (ACE2), used by SARS-CoV to infect humans. One hypothesis of SARSCoV-2 origin indicates that it is likely that bats serve as reservoir hosts for SARSCoV-2, being the intermediate host not yet determined. The predominant route of transmission of SARS-CoV-2 is from human to human. As of May 10th 2020, the number of worldwide confirmed COVID-19 cases is over 4 million, while the number of global deaths is around 279.000 people. The United States of America (USA) has the highest number of COVID-19 cases with over 1.3 million cases followed by Spain, Italy, United Kingdom, Russia, France and Germany with over 223.000, 218.000, 215.000, 209.000, 176.000, and 171.000 cases, respectively.", "qid": 3, "docid": "1enb2vxv", "rank": 24, "score": 0.8568845987319946}, {"content": "Title: SARS-CoV-2 seroconversion in health care workers Content: Background The correlates of protection against SARS-CoV-2 and their longevity remain unclear. Studies in severely ill individuals have identified robust cellular and humoral immune responses against the virus. Asymptomatic infection with SARS-CoV-2 has also been described, but it is unknown whether this is sufficient to produce antibody responses. Methods We performed a cross-sectional study recruiting 554 health care workers from University Hospitals Birmingham NHS Foundation Trust who were at work and asymptomatic. Participants were tested for current infection with SARS-CoV-2 by nasopharyngeal swab for real-time polymerase chain reaction and for seroconversion by the measurement of anti-SARS-CoV-2 spike glycoprotein antibodies by enzyme linked immunosorbent assay. Results were interpreted in the context of previous, self-reported symptoms of illness consistent with COVID-19. Results The point prevalence of infection with SARS-CoV-2, determined by the detection of SARS-CoV-2 RNA on nasopharnygeal swab was 2.39% (n=13/544). Serum was available on 516 participants. The overall rate of seroconversion in the cohort was 24.4% (n=126/516). Individuals who had previously experienced a symptomatic illness consistent with COVID-19 had significantly greater seroconversion rates than those who had remained asymptomatic (37.5% vs 17.1%, {chi}2 =21.1034, p<0.0001). In the week preceding peak COVID-19-related mortality at UHBFT, seroconversion rates amongst those who were suffering from symptomatic illnesses peaked at 77.8%. Prior symptomatic illness generated quantitatively higher antibody responses than asymptomatic seroconversion. Seroconversion rates were highest amongst those working in housekeeping (34.5%), acute medicine (33.3%) and general internal medicine (30.3%) with lower rates observed in participants working in intensive care (14.8%) and emergency medicine (13.3%). Conclusions In a large cross-sectional seroprevalence study of health-care workers, we demonstrate that asymptomatic seroconversion occurs, however prior symptomatic illness is associated with quantitatively higher antibody responses. The identification that the potential for seroconversion in health-care workers can associate differentially with certain hospital departments may inform future infection control and occupational health practices.", "qid": 3, "docid": "2a12nsnl", "rank": 25, "score": 0.8568402528762817}, {"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": 26, "score": 0.8563212752342224}, {"content": "Title: Revisi\u00f3n narrativa sobre la respuesta inmunitaria frente a coronavirus: descripci\u00f3n general, aplicabilidad para SARS-COV-2 e implicaciones terap\u00e9uticas./ [Narrative review of the immune response against coronavirus: An overview, applicability for SARS-COV-2, and therapeutic implications] Content: The new coronavirus (SARS-CoV-2) that causes a severe acute respiratory syndrome emerges 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-CoV-2 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 its applicability to SARS-CoV-2. 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": "voqzmze6", "rank": 27, "score": 0.8559558391571045}, {"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": 3, "docid": "ioihqf0r", "rank": 28, "score": 0.8555406332015991}, {"content": "Title: T-cell immunity of SARS-CoV: Implications for vaccine development against MERS-CoV Content: Abstract Over 12 years have elapsed since severe acute respiratory syndrome (SARS) triggered the first global alert for coronavirus infections. Virus transmission in humans was quickly halted by public health measures and human infections of SARS coronavirus (SARS-CoV) have not been observed since. However, other coronaviruses still pose a continuous threat to human health, as exemplified by the recent emergence of Middle East respiratory syndrome (MERS) in humans. The work on SARS-CoV widens our knowledge on the epidemiology, pathophysiology and immunology of coronaviruses and may shed light on MERS coronavirus (MERS-CoV). It has been confirmed that T-cell immunity plays an important role in recovery from SARS-CoV infection. Herein, we summarize T-cell immunological studies of SARS-CoV and discuss the potential cross-reactivity of the SARS-CoV-specific immunity against MERS-CoV, which may provide useful recommendations for the development of broad-spectrum vaccines against coronavirus infections.", "qid": 3, "docid": "wh9vvgv2", "rank": 29, "score": 0.8553225994110107}, {"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": 30, "score": 0.8551222681999207}, {"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": 31, "score": 0.8548027873039246}, {"content": "Title: Clinical features and outcomes of four HIV patients with COVID\u201019 in Wuhan, China Content: SARS-CoV-2 is the coronavirus that has been identified as the pathogen causing COVID-19.1 Human Immunodeficiency Virus (HIV) attacks the immune system and leads to acquired immune deficiency syndrome (AIDS) in the late stage of disease. Concerns have been raised on HIV as a risk factor for COVID-19. This article is protected by copyright. All rights reserved.", "qid": 3, "docid": "f9gmlkez", "rank": 32, "score": 0.8542800545692444}, {"content": "Title: Current Insight into the Novel Coronavirus Disease 2019 (COVID-19) Content: SARS-CoV-2 is a novel strain of coronavirus that has not been previously identified in humans. It has been declared a pandemic and has infected at least 1,844,683 individuals and caused 117,021 deaths as of 14th April 2020. Transmission among humans occurs via close contact with an infected individual that produces respiratory droplets. Patients have been shown to undergo acute respiratory distress syndrome, which is defined as cytokine storm. The diagnosis relies on detection of nucleic acid, IgG/IgM antibodies, and a chest radiograph of the suspected individuals. The genome of SARS-CoV-2 is similar to other coronaviruses that comprise of ten open reading frames (ORFs). SARS-CoV-2 spike protein exhibits higher affinity to ACE2 receptor as compared with SARS-CoV. Repurposing drugs like favipiravir, remdesivir, chloroquine, and TMPRSS2 protease inhibitors have been shown to be effective for the treatment of COVID-19. Personal protective measures should be followed to prevent SARS-CoV-2 infection. In addition, a clinical trial of SARS-CoV-2 vaccine, mRNA-1273, has been started. This chapter provides a glimpse of advancements made in the area of SARS-CoV-2 infection by proving recent clinical and research trials in the field.", "qid": 3, "docid": "zv0ysi8m", "rank": 33, "score": 0.854021430015564}, {"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": 34, "score": 0.8539891242980957}, {"content": "Title: Lessons for COVID-19 immunity from other coronavirus infections Content: Abstract A key goal to controlling COVID-19 is developing an effective vaccine. Development of a vaccine requires knowledge of what constitutes a protective immune response and also features that might be pathogenic. Protective and pathogenic aspects of the response to SARS-CoV-2 are not well understood, partly because the virus has infected humans for only 6 months. However, insight into coronavirus immunity can be informed by previous studies of immune responses to non-human coronaviruses, to common cold coronaviruses, and to SARS-CoV and MERS-CoV. Here we review the literature describing these responses and discuss their relevance to the SARS-CoV-2 immune response.", "qid": 3, "docid": "s6v4bgev", "rank": 35, "score": 0.8536418080329895}, {"content": "Title: Seroprevalence of IgG antibodies to SARS-coronavirus in asymptomatic or subclinical population groups. Content: We systematically reviewed the current understanding of human population immunity against SARS-CoV in different groups, settings and geography. Our meta-analysis, which included all identified studies except those on wild animal handlers, yielded an overall seroprevalence of 0.10% [95% confidence interval (CI) 0.02-0.18]. Health-care workers and others who had close contact with SARS patients had a slightly higher degree of seroconversion (0.23%, 95% CI 0.02-0.45) compared to healthy blood donors, others from the general community or non-SARS patients recruited from the health-care setting (0.16%, 95% CI 0-0.37). When analysed by the two broad classes of testing procedures, it is clear that serial confirmatory test protocols resulted in a much lower estimate (0.050%, 95% CI 0-0.15) than single test protocols (0.20%, 95% CI 0.06-0.34). Potential epidemiological and laboratory pitfalls are also discussed as they may give rise to false or inconsistent results in measuring the seroprevalence of IgG antibodies to SARS-CoV.", "qid": 3, "docid": "j8ta21zr", "rank": 36, "score": 0.8532171845436096}, {"content": "Title: SARS-CoV-2\u2013A Tough Opponent for the Immune System Content: Coronaviruses recently returned with a new one, SARS-CoV-2, related to a potentially severe respiratory disease-called the coronavirus disease (COVID-19). Research shows that the SARS-CoV-2 can be clustered with the Bat SARS-like coronavirus. Bats possess an additional, innate ability for antiviral defense, and, on the other hand, the potential to go hand-in-hand with the virus to generate variability. Besides the high potential of the novel coronavirus in compromising the respiratory system, its rapid transmission and ability to engage many hosts in severe forms of infections or immunopathological complications make it a tough opponent for the immune system. The interactions between SARS-CoV2 and the host immune system result in unleashing tremendous amounts of cytokines, and these cytokines make a storm that would determine the outcome (recovery or death) of the lungs of the patient.", "qid": 3, "docid": "703febui", "rank": 37, "score": 0.8530411124229431}, {"content": "Title: SARS-CoV-2-A Tough Opponent for the Immune System Content: Coronaviruses recently returned with a new one, SARS-CoV-2, related to a potentially severe respiratory disease-called the coronavirus disease (COVID-19). Research shows that the SARS-CoV-2 can be clustered with the Bat SARS-like coronavirus. Bats possess an additional, innate ability for antiviral defense, and, on the other hand, the potential to go hand-in-hand with the virus to generate variability. Besides the high potential of the novel coronavirus in compromising the respiratory system, its rapid transmission and ability to engage many hosts in severe forms of infections or immunopathological complications make it a tough opponent for the immune system. The interactions between SARS-CoV2 and the host immune system result in unleashing tremendous amounts of cytokines, and these cytokines make a storm that would determine the outcome (recovery or death) of the lungs of the patient.", "qid": 3, "docid": "4lm663f1", "rank": 38, "score": 0.8530411124229431}, {"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": 39, "score": 0.8528314828872681}, {"content": "Title: Human coronavirus reinfection dynamics: lessons for SARS-CoV-2 Content: In the current SARS-CoV-2 pandemic a key unsolved question is the quality and duration of acquired immunity in recovered individuals. This is crucial to solve, however SARS-CoV-2 has circulated for under five months, precluding a direct study. We therefore monitored 10 subjects over a time span of 35 years (1985-2020), providing a total of 2473 follow up person-months, and determined a) their antibody levels following infection by any of the four seasonal human coronaviruses, and b) the time period after which reinfections by the same virus can occur. An alarmingly short duration of protective immunity to coronaviruses was found by both analyses. We saw frequent reinfections at 12 months post-infection and a substantial reduction in antibody levels as soon as 6 months post-infection.", "qid": 3, "docid": "u5nxm9tu", "rank": 40, "score": 0.8527764081954956}, {"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": 3, "docid": "eml8uilb", "rank": 41, "score": 0.8527361154556274}, {"content": "Title: Distinct systems serology features in children, elderly and COVID patients Content: SARS-CoV-2, the pandemic coronavirus that causes COVID-19, has infected millions worldwide, causing unparalleled social and economic disruptions. COVID-19 results in higher pathogenicity and mortality in the elderly compared to children. Examining baseline SARS-CoV-2 cross-reactive coronavirus immunological responses, induced by circulating human coronaviruses, is critical to understand such divergent clinical outcomes. The cross-reactivity of coronavirus antibody responses of healthy children (n=89), adults (n=98), elderly (n=57), and COVID-19 patients (n=19) were analysed by systems serology. While moderate levels of cross-reactive SARS-CoV-2 IgG, IgM, and IgA were detected in healthy individuals, we identified serological signatures associated with SARS-CoV-2 antigen-specific Fc{gamma} receptor binding, which accurately distinguished COVID-19 patients from healthy individuals and suggested that SARS-CoV-2 induces qualitative changes to antibody Fc upon infection, enhancing Fc{gamma} receptor engagement. Vastly different serological signatures were observed between healthy children and elderly, with markedly higher cross-reactive SARS-CoV-2 IgA and IgG observed in elderly, whereas children displayed elevated SARS-CoV-2 IgM, including receptor binding domain-specific IgM with higher avidity. These results suggest that less-experienced humoral immunity associated with higher IgM, as observed in children, may have the potential to induce more potent antibodies upon SARS-CoV-2 infection. These key insights will inform COVID-19 vaccination strategies, improved serological diagnostics and therapeutics.", "qid": 3, "docid": "8nbmrjrw", "rank": 42, "score": 0.8518847823143005}, {"content": "Title: Trained immunity: a tool for reducing susceptibility and severity of SARS-CoV-2 infection Content: Abstract SARS-CoV-2 infection is mild in the majority of individuals, but progresses into severe pneumonia in a small proportion of patients. The increased susceptibility to severe disease in the elderly and individuals with co-morbidities argues for an initial defect in anti-viral host defense mechanisms. Long-term boosting of innate immune responses, also termed \u2018trained immunity\u2019, by certain live vaccines (BCG, oral polio vaccine, measles) induces heterologous protection against infections, through epigenetic, transcriptional and functional reprogramming of innate immune cells. We propose that induction of trained immunity by whole microorganism vaccines may represent an important tool for reducing susceptibility and severity to SARS-CoV-2.", "qid": 3, "docid": "dqs21e0q", "rank": 43, "score": 0.851750373840332}, {"content": "Title: Targets of T Cell Responses to SARS-CoV-2 Coronavirus in Humans with COVID-19 Disease and Unexposed Individuals Content: Understanding adaptive immunity to SARS-CoV-2 is important for vaccine development, interpreting coronavirus disease 2019 (COVID-19) pathogenesis, and calibration of pandemic control measures. Using HLA class I and II predicted peptide \"megapools,\" circulating SARS-CoV-2-specific CD8+ and CD4+ T cells were identified in \u00e2\u0088\u00bc70% and 100% of COVID-19 convalescent patients, respectively. CD4+ T cell responses to spike, the main target of most vaccine efforts, were robust and correlated with the magnitude of the anti-SARS-CoV-2 IgG and IgA titers. The M, spike, and N proteins each accounted for 11%-27% of the total CD4+ response, with additional responses commonly targeting nsp3, nsp4, ORF3a, and ORF8, among others. For CD8+ T cells, spike and M were recognized, with at least eight SARS-CoV-2 ORFs targeted. Importantly, we detected SARS-CoV-2-reactive CD4+ T cells in \u00e2\u0088\u00bc40%-60% of unexposed individuals, suggesting cross-reactive T cell recognition between circulating \"common cold\" coronaviruses and SARS-CoV-2.", "qid": 3, "docid": "wxti06ng", "rank": 44, "score": 0.8514049053192139}, {"content": "Title: Targets of T cell responses to SARS-CoV-2 coronavirus in humans with COVID-19 disease and unexposed individuals Content: Summary Understanding adaptive immunity to SARS-CoV-2 is important for vaccine development, interpreting coronavirus disease 2019 (COVID-19) pathogenesis, and calibration of pandemic control measures. Using HLA class I and II predicted peptide \u2018megapools\u2019, circulating SARS-CoV-2\u2212specific CD8+ and CD4+ T cells were identified in \u223c70% and 100% of COVID-19 convalescent patients, respectively. CD4+ T cell responses to spike, the main target of most vaccine efforts, were robust and correlated with the magnitude of the anti-SARS-CoV-2 IgG and IgA titers. The M, spike and N proteins each accounted for 11-27% of the total CD4+ response, with additional responses commonly targeting nsp3, nsp4, ORF3a and ORF8, among others. For CD8+ T cells, spike and M were recognized, with at least eight SARS-CoV-2 ORFs targeted. Importantly, we detected SARS-CoV-2\u2212reactive CD4+ T cells in \u223c40-60% of unexposed individuals, suggesting cross-reactive T cell recognition between circulating \u2018common cold\u2019 coronaviruses and SARS-CoV-2.", "qid": 3, "docid": "isivkz8b", "rank": 45, "score": 0.8513734340667725}, {"content": "Title: Detection of SARS-CoV-2-specific humoral and cellular immunity in COVID-19 convalescent individuals Content: Summary The World Health Organization has declared SARS-CoV-2 virus outbreak a world-wide pandemic. However, there is very limited understanding on the immune responses, especially adaptive immune responses to SARS-CoV-2 infection. Here, we collected blood from COVID-19 patients who have recently become virus-free and therefore were discharged, and detected SARS-CoV-2-specific humoral and cellular immunity in 8 newly discharged patients. Follow-up analysis on another cohort of 6 patients 2 weeks post discharge also revealed high titers of IgG antibodies. In all 14 patients tested, 13 displayed serum neutralizing activities in a pseudotype entry assay. Notably, there was a strong correlation between neutralization antibody titers and the numbers of virus-specific T cells. Our work provides 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 developing an effective vaccine to SARS-CoV-2 infection.", "qid": 3, "docid": "0tn06al2", "rank": 46, "score": 0.8510904312133789}, {"content": "Title: Co-infections among patients with COVID-19: The need for combination therapy with non-anti-SARS-CoV-2 agents? Content: Co-infection has been reported in patients with severe acute respiratory syndrome (SARS) and Middle East respiratory syndrome, but there is limited knowledge on co-infection among patients with coronavirus disease 2019 (COVID-19). The prevalence of co-infection was variable among COVID-19 patients in different studies, however, it could be up to 50% among non-survivors. Co-pathogens included bacteria, such as Streptococcus pneumoniae, Staphylococcus aureus, Klebsiella pneumoniae, Mycoplasma pneumoniae, Chlamydia pneumonia, Legionella pneumophila and Acinetobacter baumannii; Candida species and Aspergillus flavus; and viruses such as influenza, coronavirus, rhinovirus/enterovirus, parainfluenza, metapneumovirus, influenza B virus, and human immunodeficiency virus. Influenza A was one of the most common co-infective viruses, which may have caused initial false-negative results of real-time reverse-transcriptase polymerase chain reaction for severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). Laboratory and imaging findings alone cannot help distinguish co-infection from SARS-CoV-2 infection. Newly developed syndromic multiplex panels that incorporate SARS-CoV-2 may facilitate the early detection of co-infection among COVID-19 patients. By contrast, clinicians cannot rule out SARS-CoV-2 infection by ruling in other respiratory pathogens through old syndromic multiplex panels at this stage of the COVID-19 pandemic. Therefore, clinicians must have a high index of suspicion for coinfection among COVID-19 patients. Clinicians can neither rule out other co-infections caused by respiratory pathogens by diagnosing SARS-CoV-2 infection nor rule out COVID-19 by detection of non-SARS-CoV-2 respiratory pathogens. After recognizing the possible pathogens causing co-infection among COVID-19 patients, appropriate antimicrobial agents can be recommended.", "qid": 3, "docid": "zmmj0cri", "rank": 47, "score": 0.8509583473205566}, {"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": 48, "score": 0.8502917289733887}, {"content": "Title: Pathogenesis, transmission and response to re-exposure of SARS-CoV-2 in domestic cats Content: The pandemic caused by SARS-CoV-2 has reached nearly every country in the world with extraordinary person-to-person transmission. The most likely original source of the virus was spillover from an animal reservoir and subsequent adaptation to humans sometime during the winter of 2019 in Wuhan Province, China. Because of its genetic similarity to SARS-CoV-1, it is likely that this novel virus has a similar host range and receptor specificity. Due to concern for human-pet transmission, we investigated the susceptibility of domestic cats and dogs to infection and potential for infected cats to transmit to na\u00efve cats. We report that cats are highly susceptible to subclinical infection, with a prolonged period of oral and nasal viral shedding that is not accompanied by clinical signs, and are capable of direct contact transmission to other cats. These studies confirm that cats are susceptible to productive SARS-CoV-2 infection, but are unlikely to develop clinical disease. Further, we document that cats develop a robust neutralizing antibody response that prevented re-infection to a second viral challenge. Conversely, we found that dogs do not shed virus following infection, but do mount an anti-viral neutralizing antibody response. There is currently no evidence that cats or dogs play a significant role in human exposure; however, reverse zoonosis is possible if infected owners expose their domestic pets during acute infection. Resistance to re-exposure holds promise that a vaccine strategy may protect cats, and by extension humans, to disease susceptibility.", "qid": 3, "docid": "jd6fvaop", "rank": 49, "score": 0.8501977920532227}, {"content": "Title: Learning from our immunological history: What can SARS-CoV teach us about SARS-CoV-2? Content: Many strategies are being deployed to rapidly uncover targetable mechanisms of infection for SARS-CoV-2, and Hoffman et al exploit our understanding and immunological experience with SARS-CoV in our global race to understand, mitigate, and eventually prevent COVID-19.", "qid": 3, "docid": "y3envkbs", "rank": 50, "score": 0.8492218255996704}, {"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": 51, "score": 0.8491114377975464}, {"content": "Title: Post-donation COVID-19 identification in blood donors. Content: The coronavirus disease 19 (COVID-19) outbreak, which was characterized as a pandemic on 11 March 2020 by the WHO, started in December 2019 with the emergence of pneumonia cases of unknown cause in Wuhan, Hubei, China [1]. SARS-CoV-2, the causative agent of COVID-19, are enveloped, non-segmented, single stranded positive sense RNA viruses and are classified as a sister clade to the prototype human and bat severe acute respiratory syndrome coronaviruses (SARS-CoVs) of the species Severe acute respiratory syndrome-related coronavirus [2]. So far, no respiratory virus, including SARS-CoV and the Middle East Respiratory Syndrome (MERS)-CoV, has been confirmed as transfusion-transmissible [3,4].", "qid": 3, "docid": "82sc928x", "rank": 52, "score": 0.848901629447937}, {"content": "Title: Potential Treatments for COVID-19; a Narrative Literature Review. Content: SARS-CoV-2 is a newly emerging human infectious coronavirus that causes COVID-19, which has been recognized as a pandemic by the World Health Organization (WHO) on March 11th. There is still no vaccine or definitive treatment for this virus because its pathogenesis and proliferation pathways are still unknown. Therefore, in this article, new potential COVID-19 therapies are briefly reviewed.", "qid": 3, "docid": "yympgnfe", "rank": 53, "score": 0.8487462997436523}, {"content": "Title: Severe Acute Respiratory Syndrome Coronavirus -2 (SARS-CoV-2): A global pandemic and treatments strategies Content: The emergence and rapid spread of novel coronavirus disease (COVID-19) caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) as a potentially fatal disease is swiftly evolving public health crises worldwide. The origin of SARS-CoV-2 infection was first reported in people exposed to wet animal market in Wuhan City, China in December 2019. It was suggested that the infection is likely to be of zoonotic origin and transmitted to human through yet unknown intermediary. As of (22/05/2020), there are around 4,995,996 confirmed cases reported by WHO with 327,821 deaths. SARS-CoV-2 infection is transmitted via inhalation or direct contact of infected people's droplets. It has an incubation period ranging from 2 to 14 days or more. The rate of spread of SARS-CoV-2 is more than partially resembled coronavirus (SARS-CoV and MERS). The symptoms are similar to influenza like, breathlessness, sore throat and fatigue therefore, infected person is isolated and administrated with effective treatments. Infection is mild in most but in elderly (>50 years) and those with cardiac and respiratory disorder, it may progress to pneumonia, acute respiratory distress syndrome, and multi organ failure. People with strong immunity or those developed herd immunity are asymptomatic. Fatality rate ranges to 3-4% on case basis. Diagnosis of SARS-CoV-2 is recommended in respiratory secretions by special molecular tests like PCR, chest scan and common laboratory diagnosis. Currently, the existing treatment is essentially supportive and role of antiviral agents is yet to be established as there is no vaccination or therapy available. This review focuses on epidemiology, symptoms, transmission, pathogenesis, ongoing available treatments and future perspectives of SARS-CoV-2.", "qid": 3, "docid": "btiy6jhr", "rank": 54, "score": 0.8487375378608704}, {"content": "Title: Gaining insights on immune responses to the novel coronavirus, COVID-19 and therapeutic challenges Content: SARS-CoV-2 is a new member of coronaviruses that its sudden spreading put the health care system of most countries in a tremendous shock. For controlling of the new infection, COVID-19, many efforts have been done and are ongoing to defeat this virus in the combat field. In this review, we focused on how the immune system behaves toward the virus and the relative possible consequences during their interactions. Then the therapeutic steps and potential vaccine candidates have been described in a hope to provide a better prospective of effective treatment and preventive strategies to the novel SARS-CoV in near future.", "qid": 3, "docid": "59cuhfi5", "rank": 55, "score": 0.848689079284668}, {"content": "Title: Expected immune recognition of COVID-19 virus by memory from earlier infections with common coronaviruses in a large part of the world population Content: SARS-CoV-2 is the coronavirus agent of the COVID-19 pandemic causing high mortalities. In contrast, the widely spread human coronaviruses OC43, HKU1, 229E, and NL63 tend to cause only mild symptoms. The present study shows, by in silico analysis, that these common human viruses are expected to induce immune memory against SARS-CoV-2 by sharing protein fragments (antigen epitopes) for presentation to the immune system by MHC class I. A list of such epitopes is provided. The number of these epitopes and the prevalence of the common coronaviruses suggest that a large part of the world population has some degree of specific immunity against SARS-CoV-2 already, even without having been infected by that virus. For inducing protection, booster vaccinations enhancing existing immunity are less demanding than primary vaccinations against new antigens. Therefore, for the discussion on vaccination strategies against COVID-19, the available immune memory against related viruses should be part of the consideration.", "qid": 3, "docid": "majelie8", "rank": 56, "score": 0.8485539555549622}, {"content": "Title: Why continuing uncertainties are no reason to postpone challenge trials for coronavirus vaccines. Content: To counter the pandemic caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), some have proposed accelerating SARS-CoV-2 vaccine development through controlled human infection (or 'challenge') trials. These trials would involve the deliberate exposure of relatively few young, healthy volunteers to SARS-CoV-2. We defend this proposal against the charge that there is still too much uncertainty surrounding the risks of COVID-19 to responsibly run such a trial.", "qid": 3, "docid": "6dwyv4qo", "rank": 57, "score": 0.8484481573104858}, {"content": "Title: Detection of SARS-CoV-2-Specific Humoral and Cellular Immunity in COVID-19 Convalescent Individuals Content: The World Health Organization has declared SARS-CoV-2 virus outbreak a worldwide pandemic. However, there is very limited understanding on the immune responses, especially adaptive immune responses to SARS-CoV-2 infection. Here, we collected blood from COVID-19 patients who have recently become virus-free, and therefore were discharged, and detected SARS-CoV-2-specific humoral and cellular immunity in eight newly discharged patients. Follow-up analysis on another cohort of six patients 2 weeks post discharge also revealed high titers of immunoglobulin G (IgG) antibodies. In all 14 patients tested, 13 displayed serum-neutralizing activities in a pseudotype entry assay. Notably, there was a strong correlation between neutralization antibody titers and the numbers of virus-specific T cells. Our work provides 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 also has implications in developing an effective vaccine to SARS-CoV-2 infection.", "qid": 3, "docid": "53j3ly3v", "rank": 58, "score": 0.8483580350875854}, {"content": "Title: Potential Treatments for COVID-19; a Narrative Literature Review Content: SARS-CoV-2 is a newly emerging human infectious coronavirus that causes COVID-19, which has been recognized as a pandemic by the World Health Organization (WHO) on March 11(th). There is still no vaccine or definitive treatment for this virus because its pathogenesis and proliferation pathways are still unknown. Therefore, in this article, new potential COVID-19 therapies are briefly reviewed.", "qid": 3, "docid": "y29kct7v", "rank": 59, "score": 0.8478257656097412}, {"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": 3, "docid": "ocdyqqqw", "rank": 60, "score": 0.8477634191513062}, {"content": "Title: Pre-existing and de novo humoral immunity to SARS-CoV-2 in humans Content: Several related human coronaviruses (HCoVs) are endemic in the human population, causing mild respiratory infections1. Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2), the etiologic agent of Coronavirus disease 2019 (COVID-19), is a recent zoonotic infection that has quickly reached pandemic spread2,3. Zoonotic introduction of novel coronaviruses is thought to occur in the absence of pre-existing immunity in the target human population. Using diverse assays for detection of antibodies reactive with the SARS-CoV-2 Spike (S) glycoprotein, we demonstrate the presence of pre-existing immunity in uninfected and unexposed humans to the new coronavirus. SARS-CoV-2 S-reactive antibodies, exclusively of the IgG class, were readily detectable by a sensitive flow cytometry-based method in SARS-CoV-2-uninfected individuals with recent HCoV infection and targeted the S2 subunit. In contrast, SARS-CoV-2 infection induced higher titres of SARS-CoV-2 S-reactive IgG antibodies, as well as concomitant IgM and IgA antibodies throughout the observation period of 6 weeks since symptoms onset. HCoV patient sera also variably reacted with SARS-CoV-2 S and nucleocapsid (N), but not with the S1 subunit or the receptor binding domain (RBD) of S on standard enzyme immunoassays. Notably, HCoV patient sera exhibited specific neutralising activity against SARS-CoV-2 S pseudotypes, according to levels of SARS-CoV-2 S-binding IgG and with efficiencies comparable to those of COVID-19 patient sera. Distinguishing pre-existing and de novo antibody responses to SARS-CoV-2 will be critical for serology, seroprevalence and vaccine studies, as well as for our understanding of susceptibility to and natural course of SARS-CoV-2 infection.", "qid": 3, "docid": "n0actmsc", "rank": 61, "score": 0.8477461934089661}, {"content": "Title: [Pediatric impact of COVID-19]. Content: Children infected with SARS-CoV-2 are underrepresented during the current COVID-19 outbreak. Unlike other respiratory viruses, SARS-CoV-2 rather infects adults who subsequently infect their children. From recent Chinese and Italian data, children commonly present mild to moderate disease, a large proportion of them being asymptomatic. In particular, children present significantly less fever, cough and pneumonia compared to adults. However, more cases of pneumonia were reported from children infected with SARS-CoV-2 compared to those infected with H1N1. No vertical transmission of SARS-CoV-2 has been described so far.", "qid": 3, "docid": "lyi4pgwy", "rank": 62, "score": 0.8477434515953064}, {"content": "Title: Severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2): a global pandemic and treatment strategies Content: The emergence and rapid spread of coronavirus disease 2019 (COVID-19), caused by severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2), a potentially fatal disease, is swiftly leading to public health crises worldwide. The origin of SARS-CoV-2 infection was first reported in people exposed to a seafood market in Wuhan City, China in December 2019. It has been suggested that the infection is likely to be of zoonotic origin and transmitted to humans through a not-yet-known intermediary. As of 22 May 2020, the World Health Organization reported that there were approximately 4,995,996 confirmed cases and 327,821 deaths. SARS-CoV-2 is transmitted via inhalation or direct contact with droplets from infected people. It has an incubation period ranging from 2 to &#8805;14 days. The rate of spread of SARS-CoV-2 is greater than that for severe acute respiratory syndrome coronavirus and Middle East respiratory coronavirus. The symptoms are similar to influenza (i.e. breathlessness, sore throat and fatigue) and infected cases are isolated and treated. Infection is mild in most cases, but in elderly (>50 years) patients and those with cardiac and respiratory disorders, it may progress to pneumonia, acute respiratory distress syndrome and multi-organ failure. People with strong immunity or those who have developed herd immunity are asymptomatic. The fatality rate ranges from 3% to 4%. Recommended methods for diagnosis of COVID-19 are molecular tests (e.g. polymerase chain reaction) on respiratory secretions, chest scan and common laboratory diagnosis. Currently, treatment is essentially supportive, and the role of antiviral agents is yet to be established as a vaccine is not yet available. This review will focus on epidemiology, symptoms, transmission, pathogenesis, ongoing available treatments and future perspectives of SARS-CoV-2.", "qid": 3, "docid": "kkga96h9", "rank": 63, "score": 0.8475611209869385}, {"content": "Title: Molecular mechanisms and epidemiology of COVID-19 from an allergist's perspective Content: The global pandemic caused by the newly described severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) has caused worldwide suffering and death of unimaginable magnitude from coronavirus disease 2019 (COVID-19). The virus is transmitted through aerosol droplets, and causes severe acute respiratory syndrome. SARS-CoV-2 uses the receptor-binding domain of its spike protein S1 to attach to the host angiotensin-converting enzyme 2 receptor in lung and airway cells. Binding requires the help of another host protein, transmembrane protease serine S1 member 2. Several factors likely contribute to the efficient transmission of SARS-CoV-2. The receptor-binding domain of SARS-CoV-2 has a 10- to 20-fold higher receptor-binding capacity compared with previous pandemic coronaviruses. In addition, because asymptomatic persons infected with SARS-CoV-2 have high viral loads in their nasal secretions, they can silently and efficiently spread the disease. PCR-based tests have emerged as the criterion standard for the diagnosis of infection. Caution must be exercised in interpreting antibody-based tests because they have not yet been validated, and may give a false sense of security of being \"immune\" to SARS-CoV-2. We discuss how the development of some symptoms in allergic rhinitis can serve as clues for new-onset COVID-19. There are mixed reports that asthma is a risk factor for severe COVID-19, possibly due to differences in asthma endotypes. The rapid spread of COVID-19 has focused the efforts of scientists on repurposing existing Food and Drug Administration-approved drugs that inhibit viral entry, endocytosis, genome assembly, translation, and replication. Numerous clinical trials have been launched to identify effective treatments for COVID-19. Initial data from a placebo-controlled study suggest faster time to recovery in patients on remdesivir; it is now being evaluated in additional controlled studies. As discussed in this review, till effective vaccines and treatments emerge, it is important to understand the scientific rationale of pandemic-mitigation strategies such as wearing facemasks and social distancing, and implement them.", "qid": 3, "docid": "2akskxmn", "rank": 64, "score": 0.8473705053329468}, {"content": "Title: A Guide to COVID-19: a global pandemic caused by the novel coronavirus SARS-CoV-2 Content: The emergence of the SARS-CoV-2 strain of the human coronavirus has thrown the world into the midst of a new pandemic. In the human body, the virus causes COVID-19, a disease characterized by shortness of breath, fever, and pneumonia, which can be fatal in vulnerable individuals. SARS-CoV-2 has characteristics of past human coronaviruses, with close genomic similarities to SARS-CoV, the virus that causes the disease SARS. Like these related coronaviruses, SARS-CoV-2 is transmitted through the inhalation of droplets and interaction with contaminated surfaces. Across the world, laboratories are developing candidate vaccines for the virus - with vaccine trials underway in the United States and the United Kingdom - and considering various drugs for possible treatments and prophylaxis. Here, we provide an overview of SARS-CoV-2 by analyzing its virology, epidemiology, and modes of transmission while examining the current progress of testing procedures and possible treatments through drugs and vaccines.", "qid": 3, "docid": "wq7ljx2f", "rank": 65, "score": 0.8472045660018921}, {"content": "Title: Molecular mechanisms and epidemiology of COVID-19 from an allergist\u2019s perspective Content: The global pandemic caused by the newly described severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) has caused worldwide suffering and death of unimaginable magnitude from coronavirus disease 2019 (COVID-19). The virus is transmitted through aerosol droplets, and causes severe acute respiratory syndrome. SARS-CoV-2 uses the receptor-binding domain of its spike protein S1 to attach to the host angiotensin-converting enzyme 2 receptor in lung and airway cells. Binding requires the help of another host protein, transmembrane protease serine S1 member 2. Several factors likely contribute to the efficient transmission of SARS-CoV-2. The receptor-binding domain of SARS-CoV-2 has a 10- to 20-fold higher receptor-binding capacity compared with previous pandemic coronaviruses. In addition, because asymptomatic persons infected with SARS-CoV-2 have high viral loads in their nasal secretions, they can silently and efficiently spread the disease. PCR-based tests have emerged as the criterion standard for the diagnosis of infection. Caution must be exercised in interpreting antibody-based tests because they have not yet been validated, and may give a false sense of security of being \u201cimmune\u201d to SARS-CoV-2. We discuss how the development of some symptoms in allergic rhinitis can serve as clues for new-onset COVID-19. There are mixed reports that asthma is a risk factor for severe COVID-19, possibly due to differences in asthma endotypes. The rapid spread of COVID-19 has focused the efforts of scientists on repurposing existing Food and Drug Administration\u2013approved drugs that inhibit viral entry, endocytosis, genome assembly, translation, and replication. Numerous clinical trials have been launched to identify effective treatments for COVID-19. Initial data from a placebo-controlled study suggest faster time to recovery in patients on remdesivir; it is now being evaluated in additional controlled studies. As discussed in this review, till effective vaccines and treatments emerge, it is important to understand the scientific rationale of pandemic-mitigation strategies such as wearing facemasks and social distancing, and implement them.", "qid": 3, "docid": "bc2sz3ce", "rank": 66, "score": 0.8467581868171692}, {"content": "Title: COVID-19 Disease in Children: Clinical Course, Diagnosis and Treatment Overview and Literature Data Compilation Content: The novel Coronavirus is named as SARS-CoV-2 is a highly contagious infection agent compared to the previous human coronaviruses Each previous outbreak had distinctive danger The high potential of infectiousness is the primary danger of novel coronavirus While MERS-CoV infection is known to have higher mortality rate, SARS-CoV-2 has spread to many people all over the world in a concise time SARS-CoV-2 (like SARS-CoV and MERS) infects fewer children and results in milder clinical symptoms than in adults The primary pathogenesis of it is not known;the difference in children's immunities, less likelihood of exposure to the agent may be the reasons Nevertheless, along with being mostly asymptomatic, the child population is a potential source for infection spread", "qid": 3, "docid": "9ppacplo", "rank": 67, "score": 0.8465921878814697}, {"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": 3, "docid": "be38b41o", "rank": 68, "score": 0.846472978591919}, {"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": 3, "docid": "rdzeja13", "rank": 69, "score": 0.8462309837341309}, {"content": "Title: [RISK ASSESSMENT FOR AEROSOL INFECTION BY THE NEW CORONA VIRUS AND PROTECTION BY RESPIRATORS]. Content: INTRODUCTION SARS-CoV-2 is dispersed from patients by talking, coughing and sneezing. The generated micro-droplets aerosols can travel up to 8 meters, stay suspended for long periods and preserve viral infectivity for a median of 2.7 hours. An unprotected person exposed to this cloud, might inhale a considerable amount of infectious viral doses, which will attach to the ACE 2 receptors on alveoli epithelium, resulting in infection. N95 respirators and surgical masks block 95% and 50-60% respectively of inhalable particles and protect the wearer from infection. Surgical masks and N95 without exhalation valve, protect both the wearer and the environment from carriers and sick people.", "qid": 3, "docid": "k47m3e92", "rank": 70, "score": 0.8460564613342285}, {"content": "Title: SARS-CoV-2 and Guillain-Barr\u00e9 syndrome: AIDP variant with favorable outcome Content: The entire world has been experiencing the outbreak of a novel infectious agent known as severe acute respiratory syndrome corona virus 2 (SARS-CoV-2), which is responsible for the coronavirus disease 19 (COVID-19)1 . Life-threatening complications described in SARS-CoV-2 infected patients include acute respiratory distress syndrome, acute kidney failure and cardiac injury2 . Nonetheless, only few neurological complications have been described so far3 .", "qid": 3, "docid": "xui1famo", "rank": 71, "score": 0.8458939790725708}, {"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": 3, "docid": "di8lljoi", "rank": 72, "score": 0.8458517789840698}, {"content": "Title: Is COVID-19 the first pandemic that evolves into a panzootic? Content: SARS-CoV-2 is a zoonotic virus that has achieved community spread among humans and become a pandemic. Transmission from humans to dogs, domestic cats, tigers, and lions has occurred. Pigs, cats, ferrets, and primates have been identified as good candidates for susceptibility to SARS-CoV-2. The potential implications indicate the need for One Health surveillance, intervention, and management strategies to mitigate the effects on animal populations and prevent a second preparedness failure during this health emergency.", "qid": 3, "docid": "icp9ur8k", "rank": 73, "score": 0.8458082675933838}, {"content": "Title: Co-infections among patients with COVID-19: the need for combination therapy with non-anti-SARS-CoV-2 agents? Content: Abstract Co-infection has been reported in patients with severe acute respiratory syndrome (SARS) and Middle East respiratory syndrome, but there is limited knowledge on co-infection among patients with coronavirus disease 2019 (COVID-19). The prevalence of co-infection was variable among COVID-19 patients in different studies, however, it could be up to 50% among non-survivors. Co-pathogens included bacteria, such as Streptococcus pneumoniae, Staphylococcus aureus, Klebsiella pneumoniae, Mycoplasma pneumoniae, Chlamydia pneumonia, Legionella pneumophila and Acinetobacter baumannii; Candida species and Aspergillus flavus; and viruses such as influenza, coronavirus, rhinovirus/enterovirus, parainfluenza, metapneumovirus, influenza B virus, and human immunodeficiency virus. Influenza A was one of the most common co-infective viruses, which may have caused initial false-negative results of real-time reverse-transcriptase polymerase chain reaction for severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). Laboratory and imaging findings alone cannot help distinguish co-infection from SARS-CoV-2 infection. Newly developed syndromic multiplex panels that incorporate SARS-CoV-2 may facilitate the early detection of co-infection among COVID-19 patients. By contrast, clinicians cannot rule out SARS-CoV-2 infection by ruling in other respiratory pathogens through old syndromic multiplex panels at this stage of the COVID-19 pandemic. Therefore, clinicians must have a high index of suspicion for coinfection among COVID-19 patients. Clinicians can neither rule out other co-infections caused by respiratory pathogens by diagnosing SARS-CoV-2 infection nor rule out COVID-19 by detection of non-SARS-CoV-2 respiratory pathogens. After recognizing the possible pathogens causing co-infection among COVID-19 patients, appropriate antimicrobial agents can be recommended.", "qid": 3, "docid": "nv3gbpg7", "rank": 74, "score": 0.8456487655639648}, {"content": "Title: Controversies regarding shielding and susceptibility to COVID\u201019 disease in liver transplant recipients in the United Kingdom Content: December 2019 saw the emergence of a novel coronavirus, SARS-CoV-2, which rapidly escalated to a global pandemic 1 , with an unprecedented impact on healthcare systems worldwide. The objective of this case series is to report on SARS-CoV-2 infection in liver transplant recipients and discuss the role of immunosuppression, comorbidities and shielding. In the UK, transplant recipients were classified as individuals vulnerable to SARS-CoV-2 infection due to immunosuppression. They were advised in late March 2020 (Figure 1) by Public Health England to take additional social distancing precautions, a process referred to as 'shielding' 2 . This is a more rigorous form of isolation that requires the individual to not leave their place of residence or come into contact with others. In essence, completely isolate to minimise the risk of being exposed to SARS-CoV-2.", "qid": 3, "docid": "0n9xxa9h", "rank": 75, "score": 0.8454367518424988}, {"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": 76, "score": 0.8453865051269531}, {"content": "Title: Antibody dynamics to SARS-CoV-2 in Asymptomatic and Mild COVID-19 patients Content: Humoral immunity in asymptomatic infections with SARS-CoV-2 has not been well established. 63 healthy contacts, 63 asymptomatic individuals, and 51 mild patients were enrolled in this study and screened using nucleic acid testing (NAT) and commercial kits of serum IgM and IgG antibodies against recombinant nucleoprotein (N) and spike (S) proteins of SARS-CoV-2. Asymptomatic and mild patients were classified into at least four types based on NAT and serological tests, especially 81% and 25.4% negative NAT but positive IgM/IgG responses, respectively. Antibody dynamics were further demonstrated by IgM and IgG profile responses to SARS-CoV-2 proteome. IgM antibody responses against S1 were elicited in asymptomatic individuals as early to the seventh day after exposure and peaked on days from 17d to 25d, which might be used as early diagnostic biomarkers. Moreover, asymptomatic individuals evoked weaker S1 specific IgM and neutralizing antibody responses than mild patients. Most importantly, S1 specific IgM/IgG responses and the titers of neutralizing antibody in asymptomatic individuals gradually vanished in two months. Our findings might have important implications for serological survey, public health and immunization strategy.", "qid": 3, "docid": "uic18wv8", "rank": 77, "score": 0.8453457355499268}, {"content": "Title: The impact of the SARS-CoV-2 infection, with special reference to the haematological setting Content: SARS-CoV-2 is a disease known from a few months, caused by a recently arisen virus and, consequently, it is little known. The disease has a benign course in most infected subjects (children and young adults), is often symptomatic in adults over the age of 50 and often serious and life threatening in people with comorbidities and the elderly. The few data published on COVID-19 in the blood-oncology field report a serious clinical presentation, a serious course of the disease and a high mortality rate, as has also been reported for other cancer contexts. The current strategy for treating patients with SARS-CoV-2 includes antivirals that are effective against other viral infections and drugs that can moderate the cytokine storm. There is no specific vaccine and consequently all possible precautions must be taken to prevent SARS-CoV-2 infection in the areas of oncology, onco-hematology, and bone marrow transplantation. In this reviewer's article, we report the information currently available on SARS-CoV-2 infection to help young doctors and hematologists to successfully manage patients with COVID-19. This article is protected by copyright. All rights reserved.", "qid": 3, "docid": "ivzidm5v", "rank": 78, "score": 0.845323920249939}, {"content": "Title: [risk Assessment for Aerosol Infection by the New Corona Virus and Protection by Respirators] Content: INTRODUCTION: SARS-CoV-2 is dispersed from patients by talking, coughing and sneezing. The generated micro-droplets aerosols can travel up to 8 meters, stay suspended for long periods and preserve viral infectivity for a median of 2.7 hours. An unprotected person exposed to this cloud, might inhale a considerable amount of infectious viral doses, which will attach to the ACE 2 receptors on alveoli epithelium, resulting in infection. N95 respirators and surgical masks block 95% and 50-60% respectively of inhalable particles and protect the wearer from infection. Surgical masks and N95 without exhalation valve, protect both the wearer and the environment from carriers and sick people.", "qid": 3, "docid": "xlsqikjt", "rank": 79, "score": 0.845201313495636}, {"content": "Title: COVID-19: review on latest available drugs and therapies against SARS-CoV-2. Coagulation and inflammation cross-talking Content: SARS-CoV-2 is the agent responsible for COVID-19. The infection can be dived into three phases: mild infection, the pulmonary phase and the inflammatory phase. Treatment options for the pulmonary phase include: Hydroxychloroquine, Remdesivir, Lopinavir/Ritonavir. The inflammatory phase includes therapeutic options like Tocilizumab, Anakinra, Baricitinib, Eculizumab, Emapalumab and Heparin. Human clinical trials are starting to show some results, in some cases like that of Remdesivir these are controversial. Coagulopathy is a common complication in severe cases, inflammation and coagulation are intertwined and cross-talking between these two responses is known to happen. A possible amplification of this cross-talking is suggested to be implicated in the severe cases that show both a cytokine storm and coagulopathy.", "qid": 3, "docid": "v59dpmuu", "rank": 80, "score": 0.8451602458953857}, {"content": "Title: A mathematical model reveals the influence of population heterogeneity on herd immunity to SARS-CoV-2 Content: Despite various levels of preventive measures, in 2020 many countries have suffered severely from the coronavirus 2019 (COVID-19) pandemic caused by the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) virus. We show that population heterogeneity can significantly impact disease-induced immunity as the proportion infected in groups with the highest contact rates is greater than in groups with low contact rates. We estimate that if R 0 = 2.5 in an age-structured community with mixing rates fitted to social activity then the disease-induced herd immunity level can be around 43%, which is substantially less than the classical herd immunity level of 60% obtained through homogeneous immunization of the population. Our estimates should be interpreted as an illustration of how population heterogeneity affects herd immunity, rather than an exact value or even a best estimate.", "qid": 3, "docid": "3ol5ozz6", "rank": 81, "score": 0.8451554775238037}, {"content": "Title: SARS-CoV originated from bats in 1998 and may still exist in humans Content: SARS-CoV is believed to originate from civets and was thought to have been eliminated as a threat after the 2003 outbreak. Here, we show that human SARS-CoV (huSARS-CoV) originated directly from bats, rather than civets, by a cross-species jump in 1991, and formed a human-adapted strain in 1998. Since then huSARS-CoV has evolved further into highly virulent strains with genotype T and a 29-nt deletion mutation, and weakly virulent strains with genotype C but without the 29-nt deletion. The former can cause pneumonia in humans and could be the major causative pathogen of the SARS outbreak, whereas the latter might not cause pneumonia in humans, but evolved the ability to co-utilize civet ACE2 as an entry receptor, leading to interspecies transmission between humans and civets. Three crucial time points - 1991, for the cross-species jump from bats to humans; 1998, for the formation of the human-adapted SARS-CoV; and 2003, when there was an outbreak of SARS in humans - were found to associate with anomalously low annual precipitation and high temperatures in Guangdong. Anti-SARS-CoV sero-positivity was detected in 20% of all the samples tested from Guangzhou children who were born after 2005, suggesting that weakly virulent huSARS-CoVs might still exist in humans. These existing but undetected SARS-CoVs have a large potential to evolve into highly virulent strains when favorable climate conditions occur, highlighting a potential risk for the reemergence of SARS.", "qid": 3, "docid": "y5n7zsct", "rank": 82, "score": 0.8451492786407471}, {"content": "Title: A mathematical model reveals the influence of population heterogeneity on herd immunity to SARS-CoV-2 Content: Despite various levels of preventive measures, in 2020 many countries have suffered severely from the coronavirus 2019 (COVID-19) pandemic caused by the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) virus. We show that population heterogeneity can significantly impact disease-induced immunity as the proportion infected in groups with the highest contact rates is greater than in groups with low contact rates. We estimate that if R(0) = 2.5 in an age-structured community with mixing rates fitted to social activity then the disease-induced herd immunity level can be around 43%, which is substantially less than the classical herd immunity level of 60% obtained through homogeneous immunization of the population. Our estimates should be interpreted as an illustration of how population heterogeneity affects herd immunity, rather than an exact value or even a best estimate.", "qid": 3, "docid": "73oe5as9", "rank": 83, "score": 0.8451458811759949}, {"content": "Title: [Pediatric impact of COVID-19] Content: Children infected with SARS-CoV-2 are underrepresented during the current COVID-19 outbreak Unlike other respiratory viruses, SARS-CoV-2 rather infects adults who subsequently infect their children From recent Chinese and Italian data, children commonly present mild to moderate disease, a large proportion of them being asymptomatic In particular, children present significantly less fever, cough and pneumonia compared to adults However, more cases of pneumonia were reported from children infected with SARS-CoV-2 compared to those infected with H1N1 No vertical transmission of SARS-CoV-2 has been described so far", "qid": 3, "docid": "2990fbda", "rank": 84, "score": 0.8448556065559387}, {"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": 3, "docid": "znx5p3yp", "rank": 85, "score": 0.8447030186653137}, {"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": 86, "score": 0.844527006149292}, {"content": "Title: Immunological responses against SARS-coronavirus infection in humans. Content: Since the outbreak of a SARS epidemic last year, significant advances have been made on our understanding of the mechanisms of interaction between the SARS coronavirus (CoV) and the immune system. Strong humoral responses have been found in most patients following SARS-CoV infection, with high titers of neutralizing Abs present in their convalescent sera. The nucleocapsid (N) and spike (S) proteins of SARS-CoV appear to be the dominant antigens recognized by serum Abs. CD4+ T cell responses against the N protein have been observed in SARS patients and an HLA-A2-restricted cytotoxic T lymphocyte epitope in the S protein has been identified. It is likely that the immune responses induced by SARS-CoV infection could also cause pathological damage to the host, especially in the case of proinflammatory cytokines. There is also evidence suggesting that SARS-CoV might be able to directly invade cells of the immune system. Our understanding on the interaction between SARS-CoV, the immune system and local tissues is essential to future diagnosis, control and treatment of this very contagious disease.", "qid": 3, "docid": "7ro1up5b", "rank": 87, "score": 0.8445119857788086}, {"content": "Title: COVID-19: Review on latest available drugs and therapies against SARS-CoV-2. Coagulation and inflammation cross-talking Content: SARS-CoV-2 is the agent responsible for COVID-19. The infection can be dived into three phases: mild infection, the pulmonary phase and the inflammatory phase. Treatment options for the pulmonary phase include: Hydroxychloroquine, Remdesivir, Lopinavir/Ritonavir. The inflammatory phase includes therapeutic options like Tocilizumab, Anakinra, Baricitinib, Eculizumab, Emapalumab and Heparin. Human clinical trials are starting to show some results, in some cases like that of Remdesivir and corticosteroids these are controversial. Coagulopathy is a common complication in severe cases, inflammation and coagulation are intertwined and cross-talking between these two responses is known to happen. A possible amplification of this cross-talking is suggested to be implicated in the severe cases that show both a cytokine storm and coagulopathy.", "qid": 3, "docid": "ly2ytc6t", "rank": 88, "score": 0.8442069292068481}, {"content": "Title: Isolation, Sequence, Infectivity, and Replication Kinetics of Severe Acute Respiratory Syndrome Coronavirus 2 Content: Since its emergence in Wuhan, China, in December 2019, severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) has infected &#8776;6 million persons worldwide. As SARS-CoV-2 spreads across the planet, we explored the range of human cells that can be infected by this virus. We isolated SARS-CoV-2 from 2 infected patients in Toronto, Canada; determined the genomic sequences; and identified single-nucleotide changes in representative populations of our virus stocks. We also tested a wide range of human immune cells for productive infection with SARS-CoV-2. We confirm that human primary peripheral blood mononuclear cells are not permissive for SARS-CoV-2. As SARS-CoV-2 continues to spread globally, it is essential to monitor single-nucleotide polymorphisms in the virus and to continue to isolate circulating viruses to determine viral genotype and phenotype by using in vitro and in vivo infection models.", "qid": 3, "docid": "hrgb0e03", "rank": 89, "score": 0.8440842628479004}, {"content": "Title: Lessons Learned to Date on COVID-19 Hyperinflammatory Syndrome: Considerations for Interventions to Mitigate SARS-CoV-2 Viral Infection and Detrimental Hyperinflammation Content: The first case of human transmission of SARS-CoV-2 was reported in China in December 2019. A few months later, this viral infection had spread worldwide and became a pandemic. The disease caused by SARS-CoV-2, termed COVID-19, is multifactorial and associated with both specific antiviral as well as inflammatory responses, the extent of which may determine why some individuals are asymptomatic while others develop serious complications. Here we review possible life-threating immune events that can occur during disease progression to uncover key factors behind COVID-19 severity and provide suggestions for interventions with repurposed drugs in well-controlled and randomized clinical trials. These drugs include therapeutics with potential to inhibit SARS-CoV-2 entry into host cells such as serine protease inhibitors of the cellular protease TMPS2 and drugs targeting the renin-angiotensin system; antivirals with potential to block SARS-CoV-2 replication or factors that could boost the antiviral response; monoclonal antibodies targeting pro-inflammatory cytokines that drive the hyperinflammatory response during COVID-19 progression toward the severe stage and therapeutics that could ameliorate the function of the lungs. Furthermore, in order to help make more informed decisions on the timing of the intervention with the drugs listed in this review, we have grouped these therapeutics according to the stage of COVID-19 progression that we considered most appropriate for their mechanism of action.", "qid": 3, "docid": "2qugltxu", "rank": 90, "score": 0.84395432472229}, {"content": "Title: SARS-CoV-2 Infection and the Liver Content: A novel strain of coronoviridae (SARS-CoV-2) was reported in Wuhan China in December 2019. Initially, infection presented with a broad spectrum of symptoms which typically included muscle aches, fever, dry cough, and shortness of breath. SARS-CoV-2 enters cells via ACE2 receptors which are abundant throughout the respiratory tract. However, there is evidence that these receptors are abundant throughout the body, and just as abundant in cholangiocytes as alveolar cells, posing the question of possible direct liver injury. While liver enzymes and function tests do seem to be deranged in some patients, it is questionable if the injury is due to direct viral damage, drug-induced liver injury, hypoxia, or microthromboses. Likely, the injury is multifactoral, and management of infected patients with pre-existing liver disease should be taken into consideration. Ultimately, a vaccine is needed to aid in reducing cases of SARS-CoV-2 and providing immunity to the general population. However, while considering the types of vaccines available, safety concerns, particularly of RNA- or DNA-based vaccines, need to be addressed.", "qid": 3, "docid": "w3z7mxu7", "rank": 91, "score": 0.8439391255378723}, {"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": 3, "docid": "5cygqkgk", "rank": 92, "score": 0.84392249584198}, {"content": "Title: IL-33 expression in response to SARS-CoV-2 correlates with seropositivity in COVID-19 convalescent individuals Content: Our understanding of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) is still developing. We investigated seroprevalence and immune responses in subjects professionally exposed to SARS-CoV-2 and their family members (155 individuals; ages 5-79 years). Seropositivity for SARS-CoV-2 spike glycoprotein aligned with PCR results that confirmed previous infection. Anti-spike IgG titers remained high 60 days post-infection and did not associate with symptoms, but spike-specific IgM did associate with malaise and fever. We found limited household transmission, with children of infected individuals seldomly seropositive, highlighting professional exposure as the dominant route of infection in our cohort. We analyzed PBMCs from a subset of seropositive and seronegative adults. TLR7 agonist- activation revealed an increased population of IL-6+TNF-IL-1{beta}+ monocytes, while SARS-CoV-2 peptide stimulation elicited IL-33, IL-6, IFNa2, and IL-23 expression in seropositive individuals. IL-33 correlated with CD4+ T cell activation in PBMCs from convalescent subjects, and was likely due to T cell-mediated effects on IL-33- producing cells. IL-33 is associated with pulmonary infection and chronic diseases like asthma and COPD, but its role in COVID-19 is unknown. Analysis of published scRNAseq data of bronchoalveolar lavage fluid (BALF) from patients with mild to severe COVID-19 revealed a population of IL-33-producing cells that increases with disease. Together these findings show that IL-33 production is linked to SARS-CoV- 2 infection and warrant further investigation of IL-33 in COVID-19 pathogenesis and immunity.", "qid": 3, "docid": "ns2pfiua", "rank": 93, "score": 0.843816876411438}, {"content": "Title: Potential Treatments for COVID-19;a Narrative Literature Review Content: SARS-CoV-2 is a newly emerging human infectious coronavirus that causes COVID-19, which has been recognized as a pandemic by the World Health Organization (WHO) on March 11(th) There is still no vaccine or definitive treatment for this virus because its pathogenesis and proliferation pathways are still unknown Therefore, in this article, new potential COVID-19 therapies are briefly reviewed", "qid": 3, "docid": "3sewe0np", "rank": 94, "score": 0.8438090085983276}, {"content": "Title: SARS-CoV-2: the viral shedding vs infectivity dilemma Content: Since December 2019, severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) has infected over four million people worldwide. There are multiple reports of prolonged viral shedding in people infected with SARS-CoV-2 but the presence of viral RNA on a test does not necessarily correlate with infectivity. The duration of quarantine required after clinical recovery to definitively prevent transmission is therefore uncertain. In addition, asymptomatic and presymptomatic transmission may occur, and infectivity may be highest early after onset of symptoms, meaning that contact tracing, isolation of exposed individuals and social distancing are essential public health measures to prevent further spread. This review aimed to summarise the evidence around viral shedding vs infectivity of SARS-CoV-2.", "qid": 3, "docid": "l0b99hye", "rank": 95, "score": 0.8438037633895874}, {"content": "Title: SARS-CoV-2: The viral shedding vs infectivity dilemma Content: Since December 2019, severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) has infected over four million people worldwide. There are multiple reports of prolonged viral shedding in people infected with SARS-CoV-2 but the presence of viral RNA on a test does not necessarily correlate with infectivity. The duration of quarantine required after clinical recovery to definitively prevent transmission is therefore uncertain. In addition, asymptomatic and presymptomatic transmission may occur, and infectivity may be highest early after onset of symptoms, meaning that contact tracing, isolation of exposed individuals and social distancing are essential public health measures to prevent further spread. This review aimed to summarise the evidence around viral shedding vs infectivity of SARS-CoV-2.", "qid": 3, "docid": "v6nzp73y", "rank": 96, "score": 0.8438037037849426}, {"content": "Title: Clinical features and outcomes of HIV patients with coronavirus disease 2019 Content: Little is known about the clinical outcomes of HIV patients infected with SARS-CoV-2. We describe 47 patients referred to our hospital between 21 February and 16 April 2020 with proven/probable COVID-19, 45 (96%) of whom fully recovered and two died.", "qid": 3, "docid": "53n5i9ck", "rank": 97, "score": 0.8437342643737793}, {"content": "Title: Thromboinflammation and the hypercoagulability of COVID-19. Content: The pathogenic coronavirus has been wreaking havoc worldwide since January. Infection with SARS-CoV-2 is problematic as no one has prior immunity, and no specific antiviral treatments are available. While many people with COVID-19 develop mild to moderate symptoms, some develop profound seemingly unchecked inflammatory responses leading to acute lung injury and hypoxemic respiratory failure, the most common cause for death.", "qid": 3, "docid": "svwkcuxf", "rank": 98, "score": 0.8434521555900574}, {"content": "Title: COVID-19: Saving lives and livelihoods using population density driven testing Content: SARS-CoV-2 transmission risk generally increases with proximity of those shedding the virus to those susceptible to infection. Thus, this risk is a function of both number of people and the area which they occupy. However, the latter continues to evade COVID-19 testing policy. Increased testing in areas with lower population density, has the potential to induce a false sense of security even as cases continue to rise sharply overall.", "qid": 3, "docid": "netozhv1", "rank": 99, "score": 0.8434023261070251}, {"content": "Title: Isolation of infectious SARS-CoV-2 from urine of a COVID-19 patient Content: SARS-CoV-2 caused a major outbreak of severe pneumonia (COVID-19) in humans. Viral RNA was detected in multiple organs in COVID-19 patients. However, infectious SARS-CoV-2 was only isolated from respiratory specimens. Here, infectious SARS-CoV-2 was successfully isolated from urine of a COVID-19 patient. The virus isolated could infect new susceptible cells and was recognized by its' own patient sera. Appropriate precautions should be taken to avoid transmission from urine.", "qid": 3, "docid": "tco5oplr", "rank": 100, "score": 0.8432086706161499}]}
{"query": "what causes death from Covid-19?", "hits": [{"content": "Title: Causes of Death and Comorbidities in Patients with COVID-19 Content: Infection by the new corona virus strain SARS-CoV-2 and its related syndrome COVID-19 has caused several hundreds of thousands of deaths worldwide. Patients of higher age and with preexisting chronic health conditions are at an increased risk of fatal disease outcome. However, detailed information on causes of death and the contribution of comorbidities to death yet is missing. Here, we report autopsy findings on causes of death and comorbidities of 26 decedents that had clinically presented with severe COVID-19. We found that septic shock and multi organ failure was the most common immediate cause of death, often due to suppurative pulmonary infection. Respiratory failure due to diffuse alveolar damage presented as the most immediate cause of death in fewer cases. Several comorbidities, such as hypertension, ischemic heart disease, and obesity were present in the vast majority of patients. Our findings reveal that causes of death were directly related to COVID-19 in the majority of decedents, while they appear not to be an immediate result of preexisting health conditions and comorbidities. We therefore suggest that the majority of patients had died of COVID-19 with only contributory implications of preexisting health conditions to the mechanism of death.", "qid": 4, "docid": "9yb9a9vz", "rank": 1, "score": 0.8927373886108398}, {"content": "Title: COVID-19: Moving beyond the pandemic Content: Severe acute respiratory syndrome Coronavirus 2 (SARS-CoV-2) is the cause of COVID-19. As of April 11th, 2020, there were almost 2 million cases of COVID-19 internationally and over 100,000 deaths (John Hopkins University, 2020). There has been significant effort to increase hospital and healthcare capacity to reduce the number of fatalities associated with this global pandemic (Choi & Logsdon 2020).", "qid": 4, "docid": "v04vu1f5", "rank": 2, "score": 0.8853973150253296}, {"content": "Title: Thromboinflammation and the hypercoagulability of COVID-19. Content: The pathogenic coronavirus has been wreaking havoc worldwide since January. Infection with SARS-CoV-2 is problematic as no one has prior immunity, and no specific antiviral treatments are available. While many people with COVID-19 develop mild to moderate symptoms, some develop profound seemingly unchecked inflammatory responses leading to acute lung injury and hypoxemic respiratory failure, the most common cause for death.", "qid": 4, "docid": "svwkcuxf", "rank": 3, "score": 0.8820174932479858}, {"content": "Title: Electrical Storm in COVID-19 Content: Abstract COVID-19 is a global pandemic caused by SARS-CoV-2. Infection is associated with significant morbidity and mortality. Individuals with pre-existing cardiovascular disease or evidence of myocardial injury are at risk for severe disease and death. Little is understood about the mechanisms of myocardial injury or life-threatening cardiovascular sequelae.", "qid": 4, "docid": "98xisxg7", "rank": 4, "score": 0.8805152773857117}, {"content": "Title: Current perspectives on Coronavirus 2019 (COVID-19) and cardiovascular disease: A white paper by the JAHA editors. Content: Coronavirus Disease 2019 (COVID-19), caused by the Severe Acute Respiratory Syndrome Coronavirus-2 (SARS-CoV-2), has infected more than 3.0 million people worldwide and killed more than 200,000 as of April 27, 2020, making it the most lethal pandemic since the Spanish flu of 1918.1, 2 COVID-19 may preferentially infect individuals with cardiovascular conditions, is more severe in subjects with cardiovascular comorbidities, may directly or indirectly affect the heart and may interact with cardiovascular medications.3 In addition, the widespread effects of the pandemic on the global healthcare system affects the routine and emergency cardiac care for patients who are, may be, or are not infected with COVID-19.", "qid": 4, "docid": "tr5whji0", "rank": 5, "score": 0.8757681250572205}, {"content": "Title: The COVID-19 pandemic and research shutdown: staying safe and productive. Content: The Coronavirus Disease 2019 (COVID-19) pandemic, caused by SARS-CoV-2, has caused severe disease outcomes and widespread infections not seen in terms of its case fatality rate and global economic impact since the 1918-1919 Spanish flu; the latter leading to 675,000 deaths in the United States (US) (50 million worldwide).", "qid": 4, "docid": "7ow2dc7u", "rank": 6, "score": 0.8743624091148376}, {"content": "Title: Projection of COVID-19 Pandemic in Uganda Content: COVID-19 (Corona Virus) is caused by Severe Acute Respiratory Syndrome Corona Virus 2 (SARS-COV-2). The virus that was first discovered in China Wuhan Province about 3 months ago (first cases were reported in Wuhan on December 31st, 2019) has spread world wide. The six (6) top countries (excluding China) most affected so far include; USA, Italy, Spain, Germany, France, and Iran. With Italy showing the highest death toll. In Uganda where it was discovered on 19/3/2020 with one (01) case has just in nine (9) days, increased to thirty (30) infected individuals. This model is a wake-up call over the rate at which COVID-19 is likely to spread throughout the country. Thus it is a guide for policymakers and planners to benchmark on for solutions to this deadly virus.", "qid": 4, "docid": "co4ckyp9", "rank": 7, "score": 0.8725167512893677}, {"content": "Title: No Autopsies on COVID-19 Deaths: A Missed Opportunity and the Lockdown of Science Content: Background: The current outbreak of COVID-19 infection, which started in Wuhan, Hubei province, China, in December 2019, is an ongoing challenge and a significant threat to public health requiring surveillance, prompt diagnosis, and research efforts to understand a new, emergent, and unknown pathogen and to develop effective therapies. Despite the increasing number of published studies on COVID-19, in all the examined studies the lack of a well-defined pathophysiology of death among patients who died following COVID-19 infection is evident. Autopsy should be considered mandatory to define the exact cause of death, thus providing useful clinical and epidemiologic information as well as pathophysiological insights to further provide therapeutic tools. Methods: A literature review was performed on PubMed database, using the key terms: \u201cCOVID-19\u201d, \u201cnCov 19\u201d, and \u201cSars Cov 2\u201d. 9709 articles were retrieved; by excluding all duplicated articles, additional criteria were then applied: articles or abstracts in English and articles containing one of the following words: \u201cdeath\u201d, \u201cdied\u201d, \u201ccomorbidity\u201d, \u201ccause of death\u201d, \u201cbiopsy\u201d, \u201cautopsy\u201d, or \u201cpathological\u201d. Results: A total of 50 articles met the inclusion criteria. However, only 7 of these studies reported autopsy-based data. Discussion: The analysis of the main data from the selected studies concerns the complete analysis of 12,954 patients, of whom 2269 died (with a mortality rate of 17.52%). Laboratory confirmation of COVID-19 infection was obtained in all cases and comorbidities were fully reported in 46 studies. The most common comorbidities were: cardiovascular diseases (hypertension and coronary artery disease), metabolic disorders (diabetes, overweight, or obesity), respiratory disorders (chronic obstructive pulmonary disease), and cancer. The most common reported complications were: acute respiratory distress syndrome (ARDS), acute kidney injury, cardiac injury, liver insufficiency, and septic shock. Only 7 papers reported histological investigations. Nevertheless, only two complete autopsies are described and the cause of death was listed as COVID-19 in only one of them. The lack of postmortem investigation did not allow a definition of the exact cause of death to determine the pathways of this infection. Based on the few histopathological findings reported in the analyzed studies, it seems to be a clear alteration of the coagulation system: frequently prothrombotic activity with consequent thromboembolism was described in COVID-19 patients. As a scientific community, we are called on to face this global threat, and to defeat it with all the available tools necessary. Despite the improvement and reinforcement of any method of study in every field of medicine and science, encouraging the autopsy practice as a tool of investigation could also therefore, help physicians to define an effective treatment to reduce mortality.", "qid": 4, "docid": "f7cy5oad", "rank": 8, "score": 0.872124195098877}, {"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": 4, "docid": "3fp46sov", "rank": 9, "score": 0.871468186378479}, {"content": "Title: Autopsy Findings and Venous Thromboembolism in Patients With COVID-19: A Prospective Cohort Study Content: BACKGROUND: The new coronavirus, severe acute respiratory syndrome coronavirus-2 (SARS\u2013CoV-2), has caused more than 210 000 deaths worldwide. However, little is known about the causes of death and the virus's pathologic features. OBJECTIVE: To validate and compare clinical findings with data from medical autopsy, virtual autopsy, and virologic tests. DESIGN: Prospective cohort study. SETTING: Autopsies performed at a single academic medical center, as mandated by the German federal state of Hamburg for patients dying with a polymerase chain reaction\u2013confirmed diagnosis of COVID-19. PATIENTS: The first 12 consecutive COVID-19\u2013positive deaths. MEASUREMENTS: Complete autopsy, including postmortem computed tomography and histopathologic and virologic analysis, was performed. Clinical data and medical course were evaluated. Results: Median patient age was 73 years (range, 52 to 87 years), 75% of patients were male, and death occurred in the hospital (n = 10) or outpatient sector (n = 2). Coronary heart disease and asthma or chronic obstructive pulmonary disease were the most common comorbid conditions (50% and 25%, respectively). Autopsy revealed deep venous thrombosis in 7 of 12 patients (58%) in whom venous thromboembolism was not suspected before death; pulmonary embolism was the direct cause of death in 4 patients. Postmortem computed tomography revealed reticular infiltration of the lungs with severe bilateral, dense consolidation, whereas histomorphologically diffuse alveolar damage was seen in 8 patients. In all patients, SARS\u2013CoV-2 RNA was detected in the lung at high concentrations; viremia in 6 of 10 and 5 of 12 patients demonstrated high viral RNA titers in the liver, kidney, or heart. LIMITATION: Limited sample size. CONCLUSION: The high incidence of thromboembolic events suggests an important role of COVID-19\u2013induced coagulopathy. Further studies are needed to investigate the molecular mechanism and overall clinical incidence of COVID-19\u2013related death, as well as possible therapeutic interventions to reduce it. PRIMARY FUNDING SOURCE: University Medical Center Hamburg-Eppendorf.", "qid": 4, "docid": "8efdzlc0", "rank": 10, "score": 0.870341420173645}, {"content": "Title: SARS-CoV-2 receptor mutation in Egyptian population Content: The Coronavirus disease 2019 (COVID-19) is a respiratory tract infectious disease caused by Severe Acute Respiratory Syndrome coronavirus 2 (SARS-CoV-2). SARS-CoV-2 triggers severe pneumonia leading to acute respiratory distress syndrome and death in severe cases. According to WHO reported, Egypt is among the countries with low confirmed SARS CoV2 infected symptomatic cases and death. We postulate that one of the reasons for this may be due mutations in the viral receptor. Therefore this study was conducted to confirm or reject this postulation.", "qid": 4, "docid": "xirt6efg", "rank": 11, "score": 0.8698115348815918}, {"content": "Title: Registries Offer Insights on COVID-19-Cancer Connection Content: Findings from CCC19 and TERAVOLT suggest that patients with cancer may be more likely to die from COVID-19 than people in the general population. Additional mortality risk factors may include age, performance status, treatment with chemotherapy, and exposure to hydroxychloroquine plus azithromycin.", "qid": 4, "docid": "ar0lanxa", "rank": 12, "score": 0.8695052862167358}, {"content": "Title: Registries Offer Insights on COVID-19-Cancer Connection. Content: Findings from CCC19 and TERAVOLT suggest that patients with cancer may be more likely to die from COVID-19 than people in the general population. Additional mortality risk factors may include age, performance status, treatment with chemotherapy, and exposure to hydroxychloroquine plus azithromycin.", "qid": 4, "docid": "d4rphs30", "rank": 13, "score": 0.8695052862167358}, {"content": "Title: COVID\u201019: Moving beyond the pandemic Content: Severe acute respiratory syndrome Coronavirus 2 (SARS\u2010CoV\u20102) is the cause of COVID\u201019. As of April 11th, 2020, there were almost 2 million cases of COVID\u201019 internationally and over 100,000 deaths (John Hopkins University, 2020). There has been significant effort to increase hospital and healthcare capacity to reduce the number of fatalities associated with this global pandemic (Choi & Logsdon 2020).", "qid": 4, "docid": "raddzrns", "rank": 14, "score": 0.8694558143615723}, {"content": "Title: Autopsy Findings and Venous Thromboembolism in Patients With COVID-19 Content: BACKGROUND: The new coronavirus, severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2), has caused more than 210 000 deaths worldwide. However, little is known about the causes of death and the virus's pathologic features. OBJECTIVE: To validate and compare clinical findings with data from medical autopsy, virtual autopsy, and virologic tests. DESIGN: Prospective cohort study. SETTING: Autopsies performed at a single academic medical center, as mandated by the German federal state of Hamburg for patients dying with a polymerase chain reaction-confirmed diagnosis of COVID-19. PATIENTS: The first 12 consecutive COVID-19-positive deaths. MEASUREMENTS: Complete autopsy, including postmortem computed tomography and histopathologic and virologic analysis, was performed. Clinical data and medical course were evaluated. Results: Median patient age was 73 years (range, 52 to 87 years), 75% of patients were male, and death occurred in the hospital (n = 10) or outpatient sector (n = 2). Coronary heart disease and asthma or chronic obstructive pulmonary disease were the most common comorbid conditions (50% and 25%, respectively). Autopsy revealed deep venous thrombosis in 7 of 12 patients (58%) in whom venous thromboembolism was not suspected before death; pulmonary embolism was the direct cause of death in 4 patients. Postmortem computed tomography revealed reticular infiltration of the lungs with severe bilateral, dense consolidation, whereas histomorphologically diffuse alveolar damage was seen in 8 patients. In all patients, SARS-CoV-2 RNA was detected in the lung at high concentrations; viremia in 6 of 10 and 5 of 12 patients demonstrated high viral RNA titers in the liver, kidney, or heart. LIMITATION: Limited sample size. CONCLUSION: The high incidence of thromboembolic events suggests an important role of COVID-19-induced coagulopathy. Further studies are needed to investigate the molecular mechanism and overall clinical incidence of COVID-19-related death, as well as possible therapeutic interventions to reduce it. PRIMARY FUNDING SOURCE: University Medical Center Hamburg-Eppendorf.", "qid": 4, "docid": "mnta55wf", "rank": 15, "score": 0.8692317008972168}, {"content": "Title: Transmission and risk factors of OF COVID-19 Content: SARS-CoV-2, the virus that causes COVID-19, is transmitted through respiratory secretions and saliva. The virus can also live for short periods of time (1 to several hours) on fomites such as doorknobs, handrails, and tables. Aerosolization of the virus can occur during procedures including bronchoscopy, endotracheal intubation, and administration of nebulized treatments. Asymptomatic shedding of the virus does occur and may account for up to 60% of cases. Risk factors for a more severe course of COVID-19 include age 65 and older, living in a nursing home or long term care facility, chronic lung disease, and others.", "qid": 4, "docid": "eimqd5b9", "rank": 16, "score": 0.8688373565673828}, {"content": "Title: Transmission and risk factors of OF COVID-19. Content: SARS-CoV-2, the virus that causes COVID-19, is transmitted through respiratory secretions and saliva. The virus can also live for short periods of time (1 to several hours) on fomites such as doorknobs, handrails, and tables. Aerosolization of the virus can occur during procedures including bronchoscopy, endotracheal intubation, and administration of nebulized treatments. Asymptomatic shedding of the virus does occur and may account for up to 60% of cases. Risk factors for a more severe course of COVID-19 include age 65 and older, living in a nursing home or long term care facility, chronic lung disease, and others.", "qid": 4, "docid": "l1nvnvkg", "rank": 17, "score": 0.8688373565673828}, {"content": "Title: The Role of Data Registries in the Time of COVID-19. Content: On April 1, 2020, the confirmed global burden of COVID-19 was more than 900,000 with 46,413 deaths. Despite worldwide calls for social distancing and containment, the incidence of the disease continues to increase. COVID-19 is a respiratory tract infection caused by the novel coronavirus (SARS-CoV2). Preliminary analyses from the Chinese Center for Disease Control and Prevention indicated an overall case fatality rate (CFR) of 2.3%; however the CFR was higher in older adults (14.8% in those 80\u00b1 years) and 49% of all critical cases. Those with preexisting conditions (cardiovascular disease (CVD), diabetes, chronic respiratory disease, hypertension, and cancer) also had higher CRFs. In the United States, 116 million adults have hypertension, 26 million US adults have diabetes mellitus, 9% have preexisting CVD and may therefore be at greater risk of complications or adverse health outcomes from COVID-19 infection.", "qid": 4, "docid": "2tlbeqvb", "rank": 18, "score": 0.8677570819854736}, {"content": "Title: COVID-19: laboratory diagnosis for clinicians. An updating article Content: COVID-19 (coronavirus disease 2019) is an infectious disease caused by the new coronavirus associated with severe acute respiratory syndrome 2 (SARS-CoV-2) Coronaviridae comprises a large family, of which at least seven members are known to cause respiratory diseases in humans Coronaviruses have the ability to infect virtually all major groups of animals and, eventually, can infect humans SARS-CoV-2 is the third coronavirus to cross the species barrier and infect humans This virus was identified in an outbreak of pneumonia cases in Wuhan city, Hubei province, China, in December 2019 Its entire genome is inscribed on a single strand of ribonucleic acid Some proteins present on the surface of the virus act as facilitators for its entry into host cells, while others, apparently, are related to its pathogenesis Coronaviruses are responsible for respiratory infections in humans and some animals The infection is often mild to moderate in intensity, but some coronaviruses may cause serious illnesses, such as severe acute respiratory syndrome (SARS), which occurred in 2002, and the Middle East respiratory syndrome (MERS) Coronaviruses can activate an excessive and unregulated immune response, which may promote SARS development Although the lungs are one of the target organs, the hypoxia mechanism is systemic and other organs begin to suffer both through lack of oxygen and through deregulation of inflammation control mechanisms", "qid": 4, "docid": "8685l1n9", "rank": 19, "score": 0.8662919998168945}, {"content": "Title: Innate Immune Signaling and Proteolytic Pathways in the Resolution or Exacerbation of SARS-CoV-2 in Covid-19: Key Therapeutic Targets? Content: COVID-19 is caused by the Severe Acute Respiratory Syndrome (SARS) coronavirus (Cov)-2, an enveloped virus with a positive-polarity, single-stranded RNA genome. The initial outbreak of the pandemic began in December 2019, and it is affecting the human health of the global community. In common with previous pandemics (Influenza H1N1 and SARS-CoV) and the epidemics of Middle east respiratory syndrome (MERS)-CoV, CoVs target bronchial and alveolar epithelial cells. Virus protein ligands (e.g., haemagglutinin or trimeric spike glycoprotein for Influenza and CoV, respectively) interact with cellular receptors, such as (depending on the virus) either sialic acids, Dipeptidyl peptidase 4 (DPP4), or angiotensin-converting enzyme 2 (ACE2). Host proteases, e.g., cathepsins, furin, or members of the type II transmembrane serine proteases (TTSP) family, such as Transmembrane protease serine 2 (TMPRSS2), are involved in virus entry by proteolytically activating virus ligands. Also involved are Toll Like Receptor (TLR) family members, which upregulate anti-viral and pro-inflammatory mediators [interleukin (IL)-6 and IL-8 and type I and type III Interferons among others], through the activation of Nuclear Factor (NF)-kB. When these events (virus cellular entry and innate immune responses) are uncontrolled, a deleterious systemic response is sometimes encountered in infected patients, leading to the well-described \"cytokine storm\" and an ensuing multiple organ failure promoted by a downregulation of dendritic cell, macrophage, and T-cell function. We aim to describe how the lung and systemic host innate immune responses affect survival either positively, through downregulating initial viral load, or negatively, by triggering uncontrolled inflammation. An emphasis will be put on host cellular signaling pathways and proteases involved with a view on tackling these therapeutically.", "qid": 4, "docid": "ls88uo78", "rank": 20, "score": 0.8662288188934326}, {"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": 4, "docid": "ete5n5pw", "rank": 21, "score": 0.8656982183456421}, {"content": "Title: Novel Coronavirus COVID-19: Current Evidence and Evolving Strategies Content: COVID-19 is a global pandemic that has currently infected &gt;300,000 globally. Fever and cough are the most common symptoms of the disease, and it is important to remember that the virus can even be transmitted by individuals who test positive for the disease but do not have any symptoms. Currently reported mortality rates vary because of the rapid spread of the disease and different approaches to calculating this estimate, but it is clear that the risk of death is associated with age and the presence of underlying conditions. Risk mitigation techniques (i.e., hand washing, social distancing, and self-isolation) have already been emphasized across major news outlets. It is essential that we continue these practices, as the outbreak is currently expected to last for many more months and we must be mindful of the lessons learned from past pandemics to prevent a second wave from occurring.", "qid": 4, "docid": "3ateeei3", "rank": 22, "score": 0.865185022354126}, {"content": "Title: SARS\u2010CoV\u20102: a new aetiology for atypical lymphocytes Content: Coronavirus disease 2019 (COVID-19) is an infectious disease caused by a newly emerging coronavirus, SARS-CoV-2. COVID-19 has a very variable clinical picture, ranging from asymptomatic to severe acute respiratory syndrome that can lead to death. Our case, a 74-year-old female patient, presented with fever, moderate dyspnoea and leucocytosis (white blood cell count 21.6 \u00d7 109 /l, neutrophils 16.8 \u00d7 109 /l, lymphocytes 3.67 \u00d7 109 /l). RT-PCR for SARS-CoV-2 was performed, which confirmed COVID-19.", "qid": 4, "docid": "oo2s307i", "rank": 23, "score": 0.8651579022407532}, {"content": "Title: Possibly critical role of wearing masks in general population in controlling COVID\u201019 Content: Coronavirus disease 2019 (COVID\u201019), caused by severe acute respiratory syndrome coronavirus 2 (SARS\u2010CoV\u20102), is now overwhelming spreading in the world. As of April 11, 2020, totally 1.61 million COVID\u201019 patients were confirmed in more than 200 countries and regions with 99690 deaths. This article is protected by copyright. All rights reserved.", "qid": 4, "docid": "deg5hqtl", "rank": 24, "score": 0.8646227121353149}, {"content": "Title: Innate Immune Signaling and Proteolytic Pathways in the Resolution or Exacerbation of SARS-CoV-2 in Covid-19: Key Therapeutic Targets? Content: COVID-19 is caused by the Severe Acute Respiratory Syndrome (SARS) coronavirus (Cov)-2, an enveloped virus with a positive-polarity, single-stranded RNA genome. The initial outbreak of the pandemic began in December 2019, and it is affecting the human health of the global community. In common with previous pandemics (Influenza H1N1 and SARS-CoV) and the epidemics of Middle east respiratory syndrome (MERS)-CoV, CoVs target bronchial and alveolar epithelial cells. Virus protein ligands (e.g., haemagglutinin or trimeric spike glycoprotein for Influenza and CoV, respectively) interact with cellular receptors, such as (depending on the virus) either sialic acids, Dipeptidyl peptidase 4 (DPP4), or angiotensin-converting enzyme 2 (ACE2). Host proteases, e.g., cathepsins, furin, or members of the type II transmembrane serine proteases (TTSP) family, such as Transmembrane protease serine 2 (TMPRSS2), are involved in virus entry by proteolytically activating virus ligands. Also involved are Toll Like Receptor (TLR) family members, which upregulate anti-viral and pro-inflammatory mediators [interleukin (IL)-6 and IL-8 and type I and type III Interferons among others], through the activation of Nuclear Factor (NF)-kB. When these events (virus cellular entry and innate immune responses) are uncontrolled, a deleterious systemic response is sometimes encountered in infected patients, leading to the well-described \u201ccytokine storm\u201d and an ensuing multiple organ failure promoted by a downregulation of dendritic cell, macrophage, and T-cell function. We aim to describe how the lung and systemic host innate immune responses affect survival either positively, through downregulating initial viral load, or negatively, by triggering uncontrolled inflammation. An emphasis will be put on host cellular signaling pathways and proteases involved with a view on tackling these therapeutically.", "qid": 4, "docid": "5gz2dotn", "rank": 25, "score": 0.8645302057266235}, {"content": "Title: Endothelial cell dysfunction: a major player in SARS-CoV-2 infection (COVID-19)? Content: Coronavirus disease 2019 (COVID-19) represents a public health crisis of pandemic proportions. Caused by SARS-CoV-2, which stands for severe acute respiratory syndrome (SARS) coronavirus 2, the symptoms most commonly reported include cough, fever, and shortness of breath, but also extra-pulmonary symptoms, such as neurological and gastroenterological manifestations.", "qid": 4, "docid": "xzgfbvqk", "rank": 26, "score": 0.8635976314544678}, {"content": "Title: Lifestyle at Time of COVID-19: How Could Quarantine Affect Cardiovascular Risk Content: COVID-19 is causing a global pandemic with a high number of deaths and infected people. To contain the diffusion of COVID-19 virus, governments have enforced restrictions on outdoor activities or even collective quarantine on the population. Quarantine carries some long-term effects on cardiovascular disease, mainly related to unhealthy lifestyle and anxiety.", "qid": 4, "docid": "pigamjae", "rank": 27, "score": 0.863412618637085}, {"content": "Title: COVID-19 pandemic: do we need systematic screening of patients with cardiovascular risk factors in Low and Middle-Income Countries (LMICs) for preventing death? Content: COVID-19 pandemic is an emergent cardiovascular risk factor and a major cause of mortality worldwide. Thromboembolism is highly suspected as a leading cause of death in these patients through vascular inflammation caused by SARS COV2. Until now there is no real treatment of COVID-19 and many proposed drugs are under clinical trials. Considering the high incidence of thromboembolic events in critically ill patients with COVID-19, prevention of this disorder should be essential in order to reduce mortality in these patients.", "qid": 4, "docid": "yml9wuer", "rank": 28, "score": 0.8632747530937195}, {"content": "Title: Thromboembolic risks in patients with COVID-19: major concern to consider in our management Content: COVID-19 pandemic is an emergent cardiovascular risk factor and a major cause of mortality worldwide. Thromboembolism is highly suspected as a leading cause of death in these patients through vascular inflammation caused by SARS COV2. Until now there is no real treatment of COVID-19 and many proposed drugs are under clinical trials. Considering the high incidence of thromboembolic events in critically ill patients with COVID-19, prevention of this disorder should be essential in order to reduce mortality in these patients.", "qid": 4, "docid": "zy4nb6bo", "rank": 29, "score": 0.8632747530937195}, {"content": "Title: Clinical features and outcomes of four HIV patients with COVID\u201019 in Wuhan, China Content: SARS-CoV-2 is the coronavirus that has been identified as the pathogen causing COVID-19.1 Human Immunodeficiency Virus (HIV) attacks the immune system and leads to acquired immune deficiency syndrome (AIDS) in the late stage of disease. Concerns have been raised on HIV as a risk factor for COVID-19. This article is protected by copyright. All rights reserved.", "qid": 4, "docid": "f9gmlkez", "rank": 30, "score": 0.8631438612937927}, {"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 \"COVID-19 Clinical Guidance for the CV Care Team\", there is a significantly higher fatality rate in people who are elderly (8.0% 70-79 years; 14.8% &#8805;80 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.", "qid": 4, "docid": "qd4dic30", "rank": 31, "score": 0.8628547191619873}, {"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": 32, "score": 0.8625227212905884}, {"content": "Title: Preliminary Estimate of Excess Mortality During the COVID-19 Outbreak - New York City, March 11-May 2, 2020 Content: SARS-CoV-2, the virus that causes coronavirus disease 2019 (COVID-19), was first identified in December 2019 in Wuhan, China, and has since spread worldwide. On March 11, 2020, the World Health Organization declared COVID-19 a pandemic (1). That same day, the first confirmed COVID-19-associated fatality occurred in New York City (NYC). To identify confirmed COVID-19-associated deaths, defined as those occurring in persons with laboratory-confirmed SARS-CoV-2 infection, on March 13, 2020, the New York City Department of Health and Mental Hygiene (DOHMH) initiated a daily match between all deaths reported to the DOHMH electronic vital registry system (eVital) (2) and laboratory-confirmed cases of COVID-19. Deaths for which COVID-19, SARS-CoV-2, or an equivalent term is listed on the death certificate as an immediate, underlying, or contributing cause of death, but that do not have laboratory-confirmation of COVID-19 are classified as probable COVID-19-associated deaths. As of May 2, a total of 13,831 laboratory-confirmed COVID-19-associated deaths, and 5,048 probable COVID-19-associated deaths were recorded in NYC (3). Counting only confirmed or probable COVID-19-associated deaths, however, likely underestimates the number of deaths attributable to the pandemic. The counting of confirmed and probable COVID-19-associated deaths might not include deaths among persons with SARS-CoV-2 infection who did not access diagnostic testing, tested falsely negative, or became infected after testing negative, died outside of a health care setting, or for whom COVID-19 was not suspected by a health care provider as a cause of death. The counting of confirmed and probable COVID-19-associated deaths also does not include deaths that are not directly associated with SARS-CoV-2 infection. The objective of this report is to provide an estimate of all-cause excess deaths that have occurred in NYC in the setting of widespread community transmission of SARS-CoV-2. Excess deaths refer to the number of deaths above expected seasonal baseline levels, regardless of the reported cause of death. Estimation of all-cause excess deaths is used as a nonspecific measure of the severity or impact of pandemics (4) and public health emergencies (5). Reporting of excess deaths might provide a more accurate measure of the impact of the pandemic.", "qid": 4, "docid": "dmffqcq7", "rank": 33, "score": 0.8623974919319153}, {"content": "Title: Preliminary Estimate of Excess Mortality During the COVID-19 Outbreak - New York City, March 11-May 2, 2020. Content: SARS-CoV-2, the virus that causes coronavirus disease 2019 (COVID-19), was first identified in December 2019 in Wuhan, China, and has since spread worldwide. On March 11, 2020, the World Health Organization declared COVID-19 a pandemic (1). That same day, the first confirmed COVID-19-associated fatality occurred in New York City (NYC). To identify confirmed COVID-19-associated deaths, defined as those occurring in persons with laboratory-confirmed SARS-CoV-2 infection, on March 13, 2020, the New York City Department of Health and Mental Hygiene (DOHMH) initiated a daily match between all deaths reported to the DOHMH electronic vital registry system (eVital) (2) and laboratory-confirmed cases of COVID-19. Deaths for which COVID-19, SARS-CoV-2, or an equivalent term is listed on the death certificate as an immediate, underlying, or contributing cause of death, but that do not have laboratory-confirmation of COVID-19 are classified as probable COVID-19-associated deaths. As of May 2, a total of 13,831 laboratory-confirmed COVID-19-associated deaths, and 5,048 probable COVID-19-associated deaths were recorded in NYC (3). Counting only confirmed or probable COVID-19-associated deaths, however, likely underestimates the number of deaths attributable to the pandemic. The counting of confirmed and probable COVID-19-associated deaths might not include deaths among persons with SARS-CoV-2 infection who did not access diagnostic testing, tested falsely negative, or became infected after testing negative, died outside of a health care setting, or for whom COVID-19 was not suspected by a health care provider as a cause of death. The counting of confirmed and probable COVID-19-associated deaths also does not include deaths that are not directly associated with SARS-CoV-2 infection. The objective of this report is to provide an estimate of all-cause excess deaths that have occurred in NYC in the setting of widespread community transmission of SARS-CoV-2. Excess deaths refer to the number of deaths above expected seasonal baseline levels, regardless of the reported cause of death. Estimation of all-cause excess deaths is used as a nonspecific measure of the severity or impact of pandemics (4) and public health emergencies (5). Reporting of excess deaths might provide a more accurate measure of the impact of the pandemic.", "qid": 4, "docid": "6x33a6g6", "rank": 34, "score": 0.8623974919319153}, {"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": 35, "score": 0.8619446754455566}, {"content": "Title: IL-6 blockade treatment for severe COVID-19 in two patients with multiple myeloma. Content: Coronavirus disease 2019 (COVID-19) presents with a broad clinical spectrum, varying from asymptomatic infection to severe pneumonitis, leading to acute respiratory distress syndrome (ARDS) and death(Guan, et al 2020). Accumulating evidence suggests that in severe COVID-19, an acute hyperinflammatory syndrome characterised by fever, hypoxia and increased serum inflammatory markers, occurring 5-10 days from the first symptoms, is the major driver of morbidity and death(Zhou, et al 2020b). Hyperinflammation is not specific to COVID-19. Similar syndromes were previously described in respiratory disease associated with other coronaviruses, including the severe acute respiratory syndrome-coronavirus (SARS-CoV) in 2003 and Middle East respiratory syndrome-coronavirus (MERS-CoV) in 2012(Castilletti, et al 2005, Tseng, et al 2005).", "qid": 4, "docid": "pwq1ar61", "rank": 36, "score": 0.861823558807373}, {"content": "Title: Maternal mortality from COVID-19 in Mexico. Content: COVID-19, the illness caused by the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), is the deadliest pandemic to occur in this century. Common symptoms of COVID-19 include cough, myalgia, fever, chest pain, and headache. However, its clinical presentation ranges from completely asymptomatic to acute respiratory distress syndrome.[1] Pregnant women are susceptible to community spread of COVID-19 because they cannot postpone interactions with healthcare professionals and other women receiving obstetric care.", "qid": 4, "docid": "8noxjjuh", "rank": 37, "score": 0.8617690205574036}, {"content": "Title: Perspectives on Cardiopulmonary Critical Care for COVID-19 Patients: From Members of the American Heart Association Council on Cardiopulmonary, Critical Care, Perioperative and Resuscitation Content: The coronavirus disease 2019 (COVID-19) pandemic, caused by Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2), marks a global event that will permanently reshape implementation of intensive care medicine. As of June 4, 2020, there are 6,606,455 reported cases of COVID-19 including 388,556 fatalities spanning 215 countries and territories, although epidemiological data remain incomplete. Early autopsy reports emphasize proximal airway and distal airspace involvement, including alveolar epithelial inflammation and capillary thickening.", "qid": 4, "docid": "vqd79mf3", "rank": 38, "score": 0.8617426156997681}, {"content": "Title: Perspectives on Cardiopulmonary Critical Care for COVID-19 Patients: From Members of the American Heart Association Council on Cardiopulmonary, Critical Care, Perioperative and Resuscitation. Content: The coronavirus disease 2019 (COVID-19) pandemic, caused by Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2), marks a global event that will permanently reshape implementation of intensive care medicine. As of June 4, 2020, there are 6,606,455 reported cases of COVID-19 including 388,556 fatalities spanning 215 countries and territories, although epidemiological data remain incomplete. Early autopsy reports emphasize proximal airway and distal airspace involvement, including alveolar epithelial inflammation and capillary thickening.", "qid": 4, "docid": "o4ofqk5e", "rank": 39, "score": 0.8617426156997681}, {"content": "Title: New emerging dermatological symptoms in coronavirus pandemic Content: COVID\u201019 (Coronavirus Disease 2019) is a fatal disease that could lead to a serious respiratory illness. It is caused by SARS\u2010CoV\u20102 virus. In December 2019, the first of human cases were identified in China and the infection spread quickly around the world. The World Health Organisation (WHO) declared the disease, a global pandemic on 11 March 2020, even as COVID\u201019 rapidly spread across the world. According to clinical reports, fever, headache, cough and myalgia are common clinical symptoms. Many symptoms also occur, such as sputum formation, haemoptysis and diarrhea.", "qid": 4, "docid": "46njnlct", "rank": 40, "score": 0.8614659309387207}, {"content": "Title: COVID-19 infection outbreak among health care workers: perspective from a low-middle income country. Content: To the Editor, The new pandemic COVID -19 caused by Severe Acute Respiratory Syndrome Corona Virus 2 (SARS-CoV-2) is a global threat. So far, more than 11 million infections and more than five hundred thousand deaths have been reported worldwide. In India the number of cases as of 5th July, 2020 is 6,73,165 with 19,268 deaths. Health care workers (HCWs) have been the backbone of this pandemic since the very beginning...", "qid": 4, "docid": "vx3eqoak", "rank": 41, "score": 0.8609695434570312}, {"content": "Title: Review on the global epidemiological situation and the efficacy of chloroquine and hydroxychloroquine for the treatment of COVID-19 Content: Covid-19 disease is caused by SARS-CoV-2, a virus belonging to the coronavirus family. Covid-19 is so new that there is currently no specific vaccine or treatment. Clinical trials are currently underway. In vitro tests are also being conducted to assess the efficacy of chloroquine and hydroxychloroquine for the treatment of this epidemic, which is considered a pandemic by the WHO. We note that the content of this review is dated. The information it contains is subject to change and modification as the epidemic progresses.", "qid": 4, "docid": "wbkn7yjh", "rank": 42, "score": 0.8603862524032593}, {"content": "Title: Sudden cardiac death in COVID-19 patients, a report of three cases Content: The mortality rate of coronavirus disease-19 (COVID-19) has been reported as 1\u20136% in most studies. The cause of most deaths has been acute pneumonia. Nevertheless, it has been noted that cardiovascular failure can also lead to death. Three COVID-19 patients were diagnosed based on reverse transcriptase-polymerase chain reaction of a nasopharyngeal swab test and radiological examinations in our hospital. The patients received medications at the discretion of the treating physician. In this case series, chest computed tomography scans and electrocardiograms, along with other diagnostic tests were used to evaluate these individuals. Sudden cardiac death in COVID-19 patients is not common, but it is a major concern. So, it is recommended to monitor cardiac condition in selected patients with COVID-19.", "qid": 4, "docid": "378cfb23", "rank": 43, "score": 0.8602761030197144}, {"content": "Title: Anticoagulant and antiarrhythmic effects of heparin in the treatment of COVID-19 patients Content: Most severe manifestations of COVID-19 cases, such as multiple organ failure and death, have been linked to coagulation dysfunction markers, such as platelet reduction and increases in prothrombin time, fibrin degradation products and, mainly, D-dimer [1]. A recent paper by Tang et al. [2] in this journal reported that heparin treatment reduced mortality of COVID-19 patients with elevated D-dimer; similar preliminary results have been reported elsewhere [3]. A mounting body of evidence shows that SARS-CoV-2 causes a \"cytokine storm\" [1,4] that activates the coagulation cascade, leading to thrombosis. Similar to the findings in severe sepsis, generalized deposition of intravascular thrombi compromises the blood supply of several organs, leading to organ failure [5].", "qid": 4, "docid": "0ehd4oct", "rank": 44, "score": 0.8598148822784424}, {"content": "Title: Sudden cardiac death in COVID-19 patients, a report of three cases Content: The mortality rate of coronavirus disease-19 (COVID-19) has been reported as 1-6% in most studies. The cause of most deaths has been acute pneumonia. Nevertheless, it has been noted that cardiovascular failure can also lead to death. Three COVID-19 patients were diagnosed based on reverse transcriptase-polymerase chain reaction of a nasopharyngeal swab test and radiological examinations in our hospital. The patients received medications at the discretion of the treating physician. In this case series, chest computed tomography scans and electrocardiograms, along with other diagnostic tests were used to evaluate these individuals. Sudden cardiac death in COVID-19 patients is not common, but it is a major concern. So, it is recommended to monitor cardiac condition in selected patients with COVID-19.", "qid": 4, "docid": "u9omhsgu", "rank": 45, "score": 0.8598002195358276}, {"content": "Title: SnapShot: COVID-19 Content: Coronavirus disease 2019 (COVID-19) is a novel respiratory illness caused by SARS-CoV-2. Viral entry is mediated through viral spike protein and host ACE2 enzyme interaction. Most cases are mild; severe disease often involves cytokine storm and organ failure. Therapeutics including antivirals, immunomodulators, and vaccines are in development. To view this SnapShot, open or download the PDF.", "qid": 4, "docid": "q3jeu45r", "rank": 46, "score": 0.8593661785125732}, {"content": "Title: A Hypothesis on the role of the human immune system in covid-19 Content: The COVID-19 pandemic has not spared any continent. The disease has affected more than 7,500,000 individuals globally and killed approximately 450,000 individuals. The disease is caused by a very small virus named severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), which is an enveloped single-stranded RNA virus with a spike-like structure on its envelope that can interact with the angiotensin-converting enzyme 2 (ACE2) receptor after cleavage. ACE2 receptors are present in the human lungs and other organs. SARS-CoV-2 is a new virus that belongs to the subgenus Sarbecovirus; viruses in this subgenus have spread widely in the previous years and caused outbreaks of severe acute respiratory syndromes.", "qid": 4, "docid": "akt4glln", "rank": 47, "score": 0.8586941957473755}, {"content": "Title: A hypothesis on the role of the human immune system in covid-19 Content: The COVID-19 pandemic has not spared any continent. The disease has affected more than 7,500,000 individuals globally and killed approximately 450,000 individuals. The disease is caused by a very small virus named severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), which is an enveloped single-stranded RNA virus with a spike-like structure on its envelope that can interact with the angiotensin-converting enzyme 2 (ACE2) receptor after cleavage. ACE2 receptors are present in the human lungs and other organs. SARS-CoV-2 is a new virus that belongs to the subgenus Sarbecovirus; viruses in this subgenus have spread widely in the previous years and caused outbreaks of severe acute respiratory syndromes.", "qid": 4, "docid": "4oe0veq9", "rank": 48, "score": 0.8586941957473755}, {"content": "Title: Exploring Causal relationship between risk factors and vulnerability to COVID-19Cases of Italy, Spain, France, Greece, Portugal, Morocco and South Africa Content: Even though the infection rate of COVID-19 is very high as of today 31 May: 5,819,962 confirmed cases worldwide, the death rate is only about 6.23%, 362,786 deaths as for the same date. Furthermore, the rate of total infected cases is extremely different from one country to another as well as for the rate of mortality. Therefore, there may be some factors that possibly amplify the rate of infection from one country to another as well as for the rate of mortality due to COVID-19. In the literature, we have found multiple identified risk factors responsible for vulnerability to COVID19, we have chosen pertinent key risk factors for our study: Median-age, age>65 years old, weight, population density, diabetics, International arrivals, median temperature between March and May.", "qid": 4, "docid": "ito3q8da", "rank": 49, "score": 0.8586366772651672}, {"content": "Title: A fatal case of COVID-19 due to metabolic acidosis following dysregulate inflammatory response (cytokine storm) Content: The ongoing outbreak of COVID-19 has been expanding worldwide. As of 17 April 2020, the death toll stands at a sobering 147,027 and over two million cases, this has been straining the health care systems all over. Respiratory failure has been cited as the major cause of death but here we present a case about a patient who instead succumbed to severe metabolic acidosis with multiple organ failure.", "qid": 4, "docid": "96v8owb9", "rank": 50, "score": 0.8584040403366089}, {"content": "Title: Vascular skin symptoms in COVID-19: a french observational study Content: Coronavirus 19 (COVID-19) was declared as a pandemic viral infection by the World Health organization on March 11th 2020. Usual clinical manifestations of COVID-19 infection include fever, fatigue, myalgia, headache, diarrhea, dry cough, dyspnea that may lead to acute respiratory distress syndrome and death (1). Skin symptoms of COVID-19 have been poorly described but may include erythematous rash, urticaria and chicken pox like lesions (2-7). Angiotensin-converting enzyme 2 (ACE2) is a cellular receptor for COVID-19.", "qid": 4, "docid": "vp5xj8m5", "rank": 51, "score": 0.8583658933639526}, {"content": "Title: Clinical presentation and course of COVID-19 Content: Information about the clinical presentation and course of COVID-19 is evolving rapidly. On presentation, cough and fever predominate, but extrapulmonary symptoms are also common; in some patients, loss of sense of smell may be an early but favorable sign. The mortality rate varies widely in different reports but should become clearer as more data are collected. Risk factors for severe disease and death include comorbid conditions such as hypertension, cardiovascular disease, diabetes mellitus, and chronic obstructive pulmonary disease. Other implicated factors include older age, obesity, end-stage renal disease, and a higher neutrophil-lymphocyte ratio.", "qid": 4, "docid": "1gp58zxg", "rank": 52, "score": 0.8580812215805054}, {"content": "Title: COVID-19: risk for cytokine targeting in chronic inflammatory diseases? Content: COVID-19, caused by the SARS-CoV-2 virus, has become pandemic. With sharply rising infection rates, patient groups characterized by an enhanced infection risk will be challenged by the virus. In this context, patients with chronic immune-mediated inflammatory diseases are of particular interest, as these diseases are characterized by an intrinsic immune dysfunction leading to inflammation that may enhance risk for severe infection.", "qid": 4, "docid": "440j2zoi", "rank": 53, "score": 0.8580225706100464}, {"content": "Title: Living with HIV in the time of COVID\u201019: A glimpse of hope Content: As at the time of writing, the global confirmed cases of the coronavirus disease (COVID-19) stands at 5,075,181 with 330,981 deaths and 1,936,331 recoveries1 . According to the Canter for Disease Control, the aged and individuals with compromised immune systems due to infections (i.e., human immunodeficiency viruses (HIV), etc.) are at higher risk of contracting the COVID-19. This article is protected by copyright. All rights reserved.", "qid": 4, "docid": "cnxkpckr", "rank": 54, "score": 0.8575640916824341}, {"content": "Title: Estudios de imagen cardiaca en la pandemia COVID-19./ Cardiac imaging studies in the COVID-19 pandemic Content: COVID-19 is an acute respiratory syndrome caused by coronavirus-2 (SARS COV2). The different cardiac imaging methods have issued specific recommendations for the different imaging methods in this pandemic, so it is essential to emphasize the recommendations for carrying out these studies.", "qid": 4, "docid": "11q83ony", "rank": 55, "score": 0.857549786567688}, {"content": "Title: Cardiac imaging studies in the COVID-19 pandemic. Content: COVID-19 is an acute respiratory syndrome caused by coronavirus-2 (SARS COV2). The different cardiac imaging methods have issued specific recommendations for the different imaging methods in this pandemic, so it is essential to emphasize the recommendations for carrying out these studies.", "qid": 4, "docid": "9vypr79o", "rank": 56, "score": 0.857549786567688}, {"content": "Title: Estudios de imagen cardiaca en la pandemia COVID-19 Content: COVID-19 is an acute respiratory syndrome caused by coronavirus-2 (SARS COV2) The different cardiac imaging methods have issued specific recommendations for the different imaging methods in this pandemic, so it is essential to emphasize the recommendations for carrying out these studies", "qid": 4, "docid": "rcccwfl8", "rank": 57, "score": 0.8574104309082031}, {"content": "Title: Physician Deaths from Corona Virus Disease (COVID-19) Content: OBJECTIVE: The COVID-19 pandemic has caused much morbidity and mortality to patients but also health care providers. We tabulated the cases of physician deaths from COVID-19 associated with front-line work in hopes of mitigating future events. METHOD: On April 5, 2020, Google internet search was performed using the keywords doctor, physician, death, COVID, COVID-19, and coronavirus in English and Farsi, and in Chinese using the Baidu search engine. RESULTS: We found 198 physician deaths from COVID-19, but complete details were missing for 49 individuals. The average age of the physicians that died was 63.4 years (range 28 to 90 years) and the median age was 66 years of age. Ninety percent of the deceased physicians were male (175/194). General practitioners and emergency room doctors (78/192), respirologists (5/192), internal medicine specialists (11/192) and anesthesiologists (6/192) comprised 52% of those dying. Two percent of the deceased were epidemiologists (4/192), 2% were infectious disease specialists (4/192), 5% were dentists (9/192), 4% were ENT (8/192), and 4% were ophthalmologists (7/192). The countries with the most reported physician deaths were Italy (79/198), Iran (43/198), China (16/198), Philippines (14/198), United States (9/192) and Indonesia (7/192). CONCLUSION: Physicians from all specialties may die from COVID, and these deaths will likely increase as the pandemic progresses. Lack of personal protective equipment was cited as a common cause of death. Consideration should be made to exclude older physicians from front-line work.", "qid": 4, "docid": "lxkxgbun", "rank": 58, "score": 0.8567689061164856}, {"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": 4, "docid": "7rh07bii", "rank": 59, "score": 0.8567637205123901}, {"content": "Title: The need for urogenital tract monitoring in COVID-19 Content: Coronavirus disease 2019 (COVID-19) is caused by severe acute respiratory syndrome coronavirus 2, which invades a cell through binding to the ACE2 receptor and TMPRSS2 priming. Patients with severe disease predominantly present with pneumonia-related symptoms. However, evidence suggests that COVID-19 infection also has implications for the urogenital tract. Thus, urogenital organs should be considered when treating COVID-19.", "qid": 4, "docid": "kec1o4ys", "rank": 60, "score": 0.8567525148391724}, {"content": "Title: SnapShot: COVID-19 Content: Abstract Coronavirus disease 2019 (COVID-19) is a novel respiratory illness caused by SARS-CoV-2. Viral entry is mediated through viral spike protein and host ACE2 enzyme interaction. Most cases are mild; severe disease often involves cytokine storm and organ failure. Therapeutics including antivirals, immunomodulators, and vaccines are in development. To view this SnapShot, open or download the PDF.", "qid": 4, "docid": "c3rbmysh", "rank": 61, "score": 0.8566391468048096}, {"content": "Title: COVID-19: is fibrosis the killer? Content: COVID-19 is a respiratory disease A recent report in Lancet examined, retrospectively, 137 patients with COVD-19 Patients that died had elevated IL-6 levels and acute respiratory distress syndrome These data have obvious implications for how to control mortality in COVID-19", "qid": 4, "docid": "b8bl5vq5", "rank": 62, "score": 0.8565901517868042}, {"content": "Title: Severe acute respiratory syndrome-coronavirus 2 and novel coronavirus disease 2019: An extraordinary pandemic Content: COVID-19 has emerged as one of the most significant illnesses of the current century. It is caused by severe acute respiratory syndrome coronavirus 2. The world was initially viewing it as a localized outbreak in Wuhan city of China; however, it started spreading quickly to other parts of the world. Globally, half-hearted containment measures and a false sense of safety against this novel coronavirus led to the dissemination of disease. Currently, no effective therapy or vaccine is available to manage this illness. After learning a huge lesson, global efforts would hopefully lead to effective control of this pandemic.", "qid": 4, "docid": "i8opdley", "rank": 63, "score": 0.856156587600708}, {"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": 4, "docid": "uojjp4dd", "rank": 64, "score": 0.8561352491378784}, {"content": "Title: Coronavirus disease 2019 (COVID-19): a clinical update Content: Coronavirus disease 2019 (COVID-19) caused by severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2) has posed a significant threat to global health. It caused a total of 80 868 confirmed cases and 3101 deaths in Chinese mainland until March 8, 2020. This novel virus spread mainly through respiratory droplets and close contact. As disease progressed, a series of complications tend to develop, especially in critically ill patients. Pathological findings showed representative features of acute respiratory distress syndrome and involvement of multiple organs. Apart from supportive care, no specific treatment has been established for COVID-19. The efficacy of some promising antivirals, convalescent plasma transfusion, and tocilizumab needs to be investigated by ongoing clinical trials.", "qid": 4, "docid": "y7vq5m1r", "rank": 65, "score": 0.8560377359390259}, {"content": "Title: Advice regarding COVID\u201019 and use of immunomodulators, in patients with severe dermatological diseases Content: Coronavirus disease 2019 (COVID-19) is the disease caused by the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), as named by the International Committee on Taxonomy of Viruses (ICTV). There is very limited evidence base to formulate specific advice for dermatology patients on immunomodulators with regards to COVID-19. The following is based on expert opinion, taking into account known risks of influenza (a negative sense single-stranded RNA virus) and other, positive-sense single-stranded, RNA virus infections (such as SARS, MERS, and the common cold). An Australia/New Zealand consensus document is in development.", "qid": 4, "docid": "nfjxp783", "rank": 66, "score": 0.8554019927978516}, {"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": 4, "docid": "cmcv1k62", "rank": 67, "score": 0.8548578023910522}, {"content": "Title: Empfehlungen zur Durchf\u00fchrung einer Bronchoskopie in Zeiten der COVID-19-Pandemie Content: COVID-19, caused by coronavirus SARS-CoV-2 is a new and ongoing infectious disease affecting healthcare systems worldwide. Healthcare worker are at high risk for COIVD-19 and many have been infected or even died in countries severely affected by COVID-19 like China or Italy. Bronchoscopy causes cough and aerosol production and has to be considered a significant risk for the staff to get infected. Particular recommendations should guide to prevent spreading COVID-19 and to protect healthcare worker when performing a bronchoscopy.", "qid": 4, "docid": "rzi8b2gi", "rank": 68, "score": 0.8546625375747681}, {"content": "Title: Empfehlungen zur Durchf\u00fchrung einer Bronchoskopie in Zeiten der COVID-19-Pandemie./ [Recommendations for Performing Bronchoscopy in Times of the COVID-19 Pandemic] Content: COVID-19, caused by coronavirus SARS-CoV-2 is a new and ongoing infectious disease affecting healthcare systems worldwide. Healthcare worker are at high risk for COIVD-19 and many have been infected or even died in countries severely affected by COVID-19 like China or Italy. Bronchoscopy causes cough and aerosol production and has to be considered a significant risk for the staff to get infected. Particular recommendations should guide to prevent spreading COVID-19 and to protect healthcare worker when performing a bronchoscopy.", "qid": 4, "docid": "htsckkdw", "rank": 69, "score": 0.8546625375747681}, {"content": "Title: Risk Factors for Mortality among COVID-19 Patients Content: AIMS: COVID-19 is a current globalpandemic. However, comprehensive global data analyses for its mortality risk factors are lacking. The current investigation aimed to assess the predictors of death among COVID-19 patients from worldwide open access data. METHODS: A total of 828 confirmed cases of COVID-19 with definite outcomes were retrospectively identified from open access individual-level worldwide data. Univariate followed by multivariable regression analysis were used to evaluate the association between potential risk factors and mortality. RESULTS: Majority of the patients were males 59.1% located in Asia 69.3%. Based on the data, older age (adjusted odds ratio (aOR), 1.079; 95% confidence intervals (95% CI), 1.064-1.095 per year increase), males (aOR, 1.607; 95% CI, 1.002-2.576), patients with hypertension (aOR, 3.576; 95% CI, 1.694-7.548), diabetes mellitus (aOR, 12.234; 95% CI, 4.126-36.272), and patients located in America (aOR, 7.441; 95% CI, 3.546-15.617) were identified as the risk factors of mortality among COVID-19 patients. CONCLUSIONS: Males, advanced age, hypertension patients, diabetes mellitus patients, and patients located in America were the independent risk factors of death among COVID-19 patients. Extra attention is required to be given to these factors and additional studies on the underlying mechanisms of these effects.", "qid": 4, "docid": "k7a98s4e", "rank": 70, "score": 0.8544543981552124}, {"content": "Title: COVID-19: Healthy environmental impact for public safety and menaces oil market Content: COVID-19 seems as global emergency, by infectious virus, caused respiratory illness like having symptoms of flue, sickness, headache, and difficulty in breathing. Within months the world has been transformed into new order, thousands of people died and many more are fallen ill due to COVID-19 outbreak. China was the first country to see the outbreak and the first country to control it. However, the disease has broken out in Europe, the Middle East, the United States and other places. The United States has the highest number of cases in the world.", "qid": 4, "docid": "g62tz7b7", "rank": 71, "score": 0.8542789220809937}, {"content": "Title: COVID-19: Healthy environmental impact for public safety and menaces oil market. Content: COVID-19 seems as global emergency, by infectious virus, caused respiratory illness like having symptoms of flue, sickness, headache, and difficulty in breathing. Within months the world has been transformed into new order, thousands of people died and many more are fallen ill due to COVID-19 outbreak. China was the first country to see the outbreak and the first country to control it. However, the disease has broken out in Europe, the Middle East, the United States and other places. The United States has the highest number of cases in the world.", "qid": 4, "docid": "5x4k9b7j", "rank": 72, "score": 0.8542789220809937}, {"content": "Title: Covid-19: Postmortem Diagnostic and Biosafety Considerations Content: As a result of the 2019 novel human coronavirus (COVID-19) global spread, medical examiner/coroner offices will inevitably encounter increased numbers of COVID-19-infected decedents at autopsy. While in some cases a history of fever and/or respiratory distress (e.g. cough or shortness of breath) may suggest the diagnosis, epidemiologic studies indicate that the majority of individuals infected with COVID-19 develop mild to no symptoms. Those dying with-but not of-COVID-19 may still be infectious, however. While multiple guidelines have been issued regarding autopsy protocol in cases of suspected COVID-19 deaths, there is some variability in the recommendations. Additionally, limited recommendations to date have been issued regarding scene investigative protocol, and there are a paucity of publications characterizing COVID-19 postmortem gross and histologic findings. A case of sudden unexpected death due to COVID-19 is presented as a means of illustrating common autopsy findings, as well as diagnostic and biosafety considerations. We also review and summarize the current COVID-19 literature in an effort to provide practical evidence-based biosafety guidance for ME/C offices encountering COVID-19 at autopsy.", "qid": 4, "docid": "wij1cljg", "rank": 73, "score": 0.8538926243782043}, {"content": "Title: Predictors of Mortality for Patients with COVID-19 Pneumonia Caused by SARS-CoV-2: A Prospective Cohort Study Content: To identify factors associated with the death for patients with COVID-19 pneumonia caused by a novel coronavirus SARS-CoV-2. All clinical and laboratory parameters were collected prospectively from a cohort of patients with COVID-19 pneumonia who were hospitalised to Wuhan Pulmonary Hospital, Wuhan City, Hubei Province, China, between December 25, 2019 and February 7, 2020. Univariate and multivariate logistic regression was performed to investigate the relationship between each variable and the risk for death of COVID-19 pneumonia patients. A total of 179 patients with COVID-19 pneumonia (97 male and 82 female) were included in the present prospective study, of whom 21 died. Univariate and multivariate logistic regression analysis revealed that age \u226565 years (odd ratio, 3.765; 95% confidence interval, 1.146\u201217.394; p=0.023), preexisting concurrent cardiovascular or cerebrovascular diseases (2.464; 0.755\u20128.044; p=0.007), CD3(+)CD8(+) T cells \u226475 cell\u00b7\u03bcL(\u22121) (3.982; 1.132\u201214.006; p<0.001), and cardiac troponin I\u22650.05 ng\u00b7mL(\u22121) (4.077; 1.166\u201214.253; p<0.001) were associated with an increase in risk of mortality of COVID-19 pneumonia. In the sex\u2012, age\u2012, and comorbid illness-matched case study, CD3(+)CD8(+) T cells \u226475 cell\u00b7\u03bcL(\u22121) and cardiac troponin I\u22650.05 ng\u00b7mL(\u22121) remained to be the predictors for high mortality of COVID-19 pneumonia. We identified four risk factors, age \u226565 years, preexisting concurrent cardiovascular or cerebrovascular diseases, CD3(+)CD8(+) T cells \u226475 cell\u00b7\u03bcL(\u22121), and cardiac troponin I\u22650.05 ng\u00b7mL(\u22121), especially the latter two factors, were predictors for mortality of COVID-19 pneumonia patients.", "qid": 4, "docid": "h0iynw2w", "rank": 74, "score": 0.8536251783370972}, {"content": "Title: First case of COVID\u201019 in a kidney transplant recipient treated with belatacept Content: Coronavirus disease 2019 (COVID-19) caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) is an ongoing public health emergency of international concern. Acute respiratory distress syndrome (ARDS) develops in 3-30% of patients with COVID-19 (1,2), because of direct virus-induced cytopathic effects in the respiratory tract or cytokine storms triggered by the host's immune response. Comorbidities are known to increase the risk of ARDS in SARS-CoV-2-infected patients (1).", "qid": 4, "docid": "mqozfuk4", "rank": 75, "score": 0.8534771203994751}, {"content": "Title: Analysis of mortality in patients of COVID-19: clinical and laboratory parameters Content: Several reports on epidemiological and clinical features of the 2019 coronavirus disease (COVID-19) had been published. However, mortality and morbidity analysis, important for better understanding of the pathogenesis of this disease, are scarce. We examine the clinical and laboratory features of 14 patients who died of COVID-19. The cohort consisted of 11 male and 3 female patients; nine patients aged 70 years or above, and nearly all had underlying diseases. Fever with bilateral pneumonia was the main manifestation. Most patients had consolidations combined with ground glass opacity (GGO) on chest CT scan. Laboratory tests showed lymphocytopenia in 10 patients, high blood glucose in 11, GGT in 5 of the 14 patients, and high LDH in 5 of 6 patients tested. In addition, patients in this cohort had high level of cytokines such as interleukin 6 in all 8 patients tested. The clinical and laboratory parameters in the cohort of fatal cases may be incorporated into future clinical prognosis models, and will be of help in understanding the pathogenesis of this disease.", "qid": 4, "docid": "cuqpnli5", "rank": 76, "score": 0.8534049987792969}, {"content": "Title: Long-Term Care Facilities as a Risk Factor for Death Due to COVID-19 Content: A large percentage of the deaths from COVID-19 occur among residents of long-term care facilities. There are two possible reasons for this phenomenon. First, the structural features of such settings may lead to death. Alternatively, it is possible that individuals in these facilities are in poorer health than those living elsewhere, and that these individuals would have died even if they had not been in these facilities. Our findings show that, controlling for the population density and the percentage of older adults in the population, there is a significant positive association between the number of long-term care beds per capita and COVID-19 mortality rates. This finding provides support for the claim that long-term care living arrangements (of older people) are a significant risk factor for dying from COVID-19.", "qid": 4, "docid": "fhuugtq5", "rank": 77, "score": 0.8533886671066284}, {"content": "Title: Proteome Organization of COVID-19: Illustrating Targets for Vaccine Development Content: 'COVID-19' the recent virulent viral infection had influenced the lives of millions globally leading to both loss of life, economic and financial crisis Coronavirus belongs to family coronaviridae with four genus viz alpha/beta and gamma-coronavirus, infecting both aves and mammals The SARS-Cov-2 emerged in Wuhan, China in Dec, 2019 and since then had spread to 213 countries Its origin is debatable with both natural origin and conspiracy theory providing no conclusive evidences Coronavirus have '+'ive RNA and encodes for 29 proteins, which carries out its life cycle including infection and disease progression The study of its proteome organization could illustrate the proteins which act as the key molecular players in the infection cycle of the virus These proteins can also act as important drug targets in combating COVID-19 infection Majority of the drugs have been formulated in order to act as agonist to spike proteins inhibiting infection by binding to ACE2 receptors Proteome analysis has also revealed the critical mutated proteins that are responsible for COVID-19 pathogenesis and virulence mRNA based vaccines (mRNA-1273, BNT162) also targets these spike proteins Although DNA vaccine has also been attempted using RDT, but the high rate of mutation associated with COVID-19 have made such vaccines ineffective even before use Thus evolutionarily conserved proteins have been the best candidature for vaccine development Similarly phylogenetic analysis of its proteins could help us to understand the evolutionary pattern of COVID-19 It could be used to develop a predictable model for such pathogenic infections, preparing ourselves to take preventive action against its reoccurrence", "qid": 4, "docid": "69ldtdik", "rank": 78, "score": 0.8533814549446106}, {"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": 4, "docid": "ne1qvf5g", "rank": 79, "score": 0.8533554077148438}, {"content": "Title: COVID-19: POSTMORTEM DIAGNOSTIC AND BIOSAFETY CONSIDERATIONS Content: As a result of the 2019 novel human coronavirus (COVID-19) global spread, medical examiner/coroner offices will inevitably encounter increased numbers of COVID-19-infected decedents at autopsy. While in some cases a history of fever and/or respiratory distress (e.g. cough or shortness of breath) may suggest the diagnosis, epidemiologic studies indicate that the majority of individuals infected with COVID-19 develop mild to no symptoms. Those dying with\u2014but not of\u2014COVID-19 may still be infectious, however. While multiple guidelines have been issued regarding autopsy protocol in cases of suspected COVID-19 deaths, there is some variability in the recommendations. Additionally, limited recommendations to date have been issued regarding scene investigative protocol, and there are a paucity of publications characterizing COVID-19 postmortem gross and histologic findings. A case of sudden unexpected death due to COVID-19 is presented as a means of illustrating common autopsy findings, as well as diagnostic and biosafety considerations. We also review and summarize the current COVID-19 literature in an effort to provide practical evidence-based biosafety guidance for ME/C offices encountering COVID-19 at autopsy.", "qid": 4, "docid": "69nfi379", "rank": 80, "score": 0.8532230854034424}, {"content": "Title: Covid-19 outbreak and perspective in morocco Content: Coronavirus disease 2019 (COVID-19) is a respiratory illness that can spread from person to person. The virus that causes COVID-19 is a novel coronavirus that was first identified during an investigation into an outbreak in Wuhan, China and rapidly spread across the world to become the first pandemic caused by a coronavirus. As of 26 March 2020, there are 275 cases affected by COVID-19 announced by the Moroccan government, and it possible to limit the spread of this serious disease, with the cooperation of all the citizens in respect of the measures of containment and individual protection. Also, with the announce yesterday by the Moroccan government of the authorization of use of chloroquine in treatment of COVID-19 pneumonia, COVID-19 will be soon eradicated from Morocco and hopefully from all over the world.", "qid": 4, "docid": "8yr41aa8", "rank": 81, "score": 0.853041410446167}, {"content": "Title: Predictors of mortality for patients with COVID-19 pneumonia caused by SARS-CoV-2: a prospective cohort study Content: The aim of this study was to identify factors associated with the death of patients with COVID-19 pneumonia caused by the novel coronavirus SARS-CoV-2.All clinical and laboratory parameters were collected prospectively from a cohort of patients with COVID-19 pneumonia who were hospitalised to Wuhan Pulmonary Hospital (Wuhan City, Hubei Province, China) between 25 December 2019 and 7 February 2020. Univariate and multivariate logistic regression was performed to investigate the relationship between each variable and the risk of death of COVID-19 pneumonia patients.In total, 179 patients with COVID-19 pneumonia (97 male and 82 female) were included in the present prospective study, of whom 21 died. Univariate and multivariate logistic regression analysis revealed that age &#8805;65\u00e2\u0080 years (OR 3.765, 95% CI 1.146\u00e2\u0080\u009217.394; p=0.023), pre-existing concurrent cardiovascular or cerebrovascular diseases (OR 2.464, 95% CI 0.755\u00e2\u0080\u00928.044; p=0.007), CD3+CD8+ T-cells &#8804;75\u00e2\u0080 cells\u00b7\u00b5L-1 (OR 3.982, 95% CI 1.132\u00e2\u0080\u009214.006; p<0.001) and cardiac troponin I &#8805;0.05\u00e2\u0080 ng\u00b7mL-1 (OR 4.077, 95% CI 1.166\u00e2\u0080\u009214.253; p<0.001) were associated with an increase in risk of mortality from COVID-19 pneumonia. In a sex-, age- and comorbid illness-matched case-control study, CD3+CD8+ T-cells &#8804;75\u00e2\u0080 cells\u00b7\u00b5L-1 and cardiac troponin I &#8805;0.05\u00e2\u0080 ng\u00b7mL-1 remained as predictors for high mortality from COVID-19 pneumonia.We identified four risk factors: age &#8805;65\u00e2\u0080 years, pre-existing concurrent cardiovascular or cerebrovascular diseases, CD3+CD8+ T-cells &#8804;75\u00e2\u0080 cells\u00b7\u00b5L-1 and cardiac troponin I &#8805;0.05\u00e2\u0080 ng\u00b7mL-1 The latter two factors, especially, were predictors for mortality of COVID-19 pneumonia patients.", "qid": 4, "docid": "5wazfkey", "rank": 82, "score": 0.8528385758399963}, {"content": "Title: The need for neurologists in the care of COVID\u201019 patients Content: Coronavirus disease 2019 (COVID-19) is an infectious disease caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) resulting in severe acute respiratory syndrome in a substantial number of patients. Approximately 5% to 10% of patients need intensive care unit (ICU) admission and mechanical ventilation [1]. The primary symptoms of COVID-19 include fever, dry cough and fatigue [2]. However, a recent report from Shandong, China, disclosed that a subset of patients did not suffer from respiratory symptoms but had neurologic signs and symptoms [3]. Moreover, in a retrospective study from Wuhan, China, neurologic symptoms were observed in 36.4% of the hospitalized patients with COVID-19 infection and pertained to both the central and peripheral nervous system [4].", "qid": 4, "docid": "l21fin9q", "rank": 83, "score": 0.8524702191352844}, {"content": "Title: \u201cClinical Characteristics, Outcomes and Prognosticators in Adult Patients Hospitalized with COVID-19\u201d Content: BACKGROUND: COVID-19 is a novel disease caused by SARS-CoV-2. METHODS: We conducted a retrospective evaluation of patients admitted with COVID-19 to one site in March 2020. Patients were stratified into three groups: survivors who did not receive mechanical ventilation (MV), survivors who received MV and those who received MV and died during hospitalization. RESULTS: There were 140 hospitalizations; 22 deaths (mortality rate 15.7%), 83 (59%) survived and did not receive MV, 35 (25%) received MV and survived; 18 (12.9%) received MV and died. Thee mean age of each group was 57.8, 55.8 and 72.7 years respectively (p=.0001). Of those who received MV and died, 61% were male (p=.01). More than half the patients (n=90, 64%) were African American. First measured d-dimer >575.5 ng/mL, procalcitonin > 0.24 ng/mL, LDH > 445.6 units/L and BNP > 104.75 pg/mL had odds ratios of 10.5, 5, 4.5 and 2.9 respectively for MV (p < .05 for all). Peak BNP > 167.5 pg/mL had an odds ratio of 6.7 for inpatient mortality when mechanically ventilated (p= .02). CONCLUSIONS: Age and gender may impact outcomes in COVID-19. D-dimer, procalcitonin, LDH and BNP may serve as early indicators of disease trajectory.", "qid": 4, "docid": "rluya5ui", "rank": 84, "score": 0.8521837592124939}, {"content": "Title: \"Clinical Characteristics, Outcomes and Prognosticators in Adult Patients Hospitalized with COVID-19\" Content: BACKGROUND: COVID-19 is a novel disease caused by SARS-CoV-2. METHODS: We conducted a retrospective evaluation of patients admitted with COVID-19 to one site in March 2020. Patients were stratified into three groups: survivors who did not receive mechanical ventilation (MV), survivors who received MV and those who received MV and died during hospitalization. RESULTS: There were 140 hospitalizations; 22 deaths (mortality rate 15.7%), 83 (59%) survived and did not receive MV, 35 (25%) received MV and survived; 18 (12.9%) received MV and died. Thee mean age of each group was 57.8, 55.8 and 72.7 years respectively (p=.0001). Of those who received MV and died, 61% were male (p=.01). More than half the patients (n=90, 64%) were African American. First measured d-dimer >575.5 ng/mL, procalcitonin > 0.24 ng/mL, LDH > 445.6 units/L and BNP > 104.75 pg/mL had odds ratios of 10.5, 5, 4.5 and 2.9 respectively for MV (p < .05 for all). Peak BNP > 167.5 pg/mL had an odds ratio of 6.7 for inpatient mortality when mechanically ventilated (p= .02). CONCLUSIONS: Age and gender may impact outcomes in COVID-19. D-dimer, procalcitonin, LDH and BNP may serve as early indicators of disease trajectory.", "qid": 4, "docid": "ylzuh3t3", "rank": 85, "score": 0.8521837592124939}, {"content": "Title: COVID-19: The Case of Three Patients with the Same Diagnosis but Different Clinical and Laboratory Features Content: SARS-CoV-2 is an RNA virus that causes COVID-19, which has been responsible for the pandemic that was declared in early 2020. Its pathological effect is majorly in the respiratory tract, but its full pathogenicity remains a mystery. Symptoms associated with COVID-19 include fever, cough, and shortness of breath. Some patients develop other symptoms like diarrhea. However, it is possible for other organs to be affected including the central nervous system, liver, and blood cells. The purpose of this case series is to unravel other factors associated with this disease, so we report three cases of COVID-19 that were hospitalized during the pandemic.", "qid": 4, "docid": "cowt4c2c", "rank": 86, "score": 0.851886510848999}, {"content": "Title: Physician deaths from corona virus (COVID-19) disease Content: BACKGROUND: The COVID-19 pandemic has caused much morbidity and mortality to patients but also health care providers. AIMS: We tabulated the cases of physician deaths from COVID-19 associated with front-line work in hopes of mitigating future events. METHODS: On 15 April 2020, a Google internet search was performed using the keywords 'doctor', 'physician', 'death', 'COVID' and 'coronavirus' in English and Farsi, and Chinese using the Baidu search engine. The age, sex and medical speciality of physicians who died from COVID-19 in the line of duty were recorded. Individuals greater than 90 years of age were excluded. RESULTS: We found 278 physicians who died with COVID-19 infection, but complete details were missing for 108 individuals. The average age of the physicians was 63.7 years with a median age of 66 years, and 90% were male (235/261). General practitioners and emergency room doctors (108/254), respirologists (5/254), internal medicine specialists (13/254) and anaesthesiologists (6/254) comprised 52% of those dying. Two per cent of the deceased were epidemiologists (5/254), 2% were infectious disease specialists (4/254), 6% were dentists (16/254), 4% were ENT (9/254) and 3% were ophthalmologists (8/254). The countries with the most reported physician deaths were Italy (121/278; 44%), Iran (43/278; 15%), Philippines (21/278; 8%), Indonesia (17/278; 6%), China (16/278; 6%), Spain (12/278; 4%), USA (12/278; 4%) and UK (11/278;4%). CONCLUSIONS: Physicians from all specialities may die from COVID. Lack of personal protective equipment was cited as a common cause of death. Consideration should be made to exclude older physicians from front-line work.", "qid": 4, "docid": "e1lfy1m3", "rank": 87, "score": 0.8516625761985779}, {"content": "Title: A case of COVID-19 with tuberculous meningitis/ \u65b0\u578b\u51a0\u72b6\u75c5\u6bd2\u80ba\u708e\u5408\u5e76\u7ed3\u6838\u6027\u8111\u819c\u708e\u4e00\u4f8b Content: COVID\u204319 is caused by a new coronavirus that infects the lungs. Although some patients with COVID\u204319 may be combined with neurological symptoms, there is no direct evidence that this new coronavirus can directly invade nerve system. A case of COVID\u204319 with tuberculous meningitis is reported to remind that when patients with COVID\u204319 present symptom of encephalitis or meningitis, a comprehensive pathogen examination is recommended.", "qid": 4, "docid": "yi4ymv4v", "rank": 88, "score": 0.8515372276306152}, {"content": "Title: Multi-Center Evaluation of the Cepheid Xpert Xpress SARS-CoV-2 Assay for the Detection of SARS-CoV-2 in Oropharyngeal Swab Specimens Content: The coronavirus disease 2019 (COVID-19), caused by severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2) is a global health concern that has spread worldwide since December 2019 (1-4). .", "qid": 4, "docid": "vwxk5bqb", "rank": 89, "score": 0.8514876365661621}, {"content": "Title: Fecal-Oral Transmission of COVID-19: Could Hypochlorhydria Play a Role? Content: Coronavirus disease 2019 (COVID-19) is caused by severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2) which emerged in Wuhan, China in 2019 (1). Respiratory symptoms remain the most common clinical manifestations of COVID-19. However, non-respiratory symptoms are increasingly being recognized. Gastrointestinal (GI) symptoms such as anorexia, nausea, vomiting, diarrhea, and abdominal pain are noted in COVID-19 patients either alone or in association with respiratory manifestations (2). Stool viral RNA can be detected by up to 50% in patients with diarrhea (3). This article is protected by copyright. All rights reserved.", "qid": 4, "docid": "y77ui3d9", "rank": 90, "score": 0.8511574268341064}, {"content": "Title: Comorbilidad y factores pron\u00f3sticos al ingreso en una cohorte COVID-19 de un hospital general Content: Antecedents and Objective: To describe clinical features, comorbidity, and prognostic factors associated with in-hospital mortality in a cohort of COVID-19 admitted to a general hospital. Material and Methods: Retrospective cohort study of patients with COVID-19 admitted from 26th February, who had been discharged or died, up to 29th April, 2020. A descriptive study and an analysis of factors associated with intrahospital mortality were performed. Results: Out of the 101 patients, 96 were analysed. Of these, 79 (82%) recovered and were discharged, and 17 (18%) died in the hospital. Diagnosis of COVID-19 was confirmed by polymerase chain reaction to SARS-CoV2 in 92 (92.5%). The mean age was 63 years, and 66% were male. The most frequent comorbidities were hypertension (40%), diabetes mellitus (16%) y cardiopathy (14%). Patients who died were older (mean 77 vs 60 years), had higher prevalence of hypertension (71% vs 33%), and cardiopathy (47% vs 6%), and higher levels of lactate dehydrogenase (LDH) and reactive C protein (mean 662 vs 335 UI/L, and 193 vs 121 mg/L respectively) on admission. In a multivariant analysis the variables significantly associated to mortality were the presence of cardiopathy (CI 95% OR 2,58-67,07), levels of LDH >=345 IU/L (CI 95% OR 1,52-46,00), and age >= 65 years (CI 95% OR 1,23-44,62). Conclusions: The presence of cardiopathy, levels of LDH >=345 IU/L and age >=65 years are associated with a higher risk of death during hospital stay for COVID-19. This model should be validated in prospective cohorts.", "qid": 4, "docid": "hpud4ey8", "rank": 91, "score": 0.8511422872543335}, {"content": "Title: From causes of aging to death from COVID-19 Content: COVID-19 is not deadly early in life, but mortality increases exponentially with age, which is the strongest predictor of mortality. Mortality is higher in men than in women, because men age faster, and it is especially high in patients with age-related diseases, such as diabetes and hypertension, because these diseases are manifestations of aging and a measure of biological age. At its deepest level, aging (a program-like continuation of developmental growth) is driven by inappropriately high cellular functioning. The hyperfunction theory of quasi-programmed aging explains why COVID-19 vulnerability (lethality) is an age-dependent syndrome, linking it to other age-related diseases. It also explains inflammaging and immunosenescence, hyperinflammation, hyperthrombosis, and cytokine storms, all of which are associated with COVID-19 vulnerability. Anti-aging interventions, such as rapamycin, may slow aging and age-related diseases, potentially decreasing COVID-19 vulnerability.", "qid": 4, "docid": "joigb8qm", "rank": 92, "score": 0.8511340022087097}, {"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": 4, "docid": "6hzlbpxg", "rank": 93, "score": 0.851078987121582}, {"content": "Title: SARS-CoV-2 and COVID-19: The most important research questions Content: Coronavirus disease 2019 (COVID-19) caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) is an ongoing global health emergency. Here we highlight nine most important research questions concerning virus transmission, asymptomatic and presymptomatic virus shedding, diagnosis, treatment, vaccine development, origin of virus and viral pathogenesis.", "qid": 4, "docid": "hfkzu18p", "rank": 94, "score": 0.8509365916252136}, {"content": "Title: How to reduce the likelihood of coronavirus-19 (CoV-19 or SARS-CoV-2) infection and lung inflammation mediated by IL-1 Content: SARS-CoV-2, also referred to as CoV-19, is an RNA virus which can cause severe acute respiratory diseases (COVID-19), with serious infection of the lower respiratory tract followed by bronchitis, pneumonia and fibrosis. The severity of the disease depends on the efficiency of the immune system which, if it is weak, cannot stem the infection and its symptoms. The new CoV-19 spreads in the population at a rate of 0.8-3% more than normal flu and mostly affects men, since immune genes are more expressed on the X chromosome. If CoV-19 would spread with a higher incidence rate (over 10%), and affect the people who live in closed communities such as islands, it would cause many more deaths. Moreover, people from the poorest classes are most at risk because of lack of health care and should be given more assistance by the competent authorities. To avoid the aggravation of CoV-19 infection, and the collapse of the health system, individuals should remain at home in quarantine for a period of approximately one month in order to limit viral transmission. In the case of a pandemic, the severe shortage of respirators and protective clothing, due to the enormous demand and insufficient production, could lead the CoV-19 to kill a large number of individuals. At present, there is no drug capable of treating CoV-19 flu, the only therapeutic remedies are those aimed at the side effects caused by the virus, such as inflammation and pulmonary fibrosis, recognized as the first causes of death. One of the COVID-19 treatments involves inhaling a mixture of gaseous hydrogen and oxygen, obtaining better results than with oxygen alone. It was also noted that individuals vaccinated for viral and/or bacterial infectious diseases were less likely to become infected. In addition, germicidal UV radiation \"breaks down\" the oxygen O2 which then aggregate into O3 (ozone) molecules creating the ozone layer, capable of inhibiting viral replication and improving lung respiration. All these precautions should be taken into consideration to lower the risk of infection by CoV-19. New anti-viral therapies with new drugs should also be taken into consideration. For example, microbes are known to bind TLR, inducing IL-1, a pleiotropic cytokine, highly inflammatory, mediator of fever and fibrosis. Therefore, drugs that suppress IL-1 or IL-1R, also used for the treatment of rheumatoid arthritis are to be taken into consideration to treat COVID-19. We strongly believe that all these devices described above can lead to greater survival and. therefore, reduction in mortality in patients infected with CoV-19.", "qid": 4, "docid": "g5rf10n5", "rank": 95, "score": 0.8507413864135742}, {"content": "Title: How to reduce the likelihood of coronavirus-19 (CoV-19 or SARS-CoV-2) infection and lung inflammation mediated by IL-1. Content: SARS-CoV-2, also referred to as CoV-19, is an RNA virus which can cause severe acute respiratory diseases (COVID-19), with serious infection of the lower respiratory tract followed by bronchitis, pneumonia and fibrosis. The severity of the disease depends on the efficiency of the immune system which, if it is weak, cannot stem the infection and its symptoms. The new CoV-19 spreads in the population at a rate of 0.8-3% more than normal flu and mostly affects men, since immune genes are more expressed on the X chromosome. If CoV-19 would spread with a higher incidence rate (over 10%), and affect the people who live in closed communities such as islands, it would cause many more deaths. Moreover, people from the poorest classes are most at risk because of lack of health care and should be given more assistance by the competent authorities. To avoid the aggravation of CoV-19 infection, and the collapse of the health system, individuals should remain at home in quarantine for a period of approximately one month in order to limit viral transmission. In the case of a pandemic, the severe shortage of respirators and protective clothing, due to the enormous demand and insufficient production, could lead the CoV-19 to kill a large number of individuals. At present, there is no drug capable of treating CoV-19 flu, the only therapeutic remedies are those aimed at the side effects caused by the virus, such as inflammation and pulmonary fibrosis, recognized as the first causes of death. One of the COVID-19 treatments involves inhaling a mixture of gaseous hydrogen and oxygen, obtaining better results than with oxygen alone. It was also noted that individuals vaccinated for viral and/or bacterial infectious diseases were less likely to become infected. In addition, germicidal UV radiation \"breaks down\" the oxygen O2 which then aggregate into O3 (ozone) molecules creating the ozone layer, capable of inhibiting viral replication and improving lung respiration. All these precautions should be taken into consideration to lower the risk of infection by CoV-19. New anti-viral therapies with new drugs should also be taken into consideration. For example, microbes are known to bind TLR, inducing IL-1, a pleiotropic cytokine, highly inflammatory, mediator of fever and fibrosis. Therefore, drugs that suppress IL-1 or IL-1R, also used for the treatment of rheumatoid arthritis are to be taken into consideration to treat COVID-19. We strongly believe that all these devices described above can lead to greater survival and. therefore, reduction in mortality in patients infected with CoV-19.", "qid": 4, "docid": "uzfzopz5", "rank": 96, "score": 0.8507413864135742}, {"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": 4, "docid": "ot5v8n0c", "rank": 97, "score": 0.8506894111633301}, {"content": "Title: Clinical Features of 85 Fatal Cases of COVID-19 from Wuhan. A Retrospective Observational Study Content: Rationale: The global death toll from coronavirus disease (COVID-19) virus as of May 12, 2020, exceeds 286,000. The risk factors for death were attributed to advanced age and comorbidities but have not been accurately defined. Objectives: To report the clinical features of 85 fatal cases of COVID-19 in two hospitals in Wuhan. Methods: Medical records were collected of 85 fatal cases of COVID-19 between January 9, 2020, and February 15, 2020. Information recorded included medical history, exposure history, comorbidities, symptoms, signs, laboratory findings, computed tomographic scans, and clinical management. Measurements and Main Results: The median age of the patients was 65.8 years, and 72.9% were male. Common symptoms were fever (78 [91.8%]), shortness of breath (50 [58.8%]), fatigue (50 [58.8%]), and dyspnea (60 [70.6%]). Hypertension, diabetes, and coronary heart disease were the most common comorbidities. Notably, 81.2% of patients had very low eosinophil counts on admission. Complications included respiratory failure (80 [94.1%]), shock (69 [81.2%]), acute respiratory distress syndrome (63 [74.1%]), and arrhythmia (51 [60%]), among others. Most patients received antibiotic (77 [90.6%]), antiviral (78 [91.8%]), and glucocorticoid (65 [76.5%]) treatments. A total of 38 (44.7%) and 33 (38.8%) patients received intravenous immunoglobulin and IFN-\u03b12b, respectively. Conclusions: In this depictive study of 85 fatal cases of COVID-19, most cases were males aged over 50 years with noncommunicable chronic diseases. The majority of the patients died of multiple organ failure. Early onset of shortness of breath may be used as an observational symptom for COVID-19 exacerbations. Eosinophilopenia may indicate a poor prognosis. A combination of antimicrobial drugs did not offer considerable benefit to the outcome of this group of patients.", "qid": 4, "docid": "tp6qq2pu", "rank": 98, "score": 0.8506699800491333}, {"content": "Title: Clinical Features of 85 Fatal Cases of COVID-19 from Wuhan. A Retrospective Observational Study Content: Rationale: The global death toll from coronavirus disease (COVID-19) virus as of May 12, 2020, exceeds 286,000. The risk factors for death were attributed to advanced age and comorbidities but have not been accurately defined.Objectives: To report the clinical features of 85 fatal cases of COVID-19 in two hospitals in Wuhan.Methods: Medical records were collected of 85 fatal cases of COVID-19 between January 9, 2020, and February 15, 2020. Information recorded included medical history, exposure history, comorbidities, symptoms, signs, laboratory findings, computed tomographic scans, and clinical management.Measurements and Main Results: The median age of the patients was 65.8 years, and 72.9% were male. Common symptoms were fever (78 [91.8%]), shortness of breath (50 [58.8%]), fatigue (50 [58.8%]), and dyspnea (60 [70.6%]). Hypertension, diabetes, and coronary heart disease were the most common comorbidities. Notably, 81.2% of patients had very low eosinophil counts on admission. Complications included respiratory failure (80 [94.1%]), shock (69 [81.2%]), acute respiratory distress syndrome (63 [74.1%]), and arrhythmia (51 [60%]), among others. Most patients received antibiotic (77 [90.6%]), antiviral (78 [91.8%]), and glucocorticoid (65 [76.5%]) treatments. A total of 38 (44.7%) and 33 (38.8%) patients received intravenous immunoglobulin and IFN-&#945;2b, respectively.Conclusions: In this depictive study of 85 fatal cases of COVID-19, most cases were males aged over 50 years with noncommunicable chronic diseases. The majority of the patients died of multiple organ failure. Early onset of shortness of breath may be used as an observational symptom for COVID-19 exacerbations. Eosinophilopenia may indicate a poor prognosis. A combination of antimicrobial drugs did not offer considerable benefit to the outcome of this group of patients.", "qid": 4, "docid": "1qk77fqo", "rank": 99, "score": 0.8504709601402283}, {"content": "Title: Radiation therapy considerations during the COVID\u201019 Pandemic: Literature review and expert opinions Content: COVID-19 is an unprecedented pandemic that has already reached over 2 million confirmed cases globally, with at least 140,000 deaths as reported by the World Health Organization (WHO) as of April 16, 2020 1 . More than 662,000 cases have been reported in the United States with more than 29,000 deaths2 . The overall crude mortality rate now stands at 6.6% (may possibly be lower due to under-testing and under-reporting of total confirmed cases), and is highly dependent on age group, comorbidities, and the locoregional resources medically1 . A report from the United States presented age-stratified COVID-19 associated hospitalization rates among 1,482 patients during March 1-28, 2020, highlighting an alarmingly high rate of 74.5% at age > 50 years with underlining medical conditions3 . Based on a data summary report provided by New York City Health, as of April 14, 2020, the shares of a total of 6839 deaths reached 0.04%, 4.5%, 23.1%, 24.6%, and 47.7% for the age groups of 0-17, 18-44, 45-64, 65-74, and 75+ years old4 . All data suggest that adults at a more advanced age group are facing higher morbidity and mortality risks.", "qid": 4, "docid": "j1j5ghl4", "rank": 100, "score": 0.8503982424736023}]}
{"query": "what drugs have been active against SARS-CoV or SARS-CoV-2 in animal studies?", "hits": [{"content": "Title: Discovering drugs to treat coronavirus disease 2019 (COVID-19) Content: The SARS-CoV-2 virus emerged in December 2019 and then spread rapidly worldwide, particularly to China, Japan, and South Korea. Scientists are endeavoring to find antivirals specific to the virus. Several drugs such as chloroquine, arbidol, remdesivir, and favipiravir are currently undergoing clinical studies to test their efficacy and safety in the treatment of coronavirus disease 2019 (COVID-19) in China; some promising results have been achieved thus far. This article summarizes agents with potential efficacy against SARS-CoV-2.", "qid": 5, "docid": "ey939w17", "rank": 1, "score": 0.8842848539352417}, {"content": "Title: Discovering drugs to treat coronavirus disease 2019 (COVID-19). Content: The SARS-CoV-2 virus emerged in December 2019 and then spread rapidly worldwide, particularly to China, Japan, and South Korea. Scientists are endeavoring to find antivirals specific to the virus. Several drugs such as chloroquine, arbidol, remdesivir, and favipiravir are currently undergoing clinical studies to test their efficacy and safety in the treatment of coronavirus disease 2019 (COVID-19) in China; some promising results have been achieved thus far. This article summarizes agents with potential efficacy against SARS-CoV-2.", "qid": 5, "docid": "8ruux4sw", "rank": 2, "score": 0.8842848539352417}, {"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": 3, "score": 0.8826146721839905}, {"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": 4, "score": 0.882347822189331}, {"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": 5, "docid": "jd1b7asr", "rank": 5, "score": 0.8821825981140137}, {"content": "Title: Evaluation of 19 antiviral drugs against SARS-CoV-2 Infection Content: The global pandemic of the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2 or 2019-nCoV) has prompted multiple clinical trials to jumpstart search for anti-SARS-CoV-2 therapies from existing drugs, including those with reported in vitro efficacies as well as those ones that are not known to inhibit SARS-CoV-2, such as ritonavir/lopinavir and favilavir. Here we report that after screening 19 antiviral drugs that are either in clinical trials or with proposed activity against SARS-CoV-2, remdesivir was the most effective. Chloroquine only effectively protected virus-induced cytopathic effect at around 30 \u00b5M with a therapeutic index of 1.5. Our findings also suggest that velpatasvir, ledipasvir, ritonavir, litonavir, lopinavir, favilavir, sofosbuvir, danoprevir, and pocapavir do not have direct antiviral effect.", "qid": 5, "docid": "ai2zcke5", "rank": 6, "score": 0.8788626194000244}, {"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": 7, "score": 0.8741256594657898}, {"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": 5, "docid": "303b23dd", "rank": 8, "score": 0.8680896759033203}, {"content": "Title: SARS-CoV-2 and SARS-CoV differ in their cell tropism and drug sensitivity profiles Content: SARS-CoV-2 is a novel coronavirus currently causing a pandemic. We show that the majority of amino acid positions, which differ between SARS-CoV-2 and the closely related SARS-CoV, are differentially conserved suggesting differences in biological behaviour. In agreement, novel cell culture models revealed differences between the tropism of SARS-CoV-2 and SARS-CoV. Moreover, cellular ACE2 (SARS-CoV-2 receptor) and TMPRSS2 (enables virus entry via S protein cleavage) levels did not reliably indicate cell susceptibility to SARS-CoV-2. SARS-CoV-2 and SARS-CoV further differed in their drug sensitivity profiles. Thus, only drug testing using SARS-CoV-2 reliably identifies therapy candidates. Therapeutic concentrations of the approved protease inhibitor aprotinin displayed anti-SARS-CoV-2 activity. The efficacy of aprotinin and of remdesivir (currently under clinical investigation against SARS-CoV-2) were further enhanced by therapeutic concentrations of the proton pump inhibitor omeprazole (aprotinin 2.7-fold, remdesivir 10-fold). Hence, our study has also identified anti-SARS-CoV-2 therapy candidates that can be readily tested in patients.", "qid": 5, "docid": "gpr86lxe", "rank": 9, "score": 0.8668157458305359}, {"content": "Title: Current pharmacological modalities for management of novel coronavirus disease 2019 (COVID-19) and the rationale for their utilization: A review Content: SARS-CoV-2 has caused a pandemic which is putting strain on the health-care system and global economy. There is much pressure to develop both preventative and curative therapies for SARS-CoV-2 as there is no evidence to support therapies to improve outcomes in patients with SARS-CoV-2. Medications that inhibit certain steps of virus life cycle that are currently used to treat other illnesses such as Malaria, Ebola, HIV and Hepatitis C are being studied for use against SARS-CoV-2. To date, data is limited for medications that facilitate clinical improvement of COVID-19 infections.", "qid": 5, "docid": "xzqksc8j", "rank": 10, "score": 0.8667362332344055}, {"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": 5, "docid": "n3cg3w9v", "rank": 11, "score": 0.866631269454956}, {"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": 5, "docid": "px2o98cv", "rank": 12, "score": 0.866631269454956}, {"content": "Title: Discovery of clinically approved drugs capable of inhibiting SARS-CoV-2 in vitro infection using a phenotypic screening strategy and network-analysis to predict their potential to treat covid-19 Content: The disease caused by SARS-CoV2, covid-19, rapidly spreads worldwide, causing the greatest threat to global public health in the last 100 years. This scenario has become catastrophic as there are no approved vaccines to prevent the disease, and the main measures to contain the virus transmission are confinement and social distancing. One priority strategy is based on drug repurposing by pursuing antiviral chemotherapy that can control transmission and prevent complications associated with covid-19. With this aim, we performed a high content screening assay for the discovery of anti-SARS-CoV-2 compounds. From the 65 screened compounds, we have found four drugs capable to selectively inhibit SARS-CoV-2 in vitro infection: brequinar, abiraterone acetate, neomycin, and the extract of Hedera helix. Brequinar and abiraterone acetate had higher inhibition potency against SARS-CoV-2 than neomycin and Hedera helix extract, respectively. Drugs with reported antiviral activity and in clinical trials for covid-19, chloroquine, ivermectin, and nitazoxanide, were also included in the screening, and the last two were found to be non-selective. We used a data mining approach to build drug-host molecules-biological function-disease networks to show in a holistic way how each compound is interconnected with host node molecules and virus infection, replication, inflammatory response, and cell apoptosis. In summary, the present manuscript identified four drugs with active inhibition effect on SARS-CoV-2 in vitro infection, and by network analysis, we provided new insights and starting points for the clinical evaluation and repurposing process to treat SARS-CoV-2 infection. Summary sentence Discovery of drug repurposing candidates, inhibitors of SARS-CoV-2 infection in vitro, using a phenotypic screening strategy and network analysis.", "qid": 5, "docid": "40fz5r90", "rank": 13, "score": 0.8649824857711792}, {"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 employed 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 hydroxychloroquine, 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 experimental 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 virus. This also stresses the urgent need for the scientific community to devote its efforts to find other more specific antiviral strategies.", "qid": 5, "docid": "h450b2l5", "rank": 14, "score": 0.8645277619361877}, {"content": "Title: Current Drugs with Potential for Treatment of COVID-19: A Literature Review. Content: PURPOSE SARS-CoV-2 first emerged in China in December 2019 and rapidly spread worldwide. No vaccine or approved drug is available to eradicate the virus, however, some drugs that are indicated for other afflictions seems to be potentially beneficial to treat the infection albeit without unequivocal evidence. The aim of this article is to review the published background on the effectiveness of these drugs against COVID-19 Methods: A thorough literature search was conducted on recently published studies which have published between January 1 to March 25, 2020. PubMed, Google Scholar and Science Direct databases were searched Results: A total 22 articles were found eligible. 8 discuss about treatment outcomes from their applied drugs during treatment of COVID-19 patients, 4 report laboratory tests, one report animal trial and other 9 articles discuss recommendations and suggestions based on the treatment process and clinical outcomes of other diseases such as malaria, ebola, severe acute respiratory syndrome (SARS) and Middle East respiratory syndrome (MERS). The data and/or recommendations are categorized in 4 classes: (a) anti-viral and anti-inflammatory drugs, (b) anti-malaria drugs, (c) traditional Chinese drugs and (d) other treatments/drugs. CONCLUSION All examined treatments, although potentiality effective against COVID-19, need either appropriate drug development or clinical trial to be suitable for clinical use.", "qid": 5, "docid": "er8qrkz3", "rank": 15, "score": 0.8635520339012146}, {"content": "Title: Potential Antiviral Drugs for SARS-Cov-2 Treatment: Preclinical Findings and Ongoing Clinical Research Content: Severe acute respiratory syndrome coronavirus 2 (SARS-Cov-2), initially termed 2019-new CoV (2019-nCoV), is a novel coronavirus responsible for the severe respiratory illness currently ongoing worldwide from the beginning of December 2019. This beta gene virus, very close to bat coronaviruses (bat-CoV-RaTG13) and bat-SL-CoVZC45, causes a severe disease, similar to those caused by Middle East respiratory syndrome (MERS)-CoV and SARS-CoV viruses, featured by low to moderate mortality rate. Unfortunately, the antiviral drugs commonly used in clinical practice to treat viral infections, are not applicable to SARS-Cov-2 and no vaccine is available. Thus, it is extremely necessary to identify new drugs suitable for the treatment of the 2019-nCoV outbreak. Different preclinical studies conducted on other coronaviruses suggested that promising clinical outcomes for 2019-nCoV should be obtained by using alpha-interferon, chloroquine phosphate, arabinol, remdesivir, lopinavir/ritonavir, and anti-inflammatory drugs. Moreover, clinical trials with these suitable drugs should be performed on patients affected by SARS-Cov-2 to prove their efficacy and safety. Finally, a very promising therapeutic drug, tocilizumab, is discussed; it is currently used to treat patients presenting COVID-19 pneumonia. Herein, we recapitulate these experimental studies to highlight the use of antiviral drugs for the treatment of SARS-Cov-2 disease.", "qid": 5, "docid": "7wbpj88g", "rank": 16, "score": 0.8624657392501831}, {"content": "Title: Potential Antiviral Drugs for SARS-Cov-2 Treatment: Preclinical Findings and Ongoing Clinical Research. Content: Severe acute respiratory syndrome coronavirus 2 (SARS-Cov-2), initially termed 2019-new CoV (2019-nCoV), is a novel coronavirus responsible for the severe respiratory illness currently ongoing worldwide from the beginning of December 2019. This beta gene virus, very close to bat coronaviruses (bat-CoV-RaTG13) and bat-SL-CoVZC45, causes a severe disease, similar to those caused by Middle East respiratory syndrome (MERS)-CoV and SARS-CoV viruses, featured by low to moderate mortality rate. Unfortunately, the antiviral drugs commonly used in clinical practice to treat viral infections, are not applicable to SARS-Cov-2 and no vaccine is available. Thus, it is extremely necessary to identify new drugs suitable for the treatment of the 2019-nCoV outbreak. Different preclinical studies conducted on other coronaviruses suggested that promising clinical outcomes for 2019-nCoV should be obtained by using alpha-interferon, chloroquine phosphate, arabinol, remdesivir, lopinavir/ritonavir, and anti-inflammatory drugs. Moreover, clinical trials with these suitable drugs should be performed on patients affected by SARS-Cov-2 to prove their efficacy and safety. Finally, a very promising therapeutic drug, tocilizumab, is discussed; it is currently used to treat patients presenting COVID-19 pneumonia. Herein, we recapitulate these experimental studies to highlight the use of antiviral drugs for the treatment of SARS-Cov-2 disease.", "qid": 5, "docid": "lav2iavi", "rank": 17, "score": 0.8624657392501831}, {"content": "Title: Current Drugs with Potential for Treatment of COVID-19: A Literature Review Content: PURPOSE: SARS-CoV-2 first emerged in China in December 2019 and rapidly spread worldwide. No vaccine or approved drug is available to eradicate the virus, however, some drugs that are indicated for other afflictions seems to be potentially beneficial to treat the infection albeit without unequivocal evidence. The aim of this article is to review the published background on the effectiveness of these drugs against COVID-19 Methods: A thorough literature search was conducted on recently published studies which have published between January 1 to March 25, 2020. PubMed, Google Scholar and Science Direct databases were searched Results: A total 22 articles were found eligible. 8 discuss about treatment outcomes from their applied drugs during treatment of COVID-19 patients, 4 report laboratory tests, one report animal trial and other 9 articles discuss recommendations and suggestions based on the treatment process and clinical outcomes of other diseases such as malaria, ebola, severe acute respiratory syndrome (SARS) and Middle East respiratory syndrome (MERS). The data and/or recommendations are categorized in 4 classes: (a) anti-viral and anti-inflammatory drugs, (b) anti-malaria drugs, (c) traditional Chinese drugs and (d) other treatments/drugs. CONCLUSION: All examined treatments, although potentiality effective against COVID-19, need either appropriate drug development or clinical trial to be suitable for clinical use.", "qid": 5, "docid": "pnp8flc3", "rank": 18, "score": 0.8618438243865967}, {"content": "Title: In vitro data of current therapies for SARS-CoV-2 Content: BACKGROUND: In December 2019, a new coronavirus, named Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2), has emerged from China causing pneumonia outbreaks first in the Wuhan region and currently worldwide. In the light of the lack of efficient and specific treatments and the need to contain the epidemic, drug repurposing appears to be the most efficient tool to find therapeutic solution. OBJECTIVES: The aim of this study was to summarize in vitro data of current agents used for the management of SARSCoV-2 all over the world. METHODS: A literature search of articles from January 2000 until April 2020 was performed using MEDLINE, EMBASE and the Cochrane Library to assess in vitro data of current or putative therapies for SARS-CoV-2. RESULTS: Although in vitro studies are scarce, data regarding chloroquine and hydroxychloroquine, remdesivir, nitazoxanide, teicoplanin, ivermectin, lopinavir, homoharringtonine and emetine seem promising. CONCLUSION: Scientist all over the world should work together and increase their efforts in order to find feasible and efficient solutions against this new global viral threat.", "qid": 5, "docid": "kfal7g2v", "rank": 19, "score": 0.861438512802124}, {"content": "Title: Screening and druggability analysis of some plant metabolites against SARS-CoV-2: An integrative computational approach Content: The sudden outbreak of novel coronavirus has caused a global concern due to its infection rate and mortality. Despite extensive research, there are still no specific drugs or vaccines to combat SARS-CoV-2 infection. Hence, this study was designed to evaluate some plant-based active compounds for drug candidacy against SARS-CoV-2 by using virtual screening methods and various computational analyses. A total of 27 plant metabolites were screened against SARS-CoV-2 main protease proteins (MPP), Nsp9 RNA binding protein, spike receptor binding domain, spike ecto-domain and HR2 domain using a molecular docking approach. Four metabolites, i.e., asiatic acid, avicularin, guajaverin, and withaferin showed maximum binding affinity with all key proteins in terms of lowest global binding energy. The crucial binding sites and drug surface hotspots were unravelled for each viral protein. The top candidates were further employed for ADME (absorption, distribution, metabolism, and excretion) analysis to investigate their drug profiles. Results suggest that none of the compounds render any undesirable consequences that could reduce their drug likeness properties. The analysis of toxicity pattern revealed no significant tumorigenic, mutagenic, irritating, or reproductive effects by the compounds. However, withaferin was comparatively toxic among the top four candidates with considerable cytotoxicity and immunotoxicity. Most of the target class by top drug candidates belonged to enzyme groups (e.g. oxidoreductases hydrolases, phosphatases). Moreover, results of drug similarity prediction revealed two approved structural analogs of Asiatic acid i.e. Hydrocortisone (DB00741) (previously used for SARS-CoV-1 and MERS) and Dinoprost-tromethamine (DB01160) from DrugBank. In addition, two other biologically active compounds, Mupirocin (DB00410) and Simvastatin (DB00641) could be an option for the treatment of viral infections. The study may pave the way to develop effective medications and preventive measure against SARS-CoV-2. Due to the encouraging results, we highly recommend further in vivo trials for the experimental validation of our findings.", "qid": 5, "docid": "ekkgcy93", "rank": 20, "score": 0.8609007596969604}, {"content": "Title: Candidate drugs against SARS-CoV-2 and COVID-19 Content: Outbreak and pandemic of coronavirus SARS-CoV-2 in 2019/2020 will challenge global health for the future. Because a vaccine against the virus will not be available in the near future, we herein try to offer a pharmacological strategy to combat the virus. There exists a number of candidate drugs that may inhibit infection with and replication of SARS-CoV-2. Such drugs comprise inhibitors of TMPRSS2 serine protease and inhibitors of angiotensin-converting enzyme 2 (ACE2). Blockade of ACE2, the host cell receptor for the S protein of SARS-CoV-2 and inhibition of TMPRSS2, which is required for S protein priming may prevent cell entry of SARS-CoV-2. Further, chloroquine and hydroxychloroquine, and off-label antiviral drugs, such as the nucleotide analogue remdesivir, HIV protease inhibitors lopinavir and ritonavir, broad-spectrum antiviral drugs arbidol and favipiravir as well as antiviral phytochemicals available to date may limit spread of SARS-CoV-2 and morbidity and mortality of COVID-19 pandemic.", "qid": 5, "docid": "xef6fr39", "rank": 21, "score": 0.859697699546814}, {"content": "Title: Drug repositioning is an alternative for the treatment of coronavirus COVID-19 Content: Given the extreme importance of the current pandemic caused by COVID-19, and as scientists agree there is no identified pharmacological treatment, where possible, therapeutic alternatives are raised through drug repositioning. This paper presents a selection of studies involving drugs from different pharmaceutical classes with activity against SARS-CoV-2 and SARS-CoV, with the potential for use in the treatment of COVID-19 disease.", "qid": 5, "docid": "ij8wk06v", "rank": 22, "score": 0.8592038154602051}, {"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": 5, "docid": "qsd49pvm", "rank": 23, "score": 0.8585150837898254}, {"content": "Title: Repurposing old drugs as antiviral agents for coronaviruses Content: BACKGROUND: New therapeutic options to address the ongoing COVID-19 pandemic are urgently needed. One possible strategy is the repurposing of existing drugs approved for other indications as antiviral agents for 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 (EC(50)) 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 EC(50) values ranging from 11 nM to 75 \u03bcM. They are all old drugs as follows, anisomycin, antimycin A, atovaquone, chloroquine, conivaptan, emetine, gemcitabine, homoharringtonine, niclosamide, nitazoxanide, oligomycin, salinomycin, tilorone, valinomycin, 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": "fo07nxvi", "rank": 24, "score": 0.8584578037261963}, {"content": "Title: Broad-Spectrum Host-Based Antivirals Targeting the Interferon and Lipogenesis Pathways as Potential Treatment Options for the Pandemic Coronavirus Disease 2019 (COVID-19). Content: The ongoing Coronavirus Disease 2019 (COVID-19) pandemic caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) signals an urgent need for an expansion in treatment options. In this study, we investigated the anti-SARS-CoV-2 activities of 22 antiviral agents with known broad-spectrum antiviral activities against coronaviruses and/or other viruses. They were first evaluated in our primary screening in VeroE6 cells and then the most potent anti-SARS-CoV-2 antiviral agents were further evaluated using viral antigen expression, viral load reduction, and plaque reduction assays. In addition to remdesivir, lopinavir, and chloroquine, our primary screening additionally identified types I and II recombinant interferons, 25-hydroxycholesterol, and AM580 as the most potent anti-SARS-CoV-2 agents among the 22 antiviral agents. Betaferon (interferon-\u03b21b) exhibited the most potent anti-SARS-CoV-2 activity in viral antigen expression, viral load reduction, and plaque reduction assays among the recombinant interferons. The lipogenesis modulators 25-hydroxycholesterol and AM580 exhibited EC50 at low micromolar levels and selectivity indices of >10.0. Combinational use of these host-based antiviral agents with virus-based antivirals to target different processes of the SARS-CoV-2 replication cycle should be evaluated in animal models and/or clinical trials.", "qid": 5, "docid": "tzmev77c", "rank": 25, "score": 0.8580554723739624}, {"content": "Title: In vitro data of current therapies for SARS-CoV-2. Content: BACKGROUND In December 2019, a new coronavirus, named Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2), has emerged from China causing pneumonia outbreaks first in the Wuhan region and currently worldwide. In the light of the lack of efficient and specific treatments and the need to contain the epidemic, drug repurposing appears to be the most efficient tool to find therapeutic solution. OBJECTIVES The aim of this study was to summarize in vitro data of current agents used for the management of SARSCoV-2 all over the world. METHODS A literature search of articles from January 2000 until April 2020 was performed using MEDLINE, EMBASE and the Cochrane Library to assess in vitro data of current or putative therapies for SARS-CoV-2. RESULTS Although in vitro studies are scarce, data regarding chloroquine and hydroxychloroquine, remdesivir, nitazoxanide, teicoplanin, ivermectin, lopinavir, homoharringtonine and emetine seem promising. CONCLUSION Scientist all over the world should work together and increase their efforts in order to find feasible and efficient solutions against this new global viral threat.", "qid": 5, "docid": "de45x8q4", "rank": 26, "score": 0.8579862117767334}, {"content": "Title: Broad-Spectrum Host-Based Antivirals Targeting the Interferon and Lipogenesis Pathways as Potential Treatment Options for the Pandemic Coronavirus Disease 2019 (COVID-19) Content: The ongoing Coronavirus Disease 2019 (COVID-19) pandemic caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) signals an urgent need for an expansion in treatment options. In this study, we investigated the anti-SARS-CoV-2 activities of 22 antiviral agents with known broad-spectrum antiviral activities against coronaviruses and/or other viruses. They were first evaluated in our primary screening in VeroE6 cells and then the most potent anti-SARS-CoV-2 antiviral agents were further evaluated using viral antigen expression, viral load reduction, and plaque reduction assays. In addition to remdesivir, lopinavir, and chloroquine, our primary screening additionally identified types I and II recombinant interferons, 25-hydroxycholesterol, and AM580 as the most potent anti-SARS-CoV-2 agents among the 22 antiviral agents. Betaferon (interferon-\u00df1b) exhibited the most potent anti-SARS-CoV-2 activity in viral antigen expression, viral load reduction, and plaque reduction assays among the recombinant interferons. The lipogenesis modulators 25-hydroxycholesterol and AM580 exhibited EC50 at low micromolar levels and selectivity indices of >10.0. Combinational use of these host-based antiviral agents with virus-based antivirals to target different processes of the SARS-CoV-2 replication cycle should be evaluated in animal models and/or clinical trials.", "qid": 5, "docid": "u3ow62fn", "rank": 27, "score": 0.8578585386276245}, {"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": 5, "docid": "fgbilulc", "rank": 28, "score": 0.8578109741210938}, {"content": "Title: Taking aim at a fast-moving target: Targets to watch for SARS-CoV-2 and COVID-19 Content: Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) is characterized as a betacoronavirus and recognized as the seventh discrete coronavirus species capable of causing human disease. This new coronavirus causes febrile respiratory illness and on March 11, 2020, was characterized as a global pandemic. Investigators have accelerated the search for a vaccine to prevent infection and for agents to treat it. This article presents those drug targets that (as of March 20, 2020) are currently under active investigation for the treatment of COVID-19, the disease caused by SARS-CoV-2 infection.", "qid": 5, "docid": "ybzfhp8p", "rank": 29, "score": 0.8576939105987549}, {"content": "Title: Potent antiviral effect of protoporphyrin IX and verteporfin on SARS-CoV-2 infection Content: The infection of SARS-CoV-2 has spread to more than 200 countries and regions and the numbers of infected people and deaths worldwide are expected to continue to rise. Current treatment of COVID-19 is limited and mostly supportive. At present, there is no specific therapeutics against SARS-CoV-2. In this study, we discovered that protoporphyrin IX and verteporfin, two FDA-approved drugs for treatment of human diseases, had significant antiviral effect against SARS-CoV-2, with EC50 values for the reduction of viral RNA at nanomolar concentrations. Both drugs completely inhibited the cytopathic effect (CPE) produced by SARS-CoV-2 infection at lower drug concentrations than that of remdesivir. The selection indices of protoporphyrin IX and verteporfin are 952.74 and 368.93, respectively, suggesting wide safety margins. Both drugs were able to prevent SARS-CoV-2 infection as well as suppress established SARS-CoV-2 infection. The compounds share a porphyrin ring structure. Molecular docking indicates that the compounds may interact with viral receptor ACE2 and could block the cell-cell fusion mediated by ACE2 and viral S protein. Our finding suggests that protoporphyrin IX and verteporfin might be potential antivirals against SARS-CoV-2 infection and also sheds new light on the development of a novel class of small compounds against SARS-CoV-2.", "qid": 5, "docid": "l4ci8wr2", "rank": 30, "score": 0.856848955154419}, {"content": "Title: Candidate drugs against SARS-CoV-2 and COVID-19 Content: Abstract Outbreak and pandemic of coronavirus SARS-CoV-2 in 2019/2020 will challenge global health for the future. Because a vaccine against the virus will not be available in the near future, we herein try to offer a pharmacological strategy to combat the virus. There exists a number of candidate drugs that may inhibit infection with and replication of SARS-CoV-2. Such drugs comprise inhibitors of TMPRSS2 serine protease and inhibitors of angiotensin-converting enzyme 2 (ACE2). Blockade of ACE2, the host cell receptor for the S protein of SARS-CoV-2 and inhibition of TMPRSS2, which is required for S protein priming may prevent cell entry of SARS-CoV-2. Further, chloroquine and hydroxychloroquine, and off-label antiviral drugs, such as the nucleotide analogue remdesivir, HIV protease inhibitors lopinavir and ritonavir, broad-spectrum antiviral drugs arbidol and favipiravir as well as antiviral phytochemicals available to date may prevent spread of SARS-CoV-2 and morbidity and mortality of COVID-19 pandemic.", "qid": 5, "docid": "n0mz098o", "rank": 31, "score": 0.8565558195114136}, {"content": "Title: Drug repositioning is an alternative for the treatment of coronavirus COVID-19 Content: Abstract Given the extreme importance of the current pandemic caused by COVID-19, and as scientists agree there is no identified pharmacological treatment, where possible, therapeutic alternatives are raised through drug repositioning. This paper presents a selection of studies involving drugs from different pharmaceutical classes with activity against SARS-CoV-2 and SARS-CoV, with the potential for use in the treatment of COVID-19 disease.", "qid": 5, "docid": "agc89fqv", "rank": 32, "score": 0.8562774658203125}, {"content": "Title: Discovery of the FDA-approved drugs bexarotene, cetilistat, diiodohydroxyquinoline, and abiraterone as potential COVID-19 treatments with a robust two-tier screening system Content: Coronavirus Disease 2019 (COVID-19) caused by the emerging severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) is associated with a crude case fatality rate of about 0.5-10% depending on locality. A few clinically approved drugs, such as remdesivir, chloroquine, hydroxychloroquine, nafamostat, camostat, and ivermectin, exhibited anti-SARS-CoV-2 activity in vitro and/or in a small number of patients. However, their clinical use may be limited by anti-SARS-CoV-2 50% maximal effective concentrations (EC(50)) that exceeded their achievable peak serum concentrations (Cmax), side effects, and/or availability. To find more immediately available COVID-19 antivirals, we established a two-tier drug screening system that combines SARS-CoV-2 enzyme-linked immunosorbent assay and cell viability assay, and applied it to screen a library consisting 1528 FDA-approved drugs. Cetilistat (anti-pancreatic lipase), diiodohydroxyquinoline (anti-parasitic), abiraterone acetate (synthetic androstane steroid), and bexarotene (antineoplastic retinoid) exhibited potent in vitro anti-SARS-CoV-2 activity (EC(50) 1.13-2.01\u00b5M). Bexarotene demonstrated the highest Cmax:EC(50) ratio (1.69) which was higher than those of chloroquine, hydroxychloroquine, and ivermectin. These results demonstrated the efficacy of the two-tier screening system and identified potential COVID-19 treatments which can achieve effective levels if given by inhalation or systemically depending on their pharmacokinetics.", "qid": 5, "docid": "fd5rr87z", "rank": 33, "score": 0.8560717105865479}, {"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": 34, "score": 0.8557122945785522}, {"content": "Title: Early administration of ritonavir-boosted lopinavir could prevent severe COVID-19 Content: No specific treatment against SARS-CoV-2 is available after 6 months of COVID-19 worldwide outbreak Antivirals could decrease the viral load and reduce direct and indirect damages of SARSCoV-2 infection Ritonavir-bosted lopinavir is effective against SARS-CoV-2 in vitro Sequential virological and pharmacological monitoring helped to understand the efficacy of ritonavir-boosted lopinavir in a SARS-CoV-2 infected patient Ritonavir-boosted lopinavir could be proposed as early treatment for SARS-CoV-2 infection", "qid": 5, "docid": "ibmpqwc6", "rank": 35, "score": 0.855476975440979}, {"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": 36, "score": 0.8553800582885742}, {"content": "Title: Identification of potent and safe antiviral therapeutic candidates against SARS-CoV-2 Content: COVID-19 pandemic has infected millions of people with mortality exceeding 300,000. There is an urgent need to find therapeutic agents that can help clear the virus to prevent the severe disease and death. Identifying effective and safer drugs can provide with more options to treat the COVID-19 infections either alone or in combination. Here we performed a high throughput screen of approximately 1700 US FDA approved compounds to identify novel therapeutic agents that can effectively inhibit replication of coronaviruses including SARS-CoV-2. Our two-step screen first used a human coronavirus strain OC43 to identify compounds with anti-coronaviral activities. The effective compounds were then screened for their effectiveness in inhibiting SARS-CoV-2. These screens have identified 24 anti-SARS-CoV-2 drugs including previously reported compounds such as hydroxychloroquine, amlodipine, arbidol hydrochloride, tilorone 2HCl, dronedarone hydrochloride, and merfloquine hydrochloride. Five of the newly identified drugs had a safety index (cytotoxic/effective concentration) of >600, indicating wide therapeutic window compared to hydroxychloroquine which had safety index of 22 in similar experiments. Mechanistically, five of the effective compounds were found to block SARS-CoV-2 S protein-mediated cell fusion. These FDA approved compounds can provide much needed therapeutic options that we urgently need in the midst of the pandemic.", "qid": 5, "docid": "e9fjo7tl", "rank": 37, "score": 0.8551607131958008}, {"content": "Title: Discovery of the FDA-approved drugs bexarotene, cetilistat, diiodohydroxyquinoline, and abiraterone as potential COVID-19 treatments with a robust two-tier screening system Content: Coronavirus Disease 2019 (COVID-19) caused by the emerging severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) is associated with a crude case fatality rate of about 0.5-10 % depending on locality. A few clinically approved drugs, such as remdesivir, chloroquine, hydroxychloroquine, nafamostat, camostat, and ivermectin, exhibited anti-SARS-CoV-2 activity in vitro and/or in a small number of patients. However, their clinical use may be limited by anti-SARS-CoV-2 50 % maximal effective concentrations (EC50) that exceeded their achievable peak serum concentrations (Cmax), side effects, and/or availability. To find more immediately available COVID-19 antivirals, we established a two-tier drug screening system that combines SARS-CoV-2 enzyme-linked immunosorbent assay and cell viability assay, and applied it to screen a library consisting 1528 FDA-approved drugs. Cetilistat (anti-pancreatic lipase), diiodohydroxyquinoline (anti-parasitic), abiraterone acetate (synthetic androstane steroid), and bexarotene (antineoplastic retinoid) exhibited potent in vitro anti-SARS-CoV-2 activity (EC50 1.13-2.01 \u00b5M). Bexarotene demonstrated the highest Cmax:EC50 ratio (1.69) which was higher than those of chloroquine, hydroxychloroquine, and ivermectin. These results demonstrated the efficacy of the two-tier screening system and identified potential COVID-19 treatments which can achieve effective levels if given by inhalation or systemically depending on their pharmacokinetics.", "qid": 5, "docid": "458smf3g", "rank": 38, "score": 0.8550889492034912}, {"content": "Title: Identification of Antiviral Drug Candidates against SARS-CoV-2 from FDA-Approved Drugs Content: Drug repositioning is the only feasible option to immediately address the COVID-19 global challenge. We screened a panel of 48 FDA-approved drugs against severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) which were preselected by an assay of SARS-CoV. We identified 24 potential antiviral drug candidates against SARS-CoV-2 infection. Some drug candidates showed very low 50% inhibitory concentrations (IC50s), and in particular, two FDA-approved drugs-niclosamide and ciclesonide-were notable in some respects.", "qid": 5, "docid": "2gvpn4zr", "rank": 39, "score": 0.8545376658439636}, {"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": 40, "score": 0.8542318940162659}, {"content": "Title: Identification of Antiviral Drug Candidates against SARS-CoV-2 from FDA-Approved Drugs Content: Drug repositioning is the only feasible option to immediately address the COVID-19 global challenge. We screened a panel of 48 FDA-approved drugs against severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) which were preselected by an assay of SARS-CoV. We identified 24 potential antiviral drug candidates against SARS-CoV-2 infection. Some drug candidates showed very low 50% inhibitory concentrations (IC(50)s), and in particular, two FDA-approved drugs\u2014niclosamide and ciclesonide\u2014were notable in some respects.", "qid": 5, "docid": "gka6f34c", "rank": 41, "score": 0.8542047142982483}, {"content": "Title: Indomethacin has a potent antiviral activity against SARS CoV-2 in vitro and canine coronavirus in vivo Content: Background The outbreak of SARS CoV-2 has caused ever-increasing attention and public panic all over the world. Currently, there is no specific treatment against the SARS CoV-2. Therefore, identifying effective antiviral agents to combat the disease is urgently needed. Previous studies found that indomethacin has the ability to inhibit the replication of several unrelated DNA and RNA viruses, including SARS-CoV. Methods SARS CoV-2 pseudovirus-infected African green monkey kidney VERO E6 cells treated with different concentrations of indomethacin or aspirin at 48 hours post infection (p.i). The level of cell infection was determined by luciferase activity. Anti-coronavirus efficacy in vivo was confirmed by evaluating the time of recovery in canine coronavirus (CCV) infected dogs treated orally with 1mg/kg body weight indomethacin. Results We found that indomethacin has a directly and potently antiviral activity against the SARS CoV-2 pseudovirus (reduce relative light unit to zero). In CCV-infected dogs, recovery occurred significantly sooner with symptomatic treatment + oral indomethacin (1 mg/kg body weight) daily treatments than with symptomatic treatment + ribavirin (10-15 mg/kg body weight) daily treatments (P =0.0031), but was not significantly different from that with symptomatic treatment + anti-canine coronavirus serum + canine hemoglobin + canine blood immunoglobulin + interferon treatments (P =0.7784). Conclusion The results identify indomethacin as a potent inhibitor of SARS CoV-2.", "qid": 5, "docid": "7joyaz7q", "rank": 42, "score": 0.8537641167640686}, {"content": "Title: Off\u2010Label Therapies for COVID\u201019\u2014Are We All In This Together? Content: SARS-CoV-2 continues to spread rapidly outside of mainland China. As of April 6, there are over 300,000 cases and 10,000 deaths in the US. Effective therapies for the novel Coronavirus are urgently needed and over 200 clinical trials are now underway across the globe. Recognizing the need for robust randomized control trials, the World Health Organization (WHO) recently organized a multinational randomized trial-the SOLIDARITY trial-to study the effect of drugs that have been identified as promising based on in-vitro data and the early clinical experience with COVID-19: Remdesivir, lopinavir and ritonavir; lopinavir and ritonavir + interferon; and chloroquine or hydroxychloroquine.", "qid": 5, "docid": "f5tpz8ze", "rank": 43, "score": 0.853493332862854}, {"content": "Title: Clinical trials of repurposed antivirals for SARS-CoV-2 Content: The coronavirus disease 2019 (COVID-19) pandemic caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) has prompted the repurposing of drugs on the basis of promising in vitro and therapeutic results with other human coronavirus diseases such as severe acute respiratory syndrome (SARS) and Middle East respiratory syndrome (MERS). These repurposed drugs have mainly included remdesivir, favipiravir, lopinavir/ritonavir, ribavirin, interferons, and hydroxychloroquine. Unfortunately, the first open-label, randomized controlled trials are showing the poor efficacy of these repurposed drugs. These results highlight the necessity of identifying and characterizing specific and potent SARS-CoV-2 antivirals.", "qid": 5, "docid": "yvlcorrg", "rank": 44, "score": 0.8533530235290527}, {"content": "Title: Clinical trials of repurposed antivirals for SARS-CoV-2. Content: The coronavirus disease 2019 (COVID-19) pandemic caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) has prompted the repurposing of drugs on the basis of promising in vitro and therapeutic results with other human coronavirus diseases such as severe acute respiratory syndrome (SARS) and Middle East respiratory syndrome (MERS). These repurposed drugs have mainly included remdesivir, favipiravir, lopinavir/ritonavir, ribavirin, interferons, and hydroxychloroquine. Unfortunately, the first open-label, randomized controlled trials are showing the poor efficacy of these repurposed drugs. These results highlight the necessity of identifying and characterizing specific and potent SARS-CoV-2 antivirals.", "qid": 5, "docid": "5q5mele8", "rank": 45, "score": 0.8533530235290527}, {"content": "Title: Current targeted therapeutics against COVID-19: Based on first-line experience in China Content: SARS-CoV-2 is a novel strain, causing a global pandemic since the end of 2019. The majority of patients showed nonspecific symptoms such as fever, dry cough, and fatigue. Most patients have a good prognosis while some with severe conditions could rapidly progress to acute respiratory distress syndrome, septic shock, metabolic acidosis, coagulation dysfunction, and even die. The exacerbation of the patient's condition may be due to a cytokine storm in the body. Effective targeted therapies including antiviral and immunization are urgently needed. Although many clinical trials are already underway and the majority of patients have received antiviral therapy based on medication experience with severe acute respiratory syndrome (SARS) and Middle East respiratory syndrome (MERS), and preliminary results from some clinical trials, there are no antiviral drugs proven to be effective currently. We summarize the current therapeutic medicines used in the clinic, hope to be able to provide some implications for clinical medication.", "qid": 5, "docid": "x62w7qs1", "rank": 46, "score": 0.8532257080078125}, {"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": 5, "docid": "phxu6usy", "rank": 47, "score": 0.8523763418197632}, {"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": 5, "docid": "j8n06hzx", "rank": 48, "score": 0.8513715863227844}, {"content": "Title: Remdesivir, lopinavir, emetine, and homoharringtonine inhibit SARS-CoV-2 replication in vitro Content: An escalating pandemic by the novel SARS-CoV-2 virus is impacting global health and effective therapeutic options are urgently needed. We evaluated the in vitro antiviral effect of compounds that were previously reported to inhibit coronavirus replication and compounds that are currently under evaluation in clinical trials for SARS-CoV-2 patients. We report the antiviral effect of remdesivir, lopinavir, homorringtonine, and emetine against SARS-CoV-2 virus in Vero E6 cells with the estimated 50% effective concentration at 23.15 \u00b5M, 26.63 \u00b5M, 2.55 \u00b5M and 0.46 \u00b5M, respectively. Ribavirin or favipiravir that are currently evaluated under clinical trials showed no inhibition at 100 \u00b5M. Synergy between remdesivir and emetine was observed, and remdesivir at 6.25 \u00b5M in combination with emetine at 0.195 \u00b5M may achieve 64.9% inhibition in viral yield. Combinational therapy may help to reduce the effective concentration of compounds below the therapeutic plasma concentrations and provide better clinical benefits.", "qid": 5, "docid": "ygygnmgm", "rank": 49, "score": 0.8507809638977051}, {"content": "Title: Remdesivir, lopinavir, emetine, and homoharringtonine inhibit SARS-CoV-2 replication in vitro Content: An escalating pandemic by the novel SARS-CoV-2 virus is impacting global health and effective therapeutic options are urgently needed. We evaluated the in vitro antiviral effect of compounds that were previously reported to inhibit coronavirus replication and compounds that are currently under evaluation in clinical trials for SARS-CoV-2 patients. We report the antiviral effect of remdesivir, lopinavir, homorringtonine, and emetine against SARS-CoV-2 virus in Vero E6 cells with the estimated 50% effective concentration at 23.15 \u03bcM, 26.63 \u03bcM, 2.55 \u03bcM and 0.46 \u03bcM, respectively. Ribavirin or favipiravir that are currently evaluated under clinical trials showed no inhibition at 100 \u03bcM. Synergy between remdesivir and emetine was observed, and remdesivir at 6.25 \u03bcM in combination with emetine at 0.195 \u03bcM may achieve 64.9% inhibition in viral yield. Combinational therapy may help to reduce the effective concentration of compounds below the therapeutic plasma concentrations and provide better clinical benefits.", "qid": 5, "docid": "7e8zlt3t", "rank": 50, "score": 0.8503641486167908}, {"content": "Title: Drug repurposing clinical trials in the search for life-saving COVID-19 therapies;research targets and methodological and ethical issues Content: Introduction: So far, there is no vaccine, nor are there effective drugs to treat COVID-19, an emerging viral respiratory infection deadlier than influenza Objective: To take a snapshot picture of planned and ongoing clinical research addressing drugs potentially useful for treating SAR-CoV-2 infections Method: A search was conducted (20 April 2020) in an international registry of clinical studies (https://ClinicalTrials gov, US NIH) After excluding observational studies and other interventions that fell outside the scope of this study, 294 research protocols (out of 516 retrieved protocols) were selected for analysis Results: Of 294 included trials, 249 were Randomized Controlled Trials (RCT), 118 of which were double-, triple- or quadruple-blinded studies The interventions (drug therapies) were compared with \"standard-of-care\" (SOC) or with the placebo plus SOC, or yet with presumed \"active\" comparators RCT focused on the primary treatment of the disease (inhibitors of viral replication) or on the therapy for resolution of hyperinflammation in pneumonia/Acute Respiratory Distress Syndrome (ARDS) and thromboembolism associated with SARS-CoV-2 The trials found in the database involve existing antiviral compounds and drugs with multiple modes of antiviral action Antiparasitic drugs, which inhibited viral replication in cell-culture assays, are being tested as well Regarding the adjunctive immunomodulatory, anti-inflammatory and antithrombotic therapies, a number of drugs with distinct pharmacological targets are under investigation in trials enrolling patients with severe COVID-19 Conclusions: Although many clinical studies of drugs for COVID-19 are planned or in progress, only a minority of them are sufficiently large, randomized and placebo-controlled trials with masking and concealment of allocation Owing to methodological limitations, only a few clinical trials found in the registry are likely to yield robust evidence of effectiveness and safety of drugs repurposable for COVID-19", "qid": 5, "docid": "a4oibkt9", "rank": 51, "score": 0.8503590822219849}, {"content": "Title: The serotonin reuptake inhibitor Fluoxetine inhibits SARS-CoV-2 Content: To circumvent time-consuming clinical trials, testing whether existing drugs are effective inhibitors of SARS-CoV-2, has led to the discovery of Remdesivir. We decided to follow this path and screened approved medications \u201coff-label\u201d against SARS-CoV-2. In these screenings, Fluoxetine inhibited SARS-CoV-2 at a concentration of 0.8\u00b5g/ml significantly, and the EC50 was determined with 387ng/ml. Fluoxetine is a racemate consisting of both stereoisomers, while the S-form is the dominant serotonin reuptake inhibitor. We found that both isomers show similar activity on the virus. Fluoxetine treatment resulted in a decrease in viral protein expression. Furthermore, Fluoxetine inhibited neither Rabies virus, human respiratory syncytial virus replication nor the Human Herpesvirus 8 or Herpes simplex virus type 1 gene expression, indicating that it acts virus-specific. We see the role of Fluoxetine in the early treatment of SARS-CoV-2 infected patients of risk groups.", "qid": 5, "docid": "hewzgkwl", "rank": 52, "score": 0.8502291440963745}, {"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": 5, "docid": "yth9hh5q", "rank": 53, "score": 0.8501976728439331}, {"content": "Title: Battling COVID-19: using old weapons for a new enemy Content: Coronavirus disease-19 (COVID-19) has reached pandemic proportions. Most of the drugs that are being tried for the treatment have not been evaluated in any randomized controlled trials. The purpose of this review was to summarize the in-vitro and in-vivo efficacy of these drugs on Severe Acute Respiratory Syndrome (SARS-CoV-2) and related viruses (SARS and Middle East Respiratory Syndrome) and evaluate their potential for re-purposing them in the management of COVID-19.", "qid": 5, "docid": "yn7x9uit", "rank": 54, "score": 0.850116491317749}, {"content": "Title: Identification of five antiviral compounds from the Pandemic Response Box targeting SARS-CoV-2 Content: With currently over 4 million confirmed cases worldwide, including more than 300\u2019000 deaths, the current Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2) pandemic has a major impact on the economy and health care system. Currently, a limited amount of prophylactic or therapeutic intervention options are available against SARS-CoV-2. In this study, we screened 400 compounds from the antimicrobial \u2018Pandemic Response Box\u2019 library for inhibiting properties against SARS-CoV-2. We identified sixteen compounds that potently inhibited SARS-CoV-2 replication, of which five compounds displayed equal or even higher antiviral activity compared to Remdesivir. These results show that five compounds should be further investigated for their mode of action, safety and efficacy against SARS-CoV-2. Highlights 400 compounds from the pandemic response box were tested for antiviral activity against SARS-CoV-2. 5 compounds had an equal or higher antiviral efficacy towards SARS-CoV-2, compared to the nucleoside analogue Remdesivir.", "qid": 5, "docid": "sj6ts2vo", "rank": 55, "score": 0.8500392436981201}, {"content": "Title: Current targeted therapeutics against COVID-19: based on first-line experience in china Content: Abstract SARS-CoV-2 is a novel strain, causing a global pandemic since the end of 2019. The majority of patients showed nonspecific symptoms such as fever, dry cough, and fatigue. Most patients have a good prognosis while some with severe conditions could rapidly progress to acute respiratory distress syndrome, septic shock, metabolic acidosis, coagulation dysfunction, and even die. The exacerbation of the patient's condition may be due to a cytokine storm in the body. Effective targeted therapies including antiviral and immunization are urgently needed. Although many clinical trials are already underway and the majority of patients have received antiviral therapy based on medication experience with severe acute respiratory syndrome (SARS) and Middle East respiratory syndrome (MERS), and preliminary results from some clinical trials, there are no antiviral drugs proven to be effective currently. We summarize the current therapeutic medicines used in the clinic, hope to be able to provide some implications for clinical medication.", "qid": 5, "docid": "ahlgybbc", "rank": 56, "score": 0.8500015139579773}, {"content": "Title: A comprehensive review on drug repositioning against coronavirus disease 2019 (COVID19) Content: Severe acute respiratory syndrome coronavirus 2 (SARS-CoV2) is the reason for this ongoing pandemic infection diseases termed coronavirus disease 2019 (COVID-19) that has emerged since early December 2019 in Wuhan City, Hubei Province, China. In this century, it is the worst threat to international health and the economy. After 4 months of COVID-19 outbreak, there is no certain and approved medicine against it. In this public health emergency, it makes sense to investigate the possible effects of old drugs and find drug repositioning that is efficient, economical, and riskless process. Old drugs that may be effective are from different pharmacological categories, antimalarials, anthelmintics, anti-protozoal, anti-HIVs, anti-influenza, anti-hepacivirus, antineoplastics, neutralizing antibodies, immunoglobulins, and interferons. In vitro, in vivo, or preliminary trials of these drugs in the treatment of COVID-19 have been encouraging, leading to new research projects and trials to find the best drug/s. In this review, we discuss the possible mechanisms of these drugs against COVID-19. Also, it should be mentioned that in this manuscript, we discuss preliminary rationales; however, clinical trial evidence is needed to prove them. COVID-19 therapy must be based on expert clinical experience and published literature and guidelines from major health organizations. Moreover, herein, we describe current evidence that may be changed in the future.", "qid": 5, "docid": "476uhzb6", "rank": 57, "score": 0.8496437072753906}, {"content": "Title: SARS-CoV-2 RNA polymerase as target for antiviral therapy Content: A new human coronavirus named SARS-CoV-2 was identified in several cases of acute respiratory syndrome in Wuhan, China in December 2019. On March 11 2020, WHO declared the SARS-CoV-2 infection to be a pandemic, based on the involvement of 169 nations. Specific drugs for SARS-CoV-2 are obviously not available. Currently, drugs originally developed for other viruses or parasites are currently in clinical trials based on empiric data. In the quest of an effective antiviral drug, the most specific target for an RNA virus is the RNA-dependent RNA-polymerase (RdRp) which shows significant differences between positive-sense and negative-sense RNA viruses. An accurate evaluation of RdRps from different viruses may guide the development of new drugs or the repositioning of already approved antiviral drugs as treatment of SARS-CoV-2. This can accelerate the containment of the SARS-CoV-2 pandemic and, hopefully, of future pandemics due to other emerging zoonotic RNA viruses.", "qid": 5, "docid": "c0jfa5jd", "rank": 58, "score": 0.8494089841842651}, {"content": "Title: Development of antiviral therapy for severe acute respiratory syndrome Content: Abstract A new disease, the severe acute respiratory distress syndrome (SARS), caused by the SARS coronavirus (SARS-CoV), emerged at the beginning of 2003 and rapidly spread throughout the world. Although the disease had disappeared in June 2003 its re-emergence cannot be excluded. The development of vaccines against SARS-CoV may take years. Therefore, the availability of effective antiviral drugs against SARS-CoV may be crucial for the control of future SARS outbreaks. In this review, experimental and clinical data about potential anti-SARS drugs is summarised and discussed. Animal model studies will be needed to help to determine which interventions warrant controlled clinical testing.", "qid": 5, "docid": "9ujofcsm", "rank": 59, "score": 0.8493933081626892}, {"content": "Title: COVID-19 pandemic: an overview of epidemiology, parthenogenesis, diagnostics and potential vaccines and therapeutics Content: At the time of writing this review, severe acute respiratory coronavirus syndrome-2 (SARS-CoV-2) has infected more than 2,355,853 patients and resulted in more than 164,656 deaths worldwide (as of 20 April 2020). This review highlights the preventive measures, available clinical therapies and the potential of vaccine development against SARS-CoV-2 by taking into consideration the strong genetic similarities of the 2003 epidemic SARS-CoV. Recent studies are investigating the repurposing of US FDA-approved drugs as there is no available vaccine yet with many attempts under clinical evaluation. Several antivirals, antimalarials and immunomodulators that have shown activity against SARS-CoV and Middle East coronavirus respiratory syndromes are being evaluated. In particular, hydroxychloroquine, remdesivir, favipiravir, arbidol, tocilizumab and bevacizumab have shown promising results. The main aim of this review is to provide an overview of this pandemic and where we currently stand.", "qid": 5, "docid": "b0aaozmn", "rank": 60, "score": 0.8492310047149658}, {"content": "Title: COVID-19 pandemic: an overview of epidemiology, pathogenesis, diagnostics and potential vaccines and therapeutics Content: At the time of writing this review, severe acute respiratory coronavirus syndrome-2 (SARS-CoV-2) has infected more than 2,355,853 patients and resulted in more than 164,656 deaths worldwide (as of 20 April 2020). This review highlights the preventive measures, available clinical therapies and the potential of vaccine development against SARS-CoV-2 by taking into consideration the strong genetic similarities of the 2003 epidemic SARS-CoV. Recent studies are investigating the repurposing of US FDA-approved drugs as there is no available vaccine yet with many attempts under clinical evaluation. Several antivirals, antimalarials and immunomodulators that have shown activity against SARS-CoV and Middle East coronavirus respiratory syndromes are being evaluated. In particular, hydroxychloroquine, remdesivir, favipiravir, arbidol, tocilizumab and bevacizumab have shown promising results. The main aim of this review is to provide an overview of this pandemic and where we currently stand.", "qid": 5, "docid": "3framq60", "rank": 61, "score": 0.8492310047149658}, {"content": "Title: Chloroquine and COVID-19 - a potential game changer? Content: The novel coronavirus SARS-CoV-2, causing the disease COVID-19, first emerged in Wuhan, China in December 2019 and has now spread to 203 countries or territories, infected over 2 million people and caused over 133,000 deaths. There is an urgent need for specific treatments. One potential treatment is chloroquine and its derivatives, including hydroxychloroquine, which have both antiviral and anti-inflammatory effects. These compounds are effective against SARS-CoV-2 in vitro, but in vivo data are lacking. Although some encouraging outcomes have been reported, and these results have been received enthusiastically, we recommend careful and critical evaluation of current evidence only when all methods and data are available for peer review. Chloroquine is safe and cheap. However, further evidence from coordinated multicentre trials is required before it can be confidently said whether it is effective against the current pandemic.", "qid": 5, "docid": "zrx4x5sa", "rank": 62, "score": 0.849087119102478}, {"content": "Title: Research progress on repositioning drugs and specific therapeutic drugs for SARS-CoV-2 Content: SARS-CoV-2 has been widely spread around the world and COVID-19 was declared a global pandemic by the World Health Organization. Limited clinically effective antiviral drugs are available now. The development of anti-SARS-CoV-2 drugs has become an urgent work worldwide. At present, potential therapeutic targets and drugs for SARS-CoV-2 are continuously reported, and many repositioning drugs are undergoing extensive clinical research, including remdesivir and chloroquine. On the other hand, structures of many important viral target proteins and host target proteins, including that of RdRp and Mpro were constantly reported, which greatly promoted structure-based drug design. This paper summarizes the current research progress and challenges in the development of anti-SARS-CoV-2 drugs, and proposes novel short-term and long-term drug research strategies.", "qid": 5, "docid": "xb5p25gk", "rank": 63, "score": 0.8490394949913025}, {"content": "Title: Should lCU COVID-19 patients empirically receive therapeutic doses of anticoagulant? Content: In spite of many ongoing attempts to repurpose existing antivirals, no drugs have emerged yet with the desirable activity against SARS-CoV-2. Hydroxychloroquine, lopinavir/ritonavir, remdesivir, umifenovir, favipiravir, ribavirin and beta-interferon-1 gave rise to variable but still inconsistent proof of clinical efficacy in the treatment of COVID-19. Pathogenetic studies have shown significant differences between commonly defined viral pneumonia and COVID-19 pulmonary disease. In severe forms, immune/inflammatory alterations reminiscent of disease forms like Macrophage Activation Syndrome (MAS) have been described, and therapeutic options other than anti-infective have been proposed and implemented, such as anti-inflammatory and anticoagulative agents. The thrombotic phenomena described in the pulmonary vascular bed of patients with severe COVID-19 suggest the administration of low-molecular weight heparin (LMWH) as standard measure in hospitalized patients with COVID-19.", "qid": 5, "docid": "9hdo3jpb", "rank": 64, "score": 0.8488500118255615}, {"content": "Title: Comparative analysis of antiviral efficacy of FDA-approved drugs against SARS-CoV-2 in human lung cells: Nafamostat is the most potent antiviral drug candidate Content: Drug repositioning represents an effective way to control the current COVID-19 pandemic. Previously, we identified 24 FDA-approved drugs which exhibited substantial antiviral effect against SARS-CoV-2 in Vero cells. Since antiviral efficacy could be altered in different cell lines, we developed an antiviral screening assay with human lung cells, which is more appropriate than Vero cell. Comparative analysis of antiviral activities revealed that nafamostat is the most potent drug in human lung cells (IC50 = 0.0022\u00b5M).", "qid": 5, "docid": "4pywvaxi", "rank": 65, "score": 0.8487776517868042}, {"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": 66, "score": 0.8486015796661377}, {"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": 67, "score": 0.8485978841781616}, {"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": 68, "score": 0.8485710024833679}, {"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": 69, "score": 0.8484982848167419}, {"content": "Title: Dermatological therapies with relevance to COVID-19 Content: Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) is a novel single-stranded RNA virus that has gripped humanity all over. It affects primarily the respiratory system, but is not limited to it, causing widespread involvement of many organ systems. The cases are still rising at an exponential rate and manifold trials are on to test different agents with the hope for potential limitation of spread and control of symptoms. Various classes of drugs have been tried; some with moderate success while many are yet to be proven to be of definite benefit. We have observed that the drugs used in dermatology practice are featured in more than a few of such studies. Here, we wish to highlight the ones that we are familiar with, which has featured at some point, in the management of this very challenging pandemic.", "qid": 5, "docid": "a2hd6d7s", "rank": 70, "score": 0.8483833074569702}, {"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": 5, "docid": "aexlwq79", "rank": 71, "score": 0.8473716974258423}, {"content": "Title: The pharmacological development of direct acting agents for emerging needed therapy against SARS-CoV-2 Content: Recently, the SARS-CoV-2 was quickly identified as the causal pathogen leading to the outbreak of severe acute respiratory syndrome-like illness all over the world. As the SARS-CoV-2 infection pandemic proceeds, many efforts are being dedicated to the development of diverse treatment strategies. Increasing evidence showed potential therapeutic agents directly acting against SARS-CoV-2 virus, such as interferon, RNA-dependent RNA polymerase inhibitors, protease inhibitors, viral entry blockers, neuraminidase inhibitor, vaccine, antibody agent targeting the SARS-CoV-2 RNA genome, natural killer cells and nucleocytoplasmic trafficking inhibitor. To date, several direct anti-SARS-CoV-2 agents have demonstrated promising in vitro and clinical efficacy. This article reviews the current and future development of direct acting agents against SARS-CoV-2.", "qid": 5, "docid": "el7d8lck", "rank": 72, "score": 0.847321629524231}, {"content": "Title: The pharmacological development of direct acting agents for emerging needed therapy against SARS-CoV-2. Content: Recently, the SARS-CoV-2 was quickly identified as the causal pathogen leading to the outbreak of severe acute respiratory syndrome-like illness all over the world. As the SARS-CoV-2 infection pandemic proceeds, many efforts are being dedicated to the development of diverse treatment strategies. Increasing evidence showed potential therapeutic agents directly acting against SARS-CoV-2 virus, such as interferon, RNA-dependent RNA polymerase inhibitors, protease inhibitors, viral entry blockers, neuraminidase inhibitor, vaccine, antibody agent targeting the SARS-CoV-2 RNA genome, natural killer cells and nucleocytoplasmic trafficking inhibitor. To date, several direct anti-SARS-CoV-2 agents have demonstrated promising in vitro and clinical efficacy. This article reviews the current and future development of direct acting agents against SARS-CoV-2.", "qid": 5, "docid": "7ln7p715", "rank": 73, "score": 0.847321629524231}, {"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": 74, "score": 0.8472592830657959}, {"content": "Title: Compounds with Therapeutic Potential against Novel Respiratory 2019 Coronavirus Content: Currently, the expansion of the novel human respiratory coronavirus (known as SARS-CoV-2 [severe acute respiratory syndrome coronavirus 2], COVID-2019 [coronavirus disease 2019], or 2019-nCoV [2019 novel coronavirus]) has stressed the need for therapeutic alternatives to alleviate and stop this new epidemic. The previous epidemics of infections by high-morbidity human coronaviruses, such as SARS-CoV in 2003 and the Middle East respiratory syndrome coronavirus (MERS-CoV) in 2012, prompted the characterization of compounds that could be potentially active against the currently emerging novel coronavirus, SARS-CoV-2. The most promising compound is remdesivir (GS-5734), a nucleotide analog prodrug currently in clinical trials for treating Ebola virus infections. Remdesivir inhibited the replication of SARS-CoV and MERS-CoV in tissue cultures, and it displayed efficacy in nonhuman animal models. In addition, a combination of the human immunodeficiency virus type 1 (HIV-1) protease inhibitors lopinavir/ritonavir and interferon beta (LPV/RTV-IFN-\u00df) was shown to be effective in patients infected with SARS-CoV. LPV/RTV-IFN-\u00df also improved clinical parameters in marmosets and mice infected with MERS-CoV. Remarkably, the therapeutic efficacy of remdesivir appeared to be superior to that of LPV/RTV-IFN-\u00df against MERS-CoV in a transgenic humanized mouse model. The relatively high mortality rates associated with these three novel human coronavirus infections, SARS-CoV, MERS-CoV, and SARS-CoV-2, have suggested that proinflammatory responses might play a role in the pathogenesis. It remains unknown whether the generated inflammatory state should be targeted. Therapeutics that target the coronavirus alone might not be able to reverse highly pathogenic infections. This minireview aims to provide a summary of therapeutic compounds that have shown potential in fighting SARS-CoV-2 infections.", "qid": 5, "docid": "anen3dor", "rank": 75, "score": 0.8470473885536194}, {"content": "Title: Current Insight into the Novel Coronavirus Disease 2019 (COVID-19) Content: SARS-CoV-2 is a novel strain of coronavirus that has not been previously identified in humans. It has been declared a pandemic and has infected at least 1,844,683 individuals and caused 117,021 deaths as of 14th April 2020. Transmission among humans occurs via close contact with an infected individual that produces respiratory droplets. Patients have been shown to undergo acute respiratory distress syndrome, which is defined as cytokine storm. The diagnosis relies on detection of nucleic acid, IgG/IgM antibodies, and a chest radiograph of the suspected individuals. The genome of SARS-CoV-2 is similar to other coronaviruses that comprise of ten open reading frames (ORFs). SARS-CoV-2 spike protein exhibits higher affinity to ACE2 receptor as compared with SARS-CoV. Repurposing drugs like favipiravir, remdesivir, chloroquine, and TMPRSS2 protease inhibitors have been shown to be effective for the treatment of COVID-19. Personal protective measures should be followed to prevent SARS-CoV-2 infection. In addition, a clinical trial of SARS-CoV-2 vaccine, mRNA-1273, has been started. This chapter provides a glimpse of advancements made in the area of SARS-CoV-2 infection by proving recent clinical and research trials in the field.", "qid": 5, "docid": "zv0ysi8m", "rank": 76, "score": 0.847027063369751}, {"content": "Title: Potenciales efectos pro-arr\u00edtmicos de la farmacoterapia contra SARS-CoV-2 Content: The pandemic caused by the SARS-COV-2 or COVID-19 virus has been a global challenge given its high rate of transmission and lack of effective therapy or vaccine This scenario has led to the use of various drugs that have demonstrated a potential effect against the virus in vitro However, time has not been enough to properly evaluate their clinical effectiveness The use of chloroquine/hydroxychloroquine, azithromycin and antiviral treatment and has been proposed by various groups, supported by in-vitro studies and limited patient series, without the adequate scientific rigor that precedes drug prescription Although it may represent the only hope for many patients, it is important to know the main adverse effects associated with the use of these drugs and to better select patients who may benefit from them", "qid": 5, "docid": "q11bm6px", "rank": 77, "score": 0.8468494415283203}, {"content": "Title: Repositioning of 8565 Existing Drugs for COVID-19 Content: The coronavirus disease 2019 (COVID-19) pandemic caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) has infected over 7.1 million people and led to over 0.4 million deaths. Currently, there is no specific anti-SARS-CoV-2 medication. New drug discovery typically takes more than 10 years. Drug repositioning becomes one of the most feasible approaches for combating COVID-19. This work curates the largest available experimental data set for SARS-CoV-2 or SARS-CoV 3CL (main) protease inhibitors. On the basis of this data set, we develop validated machine learning models with relatively low root-mean-square error to screen 1553 FDA-approved drugs as well as another 7012 investigational or off-market drugs in DrugBank. We found that many existing drugs might be potentially potent to SARS-CoV-2. The druggability of many potent SARS-CoV-2 3CL protease inhibitors is analyzed. This work offers a foundation for further experimental studies of COVID-19 drug repositioning.", "qid": 5, "docid": "78vo1jkc", "rank": 78, "score": 0.8467218279838562}, {"content": "Title: In Silico Evaluation of the Effectivity of Approved Protease Inhibitors against the Main Protease of the Novel SARS-CoV-2 Virus Content: The coronavirus disease, COVID-19, caused by the novel coronavirus SARS-CoV-2, which first emerged in Wuhan, China and was made known to the World in December 2019 turned into a pandemic causing more than 126,124 deaths worldwide up to April 16th, 2020. It has 79.5% sequence identity with SARS-CoV-1 and the same strategy for host cell invasion through the ACE-2 surface protein. Since the development of novel drugs is a long-lasting process, researchers look for effective substances among drugs already approved or developed for other purposes. The 3D structure of the SARS-CoV-2 main protease was compared with the 3D structures of seven proteases, which are drug targets, and docking analysis to the SARS-CoV-2 protease structure of thirty four approved and on-trial protease inhibitors was performed. Increased 3D structural similarity between the SARS-CoV-2 main protease, the HCV protease and &#945;-thrombin was found. According to docking analysis the most promising results were found for HCV protease, DPP-4, &#945;-thrombin and coagulation Factor Xa known inhibitors, with several of them exhibiting estimated free binding energy lower than -8.00 kcal/mol and better prediction results than reference compounds. Since some of the compounds are well-tolerated drugs, the promising in silico results may warrant further evaluation for viral anticipation. DPP-4 inhibitors with anti-viral action may be more useful for infected patients with diabetes, while anti-coagulant treatment is proposed in severe SARS-CoV-2 induced pneumonia.", "qid": 5, "docid": "sdx64c1k", "rank": 79, "score": 0.8463553190231323}, {"content": "Title: Immunoglobulin fragment F(ab\u2019)(2) against RBD potently neutralizes SARS-CoV-2 in vitro Content: COVID-19, which is caused by the emerging human coronavirus SARS-CoV-2, has become a global pandemic that poses a serious threat to human health. To date, no vaccines or specific antiviral drugs have been approved for the treatment of this disease in clinic. Herein, therapeutic antibodies for SARS-CoV-2 were obtained from hyperimmune equine plasma. First, a recombinant SARS-CoV-2 spike protein receptor-binding domain (RBD) was obtained in gram-level quantities through high-cell density fermentation of Chinese hamster ovary cells. Then, the binding of the RBD to the SARS-CoV-2 receptor, human angiotensin-converting enzyme 2, was verified by several biochemical methods. The efficacy of the RBD in triggering antibody response in vivo was subsequently tested in both mice and equines, and the results showed that the RBD triggered high-titer neutralizing antibody production in vivo. Immunoglobulin F(ab\u2019)(2) fragments were prepared from equine antisera via removal of the Fc region from the immunoglobulins. Finally, a neutralization test with live virus demonstrated that RBD-specific F(ab\u2019)(2) inhibited SARS-CoV-2 with an EC(50) of 0.07 \u03bcg/ml and an EC(80) of 0.18 \u03bcg/ml, showing a potent inhibitory effect on SARS-CoV-2. These results highlight RBD-specific equine immunoglobulin F(ab\u2019)(2) fragment as a candidate for the treatment of SARS-CoV-2.", "qid": 5, "docid": "w33nspfl", "rank": 80, "score": 0.846206784248352}, {"content": "Title: Potential inhibitors of the interaction between ACE2 and SARS-CoV-2 (RBD), to develop a drug Content: AIMS: The COVID-19 disease caused by the SARS-CoV-2 has become a pandemic and there are no effective treatments that reduce the contagion. It is urgent to propose new treatment options, which are more effective in the interaction between viruses and cells. In this study was to develop a search for new pharmacological compounds against the angiotensin-converting enzyme 2 (ACE2), to inhibit the interaction with SARS-CoV-2. MATERIALS AND METHODS: Docking, virtual screening using almost 500,000 compounds directed to interact in the region between the residues (Gln24, Asp30, His34, Tyr41, Gln42, Met82, Lys353, and Arg357) in ACE2. The average of \u0394G(binding), the standard deviation value and the theoretical toxicity from compounds were analyzed. KEY FINDINGS: 20 best compounds directed to interact in ACE2 with a high probability to be safe in humans, validated by web servers of prediction of ADME and toxicity (ProTox-II and PreADMET), to difficult the interaction between ACE2 and region binding domain (RBD) of SARS-CoV-2. SIGNIFICANCE: In this study, 20 compounds were determined by docking focused on the region of interaction between ACE2 and RBD of SARS-CoV-2 was carried out. The compounds are publicly available to validate the effect in in vitro tests.", "qid": 5, "docid": "1c4vqaqr", "rank": 81, "score": 0.8461030125617981}, {"content": "Title: Potential inhibitors of the interaction between ACE2 and SARS-CoV-2 (RBD), to develop a drug Content: AIMS: The COVID-19 disease caused by the SARS-CoV-2 has become a pandemic and there are no effective treatments that reduce the contagion. It is urgent to propose new treatment options, which are more effective in the interaction between viruses and cells. In this study was to develop a search for new pharmacological compounds against the angiotensin-converting enzyme 2 (ACE2), to inhibit the interaction with SARS-CoV-2. MATERIALS AND METHODS: Docking, virtual screening using almost 500,000 compounds directed to interact in the region between the residues (Gln24, Asp30, His34, Tyr41, Gln42, Met82, Lys353, and Arg357) in ACE2. The average of &#916;Gbinding, the standard deviation value and the theoretical toxicity from compounds were analyzed. KEY FINDINGS: 20 best compounds directed to interact in ACE2 with a high probability to be safe in humans, validated by web servers of prediction of ADME and toxicity (ProTox-II and PreADMET), to difficult the interaction between ACE2 and region binding domain (RBD) of SARS-CoV-2. SIGNIFICANCE: In this study, 20 compounds were determined by docking focused on the region of interaction between ACE2 and RBD of SARS-CoV-2 was carried out. The compounds are publicly available to validate the effect in in vitro tests.", "qid": 5, "docid": "qotug475", "rank": 82, "score": 0.8460772633552551}, {"content": "Title: Combined prophylactic and therapeutic use maximizes hydroxychloroquine anti-SARS-CoV-2 effects in vitro Content: While the SARS-CoV-2 pandemic is hardly hitting the world, it is of extreme importance that significant in vitro observations guide the quick set up of clinical trials. In this study, we evidence that the anti-SARS-CoV2 activity of a clinically achievable hydroxychloroquine concentration is maximized only when administered before and after the infection of Vero E6 cells. This strongly suggests that only a combined prophylactic and therapeutic use of hydroxychloroquine may be effective in limiting viral replication in patients.", "qid": 5, "docid": "fhy2z49t", "rank": 83, "score": 0.8459858894348145}, {"content": "Title: COVID-19 Drug Discovery Using Intensive Approaches Content: Since the infectious disease caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) was reported in China during December 2019, the coronavirus disease 2019 (COVID-19) has spread on a global scale, causing the World Health Organization (WHO) to issue a warning. While novel vaccines and drugs that target SARS-CoV-2 are under development, this review provides information on therapeutics which are under clinical trials or are proposed to antagonize SARS-CoV-2. Based on the information gained from the responses to other RNA coronaviruses, including the strains that cause severe acute respiratory syndrome (SARS)-coronaviruses and Middle East respiratory syndrome (MERS), drug repurposing might be a viable strategy. Since several antiviral therapies can inhibit viral replication cycles or relieve symptoms, mechanisms unique to RNA viruses will be important for the clinical development of antivirals against SARS-CoV-2. Given that several currently marketed drugs may be efficient therapeutic agents for severe COVID-19 cases, they may be beneficial for future viral pandemics and other infections caused by RNA viruses when standard treatments are unavailable.", "qid": 5, "docid": "64ff1ksc", "rank": 84, "score": 0.845941424369812}, {"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": 5, "docid": "pgxew3yk", "rank": 85, "score": 0.8458406925201416}, {"content": "Title: In Silico Evaluation of the Effectivity of Approved Protease Inhibitors against the Main Protease of the Novel SARS-CoV-2 Virus Content: The coronavirus disease, COVID-19, caused by the novel coronavirus SARS-CoV-2, which first emerged in Wuhan, China and was made known to the World in December 2019 turned into a pandemic causing more than 126,124 deaths worldwide up to April 16th, 2020. It has 79.5% sequence identity with SARS-CoV-1 and the same strategy for host cell invasion through the ACE-2 surface protein. Since the development of novel drugs is a long-lasting process, researchers look for effective substances among drugs already approved or developed for other purposes. The 3D structure of the SARS-CoV-2 main protease was compared with the 3D structures of seven proteases, which are drug targets, and docking analysis to the SARS-CoV-2 protease structure of thirty four approved and on-trial protease inhibitors was performed. Increased 3D structural similarity between the SARS-CoV-2 main protease, the HCV protease and \u03b1-thrombin was found. According to docking analysis the most promising results were found for HCV protease, DPP-4, \u03b1-thrombin and coagulation Factor Xa known inhibitors, with several of them exhibiting estimated free binding energy lower than \u22128.00 kcal/mol and better prediction results than reference compounds. Since some of the compounds are well-tolerated drugs, the promising in silico results may warrant further evaluation for viral anticipation. DPP-4 inhibitors with anti-viral action may be more useful for infected patients with diabetes, while anti-coagulant treatment is proposed in severe SARS-CoV-2 induced pneumonia.", "qid": 5, "docid": "teahway7", "rank": 86, "score": 0.8456985950469971}, {"content": "Title: Potential pro-arrhythmic effects of pharmacotherapy against SARS-CoV-2. Content: The pandemic caused by the SARS-COV-2 or COVID-19 virus has been a global challenge given its high rate of transmission and lack of effective therapy or vaccine. This scenario has led to the use of various drugs that have demonstrated a potential effect against the virus in vitro. However, time has not been enough to properly evaluate their clinical effectiveness. The use of chloroquine/hydroxychloroquine, azithromycin and antiviral treatment and has been proposed by various groups, supported by in-vitro studies and limited patient series, without the adequate scientific rigor that precedes drug prescription. Although it may represent the only hope for many patients, it is important to know the main adverse effects associated with the use of these drugs and to better select patients who may benefit from them.", "qid": 5, "docid": "vx0bqbpb", "rank": 87, "score": 0.8455957770347595}, {"content": "Title: Potenciales efectos pro-arr\u00edtmicos de la farmacoterapia contra SARS-CoV-2./ Potential pro-arrhythmic effects of pharmacotherapy against SARS-CoV-2 Content: The pandemic caused by the SARS-COV-2 or COVID-19 virus has been a global challenge given its high rate of transmission and lack of effective therapy or vaccine. This scenario has led to the use of various drugs that have demonstrated a potential effect against the virus in vitro. However, time has not been enough to properly evaluate their clinical effectiveness. The use of chloroquine/hydroxychloroquine, azithromycin and antiviral treatment and has been proposed by various groups, supported by in-vitro studies and limited patient series, without the adequate scientific rigor that precedes drug prescription. Although it may represent the only hope for many patients, it is important to know the main adverse effects associated with the use of these drugs and to better select patients who may benefit from them.", "qid": 5, "docid": "wt2lshzo", "rank": 88, "score": 0.8455957174301147}, {"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": 89, "score": 0.8454481363296509}, {"content": "Title: Compounds with Therapeutic Potential against Novel Respiratory 2019 Coronavirus Content: Currently, the expansion of the novel human respiratory coronavirus (known as SARS-CoV-2 [severe acute respiratory syndrome coronavirus 2], COVID-2019 [coronavirus disease 2019], or 2019-nCoV [2019 novel coronavirus]) has stressed the need for therapeutic alternatives to alleviate and stop this new epidemic. The previous epidemics of infections by high-morbidity human coronaviruses, such as SARS-CoV in 2003 and the Middle East respiratory syndrome coronavirus (MERS-CoV) in 2012, prompted the characterization of compounds that could be potentially active against the currently emerging novel coronavirus, SARS-CoV-2. The most promising compound is remdesivir (GS-5734), a nucleotide analog prodrug currently in clinical trials for treating Ebola virus infections. Remdesivir inhibited the replication of SARS-CoV and MERS-CoV in tissue cultures, and it displayed efficacy in nonhuman animal models. In addition, a combination of the human immunodeficiency virus type 1 (HIV-1) protease inhibitors lopinavir/ritonavir and interferon beta (LPV/RTV\u2013IFN-\u03b2) was shown to be effective in patients infected with SARS-CoV. LPV/RTV\u2013IFN-\u03b2 also improved clinical parameters in marmosets and mice infected with MERS-CoV. Remarkably, the therapeutic efficacy of remdesivir appeared to be superior to that of LPV/RTV\u2013IFN-\u03b2 against MERS-CoV in a transgenic humanized mouse model. The relatively high mortality rates associated with these three novel human coronavirus infections, SARS-CoV, MERS-CoV, and SARS-CoV-2, have suggested that proinflammatory responses might play a role in the pathogenesis. It remains unknown whether the generated inflammatory state should be targeted. Therapeutics that target the coronavirus alone might not be able to reverse highly pathogenic infections. This minireview aims to provide a summary of therapeutic compounds that have shown potential in fighting SARS-CoV-2 infections.", "qid": 5, "docid": "nz8qvuw6", "rank": 90, "score": 0.8454136252403259}, {"content": "Title: Current pharmacological treatments for COVID-19: What's next? Content: Since December 2019 SARS-Cov-2 was found responsible for the disease COVID-19, which has spread worldwide. No specific therapies/vaccines are yet available for the treatment of COVID-19. Drug repositioning may offer a strategy and a number of drugs have been repurposed, including lopinavir/ritonavir, remdesivir, favipiravir and tocilizumab. This paper describes the main pharmacological properties of such drugs administered to patients with COVID-19, focusing on their antiviral, immune-modulatory and/or anti-inflammatory actions. Where available, data from clinical trials involving patients with COVID-19 are reported. Preliminary clinical trials seem to support their benefit. However, such drugs in COVID-19 patients have peculiar safety profiles. Thus, adequate clinical trials are necessary for these compounds. Nevertheless, while waiting for effective preventive measures i.e. vaccines, many clinical trials on drugs belonging to different therapeutic classes are currently underway. Their results will help us in defining the best way to treat COVID-19 and reducing its symptoms and complications.", "qid": 5, "docid": "q2debvsi", "rank": 91, "score": 0.845356822013855}, {"content": "Title: Sensitivity of SARS/MERS CoV to interferons and other drugs based on achievable serum concentrations in humans. Content: A novel coronavirus (MERS-CoV) related to SARS-CoV recently emerged in the Middle East causing more than 400 deaths with a mortality rate of about 30%, much higher than SARS-CoV. Both viruses target epithelial cells in the respiratory tract, although utilizing different cellular receptors. Because of the sporadic nature of the MERS outbreak and difficulty in collecting randomized, controlled clinical data, the objective of this review was to focus on published in vitro and in vivo drug sensitivity data using both cell lines and available animal models of SARS/MERS CoV infection. Determination of drug activity was based on achievable serum levels in humans relative to in vitro IC50 (50% inhibitory concentration) or EC50 (50% effective concentration) drug concentrations. The most active drugs against SARS/MERS CoV at clinically achievable serum levels were type I interferons and a TLR3 agonist, interferon inducer/activator.", "qid": 5, "docid": "u0kyyyb7", "rank": 92, "score": 0.8452559113502502}, {"content": "Title: Coagulation modifiers targeting SARS-CoV-2 main protease Mpro for COVID-19 treatment: an in silico approach Content: Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection depends on viral polyprotein processing, catalysed by the main proteinase (Mpro). The solution of the SARS-CoV-2 Mpro structure allowed the investigation of potential inhibitors. This work aims to provide first evidences of the applicability of commercially approved drugs to treat coronavirus disease-19 (COVID-19). We screened 4,334 compounds to found potential inhibitors of SARS-CoV-2 replication using an in silico approach. Our results evidenced the potential use of coagulation modifiers in COVID-19 treatment due to the structural similarity of SARS-CoV-2 Mpro and human coagulation factors thrombin and Factor Xa. Further in vitro and in vivo analysis are needed to corroborate these results.", "qid": 5, "docid": "jxha9b65", "rank": 93, "score": 0.8450415730476379}, {"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": 5, "docid": "yzb8pouz", "rank": 94, "score": 0.8449132442474365}, {"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": 5, "docid": "h2xn9n20", "rank": 95, "score": 0.8449132442474365}, {"content": "Title: Angiotension-converting enzyme inhibitors and angiotensin-receptor blockers are not associated with increased risk of SARS-CoV-2 infection Content: In a large Israeli dataset of 14 520 individuals tested for SARS-CoV-2, angiotension-converting enzyme inhibitors and angiotensin-receptor blockers were not found to be associated with increased SARS-CoV-2 infection after adjusting for major confounders. Patients on these medications should not stop their medication prophylactically.", "qid": 5, "docid": "amgkcxaw", "rank": 96, "score": 0.8448763489723206}, {"content": "Title: A Potently Neutralizing Antibody Protects Mice against SARS-CoV-2 Infection Content: Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) is responsible for millions of infections and hundreds of thousands of deaths globally. There are no widely available licensed therapeutics against SARS-CoV-2, highlighting an urgent need for effective interventions. The virus enters host cells through binding of a receptor-binding domain within its trimeric spike glycoprotein to human angiotensin-converting enzyme 2. In this article, we describe the generation and characterization of a panel of murine mAbs directed against the receptor-binding domain. One mAb, 2B04, neutralized wild-type SARS-CoV-2 in vitro with remarkable potency (half-maximal inhibitory concentration of <2 ng/ml). In a murine model of SARS-CoV-2 infection, 2B04 protected challenged animals from weight loss, reduced lung viral load, and blocked systemic dissemination. Thus, 2B04 is a promising candidate for an effective antiviral that can be used to prevent SARS-CoV-2 infection.", "qid": 5, "docid": "frmc8bi5", "rank": 97, "score": 0.8448508977890015}, {"content": "Title: A Potently Neutralizing Antibody Protects Mice against SARS-CoV-2 Infection. Content: Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) is responsible for millions of infections and hundreds of thousands of deaths globally. There are no widely available licensed therapeutics against SARS-CoV-2, highlighting an urgent need for effective interventions. The virus enters host cells through binding of a receptor-binding domain within its trimeric spike glycoprotein to human angiotensin-converting enzyme 2. In this article, we describe the generation and characterization of a panel of murine mAbs directed against the receptor-binding domain. One mAb, 2B04, neutralized wild-type SARS-CoV-2 in vitro with remarkable potency (half-maximal inhibitory concentration of <2 ng/ml). In a murine model of SARS-CoV-2 infection, 2B04 protected challenged animals from weight loss, reduced lung viral load, and blocked systemic dissemination. Thus, 2B04 is a promising candidate for an effective antiviral that can be used to prevent SARS-CoV-2 infection.", "qid": 5, "docid": "bwzcei28", "rank": 98, "score": 0.8448508977890015}, {"content": "Title: CNS Penetration Ability: A Critical Factor for Drugs in the Treatment of SARS-CoV-2 Brain Infection Content: Now, it has been evidenced that Covid19 (SARS-CoV-2) infects the brain tissues. Along with this, a challenge has been raised for research professionals to find effective drugs for its treatment since the recent spread of this virus from Wuhan, China. Targeting the treatment of brain infection, it has also been a challenge that the clinical drug should have good CNS penetration ability to cross the blood-brain barrier.", "qid": 5, "docid": "9orilobk", "rank": 99, "score": 0.8448185920715332}, {"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": 5, "docid": "8cvjsisw", "rank": 100, "score": 0.8447734117507935}]}
{"query": "what types of rapid testing for Covid-19 have been developed?", "hits": [{"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": 1, "score": 0.879018247127533}, {"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": 2, "score": 0.8718780875205994}, {"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": 3, "score": 0.8716321587562561}, {"content": "Title: Real-time PCR-based SARS-CoV-2 detection in Canadian laboratories Content: With emergence of pandemic COVID-19, rapid and accurate diagnostic testing is essential. This study compared laboratory-developed tests (LDTs) used for the detection of SARS-CoV-2 in Canadian hospital and public health laboratories, and some commercially available real-time RT-PCR assays. Overall, analytical sensitivities were equivalent between LDTs and most commercially available methods.", "qid": 6, "docid": "kjol6sgh", "rank": 4, "score": 0.8691369295120239}, {"content": "Title: Real-time PCR-based SARS-CoV-2 detection in Canadian Laboratories Content: With emergence of pandemic COVID-19, rapid and accurate diagnostic testing is essential. This study compared laboratory-developed tests (LDTs) used for the detection of SARS-CoV-2 in Canadian hospital and public health laboratories, and some commercially available real-time RT-PCR assays. Overall, analytical sensitivities were equivalent between LDTs and most commercially available methods.", "qid": 6, "docid": "bqbj660w", "rank": 5, "score": 0.8691369295120239}, {"content": "Title: \u00bfConocemos las propiedades diagn\u00f3sticas de las pruebas usadas en COVID-19? Una revisi\u00f3n r\u00e1pida de la literatura recientemente publicada./ \u00bfConocemos las propiedades diagn\u00f3sticas de las pruebas usadas en COVID-19? Una revisi\u00f3n r\u00e1pida de la literatura recientemente publicada./ Do we know the diagnostic properties of the tests used in COVID-19? A rapid review of recently published literature Content: COVID-19 has brought death and disease to large parts of the world. Governments must deploy strategies to screen the population and subsequently isolate the suspect cases. Diagnostic testing is critical for epidemiological surveillance, but the accuracy (sensitivity and specificity) and clinical utility (impact on health outcomes) of the current diagnostic methods used for SARS-CoV-2 detection are not known. I ran a quick search in PubMed/MEDLINE to find studies on laboratory diagnostic tests and rapid viral diagnosis. After running the search strategies, I found 47 eligible articles that I discuss in this review, commenting on test characteristics and limitations. I did not find any papers that report on the clinical utility of the tests currently used for COVID-19 detection, meaning that we are fighting a battle without proper knowledge of the proportion of false negatives that current testing is resulting in. This shortcoming should not be overlooked as it might hamper national efforts to contain the pandemic through testing community-based suspect cases.", "qid": 6, "docid": "gzrjca1l", "rank": 6, "score": 0.8685977458953857}, {"content": "Title: Do we know the diagnostic properties of the tests used in COVID-19? A rapid review of recently published literature. Content: COVID-19 has brought death and disease to large parts of the world. Governments must deploy strategies to screen the population and subsequently isolate the suspect cases. Diagnostic testing is critical for epidemiological surveillance, but the accuracy (sensitivity and specificity) and clinical utility (impact on health outcomes) of the current diagnostic methods used for SARS-CoV-2 detection are not known. I ran a quick search in PubMed/MEDLINE to find studies on laboratory diagnostic tests and rapid viral diagnosis. After running the search strategies, I found 47 eligible articles that I discuss in this review, commenting on test characteristics and limitations. I did not find any papers that report on the clinical utility of the tests currently used for COVID-19 detection, meaning that we are fighting a battle without proper knowledge of the proportion of false negatives that current testing is resulting in. This shortcoming should not be overlooked as it might hamper national efforts to contain the pandemic through testing community-based suspect cases.", "qid": 6, "docid": "vn0xu1cn", "rank": 7, "score": 0.8685977458953857}, {"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": 8, "score": 0.865234375}, {"content": "Title: Combining Point-of-Care Diagnostics and Internet of Medical Things (IoMT) to Combat the COVID-19 Pandemic Content: The current standard testing method for screening coronavirus disease 2019 (COVID-19) is through reverse real-time PCR assay (rRT-PCR), a common molecular-based assay that requires an average of four to six hours to provide results [...].", "qid": 6, "docid": "vy0x9hvr", "rank": 9, "score": 0.8620830774307251}, {"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": 10, "score": 0.8598853349685669}, {"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": 11, "score": 0.8598853349685669}, {"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": 12, "score": 0.8591407537460327}, {"content": "Title: Diagnostic Performance of a Rapid Point of Care Test for SARS-CoV-2 in an Urban ED Setting Content: The ability to rapidly and accurately identify a patient's COVID-19 status has had significant impact on emergency departments (ED) and health systems globally. Since the identification of SARS-CoV-2 illness in the United States, there has been rapid development in patient testing capacity following initial challenges including sparse availability. This was made possible by increasing availability of diagnostic molecular tests in several formats, from laboratory based traditional, RT-PCR methods to near patient testing rapid point of care PCR tests.", "qid": 6, "docid": "onhiptn7", "rank": 13, "score": 0.8576509952545166}, {"content": "Title: A Single and Two-Stage, Closed-Tube, Molecular Test for the 2019 Novel Coronavirus (COVID-19) at Home, Clinic, and Points of Entry. Content: The 2019 novel coronavirus (COVID-19) is a newly emerged strain that has never been found in humans before. At present, the laboratory-based reverse transcription-polymerase chain reaction (RT-PCR) is the main method to confirm COVID-19 infection. The intensification of the COVID-19 epidemic overwhelms limited clinical resources in particular, but not only, in developing countries, resulting in many patients not being tested for the infection and in large queues of potentially infected individuals waiting to be tested while providing a breeding ground for the disease. We describe here a rapid, highly sensitive, point-of-care, molecular test amenable for use at home, in the clinic, and at points of entry by minimally trained individuals and with minimal instrumentation. Our test is based on loop mediated isothermal amplification (COVID-19 LAMP) and for higher sensitivity on nested nucleic acid, two stage isothermal amplification (COVID-19 Penn-RAMP). Both tests can be carried out in closed tubes with either fluorescence or colorimetric (e.g., leuco crystal violet LCV) detection. COVID-19 LAMP performs on par with COVID-19 RT-PCR. COVID-19 RAMP has 10 fold better sensitivity than COVID-19 LAMP and COVID-19 RT-PCR when testing purified targets and 100 times better sensitivity than COVID-19 LAMP and COVID-19 RT-PCR when testing rapidly prepared sample mimics. Due to fortunate scarcity of COVID-19 infections in the USA, we were not able to test our assays and methods with patient samples. We hope that such tests will be carried out by colleagues in impacted countries. Our Closed-Tube Penn-RAMP has the potential to significantly reduce false negatives while being amenable to use with minimal instrumentation and training.", "qid": 6, "docid": "7fgjoqgb", "rank": 14, "score": 0.8552224636077881}, {"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": 15, "score": 0.8551684021949768}, {"content": "Title: In Vitro Diagnostic Assays for COVID-19: Recent Advances and Emerging Trends Content: There have been tremendous advances in in vitro diagnostic (IVD) assays for coronavirus disease 2019 (COVID-19) caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). The main IVD assays used for COVID-19 employ real-time reverse transcriptase polymerase chain reaction (RT-PCR) that takes a few hours. But the assay duration has been shortened to 45 min by Cepheid. Of interest is the point-of-care (POC) molecular assay by Abbott that decreased the assay duration to just 5 min. Most molecular tests have been approved by the United States Food and Drug Administration (FDA) under emergency use authorization (EUA) and are Conformit\u00e9 Europ\u00e9enne (CE) marked. A wide range of serology immunoassays (IAs) have also been developed that complement the molecular assays for the diagnosis of COVID-19. The most prominent IAs are automated chemiluminescent IA (CLIA), manual ELISA, and rapid lateral flow IA (LFIA), which detect the immunoglobulin M (IgM) and immunoglobulin G (IgG) produced in persons in response to SARS-CoV-2 infection. The ongoing research efforts and advances in complementary technologies will pave the way to new POC IVD assays in the coming months. However, the performance of IVD assays needs to be critically evaluated before they are employed for the clinical diagnosis of COVID-19.", "qid": 6, "docid": "ertno6a5", "rank": 16, "score": 0.8545751571655273}, {"content": "Title: RT-qPCR Testing of SARS-CoV-2: A Primer Content: Testing for the presence of coronavirus is an essential diagnostic tool for monitoring and managing the current COVID-19 pandemic. The only reliable test in current use for testing acute infection targets the genome of SARS-CoV-2, and the most widely used method is quantitative fluorescence-based reverse transcription polymerase chain reaction (RT-qPCR). Despite its ubiquity, there is a significant amount of uncertainty about how this test works, potential throughput and reliability. This has resulted in widespread misrepresentation of the problems faced using this test during the current COVID-19 epidemic. This primer provides simple, straightforward and impartial information about RT-qPCR.", "qid": 6, "docid": "td2r7xm1", "rank": 17, "score": 0.8539055585861206}, {"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": 18, "score": 0.853720486164093}, {"content": "Title: Assay Techniques and Test Development for COVID-19 Diagnosis Content: An ongoing theme of the COVID-19 pandemic is the need for widespread availability of accurate and e\ufb03cient diagnostic testing for detection of SARS-CoV-2 and antiviral antibodies in infected individuals. This report describes various assay techniques and tests for COVID-19 diagnosis. Most tests for early detection of SARS-CoV-2 RNA rely on the reverse transcription-polymerase chain reaction, but isothermal nucleic acid ampli\ufb01cation assays, including transcription-mediated ampli\ufb01cation and CRISPR-based methodologies, are promising alternatives. Identi\ufb01cation of individuals who have developed antibodies to the SARS-CoV-2 virus requires serological tests, including enzyme-linked immunosorbent assay (ELISA) and lateral \ufb02ow immunoassay. This report also provides an overview of current development in COVID-19 diagnostic techniques and products to facilitate future improvement and innovation.", "qid": 6, "docid": "d7xq7x5g", "rank": 19, "score": 0.852629542350769}, {"content": "Title: COVID-19 diagnostics in context Content: The coronavirus disease 2019 (COVID-19) pandemic has highlighted the need for different types of diagnostics, comparative validation of new tests, faster approval by federal agencies, and rapid production of test kits to meet global demands. In this Perspective, we discuss the utility and challenges of current diagnostics for COVID-19.", "qid": 6, "docid": "rk8pract", "rank": 20, "score": 0.852195680141449}, {"content": "Title: COVID-19 diagnostics in context. Content: The coronavirus disease 2019 (COVID-19) pandemic has highlighted the need for different types of diagnostics, comparative validation of new tests, faster approval by federal agencies, and rapid production of test kits to meet global demands. In this Perspective, we discuss the utility and challenges of current diagnostics for COVID-19.", "qid": 6, "docid": "n9ju3flv", "rank": 21, "score": 0.852195680141449}, {"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": 6, "docid": "q2b4ig1h", "rank": 22, "score": 0.852074146270752}, {"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": 6, "docid": "8hrjgcas", "rank": 23, "score": 0.852074146270752}, {"content": "Title: Evaluation of the Practicability of a Finger-Stick Whole-Blood SARS-Cov-2 Self-Test Adapted for the General Population. Content: Background COVID-19 (COronaVIrus Disease 2019) is an infectious respiratory disease caused by the novel SARS-CoV-2 virus. Rapid Diagnostic Tests (RDTs) have been developed to detect specific antibodies, IgG and IgM, to SARS-CoV-2 virus in human whole blood and easily usable by the general population are needed in order to alleviate the lockdown that many countries have initiated in response to the growing COVID-19 pandemic. A real-life study has been conducted in order to evaluate the performance of the COVID-PRESTO RDT and the results have been submitted for publication and are currently under review. Even if this test showed very high sensitivity and specificity in a laboratory setting when used by trained professionals, it needs to be further evaluated for practicability when used by common folk in order to be approved by health authorities for in-home use Methods 142 participants were recruited between March 2020 and April 2020 among non-medical populations in central France (nuclear plants workers, individuals attending the Orleans University Hospital vaccination clinic and Orleans University Hospital non-medical staff). Instructions for use with or without a tutorial video was made available to the volunteers. Two separate objectives were pursued: evaluation of the capability of participants to obtain an interpretable result, and evaluation of the users ability to read the results. Results 88.4 % of the test users judged the instruction for use leaflet to be clear and understandable. 99.3 % of the users obtained a valid results and according to the supervisors 92.7% of the tests were properly performed by the user. Overall, 95% of the users gave positive feedback toward the COVID PRESTO as a potential self-test. No influence of age and education was observed. Conclusion COVID-PRESTO was successfully used by an overwhelming majority of participants and its utilization was judged very satisfactory, therefore showing a promising potential as a self-test to be used by the general population. This RDT can become an easy-to-use tool to help know whether individuals are protected or not, particularly in the perspective of a second wave or a mass vaccination program.", "qid": 6, "docid": "nhgc6wcg", "rank": 24, "score": 0.8516749143600464}, {"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": 25, "score": 0.8503913879394531}, {"content": "Title: FAST: a Feasible, Accurate and Speedy Test Strategy for COVID-19 Content: As the COVID-19 pandemic continues worldwide, there is an urgent need to detect infected patients as quickly and accurately as possible. Group testing proposed by Technion [2] could improve efficiency greatly. However, the false negative rate (FNR) would be doubled. Using USA as an example, group testing would have over 70,000 false negatives, compared to 35,000 false negatives by individual testing. In this paper, we propose a Flexible, Accurate and Speedy Test (FAST), which is faster and more accurate than any existing tests. FAST first forms small close contact subgroups, e.g. families and friends. It then pools subgroups to form larger groups before RT-PCR test is done. FAST needs a similar number of tests to Technion's method, but could sharply reduce the FNR to a negligible level. Again taking USA as example, FAST reduces the number of false negatives to just 2000 while it is seven times faster than individual testing.", "qid": 6, "docid": "emovh954", "rank": 26, "score": 0.8503555059432983}, {"content": "Title: Evaluation of a COVID-19 IgM and IgG rapid test; an efficient tool for assessment of past exposure to SARS-CoV-2 Content: COVID-19 is the most rapidly growing pandemic in modern time, and the need for serological testing is most urgent. Although the diagnostics of acute patients by RT-PCR is both efficient and specific, we are also crucially in need of serological tools for investigating antibody responses and assessing individual and potential herd immunity. We evaluated a commercially available test developed for rapid (within 15 minutes) detection of SARS-CoV-2-specific IgM and IgG by 29 PCR-confirmed COVID-19 cases and 124 negative controls. The results revealed a sensitivity of 69% and 93.1% for IgM and IgG, respectively, based solely on PCR-positivity due to the absence of a serological gold standard. The assay specificities were shown to be 100% for IgM and 99.2% for IgG. This indicates that the test is suitable for assessing previous virus exposure, although negative results may be unreliable during the first weeks after infection. More detailed studies on antibody responses during and post infection are urgently needed.", "qid": 6, "docid": "knc0ruou", "rank": 27, "score": 0.8498484492301941}, {"content": "Title: Laboratory Tests for COVID-19: A Review of Peer-Reviewed Publications and Implications for Clinical UIse Content: Diagnostic tests for the coronavirus infection 2019 (COVID-19) are critical for prompt diagnosis, treatment and isolation to break the cycle of transmission A positive real-time reverse-transcriptase polymerase chain reaction (RT-PCR), in conjunction with clinical and epidemiologic data, is the current standard for diagnosis, but several challenges still exist Serological assays help to understand epidemiology better and to evaluate vaccine responses but they are unreliable for diagnosis in the acute phase of illness or assuming protective immunity Serology is gaining attention, mainly because of convalescent plasma gaining importance as treatment for clinically worsening COVID-19 patients We provide a narrative review of peer-reviewed research studies on RT-PCR, serology and antigen immune-assays for COVID-19, briefly describe their lab methods and discuss their limitations for clinical practice", "qid": 6, "docid": "hgc4ymok", "rank": 28, "score": 0.8483189344406128}, {"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": 29, "score": 0.848131000995636}, {"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": 6, "docid": "b7a2w4v9", "rank": 30, "score": 0.8475556373596191}, {"content": "Title: Multi-tiered screening and diagnosis strategy for COVID-19: a model for sustainable testing capacity in response to pandemic Content: Coronavirus disease 2019 (COVID-19), caused by novel enveloped single stranded RNA coronavirus (SARS-CoV-2), is responsible for an ongoing global pandemic. While other countries deployed widespread testing as an early mitigation strategy, the U.S. experienced delays in development and deployment of organism identification assays. As such, there is uncertainty surrounding disease burden and community spread, severely hampering containment efforts. COVID-19 illuminates the need for a tiered diagnostic approach to rapidly identify clinically significant infections and reduce disease spread. Without the ability to efficiently screen patients, hospitals are overwhelmed, potentially delaying treatment for other emergencies. A multi-tiered, diagnostic strategy incorporating a rapid host immune response assay as a screening test, molecular confirmatory testing and rapid IgM/IgG testing to assess benefit from quarantine/further testing and provide information on population exposure/herd immunity would efficiently evaluate potential COVID-19 patients. Triaging patients within minutes with a fingerstick rather than hours/days after an invasive swab is critical to pandemic response as reliance on the existing strategy is limited by assay accuracy, time to results, and testing capacity. Early screening and triage is achievable from the outset of a pandemic with point-of-care host immune response testing which will improve response time to clinical and public health actions.Key messagesDelayed testing deployment has led to uncertainty surrounding overall disease burden and community spread, severely hampering public health containment and healthcare system preparation efforts.A multi-tiered testing strategy incorporating rapid, host immune point-of-care tests can be used now and for future pandemic planning by effectively identifying patients at risk of disease thereby facilitating quarantine earlier in the progression of the outbreak during the weeks and months it can take for pathogen specific confirmatory tests to be developed, validated and manufactured in sufficient quantities.The ability to triage patients at the point of care and support the guidance of medical and therapeutic decisions, for viral isolation or confirmatory testing or for appropriate treatment of COVID-19 and/or bacterial infections, is a critical component to our national pandemic response and there is an urgent need to implement the proposed strategy to combat the current outbreak.", "qid": 6, "docid": "hpyh2dxy", "rank": 31, "score": 0.8473674058914185}, {"content": "Title: Developing a Point-of-Care Molecular Test to Detect SARS-CoV-2 Content: There is a need for widespread testing in India to stop the spread of the novel coronavirus in the population. While RT-PCR is the recommended diagnostic technique, its use is limited to well-equipped laboratories due to the need for specialized instrumentation, reagents and trained personnel. Immunodiagnostic tests are not yet recommended by the WHO for diagnosing active infections. There is a strong need for developing point-of-care molecular tests. Based on our past experience with paperfluidic devices for diagnosing bacterial infections by molecular tests, we propose the development of a diagnostic test for COVID-19. As a platform technology, it could be adapted to other viral outbreaks in future.", "qid": 6, "docid": "8siz9rb8", "rank": 32, "score": 0.8469655513763428}, {"content": "Title: Molecular and Serological Tests for COVID-19. A Comparative Review of SARS-CoV-2 Coronavirus Laboratory and Point-of-Care Diagnostics Content: Validated and accurate laboratory testing for Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2) is a crucial part of the timely management of Coronavirus Disease 2019 (COVID-19) disease, supporting the clinical decision-making process for infection control at the healthcare level and detecting asymptomatic cases. This would facilitate an appropriate treatment, a prompt isolation and consequently deceleration of the pandemic. Various laboratory tests can identify the genetic material of SARS-CoV-2 that causes COVID-19 in specimens, or specific anti-viral antibodies in blood/serum. Due to the current pandemic situation, a development of point-of-care diagnostics (POCD) allows us to substantially accelerate taking clinical decisions and implement strategic planning at the national level of preventative measures. This review summarizes and compares the available POCD and those currently under development, including quantitative reverse transcription PCR (RT-qPCR), serology immunoassays (SIAs) and protein microarray method (PMM) designed for standard and rapid COVID-19 diagnosis.", "qid": 6, "docid": "tb1zsuw4", "rank": 33, "score": 0.8468871116638184}, {"content": "Title: A comparison of group testing architectures for COVID-19 testing Content: An important component of every country's COVID-19 response is fast and efficient testing -- to identify and isolate cases, as well as for early detection of local hotspots. For many countries, producing a sufficient number of tests has been a serious limiting factor in their efforts to control COVID-19 infections. Group testing is a well-established mathematical tool, which can provide a serious and rapid improvement to this situation. In this note, we compare several well-established group testing schemes in the context of qPCR testing for COVID-19. We include example calculations, where we indicate which testing architectures yield the greatest efficiency gains in various settings. We find that for identification of individuals with COVID-19, array testing is usually the best choice, while for estimation of COVID-19 prevalence rates in the total population, Gibbs-Gower testing usually provides the most accurate estimates given a fixed and relatively small number of tests. This note is intended as a helpful handbook for labs implementing group testing methods.", "qid": 6, "docid": "rhmywn8n", "rank": 34, "score": 0.8468461036682129}, {"content": "Title: Diagnosis of COVID-19: Considerations, controversies and challenges Content: Coronavirus disease 2019 (COVID-19) due to a novel virus, severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), is a global pandemic that has resulted in over 1.5 million confirmed cases and close to 100 000 deaths. In the majority of symptomatic cases, COVID-19 results in a mild disease predominantly characterised by upper respiratory tract symptoms. Reverse transcription polymerase chain reaction (RT-PCR) using a nasopharyngeal sample is the mainstay of diagnosis, but there is an ~30% false negative rate early in the disease and in patients with mild disease, and therefore repeat testing may be required. RT-PCR positivity can persist for several days after resolution of symptoms. IgM and IgG antibody responses become positive several days after the onset of symptoms, and robust antibody responses are detectable in the second week of illness. Antibody-based immunoassays have a limited role in the diagnosis of early symptomatic disease. However, their incremental benefit over RT-PCR in the first 2 weeks of illness is currently being clarified in ongoing studies. Such assays may be useful for surveillance purposes. However, their role in potentially selecting individuals who may benefit from vaccination, or as a biomarker identifying persons who could be redeployed into essential employment roles, is being investigated. Rapid antibody-based immunoassays that detect viral antigen in nasopharyngeal samples are being developed and evaluated.", "qid": 6, "docid": "chp63f69", "rank": 35, "score": 0.846488893032074}, {"content": "Title: Multi-Tiered Screening and Diagnosis Strategy for COVID-19: A Model for Sustainable Testing Capacity in Response to Pandemic. Content: Coronavirus disease 2019 (COVID-19), caused by novel enveloped single stranded RNA coronavirus (SARS-CoV-2), is responsible for an ongoing global pandemic. While other countries deployed widespread testing as an early mitigation strategy, the U.S. experienced delays in development and deployment of organism identification assays. As such, there is uncertainty surrounding disease burden and community spread, severely hampering containment efforts. COVID-19 illuminates the need for a tiered diagnostic approach to rapidly identify clinically significant infections and reduce disease spread. Without the ability to efficiently screen patients, hospitals are overwhelmed, potentially delaying treatment for other emergencies.A multi-tiered, diagnostic strategy incorporating a rapid host immune response assay as a screening test; molecular confirmatory testing and rapid IgM/IgG testing to assess benefit from quarantine/further testing and provide information on population exposure/herd immunity would efficiently evaluate potential COVID-19 patients. Triaging patients within minutes with a fingerstick rather than hours/days after an invasive swab is critical to pandemic response as reliance on the existing strategy is limited by assay accuracy, time to results, and testing capacity. Early screening and triage is achievable from the outset of a pandemic with point-of-care host immune response testing which will improve response time to clinical and public health actions. Key MessagesDelayed testing deployment has led to uncertainty surrounding overall disease burden and community spread, severely hampering public health containment and healthcare system preparation efforts.A multi-tiered testing strategy incorporating rapid, host immune point-of-care tests can be used now and for future pandemic planning by effectively identifying patients at risk of disease thereby facilitating quarantine earlier in the progression of the outbreak during the weeks and months it can take for pathogen specific confirmatory tests to be developed, validated and manufactured in sufficient quantities.The ability to triage patients at the point of care and support the guidance of medical and therapeutic decisions, for viral isolation or confirmatory testing or for appropriate treatment of COVID-19 and/or bacterial infections, is a critical component to our national pandemic response and there is an urgent need to implement the proposed strategy to combat the current outbreak.", "qid": 6, "docid": "62v5ej3c", "rank": 36, "score": 0.8464305996894836}, {"content": "Title: Antibody Tests in Detecting SARS-CoV-2 Infection: A Meta-Analysis Content: The emergence of Coronavirus disease 2019 (COVID-19) caused by SARS-CoV-2 made imperative the need for diagnostic tests that can identify the infection. Although Nucleic Acid Test (NAT) is considered to be the gold standard, serological tests based on antibodies could be very helpful. However, individual studies are usually inconclusive, thus, a comparison of different tests is needed. We performed a systematic review and meta-analysis in PubMed, medRxiv and bioRxiv. We used the bivariate method for meta-analysis of diagnostic tests pooling sensitivities and specificities. We evaluated IgM and IgG tests based on Enzyme-linked immunosorbent assay (ELISA), Chemiluminescence Enzyme Immunoassays (CLIA), Fluorescence Immunoassays (FIA), and the Lateral Flow Immunoassays (LFIA). We identified 38 studies containing data from 7848 individuals. Tests using the S antigen are more sensitive than N antigen-based tests. IgG tests perform better compared to IgM ones and show better sensitivity when the samples were taken longer after the onset of symptoms. Moreover, a combined IgG/IgM test seems to be a better choice in terms of sensitivity than measuring either antibody alone. All methods yield high specificity with some of them (ELISA and LFIA) reaching levels around 99%. ELISA- and CLIA-based methods perform better in terms of sensitivity (90%\u201394%) followed by LFIA and FIA with sensitivities ranging from 80% to 89%. ELISA tests could be a safer choice at this stage of the pandemic. LFIA tests are more attractive for large seroprevalence studies but show lower sensitivity, and this should be taken into account when designing and performing seroprevalence studies.", "qid": 6, "docid": "3aoxplp3", "rank": 37, "score": 0.8461501002311707}, {"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": 6, "docid": "ij4ibrrx", "rank": 38, "score": 0.8460559248924255}, {"content": "Title: Laboratory Tests for COVID-19: A Review of Peer-Reviewed Publications and Implications for Clinical UIse. Content: Diagnostic tests for the coronavirus infection 2019 (COVID-19) are critical for prompt diagnosis, treatment and isolation to break the cycle of transmission. A positive real-time reverse-transcriptase polymerase chain reaction (RT-PCR), in conjunction with clinical and epidemiologic data, is the current standard for diagnosis, but several challenges still exist. Serological assays help to understand epidemiology better and to evaluate vaccine responses but they are unreliable for diagnosis in the acute phase of illness or assuming protective immunity. Serology is gaining attention, mainly because of convalescent plasma gaining importance as treatment for clinically worsening COVID-19 patients. We provide a narrative review of peer-reviewed research studies on RT-PCR, serology and antigen immune-assays for COVID-19, briefly describe their lab methods and discuss their limitations for clinical practice.", "qid": 6, "docid": "ey34e59f", "rank": 39, "score": 0.8458318710327148}, {"content": "Title: The Royal College of Pathologists of Australasia (RCPA) position statement on COVID-19 Content: For the detection of early COVID-19 disease, RCPA supports the use of molecular tests for SARS-CoV-2 and strongly opposes the introduction of COVID-19 IgG/IgM rapid tests for this purpose.", "qid": 6, "docid": "qyp629f6", "rank": 40, "score": 0.8455966711044312}, {"content": "Title: The Royal College of Pathologists of Australasia (RCPA) position statement on COVID-19. Content: For the detection of early COVID-19 disease, RCPA supports the use of molecular tests for SARS-CoV-2 and strongly opposes the introduction of COVID-19 IgG/IgM rapid tests for this purpose.", "qid": 6, "docid": "zzslm90b", "rank": 41, "score": 0.8455966711044312}, {"content": "Title: Diagnostic Performance of a Rapid Point of Care Test for SARS\u2010CoV\u20102 in an Urban ED Setting Content: The ability to rapidly and accurately identify a patient's COVID\u201019 status has had significant impact on emergency departments (ED) and health systems globally. Since the identification of SARS\u2010CoV\u20102 illness in the United States, there has been rapid development in patient testing capacity following initial challenges including sparse availability. This was made possible by increasing availability of diagnostic molecular tests in several formats, from laboratory based traditional, RT\u2010PCR methods to near patient testing rapid point of care PCR tests.", "qid": 6, "docid": "30umy2ai", "rank": 42, "score": 0.8449101448059082}, {"content": "Title: Trends and Innovations in Biosensors for COVID-19 Mass Testing Content: Fast and widespread diagnosis is crucial to fighting against the outbreak of COVID-19. This work surveys the landscape of available and emerging biosensor technologies for COVID-19 testing. Molecular diagnostic assays based on quantitative reverse transcription polymerase chain reaction are used in most clinical laboratories. However, the COVID-19 pandemic has overwhelmed testing capacity and motivated the development of fast point-of-care tests and the adoption of isothermal DNA amplification. Antigenic and serological rapid tests based on lateral-flow immunoassays suffer from low sensitivity. Advanced digital systems enhance performance at the expense of speed and the need for large equipment. Emerging technologies, including CRISPR gene-editing tools, benefit from high sensitivity and specificity of molecular diagnostics and the easy use of lateral-flow assays. DNA sequencing and sample pooling strategies are highlighted to bring out the full capacity of the available biosensor technologies and accelerate mass testing.", "qid": 6, "docid": "d5d10lwr", "rank": 43, "score": 0.8447729349136353}, {"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": 44, "score": 0.8443525433540344}, {"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": 6, "docid": "82iy2prw", "rank": 45, "score": 0.8441889882087708}, {"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": 6, "docid": "84yjdlab", "rank": 46, "score": 0.8441888093948364}, {"content": "Title: Towards effective diagnostic assays for COVID-19: a review Content: Countries globally are affected by the COVID-19 pandemic, with nearly two million cases and 120 000 deaths occurring within 4 months of the discovery of the severe acute respiratory syndrome coronavirus-2 in December 2019 in China. Accurate diagnoses of cases is key in managing the pandemic by identification, isolation and treatment of patients and defining the epidemiology of the virus. By mid-January 2020, a scientist from China published the full genome of the virus, which facilitated the development of accurate molecular diagnostic assays. By the end of January 2020, the WHO, in collaboration with laboratories in Asia, Europe and the USA, published several real-time reverse transcriptase PCR (rtRT-PCR) protocols that allowed identification of cases and development of commercial assays. Clinical investigations facilitated development of accurate case definition and guidance for laboratories on the optimum specimens and procedures for diagnoses. Currently, laboratory-based rtRT-PCR is the recommended test for diagnoses of acute cases to ensure patients can be identified and isolated and to facilitate the public health response. However, due to delays in diagnoses, severe shortage of tests and laboratory capacity, point-of-care molecular or antigen tests are becoming more attractive. Although serological tests are not suitable for diagnoses of acute cases, they are important to define epidemiological questions, including attack rate in the population, and to identify immune individuals. This review aimed to summarise the current available information for diagnoses of cases and to aid laboratories and healthcare workers to select the best assays and procedures.", "qid": 6, "docid": "0k6oqklv", "rank": 47, "score": 0.8441216349601746}, {"content": "Title: Towards effective diagnostic assays for COVID-19: a review. Content: Countries globally are affected by the COVID-19 pandemic, with nearly two million cases and 120 000 deaths occurring within 4 months of the discovery of the severe acute respiratory syndrome coronavirus-2 in December 2019 in China. Accurate diagnoses of cases is key in managing the pandemic by identification, isolation and treatment of patients and defining the epidemiology of the virus. By mid-January 2020, a scientist from China published the full genome of the virus, which facilitated the development of accurate molecular diagnostic assays. By the end of January 2020, the WHO, in collaboration with laboratories in Asia, Europe and the USA, published several real-time reverse transcriptase PCR (rtRT-PCR) protocols that allowed identification of cases and development of commercial assays. Clinical investigations facilitated development of accurate case definition and guidance for laboratories on the optimum specimens and procedures for diagnoses. Currently, laboratory-based rtRT-PCR is the recommended test for diagnoses of acute cases to ensure patients can be identified and isolated and to facilitate the public health response. However, due to delays in diagnoses, severe shortage of tests and laboratory capacity, point-of-care molecular or antigen tests are becoming more attractive. Although serological tests are not suitable for diagnoses of acute cases, they are important to define epidemiological questions, including attack rate in the population, and to identify immune individuals. This review aimed to summarise the current available information for diagnoses of cases and to aid laboratories and healthcare workers to select the best assays and procedures.", "qid": 6, "docid": "raxxlpa8", "rank": 48, "score": 0.8441215753555298}, {"content": "Title: Laboratory Diagnosis of Coronavirus Disease-2019 (COVID-19) Content: The outbreak of Coronavirus Disease-2019 (COVID-19) caused by Severe Acute Respiratory Syndrome Coronavirus-2 (SARS-CoV-2) has threatened health worldwide. As of the end of 2020, there were nearly 10 million confirmed cases and nearly 5 million deaths associated with COVID-19. Rapid and early laboratory diagnosis of COVID-19 is the main focus of treatment and control. Molecular tests are the basis for confirmation of COVID-19, but serological tests for SARS-CoV-2 are widely available and play an increasingly important role in understanding the epidemiology of the virus and in identifying populations at higher risk for infection. Point-of-care tests have the advantage of rapid, accurate, portable, low cost and non-specific device requirements, which provide great help for disease diagnosis and detection. This review will discuss the performance of different laboratory diagnostic tests and platforms, as well as suitable clinical samples for testing, and related biosafety protection. This review shall guide for the diagnosis of COVID-19 caused by SARS-CoV-2.", "qid": 6, "docid": "yripn8gc", "rank": 49, "score": 0.84386146068573}, {"content": "Title: Trends and innovations in biosensors for COVID-19 mass testing. Content: Fast and widespread diagnosis is crucial to fight against the outbreak of COVID-19. The present work surveys the landscape of available and emerging biosensor technologies for COVID-19 testing. Molecular diagnostic assays based on quantitative Reverse Transcription Polymerase Chain Reaction are used in most clinical laboratories. The COVID-19 pandemic has overwhelmed the testing capacity and motivated the development of fast point-of-care tests and the adoption of isothermal DNA amplification. Antigenic and serological rapid tests based on lateral flow immunoassays suffer from low sensitivity. Advanced digital systems enhance the performance at the expense of speed and large equipment requirement. Emerging technologies, including CRISPR gene-editing tools, benefit from high sensitivity and selectivity of molecular diagnostics and the easy use of lateral flow assays. DNA sequencing and sample pooling strategies are highlighted to bring out the full capacity of the available biosensor technologies and accelerate mass testing.", "qid": 6, "docid": "nswmhpzf", "rank": 50, "score": 0.8438048362731934}, {"content": "Title: Retrospective Clinical Evaluation of Four Lateral Flow Assays for the Detection of SARS-CoV-2 Antibodies Content: Coronavirus disease 2019 (COVID-19) is a potentially life-threatening respiratory infection caused by severe acute respiratory coronavirus 2 (SARS-CoV-2), for which numerous serologic assays are available. In a CLIA laboratory setting, we used a retrospective sample set (n = 457) to evaluate two lateral flow immunoassays (LFIAs; two iterations of Rapid Response COVID-19 Test Cassette, BTNX Inc.) and a subset of to evaluate SARS-COV-2 IgG/IgM Rapid Test, ACON Laboratories (n = 200); and Standard Q COVID-19 IgM/IgG Duo, SD BIOSENSOR (n = 155) for their capacity to detect of SARS-CoV-2 IgG. In a cohort of primarily hospitalized patients with RT-PCR confirmed COVID-19, the BTNX assays demonstrated 95% and 92% agreement with the Abbott SARS-CoV-2 IgG assay and sensitivity was highest at [\u2265] 14 days from symptom onset [BTNX kit 1, 95%; BTNX kit 2, 91%]. ACON and SD assays demonstrated 99% and 100% agreement with the Abbott assay at [\u2265] 14 days from symptom onset. Specificity was measured using 74 specimens collected prior to SARS-CoV-2 circulation in the United States and 31 cross-reactivity challenge specimens, including those from patients with a history of seasonal coronavirus infection and was 98% for BTNX kit 1 and ACON and 100% for BTNX kit 2 and SD. Taken with data from EUA assays, these results suggest that LFIAs may provide adequate results for rapid detection of SARS-CoV-2. Replicating these results in fingerstick blood in outpatient populations, would further support the possibility that LFIAs may be useful to increase access to serologic testing.", "qid": 6, "docid": "vpxgdvjw", "rank": 51, "score": 0.8433127999305725}, {"content": "Title: Comparison of diagnostic accuracies of rapid serological tests and ELISA to molecular diagnostics in patients with suspected coronavirus disease 2019 presenting to the hospital Content: OBJECTIVES: To assess the diagnostic performance of rapid lateral flow immunochromatographic assays (LFAs) compared with an ELISA and nucleic acid amplification tests (NATs) in individuals with suspected coronavirus disease 2019 (COVID-19). METHODS: Patients presenting to a Dutch teaching hospital were eligible between 17 March and 10 April 2020, when they had respiratory symptoms that were suspected for COVID-19. The performances of six different LFAs were evaluated in plasma samples obtained on corresponding respiratory sample dates of NATs testing. Subsequently, the best performing LFA was evaluated in 228 patients and in 50 sera of a historical patient control group. RESULTS: In the pilot analysis, sensitivity characteristics of LFA were heterogeneous, ranging from 2/20 (10%; 95% CI 0%-23%) to 11/20 (55%; 95% CI 33%-77%). In the total cohort, Orient Gene Biotech COVID-19 IgG/IgM Rapid Test LFA had a sensitivity of 43/99 (43%; 95% CI 34%-53%) and specificity of 126/129 (98%; 95% CI 95%-100%). Sensitivity increased to 31/52 (60%; 95% CI 46%-73%) in patients with at least 7 days of symptoms, and to 21/33 (64%; 95% CI 47%-80%) in patients with C-reactive protein (CRP) &#8805;100 mg/L. Sensitivity and specificity of Wantai SARS-CoV-2 Ab ELISA was 59/95 (62%; 95% CI 52%-72%) and 125/128 (98%; 95% CI 95%-100%) in all patients, respectively, but sensitivity increased to 38/48 (79%; 95% CI 68%-91%) in patients with at least 7 days of symptoms. CONCLUSIONS: There is large variability in diagnostic test performance between rapid LFAs, but overall limited sensitivity and high specificity in acutely admitted patients. Sensitivity improved in patients with longer existing symptoms or high CRP. LFAs should only be considered as additional triage tools when these may lead to the improvement of hospital logistics.", "qid": 6, "docid": "156rsxrl", "rank": 52, "score": 0.8431812524795532}, {"content": "Title: Laboratory Diagnosis of Novel Coronavirus Disease 2019 (COVID-19) Infection Content: Coronavirus disease 2019 (COVID-19) is an infection caused by the novel coronavirus severe acute respiratory coronavirus 2 (SARS-CoV-2). The infection manifests as a mild flu to severe acute respiratory infection. The World Health Organization (WHO) declared COVID-19 as a global pandemic on March 11, 2020. The disease spreads by droplet infection from person to person. Early diagnosis is the key for prompt management of cases and control of the spread of the virus. Currently, the laboratory diagnosis of SARS-CoV-2 is based on nucleic acid amplification tests (NAAT) like real-time reverse transcriptase (RT-PCR). Various genes like E, N, S, ORF and RdRp are targeted as a part of screening and confirmation of cases. Furthermore, nucleic acid sequencing may be done for the identification of mutation in the genome of SARS-CoV-2. The development of serological assays and point of care molecular test will further intensify the diagnostic modalities of SARS-CoV-2.", "qid": 6, "docid": "o4njvi62", "rank": 53, "score": 0.8431447744369507}, {"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": 6, "docid": "afcd4wc9", "rank": 54, "score": 0.8430788516998291}, {"content": "Title: Field-deployable, rapid diagnostic testing of saliva samples for SARS-CoV-2. Content: Abstract Rapid, scalable, point-of-need, COVID-19 diagnostic testing is necessary to safely re-open economies and prevent future outbreaks. We developed an assay that detects single copies of SARS-CoV-2 virus directly from saliva and swab samples in 30 min using a simple, one-step protocol that utilizes only a heat block and microcentrifuge tube prefilled with a mixture containing the necessary reagents and has a sensitivity and specificity of 97% and 100%, respectively.", "qid": 6, "docid": "8vp57c1o", "rank": 55, "score": 0.8430746793746948}, {"content": "Title: Top stories: Bungled coronavirus testing, disarming \u2018atomic bomb\u2019 cells, and jet stream blocking 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? One answer is that a test kit designed by the U S Centers for Disease Control and Prevention (CDC) and rolled out to state and local labs late last month contained a faulty reagent The problems have led many to doubt the accuracy of confirmed tallies of the disease But the situation may soon improve, as the Food and Drug Administration comes up with a workaround for the faulty CDC kit", "qid": 6, "docid": "nghjkrow", "rank": 56, "score": 0.8425979018211365}, {"content": "Title: Diagnosis of COVID-19: Considerations, Controversies and Challenges in South Africa Content: Coronavirus disease 2019 (COVID-19) due to severe acute respiratory syndrome coronavirus 2 is a global pandemic that has resulted in over 1.5 million confirmed cases and close to 100,000 deaths. In the majority of symptomatic cases COVID-19 results in a mild disease predominantly characterised by upper respiratory tract symptoms. Reverse transcription polymerase chain reaction (RT-PCR), using a nasopharyngeal sample, is the mainstay of diagnosis, but there is an ~30% false negative rate early in the disease and in patients with mild disease. RT-PCR positivity can persist for several days after a resolution of symptoms. IgM and IgG antibody responses become positive several days after the onset of symptoms, and robust antibody responses are detectable in the second week of illness. Antibody-based immunoassays have a limited role in the diagnosis of early symptomatic disease. However, their incremental benefit over RT-PCR in the first 2 weeks of illness is currently being clarified in ongoing studies. Such assays may be useful for surveillance purposes. However, their role in potentially selecting individuals that may benefit from vaccination, or as a biomarker identifying persons that could be redeployed into essential employment roles are being investigated. Rapid antibody-based immunoassays that detect viral antigen in nasopharyngeal samples are being developed and evaluated.", "qid": 6, "docid": "eh3ztsv5", "rank": 57, "score": 0.8423744440078735}, {"content": "Title: Development of a Novel, Genome Subtraction-Derived, SARS-CoV-2-Specific COVID-19-nsp2 Real-Time RT-PCR Assay and Its Evaluation Using Clinical Specimens Content: The pandemic novel coronavirus infection, Coronavirus Disease 2019 (COVID-19), has affected at least 190 countries or territories, with 465,915 confirmed cases and 21,031 deaths. In a containment-based strategy, rapid, sensitive and specific testing is important in epidemiological control and clinical management. Using 96 SARS-CoV-2 and 104 non-SARS-CoV-2 coronavirus genomes and our in-house program, GolayMetaMiner, four specific regions longer than 50 nucleotides in the SARS-CoV-2 genome were identified. Primers were designed to target the longest and previously untargeted nsp2 region and optimized as a probe-free real-time reverse transcription-polymerase chain reaction (RT-PCR) assay. The new COVID-19-nsp2 assay had a limit of detection (LOD) of 1.8 TCID50/mL and did not amplify other human-pathogenic coronaviruses and respiratory viruses. Assay reproducibility in terms of cycle threshold (Cp) values was satisfactory, with the total imprecision (% CV) values well below 5%. Evaluation of the new assay using 59 clinical specimens from 14 confirmed cases showed 100% concordance with our previously developed COVID-19-RdRp/Hel reference assay. A rapid, sensitive, SARS-CoV-2-specific real-time RT-PCR assay, COVID-19-nsp2, was developed.", "qid": 6, "docid": "9ituqb3g", "rank": 58, "score": 0.8422971963882446}, {"content": "Title: An Extended Laboratory Validation Study and Comparative Performance Evaluation of the Abbott ID NOW COVID-19 Assay in a Coastal California Tertiary Care Medical Center Content: Abstract: The Abbott ID NOW COVID-19 assay is a rapid molecular diagnostic test particularly designed for on-site, rapid turnaround point of care (POC) testing. The utilization of rapid diagnostic tests is integral to optimizing workflow within the hospital and/or procedural-based clinics. The capability to provide both rapid disposition and correct patient classification during this COVID-19 pandemic is critically important with broad infection control implications for both patients and healthcare staff. A tightly controlled, extended laboratory validation was performed at our medical center to determine the negative test agreement of the Abbott ID NOW compared with the BD MAX analyzer, a laboratory-based, two target, molecular analyzer with a sensitive cycle threshold (Ct) positive cutoff value of 42. There was strict adoption of the procedures listed in the Abbott ID NOW Instruction for Use (IFU)1 insert delineating preferred practices for optimal test performance. Under these conditions, our institution demonstrated a significant negative percent agreement with 116 out of 117 patients correlating, which equates to a 99.1% concordance similar to a recently reported correlation study2.", "qid": 6, "docid": "sag9xsjj", "rank": 59, "score": 0.8422946333885193}, {"content": "Title: Development and validation of a rapid single-step reverse transcriptase loop-mediated isothermal amplification (RT-LAMP) system potentially to be used for reliable and high-throughput screening of COVID-19 Content: The recent pandemic of COVID-19 has involved tens of thousands of patients in numerous countries and the causative virus, SARS COV-2 is highly transmissible. Molecular diagnostic tools are central to containment of the virus and initiating proper clinical care. Rapidity, user-friendliness, and high degree of sensitivity and specificity are desirable features of diagnostic assays for screening purposes. Herein, we present a single step reverse transcriptase LAMP assay (RT-LAMP), which can detect up to 500 viral copies in 30 minutes. We challenged our assay with a large number of clinical samples collected from 47 confirmed cases and 213 negative patients. Our LAMP assay showed a high degree of sensitivity and specificity compared to two commercialized qRT-PCR assay as gold standard. We present a rapid RT-LAMP assay that could extend the capacity of laboratories to process 2.5 more clinical samples relative to qRT-PCR and potentially could be used for high-throughput screening purposes.", "qid": 6, "docid": "eo2pcgix", "rank": 60, "score": 0.8422862887382507}, {"content": "Title: Development of a Novel, Genome Subtraction-Derived, SARS-CoV-2-Specific COVID-19-nsp2 Real-Time RT-PCR Assay and Its Evaluation Using Clinical Specimens Content: The pandemic novel coronavirus infection, Coronavirus Disease 2019 (COVID-19), has affected at least 190 countries or territories, with 465,915 confirmed cases and 21,031 deaths. In a containment-based strategy, rapid, sensitive and specific testing is important in epidemiological control and clinical management. Using 96 SARS-CoV-2 and 104 non-SARS-CoV-2 coronavirus genomes and our in-house program, GolayMetaMiner, four specific regions longer than 50 nucleotides in the SARS-CoV-2 genome were identified. Primers were designed to target the longest and previously untargeted nsp2 region and optimized as a probe-free real-time reverse transcription-polymerase chain reaction (RT-PCR) assay. The new COVID-19-nsp2 assay had a limit of detection (LOD) of 1.8 TCID(50)/mL and did not amplify other human-pathogenic coronaviruses and respiratory viruses. Assay reproducibility in terms of cycle threshold (Cp) values was satisfactory, with the total imprecision (% CV) values well below 5%. Evaluation of the new assay using 59 clinical specimens from 14 confirmed cases showed 100% concordance with our previously developed COVID-19-RdRp/Hel reference assay. A rapid, sensitive, SARS-CoV-2-specific real-time RT-PCR assay, COVID-19-nsp2, was developed.", "qid": 6, "docid": "4egbk4yz", "rank": 61, "score": 0.8421128988265991}, {"content": "Title: Diagnostic techniques for COVID-19 and new developments Content: COVID-19 pandemic is a serious global health issue today due to the rapid human to human transmission of SARS-CoV-2, a new type of coronavirus that causes fatal pneumonia. SARS -CoV-2 has a faster rate of transmission than other coronaviruses such as SARS and MERS and until now there are no approved specific drugs or vaccines for treatment. Thus, early diagnosis is crucial to prevent the extensive spread of the disease. The reverse transcription-polymerase chain reaction (RT-PCR) is the most routinely used method until now to detect SARS-CoV-2 infections. However, several other faster and accurate assays are being developed for the diagnosis of COVID-19 aiming to control the spread of infection through the identification of patients and immediate isolation. In this review, we will discuss the various detection methods of the SARS-CoV-2 virus including the recent developments in immunological assays, amplification techniques as well as biosensors.", "qid": 6, "docid": "0oak9ggm", "rank": 62, "score": 0.8418900370597839}, {"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": 6, "docid": "gplcop2k", "rank": 63, "score": 0.8415204286575317}, {"content": "Title: Rapid Detection of Novel Coronavirus (COVID-19) by Reverse Transcription-Loop-Mediated Isothermal Amplification Content: Novel Corona virus (COVID-19 or 2019-nCoV) is an emerging global health concern that requires a rapid diagnostic test. Quantitative reverse transcription PCR (qRT-PCR) is currently the standard for COVID-19 detection; however, Reverse Transcription Loop-Mediated Isothermal Amplification (RT-LAMP) may allow for faster and cheaper field based testing at point-of-risk. The objective of this study was to develop a rapid screening diagnostic test that could be completed in under 30 minutes. Simulated patient samples were generated by spiking serum, urine, saliva, oropharyngeal swabs, and nasopharyngeal swabs with a portion of the COVID-19 nucleic sequence. The samples were tested using RT-LAMP as well as by conventional qRT-PCR. Specificity of the RT-LAMP was evaluated by also testing against other related coronaviruses. RT-LAMP specifically detected COVID-19 in simulated patient samples. This test was performed in under 30 minutes. This approach could be used for monitoring of exposed individuals or potentially aid with screening efforts in the field and potential ports of entry.", "qid": 6, "docid": "6kpgt70s", "rank": 64, "score": 0.8412687182426453}, {"content": "Title: Comparison of Abbott ID Now and Abbott m2000 methods for the detection of SARS-CoV-2 from nasopharyngeal and nasal swabs from symptomatic patients Content: The ID NOW COVID-19 (IDNCOV) assay performed on the ID Now Instrument (Abbott Diagnostics, Scarborough, Inc. Scarborough, ME) is a rapid diagnostic test that can be performed in a point of care setting equivalent to CLIA waived testing. .", "qid": 6, "docid": "h1u4qovu", "rank": 65, "score": 0.8411563634872437}, {"content": "Title: Comparison of diagnostic accuracies of rapid serological tests and ELISA to molecular diagnostics in patients with suspected COVID-19 presenting to the hospital Content: OBJECTIVES: To assess the diagnostic performance of rapid lateral flow immunochromatographic assays (LFAs) compared to an enzyme-linked immunosorbent assay (ELISA) and nucleic acid amplification tests (NATs) in suspected coronavirus disease 2019 (COVID-19) patients. METHODS: Patients presenting to a Dutch teaching hospital were eligible between March 17 and April 10, 2020, when they had respiratory symptoms that were suspected for COVID-19. The performances of six different LFAs were evaluated in plasma samples obtained on corresponding respiratory sample dates of NATs testing. Subsequently, the best performing LFA was evaluated in 228 patients and in 50 sera of a historical patient control group. RESULTS: In the pilot analysis sensitivity characteristics of LFA were heterogenous ranging from 2/20 (10%; 95% confidence interval (CI) 0-23) to 11/20 (55%; 95% CI 33-77). In the total cohort, Orient Gene Biotech COVID-19 IgG/IgM Rapid Test LFA had a sensitivity of 43/99 (43%; 95% CI 34-53) and specificity of 126/129 (98%; 95% CI 95-100). Sensitivity increased to 31/52 (60%; 95% CI 46-73) in patients with at least seven days of symptoms, and to 21/33 (64%; 95% CI 47-80) in patients with C-reactive protein (CRP) >100 mg/L. Sensitivity and specificity of Wantai SARS-CoV-2 Ab ELISA was 59/95 (62%; 95% CI 52-72) and 125/128 (98%; 95% CI 95-100) in all patients, respectively, but sensitivity increased to 38/48 (79%; 95% CI 68-91) in patients with at least seven days of symptoms. CONCLUSIONS: There is large variability in diagnostic test performance between rapid LFAs, but overall limited sensitivity and high specificity in acutely admitted patients. Sensitivity improved in patients with longer existing symptoms or high CRP. LFAs should only be considered as additional triage tools when these may lead to the improvement of hospital logistics.", "qid": 6, "docid": "h7ikjgic", "rank": 66, "score": 0.8409866094589233}, {"content": "Title: Multicentre comparison of quantitative PCR-based assays to detect SARS-CoV-2, Germany, March 2020 Content: Containment strategies and clinical management of coronavirus disease (COVID-19) patients during the current pandemic depend on reliable diagnostic PCR assays for the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). Here, we compare 11 different RT-PCR test systems used in seven diagnostic laboratories in Germany in March 2020. While most assays performed well, we identified detection problems in a commonly used assay that may have resulted in false-negative test results during the first weeks of the pandemic.", "qid": 6, "docid": "npx45ldn", "rank": 67, "score": 0.8408902883529663}, {"content": "Title: Laboratory Diagnosis of Coronavirus Disease-2019 (COVID-19) Content: Abstract The outbreak of Coronavirus Disease-2019 (COVID-19) caused by Severe Acute Respiratory Syndrome Coronavirus-2 (SARS-CoV-2) has threatened health worldwide. As of the end of 2020, there were nearly 10 million confirmed cases and nearly 5 million deaths associated with COVID-19. Rapid and early laboratory diagnosis of COVID-19 is the main focus of treatment and control. Molecular tests are the basis for confirmation of COVID-19, but serological tests for SARS-CoV-2 are widely available and play an increasingly important role in understanding the epidemiology of the virus and in identifying populations at higher risk for infection. Point-of-care tests have the advantage of rapid, accurate, portable, low cost and non-specific device requirements, which provide great help for disease diagnosis and detection. This review will discuss the performance of different laboratory diagnostic tests and platforms, as well as suitable clinical samples for testing, and related biosafety protection. This review shall guide for the diagnosis of COVID-19 caused by SARS-CoV-2.", "qid": 6, "docid": "sy91rnse", "rank": 68, "score": 0.8407893180847168}, {"content": "Title: SARS-CoV-2 and the COVID-19 disease: a mini review on diagnostic methods Content: Coronavirus disease 2019 (COVID-19) is an infectious disease initially reported in China and currently worldwide dispersed caused by a new coronavirus (SARS-CoV-2 or 2019-nCoV) affecting more than seven million people around the world causing more than 400 thousand deaths (on June 8th, 2020). The diagnosis of COVID-19 is based on the clinical and epidemiological history of the patient. However, the gold standard for COVID-19 diagnosis is the viral detection through the amplification of nucleic acids. Although the quantitative Reverse-Transcription Polymerase Chain Reaction (RT-PCR) has been described as the gold standard for diagnosing COVID-19, there are several difficulties involving its use. Here we comment on RT-PCR and describe alternative tests developed for the diagnosis of COVID-19.", "qid": 6, "docid": "8vi60e0a", "rank": 69, "score": 0.8406333327293396}, {"content": "Title: SARS-CoV-2 and the COVID-19 disease: a mini review on diagnostic methods Content: Coronavirus disease 2019 (COVID-19) is an infectious disease initially reported in China and currently worldwide dispersed caused by a new coronavirus (SARS-CoV-2 or 2019-nCoV) affecting more than seven million people around the world causing more than 400 thousand deaths (on June 8(th), 2020). The diagnosis of COVID-19 is based on the clinical and epidemiological history of the patient. However, the gold standard for COVID-19 diagnosis is the viral detection through the amplification of nucleic acids. Although the quantitative Reverse-Transcription Polymerase Chain Reaction (RT-PCR) has been described as the gold standard for diagnosing COVID-19, there are several difficulties involving its use. Here we comment on RT-PCR and describe alternative tests developed for the diagnosis of COVID-19.", "qid": 6, "docid": "f6p9i951", "rank": 70, "score": 0.8401888608932495}, {"content": "Title: Testing for SARS-CoV-2 (COVID-19): a systematic review and clinical guide to molecular and serological in-vitro diagnostic assays Content: The severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) and its associated coronavirus disease 2019 (COVID-19) pandemic has demanded rapid upscaling of in-vitro diagnostic assays to enable mass screening and testing of high-risk groups, and simultaneous ascertainment of robust data on past SARS-CoV-2 exposure at an individual and a population level. To meet the exponential demand in testing, there has been an accelerated development of both molecular and serological assays across a plethora of platforms. The present review discusses the current literature on these modalities, including nucleic acid amplification tests, direct viral antigen tests and the rapidly expanding laboratory-based and point of care serological tests. This suite of complementary tests will inform crucial decisions by healthcare providers and policy makers, and understanding their strengths and limitations will be critical to their judicious application for the development of algorithmic approaches to treatment and public health strategies.", "qid": 6, "docid": "3ea1ngo2", "rank": 71, "score": 0.8399995565414429}, {"content": "Title: Validation and performance of a quantitative IgG assay for the screening of SARS-CoV-2 antibodies Content: The current COVID-19 epidemic imposed an unpreceded challenge to the scientific community in terms of treatment, epidemiology, diagnosis, social interaction, fiscal policies and many other areas. The development of accurate and reliable diagnostic tools (high specificity and sensitivity) is crucial in the current period, the near future and in the long term. These assays should provide guidance to identify immune presumptive protected persons, potential plasma, and/or B cell donors and vaccine development among others. Also, such assays will be contributory in supporting prospective and retrospective studies to identify the prevalence and incidence of COVID-19 and to characterize the dynamics of the immune response. As of today, only thirteen serological assays have received the Emergency Use Authorization (EUA) by the U.S. Federal Drug Administration (FDA). In this work we describe the development and validation of a quantitative IgG enzyme-linked immunoassay (ELISA) using the recombinant SARS-CoV-2 Spike Protein S1 domain, containing the receptor-binding domain (RBD), showing 98% sensitivity and 98.9% specificity. The assay showed to be useful to test for SARS-CoV-2 IgG antibodies in plasma samples from COVID-19-recovered subjects as potential donors for plasmapheresis. This assay is currently under review by the Federal Drug Administration for an Emergency Use Authorization request (Submission Number EUA201115).", "qid": 6, "docid": "sxfrjs58", "rank": 72, "score": 0.8399275541305542}, {"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": 73, "score": 0.8396987915039062}, {"content": "Title: COVID-19: Current Trends in Invitro Diagnostics Content: The novel coronavirus SARS-CoV-2 is the seventh known species of coronavirus, infectious to human beings. The pandemic COVID-19 spread all over the world with an unprecedented spreading rate after its first appearance in Wuhan, China. As a novel viral disease there in no antiviral treatment or vaccine for the COVID-19. At present, the early detection and the quarantine of infected patients are the ways to stop the spreading of the disease. This review will discuss about the current invitro diagnostic methods used worldwide for the early and accurate diagnosis of COVID-19. Currently the nucleic acid based polymerase chain reaction is used as the reliable diagnostic platform and antigen/antibody detection immunoassays are playing the role of screening tests for early detection and prognosis in COVID-19 treatment.", "qid": 6, "docid": "k2m6woow", "rank": 74, "score": 0.8396573662757874}, {"content": "Title: Low performance of rapid antigen detection test as frontline testing for COVID-19 diagnosis Content: BACKGROUND: Ensuring accurate diagnosis is essential to limit the spread of the SARS-CoV-2 and for the clinical management of COVID-19. Although real-time reverse transcription polymerase chain reaction (RT- qPCR) is the current recommended laboratory method to diagnose SARS-CoV-2 acute infection, several factors such as requirement of special equipment and skilled staff limit the use of these time-consuming molecular techniques. Recently, several easy to perform rapid antigen detection tests were developed and recommended in some countries as the first line of diagnostic. OBJECTIVES: The aim of this study was to evaluate the performances of the Coris COVID-19 Ag Respi-Strip. Study design. We performed a comparison study by testing nasopharyngeal samples with RT-qPCR and antigen rapid test. RESULTS: 148 nasopharyngeal swabs were tested. Amongst the 106 positive RT-qPCR samples, 32 were detected by the rapid antigen test, given an overall sensitivity of 30.2%. All the samples detected positive with the antigen rapid tests were also positive with RT-qPCR. CONCLUSIONS: Highest viral load is associated with better antigen detection rates. Unfortunately, the overall poor sensitivity of the COVID-19 Ag Respi-Strip does not allow using it alone as the frontline testing for COVID-19 diagnosis.", "qid": 6, "docid": "tmgmqtjq", "rank": 75, "score": 0.8395735025405884}, {"content": "Title: On Accelerated Testing for COVID-19 Using Group Testing Content: COVID-19 has resulted in a global health crisis that may become even more acute over the upcoming months. One of the main reasons behind the current rapid growth of COVID-19 in the U.S. population is the limited availability of testing kits and the relatively-high cost of screening tests. In this draft, we demonstrate the effectiveness of group testing (pooling) ideas to accelerate testing for COVID-19. This draft is semi-tutorial in nature and is written for a broad audience with interest in mathematical formulations relevant to COVID-19 testing. Therefore, ideas are presented through illustrative examples rather than through purely theoretical formulations. The focus is also on pools of size less than 64 such as what is practical with current RT-PCR technology.", "qid": 6, "docid": "m8n2p55z", "rank": 76, "score": 0.8393370509147644}, {"content": "Title: The challenges of covid-19 testing: Time for pathologists to rise to the occasion Content: An outbreak of novel coronavirus (Covid-19) was first reported in Wuhan, China in the late December 1 Since then, the positive cases have increased exponentially to 1 4 million (as of 8 April 2020) 2 The ability of a country to cope with increasing number of Covid-19 testing is the ultimate test Teaching/university hospitals should pull their resources and man-power to provide the muchneeded assistance to the demand of Covid-19 testing Inadequate testing could result in unrecognised Covid-19 infected individuals, roaming freely in the population The other issue is the sensitivity of test if samples were obtained from different sites Classically, the confirmation of diagnosis of Covid-19 depends on real time polymerase chain reaction (RT-PCR) analysis to detect viral genetic material in either a nasal swab or bronchioalveolar lavage sample Wang et al (2020) reported that bronchioalveolar lavage sample has the highest sensitivity in identifying Covid-19, followed by sputum and nasal swab with positive rates of 93%, 72% and 63%, respectively 3 Furthermore, they found that nasal swab contained the highest concentration of viral load as it required less number of cycles to achieve higher copy numbers In some patients, viral genetic material was also identified in faeces and blood 3 While the reliability of testing is a concern, the safety of the laboratory staff also has to be kept in mind In this issue, there are three review articles on Covid-19, first article described the general properties of coronavirus, second article described the diagnostic performance of Covid-19 serology assay and third article described the importance of the site of sampling for Covid-19 4-6", "qid": 6, "docid": "2buj9xrh", "rank": 77, "score": 0.8391349911689758}, {"content": "Title: Comparative performance of four nucleic acid amplification tests for SARS-CoV-2 virus Content: Coronavirus disease 2019 (COVID-19) can be screened and diagnosed through the detection of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) by real-time reverse transcription polymerase chain reaction. SARS-CoV-2 nucleic acid amplification tests (NAATs) have been rapidly developed and quickly applied to clinical testing during the pandemic. However, studies evaluating the performance of these NAAT assays are limited. We evaluated the performance of four NAATs, which were marked by the Conformit\u00e9 Europ\u00e9enne and widely used in China during the pandemic. Results showed that the analytical sensitivity of the four assays was significantly lower than that claimed by the NAAT manufacturers. The limit of detection (LOD) of Daan, Sansure, and Hybribio NAATs was 3000 copies/mL, whereas the LOD of Bioperfectus NAATs was 4000 copies/mL. The results of the consistency test using 46 samples showed that Daan, Sansure, and Hybribio NAATs could detect the samples with a specificity of 100% (30/30) and a sensitivity of 100% (16 /16), whereas Bioperfectus NAAT detected the samples with a specificity of 100% (30/30) and a sensitivity 81.25% (13/16). The sensitivity of Bioperfectus NAAT was lower than that of the three other NAATs; this finding was consistent with the result that Bioperfectus NAAT had a higher LOD than the three other kinds of NAATs. The four above mentioned reagents presented high specificity; however, for the detection of the samples with low virus concentration, Bioperfectus reagent had the risk of missing detection. Therefore, the LOD should be considered in the selection of SARS-CoV-2 NAATs.", "qid": 6, "docid": "8m6793vd", "rank": 78, "score": 0.8388722538948059}, {"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": 79, "score": 0.838329553604126}, {"content": "Title: Testing for SARS-CoV-2 (COVID-19): a systematic review and clinical guide to molecular and serological in-vitro diagnostic assays Content: The severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) and its associated Coronavirus disease 2019 (COVID-19) pandemic has demanded rapid upscaling of in-vitro diagnostic assays to enable mass screening and testing of high-risk groups, and simultaneous ascertainment of robust data on past SARS-CoV-2 exposure at an individual and population level. To meet the exponential demand in testing, there has been an accelerated development of both molecular and serological assays across a plethora of platforms. In the present review, we discuss the current literature on these modalities including the nucleic acid amplification tests, direct viral antigen tests and the rapidly expanding laboratory based and point of care serological tests. This suite of complementary tests will inform crucial decisions by healthcare providers and policy makers and understanding their strengths and limitations will be critical to their judicious application for the development of algorithmic approaches to treatment and public health strategies.", "qid": 6, "docid": "8y0v6d2i", "rank": 80, "score": 0.8380584716796875}, {"content": "Title: Comparison of Four Molecular In Vitro Diagnostic Assays for the Detection of SARS-CoV-2 in Nasopharyngeal Specimens Content: The novel human coronavirus SARS-CoV-2 was first discovered in the city of Wuhan, Hubei province, China, causing an outbreak of pneumonia in January 2020. As of April 10, 2020, the virus has rapidly disseminated to over 200 countries and territories, causing more than 1.6 million confirmed cases of COVID-19 and 97,000 deaths worldwide. The clinical presentation of COVID-19 is fairly non-specific, and symptoms overlap with other seasonal respiratory infections concurrently circulating in the population. Further, it is estimated that up to 80% of infected individuals experience mild symptoms or are asymptomatic, confounding efforts to reliably diagnose COVID-19 empirically. To support infection control measures, there is an urgent need for rapid and accurate molecular diagnostics to identify COVID-19 positive patients. In the present study, we have evaluated the analytical sensitivity and clinical performance of four SARS-CoV-2 molecular diagnostic assays granted Emergency Use Authorization by the FDA using nasopharyngeal swabs from symptomatic patients. This information is crucial for both laboratories and clinical teams, as decisions on which testing platform to implement are made.", "qid": 6, "docid": "2bf3xzni", "rank": 81, "score": 0.8380563259124756}, {"content": "Title: Antibody tests in detecting SARS-CoV-2 infection: a meta-analysis Content: With the emergence of SARS-CoV-2 and the associated Coronavirus disease 2019 (COVID-19), there is an imperative need for diagnostic tests that can identify the infection. Although Nucleic Acid Test (NAT) is considered to be the gold standard, serological tests based on antibodies could be very helpful. However, individual studies measuring the accuracy of the various tests are usually underpowered and inconsistent, thus, a comparison of different tests is needed. We performed a systematic review and meta-analysis following the PRISMA guidelines. We conducted the literature search in PubMed, medRxiv and bioRxiv. For the statistical analysis we used the bivariate method for meta-analysis of diagnostic tests pooling sensitivities and specificities. We evaluated IgM and IgG tests based on Enzyme-linked immunosorbent assay (ELISA), Chemiluminescence Enzyme Immunoassays (CLIA), Fluorescence Immunoassays (FIA) and the point-of-care (POC) Lateral Flow Immunoassays (LFIA) that are based on immunochromatography. In total, we identified 38 eligible studies that include data from 7,848 individuals. The analyses showed that tests using the S antigen are more sensitive than N antigen-based tests. IgG tests perform better compared to IgM ones, and show better sensitivity when the samples were taken longer after the onset of symptoms. Moreover, irrespective of the method, a combined IgG/IgM test seems to be a better choice in terms of sensitivity than measuring either antibody type alone. All methods yielded high specificity with some of them (ELISA and LFIA) reaching levels around 99%. ELISA- and CLIA-based methods performed better in terms of sensitivity (90-94%) followed by LFIA and FIA with sensitivities ranging from 80% to 86%. ELISA tests could be a safer choice at this stage of the pandemic. POC tests (LFIA), that are more attractive for large seroprevalence studies show high specificity but lower sensitivity and this should be taken into account when designing and performing seroprevalence studies.", "qid": 6, "docid": "yfyd2ysn", "rank": 82, "score": 0.8378898501396179}, {"content": "Title: Comparison of Abbott ID Now and Abbott m2000 methods for the detection of SARS-CoV-2 from nasopharyngeal and nasal swabs from symptomatic patients. Content: The ID NOW COVID-19 (IDNCOV) assay performed on the ID Now Instrument (Abbott Diagnostics, Scarborough, Inc. Scarborough, ME) is a rapid diagnostic test that can be performed in a point of care setting equivalent to CLIA waived testing.\u2026.", "qid": 6, "docid": "6jy6ul6j", "rank": 83, "score": 0.8378285765647888}, {"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": 84, "score": 0.8377327919006348}, {"content": "Title: INSIGHT: a scalable isothermal NASBA-based platform for COVID-19 diagnosis Content: We present here INSIGHT (Isothermal NASBA-Sequencing based hIGH-througput Test): a two-stage COVID-19 testing strategy, using a combination of an isothermal NASBA reaction and next generation sequencing. From commercially acquired human saliva with spiked-in viral RNA as input, the first stage employs isothermal amplification of viral RNA to give a rapid result in one to two hours, using either fluorescence detection or a dipstick readout, whilst simultaneously incorporating sample-specific barcodes into the amplification product. In the first stage, fluorescent viral RNA detection can be consistently achieved at 10-100 copies per 20 \u00b5l reaction. The second stage pools post-amplification barcoded products from multiple samples for scalable sequencing that could be centralised, to further improve the accuracy of the test in a massively parallel way. Our two-stage testing strategy is suitable for further development into a home-based or point-of-care assay, and is potentially scalable to population level. IMPORTANT This protocol has not been validated on patient samples and should not be used for clinical diagnosis without further validation and certification. ***This is ongoing research to develop a testing strategy for the SARS-CoV-2 virus. The Wellcome Sanger Institute is not in a position to develop this into a commercial product, but would be open to discussions with third parties about how they could develop this further to achieve the societal benefits of this work.***", "qid": 6, "docid": "66192ajk", "rank": 85, "score": 0.8376471996307373}, {"content": "Title: Low performance of rapid antigen detection test as frontline testing for COVID-19 diagnosis Content: BACKGROUND: Ensuring accurate diagnosis is essential to limit the spread of SARS-CoV-2 and for the clinical management of COVID-19. Although real-time reverse transcription polymerase chain reaction (RT- qPCR) is the current recommended laboratory method to diagnose SARS-CoV-2 acute infection, several factors such as requirement of special equipment and skilled staff limit the use of these time-consuming molecular techniques. Recently, several easy to perform rapid antigen detection tests were developed and recommended in some countries as the first line of diagnostic. OBJECTIVES: The aim of this study was to evaluate the performances of the Coris COVID-19 Ag Respi-Strip test, a rapid immunochromatographic test for the detection of SARS-CoV-2 antigen, in comparison to RT-qPCR. RESULTS: 148 nasopharyngeal swabs were tested. Amongst the 106 positive RT-qPCR samples, 32 were detected by the rapid antigen test, given an overall sensitivity of 30.2%. All the samples detected positive with the antigen rapid test were also positive with RT-qPCR. CONCLUSIONS: Higher viral loads are associated with better antigen detection rates. Unfortunately, the overall poor sensitivity of the COVID-19 Ag Respi-Strip does not allow using it alone as the frontline testing for COVID-19 diagnosis.", "qid": 6, "docid": "kx0u8w10", "rank": 86, "score": 0.8374214768409729}, {"content": "Title: The Appropriate Use of Testing for COVID-19 Content: Many public officials are calling for increased testing for the 2019 novel coronavirus disease (COVID-19), and some governments have taken extraordinary measures to increase the availability of testing. However, little has been published about the sensitivity and specificity of the reverse transcriptase-polymerase chain reaction (RT-PCR) nasopharyngeal swabs that are commonly used for testing. This narrative review evaluates the literature regarding the accuracy of these tests, and makes recommendations based on this literature. In brief, a negative RT-PCR nasopharyngeal swab test is insufficient to rule out COVID-19. Thus, over-reliance on the results of the test may be dangerous, and the push for widespread testing may be overstated.", "qid": 6, "docid": "a038jilw", "rank": 87, "score": 0.8373041749000549}, {"content": "Title: A novel comprehensive metric to assess COVID-19 testing outcomes: Effects of geography, government, and policy response Content: Testing and case identification are key strategies in controlling the COVID-19 pandemic. Contact tracing and isolation are only possible if cases have been identified. The effectiveness of testing must be tracked, but a single comprehensive metric is not available to assess testing effectiveness, and no timely estimates of case detection rate are available globally, making inter-country comparisons difficult. The purpose of this paper was to propose a single, comprehensive metric, called the COVID-19 Testing Index (CovTI) scaled from 0 to 100, that incorporated several testing metrics. The index was based on case-fatality rate, test positivity rate, active cases, and an estimate of the detection rate. It used parsimonious modeling to estimate the true total number of COVID-19 cases based on deaths, testing, health system capacity, and government transparency. Publicly reported data from 188 countries and territories were included in the index. Estimates of detection rates aligned with previous estimates in literature (R2=0.97). As of June 3, 2020, the states with the highest CovTI included Iceland, Australia, New Zealand, Hong Kong, and Thailand, and some island nations. Globally, CovTI increased from April 20 ([x]=43.2) to June 3 ([x]=52.2) but declined in ca. 10% of countries. Bivariate analyses showed the average in countries with open public testing policies (59.7, 95% CI 55.6-63.8) were significantly higher than countries with no testing policy (30.2, 95% CI 18.1-42.3) (p<0.0001). A multiple linear regression model assessed the association of independent grouping variables with CovTI. Open public testing and extensive contact tracing were shown to significantly increase CovTI, after adjusting for extrinsic factors, including geographic isolation and centralized forms of government. This tool may be useful for policymakers to assess testing effectiveness, inform decisions, and identify model countries. It may also serve as a tool for researchers in analyses by combining it with other databases.", "qid": 6, "docid": "6ed3two6", "rank": 88, "score": 0.8372611999511719}, {"content": "Title: Evaluation of COVID-19 RT-qPCR test in multi-sample pools Content: BACKGROUND: The recent emergence of SARS-CoV-2 lead to a current pandemic of unprecedented scale. Though diagnostic tests are fundamental to the ability to detect and respond, overwhelmed healthcare systems are already experiencing shortages of reagents associated with this test, calling for a lean immediately-applicable protocol. METHODS: RNA extracts of positive samples were tested for the presence of SARS-CoV-2 using RT-qPCR, alone or in pools of different sizes (2-, 4-, 8- ,16-, 32- and 64-sample pools) with negative samples. Transport media of additional 3 positive samples were also tested when mixed with transport media of negative samples in pools of 8. RESULTS: A single positive sample can be detected in pools of up to 32 samples, using the standard kits and protocols, with an estimated false negative rate of 10%. Detection of positive samples diluted in even up to 64 samples may also be attainable, though may require additional amplification cycles. Single positive samples can be detected when pooling either after or prior to RNA extraction. CONCLUSIONS: As it uses the standard protocols, reagents and equipment, this pooling method can be applied immediately in current clinical testing laboratories. We hope that such implementation of a pool test for COVID-19 would allow expanding current screening capacities thereby enabling the expansion of detection in the community, as well as in close organic groups, such as hospital departments, army units, or factory shifts.", "qid": 6, "docid": "ywkfr2nw", "rank": 89, "score": 0.8367174863815308}, {"content": "Title: A new system in qualitative RT-PCR detecting SARS-CoV-2 in biological samples: an Italian experience. Content: In the last moths the world was faced with the pandemic of a new severe acute respiratory syndrome coronavirus (SARS-CoV) and the majority of the Nations have yet to come out of it. Numerous assays have emerged to meet SARS-CoV-2 diagnostic needs. A clear knowledge of these assays parameters is essential to choose the proper test by clinical microbiologists. Unfortunately, the latter cannot be the unique criterion that guides test selection as - given the great demand - shortcomings of commercial kits is also a great issue. Aimed by the intention of overcoming both difficulties we have developed a new qualitative RT-PCR probe based for COVID-19 detection. The system detects three genes of SARS-CoV-2: RNA-dependent RNA polymerase (RdRp), envelope (E) and nucleocapsid (N) and {beta}-actin gene used as endogenous internal control. The results of our assay show a total agreement with those obtained using a commercially available kit, with the exception of two specimens which did not pass the endogenous internal control. Moreover, our kit was designed to be open either for nucleic acid extraction step or on the RT-PCR assay to be carried out on several instruments. Thus, it is free from the industrial production logics of closed systems and conversely it is hypothetically available for distribution on large numbers in any microbiological laboratories. Presently, the kit is currently distributed worldwide", "qid": 6, "docid": "e8y56vkg", "rank": 90, "score": 0.8366262912750244}, {"content": "Title: Performance & Quality Evaluation of Marketed COVID-19 RNA Detection Kits Content: Compared to other coronaviruses, COVID-19 has a longer incubation period and features asymptomatic infection at a high rate (>25%). Therefore, early detection of infection is the key to early isolation and treatment. Direct detection of the virus itself has advantages over indirect detection. Currently, the most sensitive and commercially validated method for COVID-19 testing is RT-qPCR, designed to detect amplified virus-specific RNA. Reliable testing has proven to be a bottleneck in early diagnosis of virus infection in all countries dealing with the pandemic. Significant performance and quality issues with available testing kits have caused confusion and serious health risks. In order to provide better understanding of the Quality and performance of COVID-19 RNA detection kits on the market, we designed a system to evaluate the specificity (quantitation), sensitivity (LOD) and robustness of the kits using positive RNA and pseudovirus controls based on COVID-19 genomic sequence. We evaluated 8 Nucleic Acid qPCR Kits approved in China, some of which are also approved in the US and EU. Our study showed that half of these 8 kits lack 1:1 linear relationship for virus RNA copy: qPCR signal. Of the 4 with linear response, 2 demonstrated sensitivity at 1 Copy viral RNA/Reaction, suitable for early detection of virus infection. Furthermore, we established the best RNA extraction, handling and qPCR procedures allowing highly sensitive and consistent performance using BGI qPCR kits. Our study provides an effective method to assess and compare performance quality of all COVID-19 nucleic acid testing kits, globally.", "qid": 6, "docid": "ccx61owl", "rank": 91, "score": 0.8363922834396362}, {"content": "Title: Guidelines for Laboratory Diagnosis of Coronavirus Disease 2019 (COVID-19) in Korea Content: The outbreak of coronavirus disease 2019 (COVID-19), which began in December 2019, is still ongoing in Korea, with &gt;9,000 confirmed cases as of March 25, 2020 COVID-19 is a severe acute respiratory syndrome Coronavirus 2 (SARS-CoV-2) infection, and real-time reverse transcription-PCR is currently the most reliable diagnostic method for COVID-19 around the world Korean Society for Laboratory Medicine and the Korea Centers for Disease Prevention and Control propose guidelines for diagnosing COVID-19 in clinical laboratories in Korea These guidelines are based on other related domestic and international guidelines, as well as expert opinions and include the selection of test subjects, selection of specimens, diagnostic methods, interpretation of test results, and biosafety", "qid": 6, "docid": "jv3b0r15", "rank": 92, "score": 0.8363081216812134}, {"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": 93, "score": 0.8361040353775024}, {"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": 94, "score": 0.8359106779098511}, {"content": "Title: Evaluating the adequacy of Prima Covid-19 IgG/IgM Rapid Test for the assessment of exposure to SARS-CoV-2 virus Content: The outbreak of the SARS-CoV-2 in early 2020 found health authorities worldwide unprepared to control the pandemic. The adoption of accurate, rapid and inexpensive methods to identify infected subjects in the general population is of paramount relevance for the control of the disease. We evaluated one of the available serological tests, the Prima Lab Covid-19 IgG/IgM Rapid Tests, on 739 volunteers. We first assessed the test's reproducibility by administering it twice on the same day on 104 subjects obtaining and overall score of 93 percent. Since the intensity of the color in the test line regions varies depending on the concentration of Covid-19 antibodies in each sample and that the determination of the positivity depends strictly on the subjective assessment by the reader, after excluding the subjects whose color intensity was too tenuous to be deemed unquestionably positive by the reader the reproducibility increased to 96%. The test would not perform properly for 6 subjects for a very limited overall technical failure of 0.83%. For 138 subjects information was available regarding a previous Real Time PCR nasopharyngeal swab test performed elsewhere. The correspondence of positive results between the two tests was 90.58% (125/138). In spite of some limitation owing especially to the choice of a self selected population sample, we conclude that Prima Lab Covid-19 IgG/IgM Rapid Test represents a low-cost, easily applicable and reproducible tool in detecting SARS-Cov-2 diffusion in the general population.", "qid": 6, "docid": "b21myin4", "rank": 95, "score": 0.8358175754547119}, {"content": "Title: A simplified SARS-CoV-2 detection protocol for research laboratories Content: Widespread testing is required to limit the current public health crisis caused by the COVID-19 pandemic. Multiple tests protocols have been authorized by the food and drugs administration under an emergency use authorization (EUA). The majority of these protocols are based on the gold-standard RT-qPCR test pioneered by the U.S. Centers for Disease Control and Prevention. However, there is still a widespread lack of testing in the US and many of the clinical diagnostics protocols require extensive human labor and materials, such as RNA extraction kits, that could face supply shortages and present biosafety concerns. Given the need to develop alternative reagents and approaches to allow nucleic-acid testing in the face of heightened demand and potential shortages, we have developed a simplified SARS-CoV-2 testing protocol adapted for its use in laboratory research with minimal molecular biology equipment and expertise. The protocol requires minimal BSL1 biosafety level precautions and facilities.", "qid": 6, "docid": "d0nuoomk", "rank": 96, "score": 0.8355995416641235}, {"content": "Title: Development of a rapid test kit for SARS-CoV-2: an example of product design Content: We present an example of applying \u2018need-driven\u2019 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": "5enmq7do", "rank": 97, "score": 0.8350213766098022}, {"content": "Title: COVID-19 Molecular Testing in Korea: Practical Essentials and Answers From Experts Based on Experiences of Emergency Use Authorization Assays Content: Coronavirus disease 2019 (COVID-19) is a respiratory disease caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). Early detection of COVID-19 and immediate isolation of infected patients from the naive population are important to prevent further pandemic spread of the infection. Real-time reverse transcription (RT)-PCR to detect SARS-CoV-2 RNA is currently the most reliable diagnostic method for confirming COVID-19 worldwide. Guidelines for clinical laboratories on the COVID-19 diagnosis have been recently published by Korean Society for Laboratory Medicine and the Korea Centers for Disease Control and Prevention. However, these formal guidelines do not address common practical laboratory issues related to COVID-19 real-time RT-PCR testing and their solutions. Therefore, this guideline is intended as a practical and technical supplement to the \"Guidelines for Laboratory Diagnosis of COVID-19 in Korea\".", "qid": 6, "docid": "gsuoakuy", "rank": 98, "score": 0.8349589109420776}, {"content": "Title: COVID-19 Molecular Testing in Korea: Practical Essentials and Answers From Experts Based on Experiences of Emergency Use Authorization Assays. Content: Coronavirus disease 2019 (COVID-19) is a respiratory disease caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). Early detection of COVID-19 and immediate isolation of infected patients from the naive population are important to prevent further pandemic spread of the infection. Real-time reverse transcription (RT)-PCR to detect SARS-CoV-2 RNA is currently the most reliable diagnostic method for confirming COVID-19 worldwide. Guidelines for clinical laboratories on the COVID-19 diagnosis have been recently published by Korean Society for Laboratory Medicine and the Korea Centers for Disease Control and Prevention. However, these formal guidelines do not address common practical laboratory issues related to COVID-19 real-time RT-PCR testing and their solutions. Therefore, this guideline is intended as a practical and technical supplement to the \"Guidelines for Laboratory Diagnosis of COVID-19 in Korea\".", "qid": 6, "docid": "74uwqdew", "rank": 99, "score": 0.8349589109420776}, {"content": "Title: Sensitivity and specificity of a rapid test for assessment of exposure to SARS-CoV-2 in a community-based setting in Brazil Content: Background: While the recommended laboratory diagnosis of COVID-19 is a molecular based assay, population-based studies to determine the prevalence of COVID-19 usually use serological assays. Objective: To evaluate the sensitivity and specificity of a rapid diagnostic test for COVID-19 compared to quantitative reverse transcription polymerase chain reaction (qRT-PCR). Methods: We evaluated the sensitivity using a panel of finger prick blood samples from participants >18 years of age that had been tested for COVID-19 by qRT-PCR. For assessing specificity, we used serum samples from the 1982 Pelotas (Brazil) Birth Cohort participants collected in 2012 with no exposure to SARS-CoV-2. Results: The sensitivity of the test was 77.1% (95% CI 66.6 - 85.6), based upon 83 subjects who had tested positive for qRT-PCR at least 10 days before the rapid diagnostic test (RDT). Based upon 100 sera samples, specificity was 98.0% (95% CI 92.9 - 99.8). There was substantial agreement (Kappa score 0.76) between the qRT-PCR results and the RDT. Interpretation. The validation results are well in line with previous assessments of the test, and confirm that it is sufficiently precise for epidemiological studies aimed at monitoring levels and trends of the COVID-19 pandemic.", "qid": 6, "docid": "2siuovme", "rank": 100, "score": 0.8348543047904968}]}
{"query": "are there serological tests that detect antibodies to coronavirus?", "hits": [{"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": 1, "score": 0.8851456046104431}, {"content": "Title: Prevalence of antibody to human coronaviruses 229E, OC43 and neonatal calf diarrhea coronavirus (NCDCV) in patients of Northern Italy Content: A seroepidemiological study for detection of antibody to human coronaviruses OC43, 229E, and neonatal calf diarrhea coronavirus (NCDCV), has been carried out using sera collected from hospitalized patients or healthy persons through routine laboratory tests in Northern Italy. Patients tested were children and adults with different pathological diseases. Antibody detection was performed by using an indirect immunoperoxidase staining technique (for all viruses) and, in the case of OC43 and NCDCV, antibody detection was obtained even with a hemagglutination inhibition test and a plaque reduction neutralization assay. Results obtained show a significant difference in the prevalence of antibody to 229E between children and adult group. Furthermore, a different titer was observed, within the two groups, between patients affected by hematological diseases (leukemia) and patients with other diseases. Finally, our data seem to confirm previous studies reporting a very high prevalence of antibody to coronavirus OC43 but a less detectable seropositivity to coronavirus 229E.", "qid": 7, "docid": "576xiuz8", "rank": 2, "score": 0.8846198916435242}, {"content": "Title: Antibody Tests in Detecting SARS-CoV-2 Infection: A Meta-Analysis Content: The emergence of Coronavirus disease 2019 (COVID-19) caused by SARS-CoV-2 made imperative the need for diagnostic tests that can identify the infection. Although Nucleic Acid Test (NAT) is considered to be the gold standard, serological tests based on antibodies could be very helpful. However, individual studies are usually inconclusive, thus, a comparison of different tests is needed. We performed a systematic review and meta-analysis in PubMed, medRxiv and bioRxiv. We used the bivariate method for meta-analysis of diagnostic tests pooling sensitivities and specificities. We evaluated IgM and IgG tests based on Enzyme-linked immunosorbent assay (ELISA), Chemiluminescence Enzyme Immunoassays (CLIA), Fluorescence Immunoassays (FIA), and the Lateral Flow Immunoassays (LFIA). We identified 38 studies containing data from 7848 individuals. Tests using the S antigen are more sensitive than N antigen-based tests. IgG tests perform better compared to IgM ones and show better sensitivity when the samples were taken longer after the onset of symptoms. Moreover, a combined IgG/IgM test seems to be a better choice in terms of sensitivity than measuring either antibody alone. All methods yield high specificity with some of them (ELISA and LFIA) reaching levels around 99%. ELISA- and CLIA-based methods perform better in terms of sensitivity (90%\u201394%) followed by LFIA and FIA with sensitivities ranging from 80% to 89%. ELISA tests could be a safer choice at this stage of the pandemic. LFIA tests are more attractive for large seroprevalence studies but show lower sensitivity, and this should be taken into account when designing and performing seroprevalence studies.", "qid": 7, "docid": "3aoxplp3", "rank": 3, "score": 0.8774623870849609}, {"content": "Title: Kinetics of severe acute respiratory syndrome (SARS) coronavirus-specific antibodies in 271 laboratory-confirmed cases of SARS. Content: The sensitivities and specificities of an immunofluorescence assay and an enzyme immunoassay for detection of antibodies specific for severe acute respiratory syndrome coronavirus (SARS-CoV) were compared for 148 laboratory-confirmed SARS cases. The appearance and persistence of SARS-CoV-specific antibodies were assessed, with immunoglobulin G detected in 59% of samples collected within 14 days and persisting for 60 to 95 days after the onset of illness.", "qid": 7, "docid": "e28phe9y", "rank": 4, "score": 0.8772410154342651}, {"content": "Title: A serological assay to detect SARS-CoV-2 seroconversion in humans Content: SARS-Cov-2 (severe acute respiratory disease coronavirus 2), which causes Coronavirus Disease 2019 (COVID19) was first detected in China in late 2019 and has since then caused a global pandemic. While molecular assays to directly detect the viral genetic material are available for the diagnosis of acute infection, we currently lack serological assays suitable to specifically detect SARS-CoV-2 antibodies. Here we describe serological enzyme-linked immunosorbent assays (ELISA) that we developed using recombinant antigens derived from the spike protein of SARS-CoV-2. Using negative control samples representing pre-COVID 19 background immunity in the general adult population as well as samples from COVID19 patients, we demonstrate that these assays are sensitive and specific, allowing for screening and identification of COVID19 seroconverters using human plasma/serum as early as two days post COVID19 symptoms onset. Importantly, these assays do not require handling of infectious virus, can be adjusted to detect different antibody types and are amendable to scaling. Such serological assays are of critical importance to determine seroprevalence in a given population, define previous exposure and identify highly reactive human donors for the generation of convalescent serum as therapeutic. Sensitive and specific identification of coronavirus SARS-Cov-2 antibody titers may, in the future, also support screening of health care workers to identify those who are already immune and can be deployed to care for infected patients minimizing the risk of viral spread to colleagues and other patients.", "qid": 7, "docid": "ntra3jhs", "rank": 5, "score": 0.8758484721183777}, {"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": 6, "score": 0.8756766319274902}, {"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": 7, "score": 0.8756765723228455}, {"content": "Title: A line immunoassay utilizing recombinant nucleocapsid proteins for detection of antibodies to human coronaviruses Content: Abstract Most coronaviruses infecting humans cause mild diseases, whereas severe acute respiratory syndrome (SARS)-associated coronavirus is an extremely dangerous pathogen. Here, we report the development of a serologic assay for detection of antibodies to human coronaviruses (HCoVs) based on recombinant nucleocapsid (N) proteins of all known pathogenic strains (229E, NL63, OC43, HKU1, SARS). The novel immunoassay is highly useful for epidemiologic surveys, where use of nucleic acid diagnostics often is limited. Purified recombinant antigens were immobilized on nitrocellulose membranes and applied in a line immunoassay, which allows rapid detection of antibodies to 5 different HCoVs in a single experiment. For assay evaluation, serum samples from persons infected with 229E or OC43 (acute/convalescent), recovered SARS patients and healthy donors were analyzed. Screening for nucleocapsid (N)-specific immunoglobulin G (IgG) in convalescent sera reached 100% sensitivity. With this new technique, we found that recently identified NL63 and HKU1 contribute significantly to the overall spectrum of coronavirus infections. Possibly, cross-reactive antibody responses were observed using 229E and OC43 serum pairs. However, the potential of this assay could clearly be demonstrated employing SARS-positive serum samples, where nonspecific binding to nucleocapsids of other HCoVs was not observed. This coronavirus strain-specific line immunoassay represents a powerful tool for serologic diagnostics.", "qid": 7, "docid": "m400cal3", "rank": 8, "score": 0.8755817413330078}, {"content": "Title: Prevalence of canine coronavirus antibodies by an enzyme-linked immunosorbent assay in dogs in the south of Italy Content: Abstract An enzyme-linked immunosorbent assay (Elisa), using as antigen canine coronavirus-infected CrFK cell supernatant, was developed to detect antibodies against canine coronavirus (CCoV). Out of a total of 109 dog serum samples, 80 which were positive by routine virus neutralisation test were also Elisa positive. Seventeen samples which were negative by the virus neutralisation test, were positive by Elisa and by the confirmatory Western blotting test. The Elisa was substantially more sensitive than the virus neutralisation test in detecting antibodies to CCoV and may be used as an alternative technique to virus neutralisation.", "qid": 7, "docid": "j36vajdi", "rank": 9, "score": 0.8754476308822632}, {"content": "Title: Diagnostic accuracy of an automated chemiluminescent immunoassay for anti-SARS-CoV-2 IgM and IgG antibodies: an Italian experience Content: A pandemic of coronavirus disease 2019 (COVID-19) caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) has been spreading throughout the world. Though molecular diagnostic tests are the gold standard for COVID-19, serological testing is emerging as a potential surveillance tool, in addition to its complementary role in COVID-19 diagnostics. Indubitably quantitative serological testing provides greater advantages than qualitative tests but today there is still little known about serological diagnostics and what the most appropriate role quantitative tests might play. Sixty-one COVID-19 patients and 64 patients from a control group were tested by iFlash1800 CLIA analyzer for anti-SARS CoV-2 antibodies IgM and IgG. All COVID-19 patients were hospitalized in San Giovanni di Dio Hospital (Florence, Italy) and had a positive oro/nasopharyngeal swab reverse-transcription polymerase chain reaction result. The highest sensitivity with a very good specificity performance was reached at a cutoff value of 10.0 AU/mL for IgM and of 7.1 for IgG antibodies, hence near to the manufacturer's cutoff values of 10 AU/mL for both isotypes. The receiver operating characteristic curves showed area under the curve values of 0.918 and 0.980 for anti-SARS CoV-2 antibodies IgM and IgG, respectively. iFlash1800 CLIA analyzer has shown highly accurate results for the anti-SARS-CoV-2 antibodies profile and can be considered an excellent tool for COVID-19 diagnostics.", "qid": 7, "docid": "1dbeh8q7", "rank": 10, "score": 0.8739739060401917}, {"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": 11, "score": 0.8736720085144043}, {"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": 12, "score": 0.8731744885444641}, {"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": 13, "score": 0.8725648522377014}, {"content": "Title: Antibody Detection and Dynamic Characteristics in Patients with COVID-19 Content: BACKGROUND: The corona virus disease 2019 (COVID-19) caused by the corona virus 2 (SARS-CoV-2) has been rapidly spreading nationwide and abroad. A serologic test to identify antibody dynamics and response to SARS-CoV-2 was developed. METHODS: The antibodies against SARS-CoV-2 were detected by an enzyme-linked immunosorbent assay (ELISA) based on the recombinant nucleocapsid protein of SARS-CoV-2 in patients with confirmed or suspected COVID-19 at 3-40 days after symptom onset. The gold standard for COVID-19 diagnosis was nucleic acid testing for SARS-CoV-2 by RT-PCR. The serodiagnostic power of the specific IgM and IgG antibodies against SARS-CoV-2 was investigated in terms of sensitivity, specificity, positive predictive value (PPV), negative predictive value (NPV) and consistency rate. RESULTS: The seroconversion of specific IgM and IgG antibodies were observed as early as the 4th day after symptom onset. In the confirmed patients with COVID-19, sensitivity, specificity, PPV, NPV, and consistency rate of IgM were 77.3% (51/66), 100%, 100%, 80.0%, and 88.1%, and those of IgG were 83.3.3% (55/66), 95.0%, 94.8%, 83.8%, and 88.9 %. In patients with suspected COVID-19, sensitivity, specificity, PPV, NPV, and consistency rate of IgM were 87.5% (21/24), 100%, 100%, 95.2%, and 96.4%, and those of IgG were 70.8% (17/24), 96.6%, 85.0%, 89.1%, and 88.1%. Both antibodies performed well in serodiagnosis for COVID-19 rely on great specificity. CONCLUSIONS: The antibodies against SARS-CoV-2 can be detected in the middle and later stage of the illness. Antibody detection may play an important role in the diagnosis of COVID-19 as complement approach for viral nucleid acid assays.", "qid": 7, "docid": "cf2y1cfz", "rank": 14, "score": 0.8725627660751343}, {"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": 15, "score": 0.8722361922264099}, {"content": "Title: Antibody Detection and Dynamic Characteristics in Patients with COVID-19 Content: BACKGROUND: The corona virus disease 2019 (COVID-19) caused by the corona virus 2 (SARS-CoV-2) has been rapidly spreading nationwide and abroad. A serologic test to identify antibody dynamics and response to SARS-CoV-2 was developed. METHODS: The antibodies against SARS-CoV-2 were detected by an enzyme-linked immunosorbent assay (ELISA) based on the recombinant nucleocapsid protein of SARS-CoV-2 in patients with confirmed or suspected COVID-19 at 3-40 days after symptom onset. The gold standard for COVID-19 diagnosis was nucleic acid testing for SARS-CoV-2 by RT-PCR. The serodiagnostic power of the specific IgM and IgG antibodies against SARS-CoV-2 was investigated in terms of sensitivity, specificity, positive predictive value (PPV), negative predictive value (NPV) and consistency rate. RESULTS: The seroconversion of specific IgM and IgG antibodies were observed as early as the 4(th) day after symptom onset. In the confirmed patients with COVID-19, sensitivity, specificity, PPV, NPV, and consistency rate of IgM were 77.3% (51/66), 100%, 100%, 80.0%, and 88.1%, and those of IgG were 83.3.3% (55/66), 95.0%, 94.8%, 83.8%, and 88.9 %. In patients with suspected COVID-19, sensitivity, specificity, PPV, NPV, and consistency rate of IgM were 87.5% (21/24), 100%, 100%, 95.2%, and 96.4%, and those of IgG were 70.8% (17/24), 96.6%, 85.0%, 89.1%, and 88.1%. Both antibodies performed well in serodiagnosis for COVID-19 rely on great specificity. CONCLUSIONS: The antibodies against SARS-CoV-2 can be detected in the middle and later stage of the illness. Antibody detection may play an important role in the diagnosis of COVID-19 as complement approach for viral nucleid acid assays.", "qid": 7, "docid": "uhh3owcx", "rank": 16, "score": 0.8720980882644653}, {"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": 17, "score": 0.872017502784729}, {"content": "Title: Evaluation of the EDI enzyme linked immunosorbent assays for the detection of SARS-CoV-2 IgM and IgG antibodies in human plasma Content: BACKGROUND: Besides SARS-CoV-2 RT-PCR testing, serological testing is emerging as additional option in COVID-19 diagnostics. Aim of this study was to evaluate novel immunoassays for detection of SARS-CoV-2 antibodies in human plasma. METHODS: Using EDITM Novel Coronavirus COVID-19 Enzyme Linked Immunosorbent Assays (ELISAs), we measured SARS-CoV-2 IgM and IgG antibodies in 64 SARS-CoV-2 RT-PCR confirmed COVID-19 patients with serial blood samples (n = 104) collected at different time points from symptom onset. Blood samples from 200 healthy blood donors and 256 intensive care unit (ICU) patients collected before the COVID-19 outbreak were also used. RESULTS: The positivity rates in the COVID-19 patients were 5.9% for IgM and 2.9% for IgG &#8804; 5 days after symptom onset; Between day 5 and day 10 the positivity rates were 37.1% for IgM and 37.1% for IgG and rose to 76.4% for IgM and 82.4% for IgG after > 10-15 days. After 15-22 days the \"true\" positivity rates were 94.4% for IgM and 100% for IgG. The \"false\" positivity rates were 0.5% for IgM and 1.0% for IgG in the healthy blood donors, 1.6% for IgM and 1.2% for IgG in ICU patients. CONCLUSIONS: This study shows high \"true\" vs. low \"false\" positivity rates for the EDITM SARS-CoV-2 IgM and IgG ELISAs.", "qid": 7, "docid": "zvj00qjj", "rank": 18, "score": 0.87016361951828}, {"content": "Title: Diagnosis of COVID-19: Considerations, controversies and challenges Content: Coronavirus disease 2019 (COVID-19) due to a novel virus, severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), is a global pandemic that has resulted in over 1.5 million confirmed cases and close to 100 000 deaths. In the majority of symptomatic cases, COVID-19 results in a mild disease predominantly characterised by upper respiratory tract symptoms. Reverse transcription polymerase chain reaction (RT-PCR) using a nasopharyngeal sample is the mainstay of diagnosis, but there is an ~30% false negative rate early in the disease and in patients with mild disease, and therefore repeat testing may be required. RT-PCR positivity can persist for several days after resolution of symptoms. IgM and IgG antibody responses become positive several days after the onset of symptoms, and robust antibody responses are detectable in the second week of illness. Antibody-based immunoassays have a limited role in the diagnosis of early symptomatic disease. However, their incremental benefit over RT-PCR in the first 2 weeks of illness is currently being clarified in ongoing studies. Such assays may be useful for surveillance purposes. However, their role in potentially selecting individuals who may benefit from vaccination, or as a biomarker identifying persons who could be redeployed into essential employment roles, is being investigated. Rapid antibody-based immunoassays that detect viral antigen in nasopharyngeal samples are being developed and evaluated.", "qid": 7, "docid": "chp63f69", "rank": 19, "score": 0.8697873950004578}, {"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": 20, "score": 0.8697507381439209}, {"content": "Title: Performance Characteristics of the Abbott Architect SARS-CoV-2 IgG Assay and Seroprevalence Testing in Idaho Content: Coronavirus disease-19 (COVID19), the novel respiratory illness caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), is associated with severe morbidity and mortality. The rollout of diagnostic testing in the United States was slow, leading to numerous cases that were not tested for SARS-CoV-2 in February and March 2020, necessitating the use of serological testing to determine past infections. Here, we evaluated the Abbott SARS-CoV-2 IgG test for detection of anti-SARS-CoV-2 IgG antibodies by testing 3 distinct patient populations. We tested 1,020 serum specimens collected prior to SARS-CoV-2 circulation in the United States and found one false positive, indicating a specificity of 99.90%. We tested 125 patients who tested RT-PCR positive for SARS-CoV-2 for which 689 excess serum specimens were available and found sensitivity reached 100% at day 17 after symptom onset and day 13 after PCR positivity. Alternative index value thresholds for positivity resulted in 100% sensitivity and 100% specificity. We then tested 4,856 individuals from Boise, Idaho collected over one week in April 2020 as part of the Crush the Curve initiative and detected 87 positives for a positivity rate of 1.79%. These data demonstrate excellent analytical performance of the Abbott SARS-CoV-2 IgG test as well as the limited circulation of the virus on the West Coast. We expect the availability of high-quality serological testing will be a key tool in the fight against SARS-CoV-2.", "qid": 7, "docid": "e3e48idb", "rank": 21, "score": 0.8694621324539185}, {"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": 22, "score": 0.8688258528709412}, {"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": 7, "docid": "bah2ege0", "rank": 23, "score": 0.8683485984802246}, {"content": "Title: Diagnosis of COVID-19: Considerations, Controversies and Challenges in South Africa Content: Coronavirus disease 2019 (COVID-19) due to severe acute respiratory syndrome coronavirus 2 is a global pandemic that has resulted in over 1.5 million confirmed cases and close to 100,000 deaths. In the majority of symptomatic cases COVID-19 results in a mild disease predominantly characterised by upper respiratory tract symptoms. Reverse transcription polymerase chain reaction (RT-PCR), using a nasopharyngeal sample, is the mainstay of diagnosis, but there is an ~30% false negative rate early in the disease and in patients with mild disease. RT-PCR positivity can persist for several days after a resolution of symptoms. IgM and IgG antibody responses become positive several days after the onset of symptoms, and robust antibody responses are detectable in the second week of illness. Antibody-based immunoassays have a limited role in the diagnosis of early symptomatic disease. However, their incremental benefit over RT-PCR in the first 2 weeks of illness is currently being clarified in ongoing studies. Such assays may be useful for surveillance purposes. However, their role in potentially selecting individuals that may benefit from vaccination, or as a biomarker identifying persons that could be redeployed into essential employment roles are being investigated. Rapid antibody-based immunoassays that detect viral antigen in nasopharyngeal samples are being developed and evaluated.", "qid": 7, "docid": "eh3ztsv5", "rank": 24, "score": 0.8682749271392822}, {"content": "Title: Performance Characteristics of the Abbott Architect SARS-CoV-2 IgG Assay and Seroprevalence in Boise, Idaho Content: Coronavirus disease-19 (COVID19), the novel respiratory illness caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), is associated with severe morbidity and mortality. The rollout of diagnostic testing in the United States was slow, leading to numerous cases that were not tested for SARS-CoV-2 in February and March 2020, necessitating the use of serological testing to determine past infections. Here, we evaluated the Abbott SARS-CoV-2 IgG test for detection of anti-SARS-CoV-2 IgG antibodies by testing 3 distinct patient populations. We tested 1,020 serum specimens collected prior to SARS-CoV-2 circulation in the United States and found one false positive, indicating a specificity of 99.90%. We tested 125 patients who tested RT-PCR positive for SARS-CoV-2 for which 689 excess serum specimens were available and found sensitivity reached 100% at day 17 after symptom onset and day 13 after PCR positivity. Alternative index value thresholds for positivity resulted in 100% sensitivity and 100% specificity in this cohort. We tested 4,856 individuals from Boise, Idaho collected over one week in April 2020 as part of the Crush the Curve initiative and detected 87 positives for a positivity rate of 1.79%. These data demonstrate excellent analytical performance of the Abbott SARS-CoV-2 IgG test as well as the limited circulation of the virus in the western United States. We expect the availability of high-quality serological testing will be a key tool in the fight against SARS-CoV-2.", "qid": 7, "docid": "9je1v09f", "rank": 25, "score": 0.8681566119194031}, {"content": "Title: Performance Characteristics of the Abbott Architect SARS-CoV-2 IgG Assay and Seroprevalence in Boise, Idaho. Content: Coronavirus disease-19 (COVID19), the novel respiratory illness caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), is associated with severe morbidity and mortality. The rollout of diagnostic testing in the United States was slow, leading to numerous cases that were not tested for SARS-CoV-2 in February and March 2020, necessitating the use of serological testing to determine past infections. Here, we evaluated the Abbott SARS-CoV-2 IgG test for detection of anti-SARS-CoV-2 IgG antibodies by testing 3 distinct patient populations. We tested 1,020 serum specimens collected prior to SARS-CoV-2 circulation in the United States and found one false positive, indicating a specificity of 99.90%. We tested 125 patients who tested RT-PCR positive for SARS-CoV-2 for which 689 excess serum specimens were available and found sensitivity reached 100% at day 17 after symptom onset and day 13 after PCR positivity. Alternative index value thresholds for positivity resulted in 100% sensitivity and 100% specificity in this cohort. We tested 4,856 individuals from Boise, Idaho collected over one week in April 2020 as part of the Crush the Curve initiative and detected 87 positives for a positivity rate of 1.79%. These data demonstrate excellent analytical performance of the Abbott SARS-CoV-2 IgG test as well as the limited circulation of the virus in the western United States. We expect the availability of high-quality serological testing will be a key tool in the fight against SARS-CoV-2.", "qid": 7, "docid": "uyq6urw3", "rank": 26, "score": 0.8681566119194031}, {"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": 27, "score": 0.8673487901687622}, {"content": "Title: Cross-reaction of SARS-CoV antigen with autoantibodies in autoimmune diseases. Content: To investigate the significance of the SARS-associated coronavirus (SARS-CoV) antibody, detected by ELISA and indirect immunofluorescence assays (IFA) for the SARS-CoV Vero E6 cell lysates, in non-SARS subjects, 114 serum samples from healthy controls and 104 serum specimens from autoimmune disease patients were collected. The results of ELISA showed that among 114 sera from healthy controls, 4 (3.5%) were positive of SARS-CoV-IgG antibody and 114 (100%) were all negative of SARS-CoV-IgM antibody; the specificity of SARS-CoV-IgG antibody for SARS patients was 96.5%, but the specificity of both SARS-CoV-IgG and -IgM antibodies for SARS patients was 100%. In 58 cases with SLE, positive rates of SARS-CoV-IgG and -IgM antibodies were 32.8% (19/58) and 8.6% (5/58), respectively, in which 11 cases (19%) were positive of both SARS-CoV-IgG and -IgM antibodies; in 10 cases with SS, positive rate of both SARS-CoV-IgG and -IgM antibodies was 10% (1/10); in 16 cases with MCTD, positive rate of SARS-CoV-IgG was 37.5% (6/16), positive rate of both SARS-CoV-IgG and -IgM antibodies was 6.3% (1/16); in 20 cases with RA, one case was positive (5%) of SARS-CoV-IgG. However, of all samples with positive SARS-CoV-IgG and -IgM antibodies for autoimmune diseases and healthy controls, SARS-CoV RNA and antibodies were all negative by RT-PCR and IFA. All sera for negative or positive ELISA results were also negative or positive results using ELISA with Vero E6 cells lysates. These studies showed that SARS-CoV Vero E6 cell lysates for the ELISA to detect SARS-CoV antibodies could lead to the false-positive reactions or cross-reactions of SARS-CoV antibodies in non-SARS diseases and healthy controls, and the false-positive reactions or cross-reactions were related to Vero E6 cell lysates and autoantibodies in non-SARS population.", "qid": 7, "docid": "1btyocn4", "rank": 28, "score": 0.8666694164276123}, {"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": 29, "score": 0.8659049272537231}, {"content": "Title: Towards the next phase: evaluation of serological assays for 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 comprehensive comparison of serological COVID-19 assays. We show that the assay detecting total immunoglobulins against the receptor binding domain of SARS CoV-2, had optimal characteristics for antibody detection in different stages of disease.", "qid": 7, "docid": "nxy21x7k", "rank": 30, "score": 0.8652737140655518}, {"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": 31, "score": 0.8652253150939941}, {"content": "Title: Specific serology for emerging human coronaviruses by protein microarray. Content: We present a serological assay for the specific detection of IgM and IgG antibodies against the emerging human coronavirus hCoV-EMC and the SARS-CoV based on protein microarray technology. The assay uses the S1 receptor-binding subunit of the spike protein of hCoV-EMC and SARS-CoV as antigens. The assay has been validated extensively using putative cross-reacting sera of patient cohorts exposed to the four common hCoVs and sera from convalescent patients infected with hCoV-EMC or SARS-CoV.", "qid": 7, "docid": "79bzd4nl", "rank": 32, "score": 0.8652150630950928}, {"content": "Title: Antigenic relationships amongst coronaviruses Content: Several serological interrelationships between various members of the corona-virus group have been revealed in neutralization, complement fixation, and gel-diffusion tests, using human and hyperimmune animal sera. Several members of this group of human and animal pathogens are shown to cross-react in one or more type of test, but one member, avian infectious bronchitis virus, was shown to be unrelated. Mouse hepatitis virus (MHV(3)) was found to be antigenically related to a number of human types of coronavirus. Difficulties were encountered in the investigation of paired human sera in demonstrating the specificity of antibody rises, placing doubt on the values of some serological studies. The significance of these interrelationships is discussed in the light of other investigations.", "qid": 7, "docid": "cxt9oq0j", "rank": 33, "score": 0.8652141094207764}, {"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": 34, "score": 0.864397406578064}, {"content": "Title: Evaluation of the EDI enzyme linked immunosorbent assays for the detection of SARS-CoV-2 IgM and IgG antibodies in human plasma Content: BACKGROUND: Besides SARS-CoV-2 RT-PCR testing, serological testing is emerging as additional option in COVID-19 diagnostics. Aim of this study was to evaluate novel immunoassays for detection of SARS-CoV-2 antibodies in human plasma. METHODS: Using EDI(TM) Novel Coronavirus COVID-19 Enzyme Linked Immunosorbent Assays (ELISAs), we measured SARS-CoV-2 IgM and IgG antibodies in 64 SARS-CoV-2 RT-PCR confirmed COVID-19 patients with serial blood samples (n=104) collected at different time points from symptom onset. Blood samples from 200 healthy blood donors and 256 intensive care unit (ICU) patients collected before the COVID-19 outbreak were also used. RESULTS: The positivity rates in the COVID-19 patients were 5.9% for IgM and 2.9% for IgG \u22645 days after symptom onset; Between day 5 and day 10 the positivity rates were 37.1% for IgM and 37.1% for IgG and rose to 76.4% for IgM and 82.4% for IgG after >10-15 days. After 15-22 days the \u201ctrue\u201d positivity rates were 94.4% for IgM and 100% for IgG. The \u201cfalse\u201d positivity rates were 0.5% for IgM and 1.0% for IgG in the healthy blood donors, 1.6% for IgM and 1.2% for IgG in ICU patients. CONCLUSIONS: This study shows high \u201ctrue\u201d vs. low \u201cfalse\u201d positivity rates for the EDI(TM) SARS-CoV-2 IgM and IgG ELISAs.", "qid": 7, "docid": "uqg2xkie", "rank": 35, "score": 0.8643582463264465}, {"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": 36, "score": 0.8642248511314392}, {"content": "Title: Detection of bovine coronavirus by enzyme-linked immunosorbent assay using monoclonal antibodies. Content: A sensitive and highly specific enzyme-linked immunosorbent assay (ELISA) system for detection of bovine coronavirus was developed using monoclonal antibodies, which showed both neutralization and hemagglutination inhibition activities. A monoclonal antibody was coated onto microplates for capturing antigen and a mixture of two monoclonal antibodies served as detecting antibodies. Using this assay, 40 of 202 fecal specimens from 29 herds were shown to be positive for viral antigen. From 10 ELISA positive specimens from 5 herds, the virus was isolated after several passages on human rectal adenocarcinoma (HRT-18) cell culture.", "qid": 7, "docid": "sza605p7", "rank": 37, "score": 0.8640822172164917}, {"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": 38, "score": 0.8636816740036011}, {"content": "Title: Are antibodies tests accurate? Understanding predictive values and uncertainty of serology tests for the novel coronavirus. Content: Antibodies testing in the coronavirus era is frequently promoted, but the underlying statistics behind their validation has come under more scrutiny in recent weeks. We provide calculations, interpretations, and plots of positive and negative predictive values under a variety of scenarios. Prevalence, sensitivity, and specificity are estimated within ranges of values from researchers and antibodies manufacturers. Illustrative examples are highlighted, and interactive plots are provided in the Supplementary Material. Implications are discussed for society overall and across diverse locations with different levels of disease burden. Specifically, the proportion of positive serology tests that are false can differ drastically from up to 3% to 88% for people from different places with different proportions of infected people in the populations while the false negative rate is typically under 10%.", "qid": 7, "docid": "k54lmjxk", "rank": 39, "score": 0.8636095523834229}, {"content": "Title: Antibody tests in detecting SARS-CoV-2 infection: a meta-analysis Content: With the emergence of SARS-CoV-2 and the associated Coronavirus disease 2019 (COVID-19), there is an imperative need for diagnostic tests that can identify the infection. Although Nucleic Acid Test (NAT) is considered to be the gold standard, serological tests based on antibodies could be very helpful. However, individual studies measuring the accuracy of the various tests are usually underpowered and inconsistent, thus, a comparison of different tests is needed. We performed a systematic review and meta-analysis following the PRISMA guidelines. We conducted the literature search in PubMed, medRxiv and bioRxiv. For the statistical analysis we used the bivariate method for meta-analysis of diagnostic tests pooling sensitivities and specificities. We evaluated IgM and IgG tests based on Enzyme-linked immunosorbent assay (ELISA), Chemiluminescence Enzyme Immunoassays (CLIA), Fluorescence Immunoassays (FIA) and the point-of-care (POC) Lateral Flow Immunoassays (LFIA) that are based on immunochromatography. In total, we identified 38 eligible studies that include data from 7,848 individuals. The analyses showed that tests using the S antigen are more sensitive than N antigen-based tests. IgG tests perform better compared to IgM ones, and show better sensitivity when the samples were taken longer after the onset of symptoms. Moreover, irrespective of the method, a combined IgG/IgM test seems to be a better choice in terms of sensitivity than measuring either antibody type alone. All methods yielded high specificity with some of them (ELISA and LFIA) reaching levels around 99%. ELISA- and CLIA-based methods performed better in terms of sensitivity (90-94%) followed by LFIA and FIA with sensitivities ranging from 80% to 86%. ELISA tests could be a safer choice at this stage of the pandemic. POC tests (LFIA), that are more attractive for large seroprevalence studies show high specificity but lower sensitivity and this should be taken into account when designing and performing seroprevalence studies.", "qid": 7, "docid": "yfyd2ysn", "rank": 40, "score": 0.8631278276443481}, {"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": 7, "docid": "0yj3xp9s", "rank": 41, "score": 0.8629892468452454}, {"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": 7, "docid": "0jl6qu0i", "rank": 42, "score": 0.8629892468452454}, {"content": "Title: Serological detection of 2019-nCoV respond to the epidemic: A useful complement to nucleic acid testing Content: Corona Virus Disease 2019 (COVID-19) has spread rapidly to more than 70 countries and regions overseas and over 80000 cases have been infected, resulting in more than three thousand deaths. Rapid diagnosis of patients remains a bottleneck in containing the progress of the epidemic. We used automated chemiluminescent immunoassay to detect serum IgM and IgG antibodies to 2019-nCoV of 736 subjects. COVID-19 patients were becoming reactive(positive) for specific antibodies from 7-12 days after the onset of morbidity. Specific IgM and IgG increased with the progression of the disease. The areas under the ROC curves of IgM and IgG were 0.988 and 1.000, respectively. Specific antibody detection has good sensitivity and specificity. Detection of specific antibodies in patients with fever can be a good distinction between COVID-19 and other diseases, so as to be a complement to nucleic acid diagnosis to early diagnosis of suspected cases.", "qid": 7, "docid": "na8odvj7", "rank": 43, "score": 0.8627184629440308}, {"content": "Title: Serologic Detection of Middle East Respiratory Syndrome Coronavirus Functional Antibodies Content: We developed and validated 2 species-independent protein-based assays to detect Middle East respiratory syndrome coronavirus functional antibodies that can block virus receptor-binding or sialic acid-attachment. Antibody levels measured in both assays correlated strongly with virus-neutralizing antibody titers, proving their use for serologic confirmatory diagnosis of Middle East respiratory syndrome.", "qid": 7, "docid": "blrfn8qh", "rank": 44, "score": 0.8623483777046204}, {"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": 7, "docid": "9skvbk8m", "rank": 45, "score": 0.8622438311576843}, {"content": "Title: Use of the COOH portion of the nucleocapsid protein in an antigen-capturing enzyme-linked immunosorbent assay for specific and sensitive detection of severe acute respiratory syndrome coronavirus. Content: Antibody detection with a recombinant COOH portion of the severe acute respiratory syndrome (SARS) coronavirus nucleocapsid (N) protein, N13 (amino acids 221 to 422), was demonstrated to be more specific and sensitive than that with the full-length N protein, and an N13-based antigen-capturing enzyme-linked immunosorbent assay providing a convenient and specific test for serodiagnosis and epidemiological study of SARS was developed.", "qid": 7, "docid": "dyutsd8t", "rank": 46, "score": 0.8622289896011353}, {"content": "Title: A HIGH THROUGH-PUT ASSAY FOR CIRCULATING ANTIBODIES DIRECTED AGAINST THE S PROTEIN OF SEVERE ACUTE RESPIRATORY SYNDROME CORONAVIRUS 2 (SARS-CoV-2) Content: BACKGROUND. More than one million infections with the severe acute respiratory syndrome corona virus 2 (SARS-CoV-2) have been confirmed. While PCR-based assays are used for diagnosis, high through-put serologic methods are needed to detect antibodies for seroserveillance and for identification of seroconversion, potential plasma donors, and the nature of the immune response to this pathogen. METHODS. A Luminex binding assay was used to assess the presence of antibodies in human sera from COVID-19-infected and -uninfected individuals specific for two recombinant proteins of SARS-CoV-2. FINDINGS. Fluorochrome-labeled beads were coated with a recombinant soluble stabilized trimeric SARS-CoV-2 S protein ectodomain or its central portion, the receptor binding domain (RBD). Coated beads were incubated with sera, followed by incubation with biotinylated anti-human total Ig antibodies and phycoerythrin (PE)-labeled streptavidin. Readout using a Luminex analyzer clearly differentiated between sera of the infected and uninfected subjects, delineating a wide range of serum antibody levels in infected subjects. INTERPRETATION. Antibody assays of sera can identify individuals who are infected with SARS-CoV-2 and have seroconverted, as well as subjects who have been infected and recovered. The use of the Luminex binding Ab assay has the advantage that it can be run in approximately 2.5 hours, uses very little antigen, and permits a high through-put of samples/day. FUNDING. NIAID contracts and grants, Department of Veterans Affairs\u2019 grants, the Microbiology Laboratory Clinical Services, Translational Science Hub, and Personalized Virology Initiative, and Department of Medicine of Mount Sinai Health System and Icahn School of Medicine at Mount Sinai.", "qid": 7, "docid": "9iwjtwyx", "rank": 47, "score": 0.8619722127914429}, {"content": "Title: Prevalence of coronavirus antibodies in rabbits. Content: Antibodies to coronavirus were detected by an indirect fluorescent antibody test in rabbit sera from six rabbitries. The prevalence ranged from 3 to 40% in different rabbitries and most seropositive rabbits were more than 4 months old. A rabbitry with high prevalence of antibodies and high incidence of diarrhea could serve as a source of virus and aid in studying the natural history of coronavirus infection in rabbits.", "qid": 7, "docid": "hn69l5mq", "rank": 48, "score": 0.8619657754898071}, {"content": "Title: [Acute respiratory disease caused by coronaviruses]. Content: Serological evidence of coronavirus aetiology was found in 11 patients out of 218 persons examined (5%) in the period of 1986-1987, and in 23 cases out of 311 patients (7.4%) in the period of 1987-1988. Antibody titres with a minimum of four-time elevated values in paired sera using the ELISA method were considered conclusive. Coronaviruses 229E and OC43 were employed. During the first period, more persons were infected by coronavirus 229E, while in the second period, by coronavirus OC43. The disease was equally spread over all the months of the years. For example, in the 1987-1988 period, most infections occurred in February, when out of 60 examined patients, 9 were coronavirus positive (15%).", "qid": 7, "docid": "sl1yd3ym", "rank": 49, "score": 0.8617331981658936}, {"content": "Title: Evaluation of the EUROIMMUN Anti-SARS-CoV-2 ELISA Assay for detection of IgA and IgG antibodies Content: As the Coronavirus 2019 (COVID-19) pandemic evolves, the development of immunoassays to help determine exposure and potentially predict immunity has become a pressing priority. In this report we present the performance of the EUROIMMUN enzyme-linked immunosorbent assay (ELISA) for semi-quantitative detection of IgA and IgG antibodies in serum and plasma samples using recombinant S1 domain of the SARS-CoV-2 spike protein as antigen. Specimens from patients, with and without COVID-19 infection, were tested at the University of Chicago Clinical Microbiology and Immunology Laboratory. Of 86 samples from COVID-19 PCR-negative patients, including 28 samples positive for common human coronavirus strains, 76 tested negative and 10 tested positive for IgA (88.4% agreement, 95% CI: 79.9\u201393.6) while 84 tested negative and 2 tested positive for IgG (97.7% agreement, 95% CI: 91.9\u201399.6). Of 82 samples from COVID-19 PCR-positive patients, 14 tested negative and 68 tested positive for IgA (82.9% agreement, 95% CI: 73.4\u201389.5) while 27 tested negative and 55 tested positive for IgG (67.1% agreement, 95% CI: 56.3\u201376.3). Samples collected \u22654 days after positive PCR 38 of 42 (90.5% CI: 77.9\u201396.2) were positive for IgA, and 42 of 42 (100% 95% CI: 91.6\u2013100) were positive for IgG, respectively. The EUROIMMUN Anti-SARS-CoV-2 ELISA Assay demonstrates good sensitivity for detection of IgA and excellent sensitivity for detection of IgG antibodies from samples collected \u22654 days, after COVID-19 diagnosis by PCR. This assay demonstrated only borderline cross reaction in 2 of the 28 samples from patients with common human coronaviruses infection, types NL63 and OC43.", "qid": 7, "docid": "n3lrzw3o", "rank": 50, "score": 0.8615182638168335}, {"content": "Title: Evaluation of the EUROIMMUN Anti-SARS-CoV-2 ELISA Assay for detection of IgA and IgG antibodies Content: As the Coronavirus 2019 (COVID-19) pandemic evolves, the development of immunoassays to help determine exposure and potentially predict immunity has become a pressing priority. In this report we present the performance of the EUROIMMUN enzyme-linked immunosorbent assay (ELISA) for semi-quantitative detection of IgA and IgG antibodies in serum and plasma samples using recombinant S1 domain of the SARS-CoV-2 spike protein as antigen. Specimens from patients, with and without COVID-19 infection, were tested at the University of Chicago Clinical Microbiology and Immunology Laboratory. Of 57 samples from COVID-19 PCR-negative patients, including 28 samples positive for common human coronavirus strains, 53 tested negative and 4 tested positive for IgA (93.0% agreement) while 56 tested negative and 1 tested positive for IgG (98.2% agreement). For COVID-19 PCR-positive patients, 29 of 30 (96.7%) samples collected \u22653 days after positive PCR were positive for IgA, and 28 of 28 samples collected \u22654 days after positive PCR were positive for IgG. The EUROIMMUN Anti-SARS-CoV-2 ELISA Assay demonstrates excellent sensitivity for detection of IgA and IgG antibodies from samples collected \u22653 days and \u22654 days, respectively, after COVID-19 diagnosis by PCR. This assay did not demonstrate cross reaction in any of the 28 samples from patients with common human coronaviruses, including types HKU1, NL63, CV229E, and OC43.", "qid": 7, "docid": "jzpwo5un", "rank": 51, "score": 0.86133873462677}, {"content": "Title: Coronative antibody tires in sera of healthy adults and experimentally infected volunteers. Content: Six coronaviruses isolated in the U.S.A. have been inoculated into volunteers and all produced colds. Between 10 and 20% of infected volunteers developed heterologous antibody responses after these and other experimental infections with coronaviruses. The haemagglutination-inhibition test with the OC43 virus strain was found to detect antibody rises after infection with a variety of strains.Studies on normal adult sera taken between 1965 and 1970 revealed a high frequency of neutralizing antibody to one strain (229 E) and a frequency of HI antibody to strain OC43 which fluctuated from year to year. Complement-fixing antibodies to these two viruses were also found, revealing an apparent increase in the activity of coronaviruses in the general population of the U.K., during the winter of 1968-9.", "qid": 7, "docid": "utnqvdvl", "rank": 52, "score": 0.8612697124481201}, {"content": "Title: Establishment and Characterization of Monoclonal Antibodies Against SARS Coronavirus Content: Immunological detection of viruses and their components by monoclonal antibodies is a powerful method for studying the structure and function of viral molecules. Here we describe detailed methods for establishing monoclonal antibodies against severe acute respiratory syndrome coronavirus (SARS-CoV). B cell hybridomas are generated from mice that are hyperimmunized with inactivated SARS-CoV virions. The hybridomas produce monoclonal antibodies that recognize viral component molecules, including the spike protein (S) and the nucleocapsid protein (N), enabling the immunological detection of SARS-CoV by immunofluorescence staining, immunoblot, or an antigen-capture ELISA system. In addition, several S protein-specific antibodies are shown to have in vitro neutralization activity. Thus the monoclonal antibody approach provides useful tools for rapid and specific diagnosis of SARS, as well as for possible antibody-based treatment of the disease.", "qid": 7, "docid": "r0x8yaqj", "rank": 53, "score": 0.8611278533935547}, {"content": "Title: Evaluation of commercial and automated SARS-CoV-2 IgG and IgA ELISAs using coronavirus disease (COVID-19) patient samples Content: Antibody-screening methods to detect severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) need to be validated. We evaluated SARS-CoV-2 IgG and IgA ELISAs in conjunction with the EUROLabworkstation (Euroimmun, L\u00fcbeck, Germany). Overall specificities were 91.9% and 73.0% for IgG and IgA ELISAs, respectively. Of 39 coronavirus disease patients, 13 were IgG and IgA positive and 11 IgA alone at sampling. IgGs and IgAs were respectively detected at a median of 12 and 11 days after symptom onset.", "qid": 7, "docid": "5najee33", "rank": 54, "score": 0.8610683679580688}, {"content": "Title: Evaluation of the EUROIMMUN Anti-SARS-CoV-2 ELISA Assay for detection of IgA and IgG antibodies Content: As the Coronavirus 2019 (COVID-19) pandemic evolves, the development of immunoassays to help determine exposure and potentially predict immunity has become a pressing priority. In this report we present the performance of the EUROIMMUN enzyme-linked immunosorbent assay (ELISA) for semi-quantitative detection of IgA and IgG antibodies in serum and plasma samples using recombinant S1 domain of the SARS-CoV-2 spike protein as antigen. Specimens from patients, with and without COVID-19 infection, were tested at the University of Chicago Clinical Microbiology and Immunology Laboratory. Of 86 samples from SARS-CoV-2 PCR-negative patients, including 28 samples positive for common human coronavirus strains, 76 tested negative and 10 tested positive for IgA (88.4% agreement, 95% CI: 79.9-93.6) while 84 tested negative and 2 tested positive for IgG (97.7% agreement, 95% CI: 91.9-99.6). Of 82 samples from SARS-CoV-2 PCR-positive patients, 14 tested negative and 68 tested positive for IgA (82.9% agreement, 95% CI: 73.4-89.5) while 27 tested negative and 55 tested positive for IgG (67.1% agreement, 95% CI: 56.3-76.3). Of samples collected &#8805;4 days after positive PCR, 38 of 42 (90.5% agreement, 95% CI: 77.9-96.2) were positive for IgA, and 42 of 42 (100% agreement, 95% CI: 91.6-100) were positive for IgG, respectively. The EUROIMMUN Anti-SARS-CoV-2 ELISA Assay demonstrated good sensitivity for detection of IgA and excellent sensitivity for detection of IgG antibodies from samples collected &#8805;4 days, after COVID-19 diagnosis by PCR. This assay demonstrated good specificity for IgA and excellent specificity for IgG and demonstrated only borderline cross reaction in 2 of the 28 samples from patients with common human coronaviruses infection, types NL63 and OC43.", "qid": 7, "docid": "nbqxy846", "rank": 55, "score": 0.8606833219528198}, {"content": "Title: Characteristics of patients with coronavirus disease (COVID-19) confirmed using an IgM-IgG antibody test Content: Coronavirus disease (COVID-19), caused by a novel betacoronavirus, severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), has rapidly developed into a pandemic since it was first reported in December 2019. Nucleic acid testing is the standard method for the diagnosis of viral infections. However, this method reportedly has a low positivity rate. To increase the sensitivity of COVID-19 diagnoses, we developed an IgM-IgG combined assay and tested it in patients with suspected SARS-CoV-2 infection. In total, 56 patients were enrolled in this study and SARS-CoV-2 was detected by using both IgM-IgG antibody and nucleic acid tests. Clinical and laboratory data were collected and analyzed. Our findings suggest that patients who develop severe illness might experience longer virus exposure times and develop a more severe inflammatory response. The IgM-IgG test is an accurate and sensitive diagnostic method. A combination of nucleic acid and IgM-IgG testing is a more sensitive and accurate approach for diagnosis and early treatment of COVID-19.", "qid": 7, "docid": "xwjl3mjp", "rank": 56, "score": 0.8606059551239014}, {"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": 57, "score": 0.8602209091186523}, {"content": "Title: Pre-existing and de novo humoral immunity to SARS-CoV-2 in humans Content: Several related human coronaviruses (HCoVs) are endemic in the human population, causing mild respiratory infections1. Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2), the etiologic agent of Coronavirus disease 2019 (COVID-19), is a recent zoonotic infection that has quickly reached pandemic spread2,3. Zoonotic introduction of novel coronaviruses is thought to occur in the absence of pre-existing immunity in the target human population. Using diverse assays for detection of antibodies reactive with the SARS-CoV-2 Spike (S) glycoprotein, we demonstrate the presence of pre-existing immunity in uninfected and unexposed humans to the new coronavirus. SARS-CoV-2 S-reactive antibodies, exclusively of the IgG class, were readily detectable by a sensitive flow cytometry-based method in SARS-CoV-2-uninfected individuals with recent HCoV infection and targeted the S2 subunit. In contrast, SARS-CoV-2 infection induced higher titres of SARS-CoV-2 S-reactive IgG antibodies, as well as concomitant IgM and IgA antibodies throughout the observation period of 6 weeks since symptoms onset. HCoV patient sera also variably reacted with SARS-CoV-2 S and nucleocapsid (N), but not with the S1 subunit or the receptor binding domain (RBD) of S on standard enzyme immunoassays. Notably, HCoV patient sera exhibited specific neutralising activity against SARS-CoV-2 S pseudotypes, according to levels of SARS-CoV-2 S-binding IgG and with efficiencies comparable to those of COVID-19 patient sera. Distinguishing pre-existing and de novo antibody responses to SARS-CoV-2 will be critical for serology, seroprevalence and vaccine studies, as well as for our understanding of susceptibility to and natural course of SARS-CoV-2 infection.", "qid": 7, "docid": "n0actmsc", "rank": 58, "score": 0.8596054315567017}, {"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": 59, "score": 0.8594317436218262}, {"content": "Title: [Analysis of false-positive associated with antibody tests for SARS-CoV in SLE patients]. Content: To discuss the false-positive of serological diagnostic testing for coronavirus antibody in patients with systemic lupus erythematosus(SLE), 66 normal individual and 31 SLE with non-SARS patients were detected for SARS-associated coronavirus (SARS-CoV) antibody and RNA by enzymelinked immunosorbent assays(ELISA) and reverse transcriptase-polymerase chain reaction(RT-PCR). The result showed 2/66 cases(3.0%) were positive of SARS-CoV-IgG antibody and 66 cases were negative of SARS-CoV-IgM antibody in the 66 cases healthy controls; in 31 cases with SLE, positive rates of SARS-CoV-IgG and IgM antibody were 58.1% (18/31) and 29% (9/31), respectively, in which 7 cases(22.6%) were positive of both SARS-CoV-IgG and IgM antibody. All samples of positive SARS-CoV-IgG and IgM antibody were negative by RT-PCR. The ELISA kit coated by non-purification antigen may induce the false-positive of SARS-CoV antibody in patients with SLE. This result suggested that the specificity of ELISA tests for SARS was excellent and has low false-positive rates when using SARS-CoV-IgG and IgM antibody tests. A possible cause of false-positive of SARS-CoV-IgG and IgM antibody in SLE patients is coated antigens with SARS-CoV and Vero-E6 cells in ELISA methods.", "qid": 7, "docid": "r9dbf4u3", "rank": 60, "score": 0.8593114614486694}, {"content": "Title: Serological Approaches for COVID-19: Epidemiologic Perspective on Surveillance and Control Content: Since December 2019, the novel coronavirus, SARS-CoV-2, has garnered global attention due to its rapid transmission, which has infected more than two million people worldwide. Early detection of SARS-CoV-2 is one of the crucial interventions to control virus spread and dissemination. Molecular assays have been the gold standard to directly detect for the presence of viral genetic material in infected individuals. However, insufficient viral RNA at the point of detection may lead to false negative results. As such, it is important to also employ immune-based assays to determine one's exposure to SARS-CoV-2, as well as to assist in the surveillance of individuals with prior exposure to SARS-CoV-2. Within a span of 4 months, extensive studies have been done to develop serological systems to characterize the antibody profiles, as well as to identify and generate potentially neutralizing antibodies during SARS-CoV-2 infection. The vast diversity of novel findings has added value to coronavirus research, and a strategic consolidation is crucial to encompass the latest advances and developments. This review aims to provide a concise yet extensive collation of current immunoassays for SARS-CoV-2, while discussing the strengths, limitations and applications of antibody detection in SARS-CoV-2 research and control.", "qid": 7, "docid": "sgemwase", "rank": 61, "score": 0.8592199087142944}, {"content": "Title: Diagnosis of human coronavirus infections in children using enzyme\u2010linked immunosorbent assay Content: An enzyme\u2010linked immunosorbent assay (ELISA) was developed for diagnosing human coronavirus (HCV) infections in children. One hundred and seventy seven nose swabs, throat swabs, and nasopharyngeal aspirates were collected from 30 children suffering from acute respiratory infections. These samples were tested for HCV antigens by ELISA and 28.2% of the samples were shown to be HCV positive. These results indicate that our ELISA should prove useful in the diagnosis of HCV infections in children. Further studies are in progress to extend the ELISA to detect HCVs in experimentally and naturally acquired infections in adults.", "qid": 7, "docid": "qtz3r5di", "rank": 62, "score": 0.858809232711792}, {"content": "Title: Diagnostic accuracy of an automated chemiluminescent immunoassay for anti\u2010SARS\u2010CoV\u20102 IgM and IgG antibodies: an Italian experience Content: A pandemic of coronavirus disease 2019 (COVID\u201019) caused by severe acute respiratory syndrome coronavirus 2 (SARS\u2010CoV\u20102) has been spreading throughout the world. Though molecular diagnostic tests are the gold standard for COVID\u201019, serological testing is emerging as a potential surveillance tool, in addition to its complementary role in COVID\u201019 diagnostics. Indubitably quantitative serological testing provides greater advantages than qualitative tests but today there is still little known about serological diagnostics and what the most appropriate role quantitative tests might play. Sixty\u2010one COVID\u201019 patients and 64 patients from a control group were tested by iFlash1800 CLIA analyzer for anti\u2010SARS CoV\u20102 antibodies IgM and IgG. All COVID\u201019 patients were hospitalized in San Giovanni di Dio Hospital (Florence, Italy) and had a positive oro/nasopharyngeal swab reverse\u2010transcription polymerase chain reaction result. The highest sensitivity with a very good specificity performance was reached at a cutoff value of 10.0 AU/mL for IgM and of 7.1 for IgG antibodies, hence near to the manufacturer's cutoff values of 10 AU/mL for both isotypes. The receiver operating characteristic curves showed area under the curve values of 0.918 and 0.980 for anti\u2010SARS CoV\u20102 antibodies IgM and IgG, respectively. iFlash1800 CLIA analyzer has shown highly accurate results for the anti\u2010SARS\u2010CoV\u20102 antibodies profile and can be considered an excellent tool for COVID\u201019 diagnostics.", "qid": 7, "docid": "px4fe7mn", "rank": 63, "score": 0.8587190508842468}, {"content": "Title: Singapore claims first use of antibody test to track coronavirus infections ;Science ;AAAS Content: In what appears to be a first, disease trackers in Singapore have used an experimental antibody test for COVID-19 to confirm that a suspected patient was infected with the coronavirus The patient was one of two people who together formed a missing link between two clusters of cases that each occurred in a Singaporean church Researchers around the world are racing to develop antibody tests, also called serological tests, that can confirm whether someone was infected even after their immune system has cleared the virus that causes COVID-19 The group that developed the test, at Duke-NUS Medical School in Singapore, is among the front-runners, although its assay has to be validated before it is taken into production and deployed widely", "qid": 7, "docid": "g693adjd", "rank": 64, "score": 0.8585889339447021}, {"content": "Title: An immunofluorescence test for detection of serum antibody to rodent coronaviruses. Content: An indirect immunofluorescence test, using cultured cells infected with two strains of mouse hepatitis virus, was developed for detection of antibody to rodent coronaviruses. The immunofluorescence test detected serum antibody to mouse hepatitis virus and rat sialodacryoadenitis virus earlier than the neutralization test. In the case of mouse hepatitis virus, the results of the immunofluorescence test closely paralleled those obtained with a commercially available enzyme-linked immunosorbent assay.", "qid": 7, "docid": "agtm3afi", "rank": 65, "score": 0.858304500579834}, {"content": "Title: Rapid detection and monitoring of human coronavirus infections Content: Human coronaviruses (CoVs) are increasingly recognized as important respiratory pathogens associated with a broad range of clinical diseases. We sought to increase the insight into clinically relevant CoV infections by monitoring antigen concentrations in six confirmed CoV-positive patients using a newly developed assay for rapid detection of CoV OC43 infections. Antigen positivity lasted 3 to 6 days in secondary infections and 13 days in primary infection. CoV infections are clinically diverse, are common, and cannot be diagnosed from clinical symptoms alone.", "qid": 7, "docid": "rl66trp0", "rank": 66, "score": 0.8582919239997864}, {"content": "Title: First external quality assurance of antibody diagnostic for SARS-new coronavirus Content: Abstract To confirm an infection with the new coronavirus (SARS-CoV) causing the severe acute respiratory syndrome (SARS) diagnostic assays for detection of SARS-CoV specific antibody are necessary. To evaluate the diagnostic performance of laboratories an external quality assurance (EQA) study was performed in 2004. Participating laboratories (9/20) correctly detected anti-SARS antibodies in serum samples without false positive results in an immunofluorescence assay. In contrast, only 4/13 laboratories detected most of the anti-SARS antibody positive samples without false positive results using enzyme immunoassays (EIA) and/or immunoblot. The overall results clearly demonstrate that serological diagnosis of SARS-CoV remains at an early stage of development, with further technical improvements required, particularly with respect to the use of SARS specific EIAs.", "qid": 7, "docid": "bt4oi1xf", "rank": 67, "score": 0.8582046627998352}, {"content": "Title: Antibody assays against SARS-CoV-2: Why a good test does not always produce proper results/ Antik\u00f6rpertests gegen SARS-CoV-2: Warum ein guter test nicht immer gute ergebnisse produziert Content: Assays to test for antibodies against SARS-CoV-2 can display a high proportion of false-positive results if the frequency of the disease in the general population is low. Testing is not suitable for proving or ruling out an acute infection. Judging an individual patient, a positive antibody titer does not necessarily mean that this person is immune. Currently ELISA assays are not appropriate for individual screening purposes but possibly can complement diagnostic procedures. They are suitable for population-based screening in the context of studies.", "qid": 7, "docid": "g37ium3a", "rank": 68, "score": 0.8580637574195862}, {"content": "Title: Detection of SARS-CoV-2 in formalin-fixed paraffin-embedded tissue sections using commercially available reagents Content: Coronavirus Disease-19 (COVID-19), caused by the coronavirus SARS-CoV-2, was initially recognized in Wuhan, China and subsequently spread to all continents. The disease primarily affects the lower respiratory system, but may involve other organs and systems. Histopathologic evaluation of tissue from affected patients is crucial for diagnostic purposes, but also for advancing our understanding of the disease. For that reason, we developed immunohistochemical (IHC) and in situ hybridization (ISH) assays for detection of the. virus. A total of eight autopsy lungs, one placenta, and ten kidney biopsies from COVID-19 patients were stained with a panel of commercially available antibodies for IHC and commercially available RNA probes for ISH. Similarly, autopsy lungs, placentas and renal biopsies from non-COVID-19 patients were stained with the same antibodies and probes. All eight lungs and the placenta from COVID-19 patients stained positive by IHC and ISH, while the kidney biopsies stained negative by both methodologies. As expected, all specimens from non-COVID-19 patients were IHC and ISH negative. These two assays represent a sensitive and specific method for detecting the virus in tissue samples. We provide the protocols and the list of commercially available antibodies and probes for these assays, so they can be readily implemented in pathology laboratories and medical examiner offices for diagnostic and research purposes.", "qid": 7, "docid": "863nt8yy", "rank": 69, "score": 0.8578360080718994}, {"content": "Title: Comparison of immunofluorescence with monoclonal antibodies and RT-PCR for the detection of human coronaviruses 229E and OC43 in cell culture Content: Abstract Human coronaviruses, with two known serogroups named 229E and OC43, cause up to one third of common colds and may be associated with serious diseases such as nosocomial respiratory infections, enterocolitis, pericarditis and neurological disorders. Reliable methods of detection in clinical samples are needed for a better understanding of their role in pathology. As a first step in the design of such diagnostic procedures, the sensitivities and specificities of two viral diagnostic assays were compared in an experimental cell culture model: an indirect immuno-fluorescence assay using monoclonal antibodies and reverse transcriptase-polymerase chain reaction amplification of viral RNA from infected cells. Immunofluorescence detected human coronaviruses in cells infected at a MOI as low as 10\u22122 (log TCID50/ml=4.25 for HCV-229E and 2.0 for HCV-OC43; log PFU/ml=4.83 for HCV-229E and 1.84 for HCV-OC43) versus 10\u22123 (HCV-OC43) or 10\u22124 (HCV-229E) for reverse transcriptase-polymerase chain reaction amplification (log TCID50/ml=1.75 for HCV-229E and 1.5 for HCV-OC43; log PFU/ml=2.3 for HCV-229E and 1.34 for HCV-OC43). There were no false positive signals with other human respiratory pathogens: influenza virus, respiratory syncytial virus and adenovirus. Moreover, each assay was coronavirus serogroup-specific. These results demonstrate the potential usefulness of immunofluorescence with monoclonal antibodies and reverse transcriptase-polymerase chain reaction RNA amplification for the rapid detection of human coronaviruses in infected cell cultures. Both methods could be applied to clinical specimens for the diagnosis of human infections.", "qid": 7, "docid": "salhgyfk", "rank": 70, "score": 0.8578317761421204}, {"content": "Title: Antigenic Cross-Reactivity between Severe Acute Respiratory Syndrome\u2014Associated Coronavirus and Human Coronaviruses 229E and OC43 Content: Cross-reactivity between antibodies to different human coronaviruses (HCoVs) has not been systematically studied. By use of Western blot analysis, indirect immunofluorescence assay (IFA), and enzyme-linked immunosorbent assay (ELISA), antigenic cross-reactivity between severe acute respiratory syndrome (SARS)\u2014associated coronavirus (SARS-CoV) and 2 HCoVs (229E and OC43) was demonstrated in immunized animals and human serum. In 5 of 11 and 10 of 11 patients with SARS, paired serum samples showed a \u2a7e4-fold increase in antibody titers against HCoV-229E and HCoV-OC43, respectively, by IFA. Overall, serum samples from convalescent patients who had SARS had a 1-way cross-reactivity with the 2 known HCoVs. Antigens of SARS-CoV and HCoV-OC43 were more cross-reactive than were those of SARS-CoV and HCoV-229E.", "qid": 7, "docid": "w5sub348", "rank": 71, "score": 0.8573410511016846}, {"content": "Title: Determination of coronavirus 229E antibody by an immune\u2010adherence hemagglutination method Content: An immune\u2010adherence hemagglutination (IAHA) method for coronavirus 229E antibody determination has been developed both for diagnosis of recent infections and for detection of long\u2010past infections. Results have been compared with those obtained by complement fixation (CF), neutralization (Nt), and indirect hemagglutination (IHA) tests. The IAHA method has been shown to be as sensitive as the CF, Nt, and IHA tests in detecting cases of acute 229E infection. However, in a seroepidemiological survey of 343 healthy people of all ages, IAHA detected 229E antibody in 254 individuals (74.0%), Nt in 166 (48.3%), IHA in 89 (25.9%), and CF in 30 (8.7%). A study of the prevalence of coronavirus 229E IAHA antibody in the different age groups has shown that during the second decade of life nearly 100% of the population acquire this type of antibody, whereas only 50% are positive at the end of the first decade. In the older age groups, the high frequency of CF antibody (\u201cmarker\u201d of recent infection) indirectly confirms the high rate of 229E reinfections and the nonprotective nature of IAHA antibody. CF titer \u2a7e 1:8 in 90% of cases corresponded to IAHA titers \u2a7e 1:64. However, sera with IAHA titers of \u2a7e 1:128 were often CF\u2010negative. Recent 229E infections (or reinfections), as determined by the presence of CF antibody, were more frequent in April\u2010May than in October\u2010November. Three cases of acute infection showing 229E seroconversion (two adults and one child) were observed during the winter\u2010spring season. IAHA appears to be the test of choice for seroepidemiological surveys.", "qid": 7, "docid": "yaiadylf", "rank": 72, "score": 0.8572450876235962}, {"content": "Title: Profiles of antibody responses against severe acute respiratory syndrome coronavirus recombinant proteins and their potential use as diagnostic markers. Content: A new coronavirus (severe acute respiratory syndrome coronavirus [SARS-CoV]) has been identified to be the etiological agent of severe acute respiratory syndrome. Given the highly contagious and acute nature of the disease, there is an urgent need for the development of diagnostic assays that can detect SARS-CoV infection. For determination of which of the viral proteins encoded by the SARS-CoV genome may be exploited as diagnostic antigens for serological assays, the viral proteins were expressed individually in mammalian and/or bacterial cells and tested for reactivity with sera from SARS-CoV-infected patients by Western blot analysis. A total of 81 sera, including 67 from convalescent patients and seven pairs from two time points of infection, were analyzed, and all showed immunoreactivity towards the nucleocapsid protein (N). Sera from some of the patients also showed immunoreactivity to U274 (59 of 81 [73%]), a protein that is unique to SARS-CoV. In addition, all of the convalescent-phase sera showed immunoreactivity to the spike (S) protein when analyzed by an immunofluorescence method utilizing mammalian cells stably expressing S. However, samples from the acute phase (2 to 9 days after the onset of illness) did not react with S, suggesting that antibodies to N may appear earlier than antibodies to S. Alternatively, this could be due to the difference in the sensitivities of the two methods. The immunoreactivities to these recombinant viral proteins are highly specific, as sera from 100 healthy donors did not react with any of them. These results suggest that recombinant N, S, and U274 proteins may be used as antigens for the development of serological assays for SARS-CoV.", "qid": 7, "docid": "t9mug53v", "rank": 73, "score": 0.857230544090271}, {"content": "Title: Antik\u00f6rpertests bei COVID-19 - Was uns die Ergebnisse sagen Content: INTRODUCTION: In the context of the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) pandemic, the detection of virus-specific antibodies (AB) will play an increasing role. The presence or absence of such antibodies can potentially lead to considerations regarding immunity and infection. ISSUE: How reliable are inferences from positive or negative test results regarding the actual presence of SARS-CoV-2 specific antibodies? METHODS: Calculation of the probability that, depending on the pretest probability (prevalence of SARS-CoV-2 infection) and test properties, antibodies are present or absent in the case of positive or negative test results. RESULTS: Sensitivity and specificity of different SARS-CoV-2 AB test systems vary between 53 % and 94 % and between 91 % and 99.5 %, respectively. When using a test with high test quality, the positive predictive value (PPV) is 42 % and 7 9%, respectively, with a pre-test probability of 1 % to 5 %, as can currently be assumed for the general population in Austria or Germany. For persons with an increased pre-test probability of 20 %, e. g. persons from high-risk professions, the PPW is 95 %, with a pre-test probability of 80 % the PPW is almost 100 %. The negative predictive value (NPV) is at least 99.7 % for persons with a low pre-test probability of up to 5 % and 79.1 % for persons with a pre-test probability of 80 %. When using test systems with lower sensitivity and specificity, the reliability of the results decreases considerably. The PPV is 5.9 % with a pre-test probability of 1 %. CONCLUSIONS: A sufficiently high sensitivity and specificity are prerequisites for the application of antibody test systems. Positive test results are often false if the pre-test probability is low. Depending on the assumed prevalence of a SARS-CoV-2 infection, there are substantial differences in the significance of a concrete test result for the respective affected persons.", "qid": 7, "docid": "1ytcd0ax", "rank": 74, "score": 0.8570464253425598}, {"content": "Title: Antik\u00f6rpertests bei COVID-19 - Was uns die Ergebnisse sagen./ [Antibody tests for COVID-19: What the results tell us] Content: INTRODUCTION: In the context of the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) pandemic, the detection of virus-specific antibodies (AB) will play an increasing role. The presence or absence of such antibodies can potentially lead to considerations regarding immunity and infection. ISSUE: How reliable are inferences from positive or negative test results regarding the actual presence of SARS-CoV-2 specific antibodies? METHODS: Calculation of the probability that, depending on the pretest probability (prevalence of SARS-CoV-2 infection) and test properties, antibodies are present or absent in the case of positive or negative test results. RESULTS: Sensitivity and specificity of different SARS-CoV-2 AB test systems vary between 53 % and 94 % and between 91 % and 99.5 %, respectively. When using a test with high test quality, the positive predictive value (PPV) is 42 % and 7 9%, respectively, with a pre-test probability of 1 % to 5 %, as can currently be assumed for the general population in Austria or Germany. For persons with an increased pre-test probability of 20 %, e. g. persons from high-risk professions, the PPW is 95 %, with a pre-test probability of 80 % the PPW is almost 100 %. The negative predictive value (NPV) is at least 99.7 % for persons with a low pre-test probability of up to 5 % and 79.1 % for persons with a pre-test probability of 80 %. When using test systems with lower sensitivity and specificity, the reliability of the results decreases considerably. The PPV is 5.9 % with a pre-test probability of 1 %. CONCLUSIONS: A sufficiently high sensitivity and specificity are prerequisites for the application of antibody test systems. Positive test results are often false if the pre-test probability is low. Depending on the assumed prevalence of a SARS-CoV-2 infection, there are substantial differences in the significance of a concrete test result for the respective affected persons.", "qid": 7, "docid": "4bdn6xje", "rank": 75, "score": 0.8570464253425598}, {"content": "Title: Detection of Nucleocapsid Antibody to SARS-CoV-2 is More Sensitive than Antibody to Spike Protein in COVID-19 Patients Content: Background: SARS-CoV-2, the cause of coronavirus disease 2019 (COVID-19), is associated with respiratory-related morbidity and mortality. Assays to detect virus-specific antibodies are important to understand the prevalence of infection and the course of the immune response. Methodology: Quantitative measurements of plasma or serum antibodies by luciferase immunoprecipitation assay systems (LIPS) to the nucleocapsid and spike proteins were analyzed in 100 cross-sectional or longitudinal samples from SARS-CoV-2-infected patients. A subset of samples was tested with and without heat inactivation. Results: Fifteen or more days after symptom onset, antibodies against SARS-CoV-2 nucleocapsid protein showed 100% sensitivity and 100% specificity, while antibodies to spike protein were detected with 91% sensitivity and 100% specificity. Neither antibody levels nor the rate of seropositivity were significantly reduced by heat inactivation of samples. Analysis of daily samples from six patients with COVID-19 showed anti-nucleocapsid and spike antibodies appearing between day 8 to day 14 after initial symptoms. Immunocompromised patients generally had a delayed antibody response to SARS-CoV-2 compared to immunocompetent patients. Conclusions: Antibody to the nucleocapsid protein of SARS-CoV-2 is more sensitive than spike protein antibody for detecting early infection. Analyzing heat-inactivated samples by LIPS is a safe and sensitive method for detecting SARS-CoV-2 antibodies.", "qid": 7, "docid": "3g67hjk8", "rank": 76, "score": 0.8567770719528198}, {"content": "Title: Prevalence of feline coronavirus antibodies in cats in Bursa province, Turkey, by an enzyme-linked immunosorbent assay Content: Feline sera from Bursa province (Turkey) were assayed for coronavirus antibody using an enzyme-linked immunosorbent assay (ELISA). The study was performed on 100 sera collected from cats belonging to catteries or community shelters and to households. The serum samples were initially tested with the virus neutralisation (VN) test and the results were then compared with the ELISA. The VN yielded 79 negative and 21 positive sera but the ELISA confirmed only 74 as negative. The ELISA-negative sera were also found to be free of feline coronoviruses-specific antibodies by Western blotting. Using the VN as the gold standard test, ELISA had a sensitivity of 100% and a specificity of 93.6%, with an overall agreement of 95%. The Kappa (\u03ba) test indicated high association between the two tests (\u03ba =0.86, 95% confidence interval (CI) 0.743\u20130.980). The positive predictive value (PPV) was 0.8, and the negative predictive value (NPV) was 0.93. The prevalence of FCoV II antibodies in the sampled population based on the gold standard was 62% (95% CI 0.44\u20130.77) among multi-cat environments, and 4% (95% CI 0.01\u20130.11) among single cat households.", "qid": 7, "docid": "se27uebt", "rank": 77, "score": 0.8564826250076294}, {"content": "Title: Immunofluorescence assay for detection of the nucleocapsid antigen of the severe acute respiratory syndrome (SARS)-associated coronavirus in cells derived from throat wash samples of patients with SARS. Content: An antigen detection assay for severe acute respiratory syndrome (SARS) coronavirus was established in this study by an indirect immunofluorescence test, which utilized cells derived from throat wash samples of patients with SARS and a rabbit serum that recognized the nucleocapsid protein of SARS-associated coronavirus (SARS-CoV) but not that of other human coronavirus tested. It detected SARS-CoV in 11 of 17 (65%) samples from SARS patients as early as day 2 of illness but in none of the 10 samples from healthy controls. Compared with other diagnostic modalities for detecting SARS-CoV, this assay is simpler, more convenient, and economical. It could be an alternative for early and rapid diagnosis, should SARS return in the future.", "qid": 7, "docid": "trluj8r6", "rank": 78, "score": 0.8564715385437012}, {"content": "Title: Role of Anti-SARS-CoV-2 antibodies in different cohorts: Can they provide clues for appropriate patient triaging? Content: The emergence of coronavirus disease 2019 (COVID-19) has become a major global health crisis. Currently, diagnosis is based on molecular techniques, which detect the viral nucleic acids when present at detectable levels. The serum IgG response against SARS-CoV-2 was examined by using an ELISA-based assay. Serum samples, along with nasopharyngeal specimens were collected from various cohorts and analyzed by ELISA and rRT-PCR, respectively. A total of 167 serum samples were tested for serum IgG antibodies against SARS-CoV-2 in outpatient cohorts, 15 (8.9%) were positive by rRT-PCR and the remaining 152 (91%) were negative. We used these data to generate two different assay cutoffs for serum IgG assay and investigated percent concordance with rRT-PCR test results. The emergency department data revealed, out of 151 nasopharyngeal swabs, 4 (2.6%) were positive by rRT-PCR and 18 (11.9%) were positive for serum IgG assay. Among the 18 patients that were positive for serum IgG, 13 (72.2%) exhibited 1-3 symptoms of COVID-19 and 5 (27.7%) patients did not present with any COVID-19 related symptoms, per CDC criteria. All 4 (100%) patients that were positive by rRT-PCR had symptoms of COVID-19 disease. A longitudinal study from the inpatient population suggested there was a sharp increase in the serum IgG titers in 5 patients, a moderate increase in 1 patient and a plateau in 3 patients. Sero-prevalence of COVID-19 disease in pre-procedure patients was 5.5%. Our findings suggest serological tests can be used for appropriate patient triaging when performed as an adjunct to existing molecular testing.", "qid": 7, "docid": "vt8se423", "rank": 79, "score": 0.8564040064811707}, {"content": "Title: Identification of IgG antibody response to SARS-CoV-2 spike protein and its receptor binding domain does not predict rapid recovery from COVID-19 Content: Diagnostic testing and evaluation of patient immunity against the novel severe acute respiratory syndrome (SARS) corona virus that emerged last year (SARS-CoV-2) are essential for health and economic crisis recovery of the world. It is suggested that potential acquired immunity against SARS-CoV-2 from prior exposure may be determined by detecting the presence of circulating IgG antibodies against viral antigens, such as the spike glycoprotein and its receptor binding domain (RBD). Testing our asymptomatic population for evidence of COVID-19 immunity would also offer valuable epidemiologic data to aid health care policies and health care management. Currently, there are over 100 antibody tests that are being used around the world without approval from the FDA or similar regulatory bodies, and they are mostly for rapid and qualitative assessment, with different degrees of error rates. ELISA-based testing for sensitive and rigorous quantitative assessment of SARS-CoV-2 antibodies can potentially offer mechanistic insights into the COVID-19 disease and aid communities uniquely challenged by limited financial resources and access to commercial testing products. Employing recombinant SARS-CoV-2 RBD and spike protein generated in the laboratory, we devised a quantitative ELISA for the detection of circulating serum antibodies. Serum from twenty SARS-CoV-2 RT-PCR confirmed COVID-19 hospitalized patients were used to detect circulating IgG titers against SARS-CoV-2 spike protein and RBD. Quantitative detection of IgG antibodies to the spike glycoprotein or the RBD in patient samples was not always associated with faster recovery, compared to patients with borderline antibody response to the RBD. One patient who did not develop antibodies to the RBD completely recovered from COVID-19. In surveying 99 healthy donor samples (procured between 2017-February 2020), we detected RBD antibodies in one donor from February 2020 collection with three others exhibiting antibodies to the spike protein but not the RBD. Collectively, our study suggests that more rigorous and quantitative analysis, employing large scale sample sets, is required to determine whether antibodies to SARS-CoV-2 spike protein or RBD is associated with protection from COVID-19 disease. It is also conceivable that humoral response to SARS-CoV-2 spike protein or RBD works in association with adaptive T cell response to determine clinical sequela and severity of COVID-19 disease.", "qid": 7, "docid": "y1afswkm", "rank": 80, "score": 0.855721116065979}, {"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": 81, "score": 0.8556270003318787}, {"content": "Title: Evaluation of a COVID-19 IgM and IgG rapid test; an efficient tool for assessment of past exposure to SARS-CoV-2 Content: COVID-19 is the most rapidly growing pandemic in modern time, and the need for serological testing is most urgent. Although the diagnostics of acute patients by RT-PCR is both efficient and specific, we are also crucially in need of serological tools for investigating antibody responses and assessing individual and potential herd immunity. We evaluated a commercially available test developed for rapid (within 15 minutes) detection of SARS-CoV-2-specific IgM and IgG by 29 PCR-confirmed COVID-19 cases and 124 negative controls. The results revealed a sensitivity of 69% and 93.1% for IgM and IgG, respectively, based solely on PCR-positivity due to the absence of a serological gold standard. The assay specificities were shown to be 100% for IgM and 99.2% for IgG. This indicates that the test is suitable for assessing previous virus exposure, although negative results may be unreliable during the first weeks after infection. More detailed studies on antibody responses during and post infection are urgently needed.", "qid": 7, "docid": "knc0ruou", "rank": 82, "score": 0.8553159832954407}, {"content": "Title: Enzyme-linked immunosorbent assay for detection of antibody in volunteers experimentally infected with human coronavirus strain 229 E. Content: An enzyme-linked immunosorbent assay was developed for detecting antibody rises to human coronavirus strain 229E and related strains in paired sera from infected volunteers. There was a close correlation between development of colds infected volunteers. There was a close correlation between development of colds and significant antibody rises detected by the enzyme-linked immunosorbent assay. Furthermore, the assay was more sensitive than a neutralization assay. This enzyme-linked immunosorbent assay is an easy, accurate, and sensitive assay for measuring significant antibody rises to human coronavirus strain 229E group viruses, and it could be useful in the clinical diagnosis of these infections.", "qid": 7, "docid": "hoh3z39d", "rank": 83, "score": 0.8551476001739502}, {"content": "Title: Utilization of monoclonal antibodies for antigenic characterization of coronaviruses. Content: Hybrid cells secreting monoclonal antibodies against Bovine Enteric Coronavirus (BECV strain G110) were obtained by fusion between SP2/O myeloma cells and splenocytes of mice hyperimmunized with purified virus. Specificity of 8 from the 12 monoclonal antibodies was established to be anti-GP105 by immunochemical staining of viral polypeptides and by immunoprecipitation of radioactive-labelled viral proteins. The reactivity of three BECV isolates (strain G110, F15 and NCDCV) with the different monoclonal antibodies was studied by indirect immunofluorescence (IIF), ELISA, hemagglutination-inhibition and seroneutralization. G110 and F15 interacted in a similar manner with the monoclonal antibodies, but NCDCV failed to react with A9 monoclonal antibody. IIF test allowed us to detect another difference between U.K. BECV isolate and other BECV, in that the U.K. isolate did not react with F7 monoclonal antibody. No differences could be seen by IIF in the reactivity of Danish BECV isolate, Human Enteric Coronavirus (HECV), Bovine Respiratory Coronavirus (BRCV) and our BECV strains, with the 12 monoclonal antibodies. Human Respiratory Coronavirus (OC43), Porcine Hemagglutinating Encephalitis Virus (HEV) and BECV share common antigenic determinants which are outlined by the 6 non-neutralizing monoclonal antibodies. On the basis of the reactivity of coronaviruses with anti-BECV monoclonal antibodies, a distinction can be easily made between BECV and other coronaviruses, and differences were also detected within the BECV isolates. Interestingly HECV were found to be more closely related to BECV than to human OC43. These results show that monoclonal antibodies are of valuable help for biochemical and antigenic studies as well as for diagnostic procedures.", "qid": 7, "docid": "b69wakcj", "rank": 84, "score": 0.8544358611106873}, {"content": "Title: Enzyme-linked immunosorbent assay for the detection of canine coronavirus and its antibody in dogs Content: Abstract Two methods of enzyme-linked immunosorbent assay (ELISA) were developed for the diagnosis of canine coronavirus (CCV) infection in dogs. One ELISA, in which CCV-infected CRFK cell lysate is used as antigen, is for the detection and titration of antibody against CCV, and the other ELISA uses the double antibody sandwich method for the detection of CCV antigen. The first ELISA procedure demonstrated antibody responses in dogs inoculated with CCV, as did the virus neutralization test; the second ELISA detected specific CCV antigen in feces and organ homogenates of inoculated dogs.", "qid": 7, "docid": "ldeylpne", "rank": 85, "score": 0.8539716005325317}, {"content": "Title: Evaluation of ELISA tests for the qualitative determination of IgG, IgM and IgA to SARS-CoV-2 Content: Serological assays for anti-SARS-CoV-2 antibodies are now of critical importance to support diagnosis, guide epidemiological intervention, and understand immune response to natural infection and vaccine administration. We developed and validated new anti-SARS-CoV-2 IgG, IgM and IgA ELISA tests (ENZY-WELL SARS-CoV-2 ELISA, DIESSE Diagnostica Senese S.p.a.) based on whole-virus antigens. We used a total of 553 serum samples including samples from COVID-19 suspected and confirmed cases, healthy donors, and patients positive for other infections or autoimmune conditions. Overall, the assays showed good concordance with the indirect immunofluorescence reference test in terms of sensitivity and specificity. Especially for IgG and IgA, we observed high sensitivity (92.5 and 93.6%, respectively); specificity was high (>96%) for all antibody types ELISAs. In addition, sensitivity was linked to the days from symptoms onset (DSO) due to the seroconversion window, and for ENZY-WELL SARS-CoV-2 IgG and IgA ELISAs resulted 100% in those samples collected after 10 and 12 DSO, respectively. The results showed that ENZY-WELL SARS-CoV-2 ELISAs may represent a valid option for both diagnostic and epidemiological purposes, covering all different antibody types developed in SARS-CoV-2 immune response.", "qid": 7, "docid": "0w7tq79d", "rank": 86, "score": 0.8536859154701233}, {"content": "Title: Antibody responses to SARS-CoV-2 in patients of novel coronavirus disease 2019 Content: Summary 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 confirmed SARS-CoV-2 infection were enrolled. Their serial plasma samples (n = 535) collected during the hospitalization period were tested for total antibodies (Ab), IgM and IgG against SARS-CoV-2 using immunoassays. The dynamics of antibodies with the progress and severity of disease was analyzed. Findings Among 173 patients, the seroconversion rate for Ab, IgM and IgG was 93.1% (161/173), 82.7% (143/173) and 64.7% (112/173), respectively. Twelve patients who had not seroconverted were those only blood samples at the early stage of illness were collected. The seroconversion sequentially appeared for Ab, IgM and then IgG, with a median time of 11, 12 and 14 days, respectively. The presence of antibodies was < 40% among patients in the first 7 days of illness, and then rapidly increased to 100.0%, 94.3% and 79.8% for Ab, IgM and IgG respectively since day 15 after onset. In contrast, the positive rate of RNA decreased from 66.7% (58/87) in samples collected before day 7 to 45.5% (25/55) during days 15 to 39. Combining RNA and antibody detections significantly improved the sensitivity of pathogenic diagnosis for COVID-19 patients (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). Interpretation 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": "llqpfhwg", "rank": 87, "score": 0.8532837629318237}, {"content": "Title: Immunochromatographic assays for COVID-19 epidemiological screening: our experience Content: In March 2020, the World Health Organization (WHO) declared a pandemic caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). Due to the absence of effective treatment or biomedical prevention, understanding potential post infection immunity has important implications for epidemiologic assessments. For this reason, increasing number of in vitro diagnostic companies are developing serological assays to detect antibodies against SARS-CoV-2, but most of them lack the validation by third parties in relation to their quality, limiting their usefulness. We submitted to serological screening by two different immunochromatographic (IC) rapid testing for detection of IgG and IgM against SARS-CoV-2, 151 asymptomatic or minimally symptomatic healthcare workers previously tested positive for SARS-CoV-2 RT-PCR in order to evaluate the performance of rapid assays. Results showed discrepancies between molecular and IC results, and an inconsistency of immunoglobulins positivity patterns when compared to ELISA/CLIA results, highlighting the absolute necessity of assays performance validation before their marketing and use, in order to avoid errors in the results evaluation at both clinical and epidemiological level.", "qid": 7, "docid": "uq6gy24x", "rank": 88, "score": 0.8531270027160645}, {"content": "Title: Analysis of SARS-CoV-2 Antibodies in COVID-19 Convalescent Plasma using a Coronavirus Antigen Microarray Content: The current practice for diagnosis of COVID-19, based on SARS-CoV-2 PCR testing of pharyngeal or respiratory specimens in a symptomatic patient at high epidemiologic risk, likely underestimates the true prevalence of infection. Serologic methods can more accurately estimate the disease burden by detecting infections missed by the limited testing performed to date. Here, we describe the validation of a coronavirus antigen microarray containing immunologically significant antigens from SARS-CoV-2, in addition to SARS-CoV, MERS-CoV, common human coronavirus strains, and other common respiratory viruses. A comparison of antibody profiles detected on the array from control sera collected prior to the SARS-CoV-2 pandemic versus convalescent blood specimens from virologically confirmed COVID-19 cases demonstrates complete discrimination of these two groups. This array can be used as a diagnostic tool, as an epidemiologic tool to more accurately estimate the disease burden of COVID-19, and as a research tool to correlate antibody responses with clinical outcomes.", "qid": 7, "docid": "ax9btc74", "rank": 89, "score": 0.8528373837471008}, {"content": "Title: Profiling Early Humoral Response to Diagnose Novel Coronavirus Disease (COVID-19) Content: BACKGROUND: The emergence of coronavirus disease 2019 (COVID-19) is a major healthcare threat. The current method of detection involves a quantitative polymerase chain reaction (qPCR)\u2013based technique, which identifies the viral nucleic acids when present in sufficient quantity. False-negative results can be achieved and failure to quarantine the infected patient would be a major setback in containing the viral transmission. We aim to describe the time kinetics of various antibodies produced against the 2019 novel coronavirus (SARS-CoV-2) and evaluate the potential of antibody testing to diagnose COVID-19. METHODS: The host humoral response against SARS-CoV-2, including IgA, IgM, and IgG response, was examined by using an ELISA-based assay on the recombinant viral nucleocapsid protein. 208 plasma samples were collected from 82 confirmed and 58 probable cases (qPCR negative but with typical manifestation). The diagnostic value of IgM was evaluated in this cohort. RESULTS: The median duration of IgM and IgA antibody detection was 5 (IQR, 3\u20136) days, while IgG was detected 14 (IQR, 10\u201318) days after symptom onset, with a positive rate of 85.4%, 92.7%, and 77.9%, respectively. In confirmed and probable cases, the positive rates of IgM antibodies were 75.6% and 93.1%, respectively. The detection efficiency by IgM ELISA is higher than that of qPCR after 5.5 days of symptom onset. The positive detection rate is significantly increased (98.6%) when combining IgM ELISA assay with PCR for each patient compared with a single qPCR test (51.9%). CONCLUSIONS: The humoral response to SARS-CoV-2 can aid in the diagnosis of COVID-19, including subclinical cases.", "qid": 7, "docid": "wxhbwcfr", "rank": 90, "score": 0.8528202176094055}, {"content": "Title: Antibodies to human coronaviruses 229E and OC43 in the population of C.R. Content: Of 1200 human sera tested by enzyme-linked immunosorbent assay (ELISA), 53% contained antibodies to human coronavirus (HCV) 229E and 88% to HCV OC43. The sera were from persons aged 13 months to 80 years, both males and females, and were collected in four different regions in 1986. The percentage of positives increased with increasing age and tended to vary according to the geographic area. Additional paired human sera from 218 patients with acute respiratory diseases (ARD) were collected between October 1986 and June 1987 in Prague. Significant antibody rises to HCV strain 229E were detected in 7 (3.2%) patients 9 months to 17 years old, to HCV strain OC43 in 4 (1.8%) patients under 2 years of age.", "qid": 7, "docid": "y6gd1zku", "rank": 91, "score": 0.8528187274932861}, {"content": "Title: Development and applications of a bovine coronavirus antigen detection enzyme-linked immunosorbent assay. Content: We developed a monoclonal antibody-based, antigen capture sandwich enzyme-linked immunosorbent assay (ELISA) for bovine coronavirus. We compared the ELISA with electron microscopy and the hemagglutination test and found a close correlation between them. The sensitivity of the ELISA was 10(4) bovine coronavirus particles per ml of 10% fecal suspension. Compared with electron microscopy, bovine coronavirus ELISA had 96% specificity.", "qid": 7, "docid": "6r0gfdma", "rank": 92, "score": 0.8520771861076355}, {"content": "Title: SARS-related Virus Predating SARS Outbreak, Hong Kong Content: Using immunofluorescence and neutralization assays, we detected antibodies to human severe acute respiratory syndrome\u2013associated coronavirus (SARS-CoV) and/or animal SARS-CoV\u2013like virus in 17 (1.8%) of 938 adults recruited in 2001. This finding suggests that a small proportion of healthy persons in Hong Kong had been exposed to SARS-related viruses at least 2 years before the recent SARS outbreak.", "qid": 7, "docid": "kfhxm9oi", "rank": 93, "score": 0.8520275354385376}, {"content": "Title: Brief clinical evaluation of six high-throughput SARS-CoV-2 IgG antibody assays Content: Serological SARS-CoV-2 assays are urgently needed for diagnosis, contact tracing and for epidemiological studies. So far, there is limited data on how recently commercially available, high-throughput immunoassays, using different recombinant SARS-CoV-2 antigens, perform with clinical samples. Focusing on IgG and total antibodies, we demonstrate the performance of four automated immunoassays (Abbott Architect&#8482; i2000 (N protein-based)), Roche cobas&#8482; e 411 analyzer (N protein-based, not differentiating between IgA, IgM or IgG antibodies), LIAISON\u00aeXL platform (S1 and S2 protein-based), VIRCLIA\u00ae automation system (S1 and N protein-based) in comparison to two ELISA assays (Euroimmun SARS-CoV-2 IgG (S1 protein-based) and Virotech SARS-CoV-2 IgG ELISA (N protein-based)) and an in-house developed plaque reduction neutralization test (PRNT). We tested follow up serum/plasma samples of individuals PCR-diagnosed with COVID-19. When calculating the overall sensitivity, in a time frame of 49 days after first PCR-positivity, the PRNT as gold standard, showed the highest sensitivity with 93.3% followed by the dual-target assay for the VIRCLIA\u00ae automation system with 89%. The overall sensitivity in the group of N protein-based assays ranged from 66.7 to 77.8% and in the S protein-based-assays from 71.1 to 75.6%. Five follow-up samples of three individuals were only detected in either an S and/or N protein-based assay, indicating an individual different immune response to SARS-CoV-2 and the influence of the used assay in the detection of IgG antibodies. This should be further analysed. The specificity of the examined assays was &#8805; 97%. However, because of the low or unknown prevalence of SARS-CoV-2, the examined assays in this study are currently primarily eligible for epidemiological investigations, as they have limited information in individual testing.", "qid": 7, "docid": "gchd14rx", "rank": 94, "score": 0.8519442081451416}, {"content": "Title: Efficacy of Serology Testing in Predicting Reinfection in Patients with SARS-CoV-2 Content: In many parts of the United States, SARS-CoV-2 cases have reached peak infection rates, prompting administrators to create protocols to resume elective cases. As elective procedures and surgeries get scheduled, ASCs must implement some form of widespread testing in order to ensure the safety of both the ASC staff as well as the patients being seen. The CDC recently announced the approval of new serological testing for SARS-CoV-2, a test that can indicate the presence of IgM and IgG antibodies in the serum against viral particles. However, the possibility for reinfection raises questions about the utility of this new serological test, as the presence of IgG may not correspond to long-term immunity. The coronavirus has been known to form escape mutations, which may correspond to reduction in immunoglobulin binding capacity. Patients who develop more robust immune responses with formation of memory CD8+ T-cells and helper CD4+ T-cells will be the most equipped if exposed to the virus, but unfortunately the serology test will not help us in distinguishing those individuals. Given the inherent disadvantages of serological testing, antibody testing alone should not be used when deciding patient care and should be combined with PCR testing.", "qid": 7, "docid": "m71ut1sd", "rank": 95, "score": 0.8519291877746582}, {"content": "Title: Efficacy of Serology Testing in Predicting Reinfection in Patients with SARS-CoV-2. Content: In many parts of the United States, SARS-CoV-2 cases have reached peak infection rates, prompting administrators to create protocols to resume elective cases. As elective procedures and surgeries get scheduled, ASCs must implement some form of widespread testing in order to ensure the safety of both the ASC staff as well as the patients being seen. The CDC recently announced the approval of new serological testing for SARS-CoV-2, a test that can indicate the presence of IgM and IgG antibodies in the serum against viral particles. However, the possibility for reinfection raises questions about the utility of this new serological test, as the presence of IgG may not correspond to long-term immunity. The coronavirus has been known to form escape mutations, which may correspond to reduction in immunoglobulin binding capacity. Patients who develop more robust immune responses with formation of memory CD8+ T-cells and helper CD4+ T-cells will be the most equipped if exposed to the virus, but unfortunately the serology test will not help us in distinguishing those individuals. Given the inherent disadvantages of serological testing, antibody testing alone should not be used when deciding patient care and should be combined with PCR testing.", "qid": 7, "docid": "g1dij8ty", "rank": 96, "score": 0.8519290685653687}, {"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": 97, "score": 0.8517024517059326}, {"content": "Title: False-positive results in a recombinant severe acute respiratory syndrome-associated coronavirus (SARS-CoV) nucleocapsid enzyme-linked immunosorbent assay due to HCoV-OC43 and HCoV-229E rectified by Western blotting with recombinant SARS-CoV spike polypeptide. Content: Using paired serum samples obtained from patients with illness associated with increases in anti-human coronavirus OC43 (HCoV-OC43) or anti-HCoV-229E antibodies, we examined the possibility of false-positive results detected in a recombinant severe acute respiratory syndrome (SARS)-associated coronavirus (SARS-CoV) nucleocapsid protein immunoglobulin G enzyme-linked immunosorbent assay (ELISA). Three of the 21 and 1 of the 7 convalescent-phase serum samples from persons with increases in antibodies against HCoV-OC43 and HCoV-229E, respectively, tested positive by the recombinant SARS-CoV nucleocapsid protein-based ELISA. None of these samples were found to contain a specific antibody in the recombinant SARS-CoV spike polypeptide-based Western blot assay.", "qid": 7, "docid": "pjyfz0pm", "rank": 98, "score": 0.851348876953125}, {"content": "Title: Nonspecific inhibitors of coronavirus OC43 haemagglutination in human sera Content: Antibodies against the human coronavirus OC43 in human sera were measured by haemagglutination inhibition (HI), complement fixation (CF), and radial diffusion-haemolysis in gel (HIG) techniques. The apparent HI titres in a fraction of sera with no antibodies detectable by the two other methods were found to be reduced considerably after treating the sera with phospholipase C (PLC). The PLC treatment also reduced the apparent HI titres in some sera containing variable amounts of CF and/or HIG antibodies, but did not affect antibody determinations by the two latter methods. These results suggest that false positive results can be obtained in the OC43 HI test unless the sera are treated with phospholipase C before the assay.", "qid": 7, "docid": "0s2rx3gc", "rank": 99, "score": 0.8510683178901672}, {"content": "Title: [Development of a SPA-ELISA method for detecting anti-coronavirus IgG antibodies in serum samples from fulvous fruit bats]. Content: OBJECTIVE To develop an simple and sensitive method for detecting anti-coronavirus IgG antibodies in bat sera based on enzyme-linked immunosorbent assay (ELISA). METHODS A commercial ELISA kit for detecting SARS-CoV antibody was modified for detecting coronavirus antibodies in bat serum samples. The second antibody in the kit was replaced with horseradish peroxidase-conjugated protein-A (HRP-SPA) based on the characteristics of binding between Staphylococcus aureus protein A (SPA) and mammal IgG Fc fragment. The sera of 55 fulvous fruit bats (Rousettus dasymallus) were tested using the SPA-ELISA. RESULTS The test results of the positive and negative controls in the kit and the serum samples from convalescent ;patient were consistent with expectation. Coronavirus antibody was detected in 2 out of the 55 bat serum samples. Serum neutralization test confirmed the validity of the SPA-ELISA method. CONCLUSION This SPA-ELISA method is applicable for detecting coronavirus antibody in bat sera.", "qid": 7, "docid": "vwy25qah", "rank": 100, "score": 0.8510466814041138}]}
{"query": "how has lack of testing availability led to underreporting of true incidence of Covid-19?", "hits": [{"content": "Title: \u00bfConocemos las propiedades diagn\u00f3sticas de las pruebas usadas en COVID-19? Una revisi\u00f3n r\u00e1pida de la literatura recientemente publicada./ \u00bfConocemos las propiedades diagn\u00f3sticas de las pruebas usadas en COVID-19? Una revisi\u00f3n r\u00e1pida de la literatura recientemente publicada./ Do we know the diagnostic properties of the tests used in COVID-19? A rapid review of recently published literature Content: COVID-19 has brought death and disease to large parts of the world. Governments must deploy strategies to screen the population and subsequently isolate the suspect cases. Diagnostic testing is critical for epidemiological surveillance, but the accuracy (sensitivity and specificity) and clinical utility (impact on health outcomes) of the current diagnostic methods used for SARS-CoV-2 detection are not known. I ran a quick search in PubMed/MEDLINE to find studies on laboratory diagnostic tests and rapid viral diagnosis. After running the search strategies, I found 47 eligible articles that I discuss in this review, commenting on test characteristics and limitations. I did not find any papers that report on the clinical utility of the tests currently used for COVID-19 detection, meaning that we are fighting a battle without proper knowledge of the proportion of false negatives that current testing is resulting in. This shortcoming should not be overlooked as it might hamper national efforts to contain the pandemic through testing community-based suspect cases.", "qid": 8, "docid": "gzrjca1l", "rank": 1, "score": 0.8751233220100403}, {"content": "Title: Do we know the diagnostic properties of the tests used in COVID-19? A rapid review of recently published literature. Content: COVID-19 has brought death and disease to large parts of the world. Governments must deploy strategies to screen the population and subsequently isolate the suspect cases. Diagnostic testing is critical for epidemiological surveillance, but the accuracy (sensitivity and specificity) and clinical utility (impact on health outcomes) of the current diagnostic methods used for SARS-CoV-2 detection are not known. I ran a quick search in PubMed/MEDLINE to find studies on laboratory diagnostic tests and rapid viral diagnosis. After running the search strategies, I found 47 eligible articles that I discuss in this review, commenting on test characteristics and limitations. I did not find any papers that report on the clinical utility of the tests currently used for COVID-19 detection, meaning that we are fighting a battle without proper knowledge of the proportion of false negatives that current testing is resulting in. This shortcoming should not be overlooked as it might hamper national efforts to contain the pandemic through testing community-based suspect cases.", "qid": 8, "docid": "vn0xu1cn", "rank": 2, "score": 0.8751233220100403}, {"content": "Title: The challenges of covid-19 testing: Time for pathologists to rise to the occasion Content: An outbreak of novel coronavirus (Covid-19) was first reported in Wuhan, China in the late December 1 Since then, the positive cases have increased exponentially to 1 4 million (as of 8 April 2020) 2 The ability of a country to cope with increasing number of Covid-19 testing is the ultimate test Teaching/university hospitals should pull their resources and man-power to provide the muchneeded assistance to the demand of Covid-19 testing Inadequate testing could result in unrecognised Covid-19 infected individuals, roaming freely in the population The other issue is the sensitivity of test if samples were obtained from different sites Classically, the confirmation of diagnosis of Covid-19 depends on real time polymerase chain reaction (RT-PCR) analysis to detect viral genetic material in either a nasal swab or bronchioalveolar lavage sample Wang et al (2020) reported that bronchioalveolar lavage sample has the highest sensitivity in identifying Covid-19, followed by sputum and nasal swab with positive rates of 93%, 72% and 63%, respectively 3 Furthermore, they found that nasal swab contained the highest concentration of viral load as it required less number of cycles to achieve higher copy numbers In some patients, viral genetic material was also identified in faeces and blood 3 While the reliability of testing is a concern, the safety of the laboratory staff also has to be kept in mind In this issue, there are three review articles on Covid-19, first article described the general properties of coronavirus, second article described the diagnostic performance of Covid-19 serology assay and third article described the importance of the site of sampling for Covid-19 4-6", "qid": 8, "docid": "2buj9xrh", "rank": 3, "score": 0.8749839067459106}, {"content": "Title: Testing for SARS-CoV-2: Can We Stop at Two? Content: The COVID-19 epidemic requires accurate identification and isolation of confirmed cases for effective control. This report describes the effectiveness of our testing strategy and highlights the importance of repeat testing in suspect cases in our cohort.", "qid": 8, "docid": "vrpms6yz", "rank": 4, "score": 0.867044985294342}, {"content": "Title: Statistically-based methodology for revealing real contagion trends and correcting delay-induced errors in the assessment of COVID-19 pandemic Content: COVID-19 pandemic has reshaped our world in a timescale much shorter than what we can understand. Particularities of SARS-CoV-2, such as its persistence in surfaces and the lack of a curative treatment or vaccine against COVID-19, have pushed authorities to apply restrictive policies to control its spreading. As data drove most of the decisions made in this global contingency, their quality is a critical variable for decision-making actors, and therefore should be carefully curated. In this work, we analyze the sources of error in typically reported epidemiological variables and usual tests used for diagnosis, and their impact on our understanding of COVID-19 spreading dynamics. We address the existence of different delays in the report of new cases, induced by the incubation time of the virus and testing-diagnosis time gaps, and other error sources related to the sensitivity/specificity of the tests used to diagnose COVID-19. Using a statistically-based algorithm, we perform a temporal reclassification of cases to avoid delay-induced errors, building up new epidemiologic curves centered in the day where the contagion effectively occurred. We also statistically enhance the robustness behind the discharge/recovery clinical criteria in the absence of a direct test, which is typically the case of non-first world countries, where the limited testing capabilities are fully dedicated to the evaluation of new cases. Finally, we applied our methodology to assess the evolution of the pandemic in Chile through the Effective Reproduction Number R(t), identifying different moments in which data was misleading governmental actions. In doing so, we aim to raise public awareness of the need for proper data reporting and processing protocols for epidemiological modelling and predictions.", "qid": 8, "docid": "iydjrmhh", "rank": 5, "score": 0.8646644949913025}, {"content": "Title: Substantial underestimation of SARS-CoV-2 infection in the United States due to incomplete testing and imperfect test accuracy Content: Accurate estimates of the burden of SARS-CoV-2 infection are critical to informing pandemic response. Current confirmed COVID-19 case counts in the U.S. do not capture the total burden of the pandemic because testing has been primarily restricted to individuals with moderate to severe symptoms due to limited test availability. Using a semi-Bayesian probabilistic bias analysis to account for incomplete testing and imperfect diagnostic accuracy, we estimated 6,275,072 cumulative infections compared to 721,245 confirmed cases (1.9% vs. 0.2% of the population) as of April 18, 2020. Accounting for uncertainty, the number of infections was 3 to 20 times higher than the number of confirmed cases. 86% (simulation interval: 64-99%) of this difference was due to incomplete testing, while 14% (0.3-36%) was due to imperfect test accuracy. Estimates of SARS-CoV-2 infections that transparently account for testing practices and diagnostic accuracy reveal that the pandemic is larger than confirmed case counts suggest.", "qid": 8, "docid": "ehcikhnw", "rank": 6, "score": 0.861871063709259}, {"content": "Title: Global analysis of daily new COVID-19 cases reveals many static-phase countries including US and UK potentially with unstoppable epidemics Content: The COVID-19 epidemics are differentially progressing in different countries. Here, comparative analyses of daily new cases reveal that 61 most affected countries can be classified into four types: downward (22), upward (20), static-phase (12) and uncertain ones (7). In particular, the 12 static-phase countries including US and UK are characterized by largely constant numbers of daily new cases in the past over 14 days. Furthermore, these static-phase countries are overall significantly lower in testing density but higher in the level of positive COVID-19 tests than downward countries. These findings suggest that the testing capacity in static-phase countries is lagging behind the spread of the outbreak, i.e., daily new cases (confirmed) are likely less than daily new infections and the remaining undocumented infections are thus still expanding, resulting in unstoppable epidemics. As such, increasing the testing capacity and/or reducing the COVID-19 transmission are urgently needed to stop the severing crisis in static-phase countries.", "qid": 8, "docid": "ajfdwt4q", "rank": 7, "score": 0.8604673147201538}, {"content": "Title: Severe underestimation of COVID-19 case numbers: effect of epidemic growth rate and test restrictions Content: To understand the scope and development of the COVID-19 pandemic, knowledge of the number of infected persons is essential. Often, the number of \"confirmed cases\", which is based on positive RT-PCR test results, is regarded as a reasonable indicator. However, limited COVID-19 test capacities in many countries are restricting the amount of testing that can be done. This can lead to the implementation of testing policies that restrict access to COVID-19 tests, and to testing backlogs and delays. As a result, confirmed case numbers can be significantly lower than the actual number of infections, especially during rapid growth phases of the epidemic. This study examines the quantitative relation between infections and reported confirmed case numbers for two different testing strategies, \"limited\" and \"inclusive\" testing, in relation to the growth rate of the epidemic. The results indicate that confirmed case numbers understate the actual number of infections substantially; during rapid growth phases where the daily growth rate can reach or exceed 30%, as has been seen in many countries, the confirmed case numbers under-report actual infections by up to 50 to 100-fold.", "qid": 8, "docid": "p0rqg7uk", "rank": 8, "score": 0.859974205493927}, {"content": "Title: The Challenge of Using Epidemiological Case Count Data: The Example of Confirmed COVID-19 Cases and the Weather Content: The publicly available data on COVID-19 cases provides an opportunity to better understand this new disease. However, strong attention needs to be paid to the limitations of the data to avoid making inaccurate conclusions. This article, which focuses on the relationship between the weather and COVID-19, raises the concern that the same factors influencing the spread of the disease might also affect the number of tests performed and who gets tested. For example, weather conditions impact the prevalence of respiratory diseases with symptoms similar to COVID-19, and this will likely influence the number of tests performed. This general limitation could severely undermine any similar analysis using existing COVID-19 data or similar epidemiological data, which could, therefore, mislead decision-makers on questions of great policy relevance.", "qid": 8, "docid": "0jm73t0s", "rank": 9, "score": 0.8597452640533447}, {"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": 10, "score": 0.8579277992248535}, {"content": "Title: COVID-19: Should We Test Everyone? Content: Since the beginning of 2020, the coronavirus disease 2019 (COVID-19) has spread rapidly in the city of Wuhan, P.R. China, and subsequently, across the world. The swift spread of the virus is largely attributed to its stealth transmissions in which infected patients may be asymptomatic. Undetected transmissions present a remarkable challenge for the containment of the virus and pose an appalling threat to the public. An urgent question that has been asked by the public is\"Should I be tested for COVID-19 if I am sick?\". While different regions established their own criteria for screening infected cases, the screening criteria have been modified based on new evidence and understanding of the virus as well as the availability of resources. The shortage of test kits and medical personnel has considerably limited our ability to do as many tests as possible. Public health officials and clinicians are facing a dilemma of balancing the limited resources and unlimited demands. On one hand, they are striving to achieve the best outcome by optimizing the usage of the scant resources. On the other hand, they are challenged by the patients' frustrations and anxieties, stemming from the concerns of not being tested for COVID-19 for not meeting the definition of PUI (person under investigation). In this paper, we evaluate the situation from the statistical viewpoint by factoring into the considerations of the uncertainty and inaccuracy of the test, an issue that is often overlooked by the general public. We aim to shed light on the tough situation by providing evidence-based reasoning from the statistical angle, and we expect this examination will help the general public understand and assess the situation rationally. Most importantly, the development offers recommendations for physicians to make sensible evaluations to optimally use the limited resources for the best medical outcome.", "qid": 8, "docid": "1mfize6h", "rank": 11, "score": 0.8573257327079773}, {"content": "Title: False positives in reverse transcription PCR testing for SARS-CoV-2 Content: Background: Large-scale testing for SARS-CoV-2 by RT-PCR is a key element of the response to COVID-19, but little attention has been paid to the potential frequency and impacts of false positives. Method: From a meta-analysis of external quality assessments of RT-PCR assays of RNA viruses, we derived a conservative estimate of the range of false positive rates that can reasonably be expected in SARS-CoV-2 testing, and analyzed the effect of such rates on analyses of regional test data and estimates of population prevalence and asymptomatic ratio. Findings: Review of external quality assessments revealed false positive rates of 0-16.7%, with an interquartile range of 0.8-4.0%. Such rates would have large impacts on test data when prevalence is low. Inclusion of such rates significantly alters four published analyses of population prevalence and asymptomatic ratio. Interpretation: The high false discovery rate that results, when prevalence is low, from false positive rates typical of RT-PCR assays of RNA viruses raises questions about the usefulness of mass testing; and indicates that across a broad range of likely prevalences, positive test results are more likely to be wrong than are negative results, contrary to public health advice about SARS-CoV-2 testing. There are myriad clinical and case management implications. Failure to appreciate the potential frequency of false positives and the consequent unreliability of positive test results across a range of scenarios could unnecessarily remove critical workers from service, expose uninfected individuals to greater risk of infection, delay or impede appropriate medical treatment, lead to inappropriate treatment, degrade patient care, waste personal protective equipment, waste human resources in unnecessary contact tracing, hinder the development of clinical improvements, and weaken clinical trials. Measures to raise awareness of false positives, reduce their frequency, and mitigate their effects should be considered.", "qid": 8, "docid": "ywvk6gu6", "rank": 12, "score": 0.8570387959480286}, {"content": "Title: SARS-CoV2 Testing: The Limit of Detection Matters Content: Resolving the COVID-19 pandemic requires diagnostic testing to determine which individuals are infected and which are not. The current gold standard is to perform RT-PCR on nasopharyngeal samples. Best-in-class assays demonstrate a limit of detection (LoD) of ~100 copies of viral RNA per milliliter of transport media. However, LoDs of currently approved assays vary over 10,000-fold. Assays with higher LoDs will miss more infected patients, resulting in more false negatives. However, the false-negative rate for a given LoD remains unknown. Here we address this question using over 27,500 test results for patients from across our healthcare network tested using the Abbott RealTime SARS-CoV-2 EUA. These results suggest that each 10-fold increase in LoD is expected to increase the false negative rate by 13%, missing an additional one in eight infected patients. The highest LoDs on the market will miss a majority of infected patients, with false negative rates as high as 70%. These results suggest that choice of assay has meaningful clinical and epidemiological consequences. The limit of detection matters.", "qid": 8, "docid": "3hazdvbl", "rank": 13, "score": 0.8568621873855591}, {"content": "Title: Estimating the COVID-19 infection rate: Anatomy of an inference problem Content: As a consequence of missing data on tests for infection and imperfect accuracy of tests, reported rates of cumulative population infection by the SARS CoV-2 virus are lower than actual rates of infection. Hence, reported rates of severe illness conditional on infection are higher than actual rates. Understanding the time path of the COVID-19 pandemic has been hampered by the absence of bounds on infection rates that are credible and informative. This paper explains the logical problem of bounding these rates and reports illustrative findings, using data from Illinois, New York, and Italy. We combine the data with assumptions on the infection rate in the untested population and on the accuracy of the tests that appear credible in the current context. We find that the infection rate might be substantially higher than reported. We also find that the infection fatality rate in Illinois, New York, and Italy is substantially lower than reported.", "qid": 8, "docid": "8wg27hcu", "rank": 14, "score": 0.8562517762184143}, {"content": "Title: Towards reduction in bias in epidemic curves due to outcome misclassification through Bayesian analysis of time-series of laboratory test results: case study of COVID-19 in Alberta, Canada and Philadelphia, USA Content: BACKGROUND: Despite widespread use, the accuracy of the diagnostic test for SARS-CoV-2 infection is poorly understood. The aim of our work was to better quantify misclassification errors in identification of true cases of COVID-19 and to study the impact of these errors in epidemic curves using publicly available surveillance data from Alberta, Canada and Philadelphia, USA. METHODS: We examined time-series data of laboratory tests for SARS-CoV-2 viral infection, the causal agent for COVID-19, to try to explore, using a Bayesian approach, the sensitivity and specificity of the diagnostic test. RESULTS: Our analysis revealed that the data were compatible with near-perfect specificity, but it was challenging to gain information about sensitivity. We applied these insights to uncertainty/bias analysis of epidemic curves under the assumptions of both improving and degrading sensitivity. If the sensitivity improved from 60 to 95%, the adjusted epidemic curves likely falls within the 95% confidence intervals of the observed counts. However, bias in the shape and peak of the epidemic curves can be pronounced, if sensitivity either degrades or remains poor in the 60\u201370% range. In the extreme scenario, hundreds of undiagnosed cases, even among the tested, are possible, potentially leading to further unchecked contagion should these cases not self-isolate. CONCLUSION: The best way to better understand bias in the epidemic curves of COVID-19 due to errors in testing is to empirically evaluate misclassification of diagnosis in clinical settings and apply this knowledge to adjustment of epidemic curves.", "qid": 8, "docid": "vvm1gfku", "rank": 15, "score": 0.8546501994132996}, {"content": "Title: Towards reduction in bias in epidemic curves due to outcome misclassification through Bayesian analysis of time-series of laboratory test results: case study of COVID-19 in Alberta, Canada and Philadelphia, USA Content: BACKGROUND: Despite widespread use, the accuracy of the diagnostic test for SARS-CoV-2 infection is poorly understood. The aim of our work was to better quantify misclassification errors in identification of true cases of COVID-19 and to study the impact of these errors in epidemic curves using publicly available surveillance data from Alberta, Canada and Philadelphia, USA. METHODS: We examined time-series data of laboratory tests for SARS-CoV-2 viral infection, the causal agent for COVID-19, to try to explore, using a Bayesian approach, the sensitivity and specificity of the diagnostic test. RESULTS: Our analysis revealed that the data were compatible with near-perfect specificity, but it was challenging to gain information about sensitivity. We applied these insights to uncertainty/bias analysis of epidemic curves under the assumptions of both improving and degrading sensitivity. If the sensitivity improved from 60 to 95%, the adjusted epidemic curves likely falls within the 95% confidence intervals of the observed counts. However, bias in the shape and peak of the epidemic curves can be pronounced, if sensitivity either degrades or remains poor in the 60-70% range. In the extreme scenario, hundreds of undiagnosed cases, even among the tested, are possible, potentially leading to further unchecked contagion should these cases not self-isolate. CONCLUSION: The best way to better understand bias in the epidemic curves of COVID-19 due to errors in testing is to empirically evaluate misclassification of diagnosis in clinical settings and apply this knowledge to adjustment of epidemic curves.", "qid": 8, "docid": "t2utj1a6", "rank": 16, "score": 0.8545209169387817}, {"content": "Title: The Appropriate Use of Testing for COVID-19 Content: Many public officials are calling for increased testing for the 2019 novel coronavirus disease (COVID-19), and some governments have taken extraordinary measures to increase the availability of testing. However, little has been published about the sensitivity and specificity of the reverse transcriptase-polymerase chain reaction (RT-PCR) nasopharyngeal swabs that are commonly used for testing. This narrative review evaluates the literature regarding the accuracy of these tests, and makes recommendations based on this literature. In brief, a negative RT-PCR nasopharyngeal swab test is insufficient to rule out COVID-19. Thus, over-reliance on the results of the test may be dangerous, and the push for widespread testing may be overstated.", "qid": 8, "docid": "a038jilw", "rank": 17, "score": 0.8531039953231812}, {"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": 18, "score": 0.8530232310295105}, {"content": "Title: SARS-CoV-2 Laboratory Testing in India's Pandemic Response: A Public Health Perspective. Content: Coronavirus disease 2019 (COVID-19) caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) has resulted (at the time of writing) in over 3.3 million cases and 233,000 deaths globally and ~33,000 cases and ~1,100 deaths in India. The mainstay of the diagnosis is a reverse-transcription polymerase chain reaction assay to detect SARS-CoV-2 RNA. The accurate diagnosis is contingent on appropriate specimen choice, time of collection, and assay employed. In this commentary, we highlight the role of laboratory diagnostic tests used in the different stages of India's COVID-19 pandemic response.", "qid": 8, "docid": "mvrrenww", "rank": 19, "score": 0.8529045581817627}, {"content": "Title: SARS-CoV-2 Laboratory Testing in India's Pandemic Response: A Public Health Perspective Content: Coronavirus disease 2019 (COVID-19) caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) has resulted (at the time of writing) in over 3.3 million cases and 233,000 deaths globally and ~33,000 cases and ~1,100 deaths in India. The mainstay of the diagnosis is a reverse-transcription polymerase chain reaction assay to detect SARS-CoV-2 RNA. The accurate diagnosis is contingent on appropriate specimen choice, time of collection, and assay employed. In this commentary, we highlight the role of laboratory diagnostic tests used in the different stages of India's COVID-19 pandemic response.", "qid": 8, "docid": "baymfp6m", "rank": 20, "score": 0.8529044985771179}, {"content": "Title: Disentangling Increased Testing From Covid-19 Epidemic Spread Content: To design effective disease control strategies, it is critical to understand the incidence of diseases. In the Covid-19 epidemic in the United States (caused by outbreak of the SARS-CoV-2 virus), testing capacity was initially very limited and has been increasing at the same time as the virus has been spreading. When estimating the incidence, it can be difficult to distinguish whether increased numbers of positive tests stem from increases in the spread of the virus or increases in testing. This has made it very difficult to identify locations in which the epidemic poses the largest public health risks. Here, we use a probabilistic model to quantify beliefs about testing strategies and understand implications regarding incidence. We apply this model to estimate the incidence in each state of the United States, and find that: (1) the Covid-19 epidemic is likely to be more widespread than reported by limited testing, (2) the Covid-19 epidemic growth in the summer months is likely smaller than it was during the spring months, and (3) the regions which are at highest risk of Covid-19 epidemic outbreaks are not always those with the largest number of positive test results.", "qid": 8, "docid": "l7jme343", "rank": 21, "score": 0.8523715138435364}, {"content": "Title: Estimating the COVID-19 Infection Rate: Anatomy of an Inference Problem Content: As a consequence of missing data on tests for infection and imperfect accuracy of tests, reported rates of population infection by the SARS CoV-2 virus are lower than actual rates of infection. Hence, reported rates of severe illness conditional on infection are higher than actual rates. Understanding the time path of the COVID-19 pandemic has been hampered by the absence of bounds on infection rates that are credible and informative. This paper explains the logical problem of bounding these rates and reports illustrative findings, using data from Illinois, New York, and Italy. We combine the data with assumptions on the infection rate in the untested population and on the accuracy of the tests that appear credible in the current context. We find that the infection rate might be substantially higher than reported. We also find that the infection fatality rate in Italy is substantially lower than reported.", "qid": 8, "docid": "4kkzi70v", "rank": 22, "score": 0.8522858619689941}, {"content": "Title: Urgent need for individual mobile phone and institutional reporting of at home, hospitalized, and intensive care unit cases of SARS-CoV-2 (COVID-19) infection Content: Approximately 90 days of the SARS-CoV-2 (COVID-19) spreading originally from Wuhan, China, and across the globe has led to a widespread chain of events with imminent threats to the fragile relationship between community health and economic health. Despite near hourly reporting on this crisis, there has been no regular, updated, or accurate reporting of hospitalizations for COVID-19. It is known that many test-positive individuals may not develop symptoms or have a mild self-limited viral syndrome consisting of fever, malaise, dry cough, and constitutional symptoms. However some individuals develop a more fulminant syndrome including viral pneumonia, respiratory failure requiring oxygen, acute respiratory distress syndrome requiring mechanical ventilation, and in substantial fractions leading to death attributable to COVID-19. The pandemic is evolving in a clustered, non-inform fashion resulting in many hospitals with preparedness but few or no cases, and others that are completely overwhelmed. Thus, a considerable risk of spread when personal protection equipment becomes exhausted and a large fraction of mortality in those not offered mechanical ventilation are both attributable to a crisis due to maldistribution of resources. The pandemic is amenable to self-reporting through a mobile phone application that could obtain critical information on suspected cases and report on the results of self testing and actions taken. The only method to understand the clustering and the immediate hospital resource needs is mandatory, uniform, daily reporting of hospital censuses of COVID-19 cases admitted to hospital wards and intensive care units. Current reports of hospitalizations are delayed, uncertain, and wholly inadequate. This paper urges all the relevant stakeholders to take up self-reporting and reporting of hospitalizations of COVID-19 as an urgent task in combating this devastating pandemic.", "qid": 8, "docid": "03tzip4q", "rank": 23, "score": 0.8518624305725098}, {"content": "Title: Urgent need for individual mobile phone and institutional reporting of at home, hospitalized, and intensive care unit cases of SARS-CoV-2 (COVID-19) infection. Content: Approximately 90 days of the SARS-CoV-2 (COVID-19) spreading originally from Wuhan, China, and across the globe has led to a widespread chain of events with imminent threats to the fragile relationship between community health and economic health. Despite near hourly reporting on this crisis, there has been no regular, updated, or accurate reporting of hospitalizations for COVID-19. It is known that many test-positive individuals may not develop symptoms or have a mild self-limited viral syndrome consisting of fever, malaise, dry cough, and constitutional symptoms. However some individuals develop a more fulminant syndrome including viral pneumonia, respiratory failure requiring oxygen, acute respiratory distress syndrome requiring mechanical ventilation, and in substantial fractions leading to death attributable to COVID-19. The pandemic is evolving in a clustered, non-inform fashion resulting in many hospitals with preparedness but few or no cases, and others that are completely overwhelmed. Thus, a considerable risk of spread when personal protection equipment becomes exhausted and a large fraction of mortality in those not offered mechanical ventilation are both attributable to a crisis due to maldistribution of resources. The pandemic is amenable to self-reporting through a mobile phone application that could obtain critical information on suspected cases and report on the results of self testing and actions taken. The only method to understand the clustering and the immediate hospital resource needs is mandatory, uniform, daily reporting of hospital censuses of COVID-19 cases admitted to hospital wards and intensive care units. Current reports of hospitalizations are delayed, uncertain, and wholly inadequate. This paper urges all the relevant stakeholders to take up self-reporting and reporting of hospitalizations of COVID-19 as an urgent task in combating this devastating pandemic.", "qid": 8, "docid": "qwnmc1wd", "rank": 24, "score": 0.8518624305725098}, {"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": 25, "score": 0.8509213328361511}, {"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": 8, "docid": "59prqbb3", "rank": 26, "score": 0.8497475385665894}, {"content": "Title: Active Monitoring of Persons Exposed to Patients with Confirmed COVID-19 - United States, January-February 2020 Content: In December 2019, an outbreak of coronavirus disease 2019 (COVID-19), caused by the virus SARS-CoV-2, began in Wuhan, China (1). The disease spread widely in China, and, as of February 26, 2020, COVID-19 cases had been identified in 36 other countries and territories, including the United States. Person-to-person transmission has been widely documented, and a limited number of countries have reported sustained person-to-person spread.* On January 20, state and local health departments in the United States, in collaboration with teams deployed from CDC, began identifying and monitoring all persons considered to have had close contact\u0086 with patients with confirmed COVID-19 (2). The aims of these efforts were to ensure rapid evaluation and care of patients, limit further transmission, and better understand risk factors for transmission.", "qid": 8, "docid": "npyo0597", "rank": 27, "score": 0.8493557572364807}, {"content": "Title: Active Monitoring of Persons Exposed to Patients with Confirmed COVID-19 - United States, January-February 2020. Content: In December 2019, an outbreak of coronavirus disease 2019 (COVID-19), caused by the virus SARS-CoV-2, began in Wuhan, China (1). The disease spread widely in China, and, as of February 26, 2020, COVID-19 cases had been identified in 36 other countries and territories, including the United States. Person-to-person transmission has been widely documented, and a limited number of countries have reported sustained person-to-person spread.* On January 20, state and local health departments in the United States, in collaboration with teams deployed from CDC, began identifying and monitoring all persons considered to have had close contact\u2020 with patients with confirmed COVID-19 (2). The aims of these efforts were to ensure rapid evaluation and care of patients, limit further transmission, and better understand risk factors for transmission.", "qid": 8, "docid": "mvm1t0y7", "rank": 28, "score": 0.8486090302467346}, {"content": "Title: Catastrophic failure of outbreak containment: Limited testing causes discontinuity in epidemic transition Content: Standard measures such as quarantining suspects and contact tracing could not contain the ongoing COVID-19 pandemic. Unlike for other recent epidemics where such instruments were successful, in the present case a large fraction of the infected have only mild unspecific symptoms. By employing network models we here show that even for near perfect contact tracing and unlimited suspect testing, containment starts to fail when more than approximately half of the carriers fall into the weak-symptom category. The situation becomes considerably more severe if the number of daily available tests is limited. In this case the epidemic transition becomes discontinuous and a much larger percentage of the population becomes infected. While moderate levels of social distancing can bring the situation back under control, the limited number of daily tests introduces a finite time horizon: If social distancing is implemented after the cut off date, containment catastrophically breaks down resulting in an exponential disease spread.", "qid": 8, "docid": "ekglbwrl", "rank": 29, "score": 0.8485691547393799}, {"content": "Title: \"No test is better than a bad test\": Impact of diagnostic uncertainty in mass testing on the spread of Covid-19 Content: Background: The cessation of lock-down measures will require an effective testing strategy. Much focus at the beginning of the UK's Covid-19 epidemic was directed to deficiencies in the national testing capacity. The quantity of tests may seem an important focus, but other characteristics are likely more germane. False positive tests are more probable than positive tests when the overall population has a low prevalence of the disease, even with highly accurate tests. Methods: We modify an SIR model to include quarantines states and test performance using publicly accessible estimates for the current situation. Three scenarios for cessation of lock-down measures are explored: (1) immediate end of lock-down measures, (2) continued lock-down with antibody testing based immunity passports, and (3) incremental relaxation of lock-down measures with active viral testing. Sensitivity, specifcity, prevalence and test capacity are modified for both active viral and antibody testing to determine their population level effect on the continuing epidemic. Findings: Diagnostic uncertainty can have a large effect on the epidemic dynamics of Covid-19 within the UK. The dynamics of the epidemic are more sensitive to test performance and targeting than test capacity. The quantity of tests is not a substitute for an effective strategy. Poorly targeted testing has the propensity to exacerbate the peak in infections. Interpretation: The assessment that 'no test is better than a bad test' is broadly supported by the present analysis. Antibody testing is unlikely to be a solution to the lock-down, regardless of test quality or capacity. A well designed active viral testing strategy combined with incremental relaxation of the lock-down measures is shown to be a potential strategy to restore some social activity whilst continuing to keep infections low.", "qid": 8, "docid": "2jwuzfan", "rank": 30, "score": 0.8484830856323242}, {"content": "Title: The usefulness of SARS-CoV-2 test positive proportion as a surveillance tool Content: Comparison of COVID-19 case numbers over time and between locations is complicated by limits to virologic testing confirm SARS-CoV-2 infection, leading to under-reporting of incidence, and by variations in testing capacity between locations and over time. The proportion of tested individuals who have tested positive (test positive proportion, TPP) can potentially be used to qualitatively assess the testing capacity of a location; a high TPP could provide evidence that too few people are tested, leading to more under-reporting. In this study we propose a simple model for testing in a population experiencing an epidemic of COVID-19, and derive an expression for TPP in terms of well-defined parameters in the model, related to testing and presence of other pathogens causing COVID-19 like symptoms. We use simulations to show situations in which the TPP is higher or lower than we expect based on these parameters, and the effect of testing strategies on the TPP. In our simulations, we find in the absence of dramatic shifts of testing practices in time or between spatial locations, the TPP is positively correlated with the incidence of infection. As a corollary, the TPP can be used to distinguish between a decline in confirmed cases due to decline in incidence (in which case TPP should decline) and a decline in confirmed cases due to testing constraints (in which case TPP should remain constant). We show that the proportion of tested individuals who present COVID-19 like symptoms (test symptomatic proportion, TSP) encodes similar information to the TPP but has different relationships with the testing parameters, and can thus provide additional information regarding dynamic changes in TPP and incidence. Finally, we compare data on confirmed cases and TPP from US states. We conjecture why states may have higher or lower TPP than average. We suggest that collection of symptom status and age/risk category of tested individuals can aid interpretation of changes in TPP and increase the utility of TPP in assessing the state of the pandemic in different locations and times.", "qid": 8, "docid": "ole70vk0", "rank": 31, "score": 0.8483960628509521}, {"content": "Title: Application of pooled testing in screening and estimating the prevalence of Covid-19 Content: The recent emergence of the COVID-19 pandemic has posed an unprecedented healthcare challenge and catastrophic economic and social consequences to the countries across the world. The situation is even worse for emerging economies like India. WHO recommends mass scale testing as one of the most effective ways to contain its spread and fight the pandemic. But, due to the high cost and shortage of test kits, specifically in India, the testing is restricted to only those who are symptomatic. In this context, pooled testing is recommended by some experts as a partial solution to overcome this problem. In this article, we explain the basic statistical theory behind the pooled testing procedure for screening as well as prevalence estimation. In real world situations, the tests are imperfect, and lead to false positive and false negative results. We provide theoretical explanation of the impact of these diagnostic errors on the performances of individual testing and pooled testing procedures. Finally, we study the effect of misspecification of sensitivity and specificity of tests on the estimate of prevalence, an issue, which is debated a lot among the scientists in the context of COVID-19. Our theoretical investigations lead to some interesting and precise understanding of some of these issues.", "qid": 8, "docid": "dbzpcy5v", "rank": 32, "score": 0.8482131958007812}, {"content": "Title: Reconstructing the global dynamics of under-ascertained COVID-19 cases and infections Content: Background: Asymptomatic or subclinical SARS-CoV-2 infections are often unreported, which means that confirmed case counts may not accurately reflect underlying epidemic dynamics. Understanding the level of ascertainment (the ratio of confirmed symptomatic cases to the true number of symptomatic individuals) and undetected epidemic progression is crucial to informing COVID-19 response planning, including the introduction and relaxation of control measures. Estimating case ascertainment over time allows for accurate estimates of specific outcomes such as seroprevalence, which is essential for planning control measures. Methods: Using reported data on COVID-19 cases and fatalities globally, we estimated the proportion of symptomatic cases (i.e. any person with any of fever >= to 37.5C, cough, shortness of breath, sudden onset of anosmia, ageusia or dysgeusia illness) that were reported in 210 countries and territories, given those countries had experienced more than ten deaths. We used published estimates of the case fatality ratio (CFR) as an assumed baseline. We then calculated the ratio of this baseline CFR to an estimated local delay-adjusted CFR to estimate the level of under-ascertainment in a particular location. We then fit a Bayesian Gaussian process model to estimate the temporal pattern of under-ascertainment. Results: We estimate that, during March 2020, the median percentage of symptomatic cases detected across the 84 countries which experienced more than ten deaths ranged from 2.38% (Bangladesh) to 99.6% (Chile). Across the ten countries with the highest number of total confirmed cases as of 6th July 2020, we estimated that the peak number of symptomatic cases ranged from 1.4 times (Chile) to 17.8 times (France) larger than reported. Comparing our model with national and regional seroprevalence data where available, we find that our estimates are consistent with observed values. Finally, we estimated seroprevalence for each country. Despite low case detection in some countries, our results that adjust for this still suggest that all countries have had only a small fraction of their populations infected as of July 2020. Conclusions: We found substantial under-ascertainment of symptomatic cases, particularly at the peak of the first wave of the SARS-CoV-2 pandemic, in many countries. Reported case counts will therefore likely underestimate the rate of outbreak growth initially and underestimate the decline in the later stages of an epidemic. Although there was considerable under-reporting in many locations, our estimates were consistent with emerging serological data, suggesting that the proportion of each country's population infected with SARS-CoV-2 worldwide is generally low.", "qid": 8, "docid": "no0xh7t0", "rank": 33, "score": 0.8477904200553894}, {"content": "Title: Effectiveness of a COVID-19 screening questionnaire for pregnant women at admission to an obstetric unit in Milan. Content: Sutton et al. [1] recently reported on universal testing with nasopharyngeal swabs to detect severe acute respiratory syndrome coronavirus 2 (SARS-Cov-2) infection in 215 women admitted for delivery at the Presbyterian Allen Hospital in New York, USA. They identified 33 (15.3%) infected women, of whom only four had fever or symptoms suggesting coronavirus disease 2019 (COVID-19). These findings suggest that only universal testing can reliably recognize infected cases. However, this approach is only feasible in major hospitals in high-resource countries with efficient lab facilities in-house. Alternative approaches deserve consideration.", "qid": 8, "docid": "3g7oersj", "rank": 34, "score": 0.8477253913879395}, {"content": "Title: RT-qPCR Testing of SARS-CoV-2: A Primer Content: Testing for the presence of coronavirus is an essential diagnostic tool for monitoring and managing the current COVID-19 pandemic. The only reliable test in current use for testing acute infection targets the genome of SARS-CoV-2, and the most widely used method is quantitative fluorescence-based reverse transcription polymerase chain reaction (RT-qPCR). Despite its ubiquity, there is a significant amount of uncertainty about how this test works, potential throughput and reliability. This has resulted in widespread misrepresentation of the problems faced using this test during the current COVID-19 epidemic. This primer provides simple, straightforward and impartial information about RT-qPCR.", "qid": 8, "docid": "td2r7xm1", "rank": 35, "score": 0.8474262356758118}, {"content": "Title: Infections and Identified Cases of COVID-19 from Random Testing Data Content: There are many hard-to-reconcile numbers circulating concerning Covid-19. Using reports from random testing, the fatality ratio per infection is evaluated and used to extract further information on the actual fraction of infections and the success of their identification for different countries.", "qid": 8, "docid": "ncz1b8dl", "rank": 36, "score": 0.8473889827728271}, {"content": "Title: Comparing and Integrating US COVID-19 Daily Data from Multiple Sources: A County-Level Dataset with Local Characteristics Content: Over the past several months, the outbreak of COVID-19 has been expanding over the world. A reliable and accurate dataset of the cases is vital for scientists to conduct related research and for policy-makers to make better decisions. We collect the COVID-19 daily reported data from four open sources: the New York Times, the COVID-19 Data Repository by Johns Hopkins University, the COVID Tracking Project at the Atlantic, and the USAFacts, and compare the similarities and differences among them. In addition, we examine the following problems which occur frequently: (1) the order dependencies violation, (2) the delay-reported issue on weekends and/or holidays, and (3) abnormal data point or data period. We also integrate the COVID-19 reported cases with the county-level auxiliary information of the local features from official sources, such as health infrastructure, demographic, socioeconomic, and environment information, which are important for understanding the spread of the virus.", "qid": 8, "docid": "yfuq8na6", "rank": 37, "score": 0.847258448600769}, {"content": "Title: [Advances on presymptomatic or asymptomatic carrier transmission of COVID-19] Content: COVID-19 is rapidly spreading. Patients in incubation period and healthy carriers are possible sources for transmission. However, such sources of infection cannot be effectively identified due to the symptoms absent. The research evidence is very lacking so far, although there are a few studies suggesting that presymptomatic or asymptomatic carrier may cause COVID-19 transmission. Nearly half of the literature is in the state of preprint without peer review. The question of \"the degree to which presymptomatic or asymptomatic infections can transmit\" is not fully understood. There is an urgent need to screen infected carriers in larger close contacts or in the general population, and assess their risk for transmission.", "qid": 8, "docid": "3fd81ovn", "rank": 38, "score": 0.8471511602401733}, {"content": "Title: [Advances on presymptomatic or asymptomatic carrier transmission of COVID-19]. Content: COVID-19 is rapidly spreading. Patients in incubation period and healthy carriers are possible sources for transmission. However, such sources of infection cannot be effectively identified due to the symptoms absent. The research evidence is very lacking so far, although there are a few studies suggesting that presymptomatic or asymptomatic carrier may cause COVID-19 transmission. Nearly half of the literature is in the state of preprint without peer review. The question of \"the degree to which presymptomatic or asymptomatic infections can transmit\" is not fully understood. There is an urgent need to screen infected carriers in larger close contacts or in the general population, and assess their risk for transmission.", "qid": 8, "docid": "xbv0b96w", "rank": 39, "score": 0.8471511602401733}, {"content": "Title: COVID-19 Serological Tests: How Well Do They Actually Perform? Content: In only a few months after initial discovery in Wuhan, China, SARS-CoV-2 and the associated coronavirus disease 2019 (COVID-19) have become a global pandemic causing significant mortality and morbidity and implementation of strict isolation measures In the absence of vaccines and effective therapeutics, reliable serological testing must be a key element of public health policy to control further spread of the disease and gradually remove quarantine measures Serological diagnostic tests are being increasingly used to provide a broader understanding of COVID-19 incidence and to assess immunity status in the population However, there are discrepancies between claimed and actual performance data for serological diagnostic tests on the market In this study, we conducted a review of independent studies evaluating the performance of SARS-CoV-2 serological tests We found significant variability in the accuracy of marketed tests and highlight several lab-based and point-of-care rapid serological tests with high levels of performance The findings of this review highlight the need for ongoing independent evaluations of commercialized COVID-19 diagnostic tests", "qid": 8, "docid": "upwn9o2m", "rank": 40, "score": 0.8468413352966309}, {"content": "Title: Covid-19 Pandemic- Pits and falls of major states of India. Content: Covid-19, just like SARS and MERS before it, is a disease caused by corona virus and can lead to severe respiratory diseases in humans. With the outbreak of novel corona virus, WHO on 30th January 2020 declared it a Public Health Emergency and further on 11th March 2020, Covid-19 disease was declared a pandemic. India in the initial stages of the pandemic dealt with it in a very effective manner. With timely implementation of lockdown, India was able to contain the spread of Covid-19 to some extent. However with the recently announced Unlock 1.0, the SARS CoV-2 is expected to spread. This study aims to track and analyze the Covid-19 situation in major states that constitute of 70 percent of the total cases. Thus the states selected for the study are: Maharashtra, Delhi, Tamil Nadu, Gujarat, Uttar Pradesh and Rajasthan. These are the states which had more than ten thousand Covid-19 patients as/on June 10th 2020. The analysis period is from March 25th to June 10th and the data source is India Covid-19 tracker. To assess the previous and current Covid-19 situations in these states indicators such as Active rates, Recovery rate, Case fatality rate, Test positivity rate, tests per million, cases per million, test per confirmed case has been used. The study finds that although the absolute number of active cases may be rising, however it is showing a decreasing trend with an increase in recovery rates. With increasing number of Covid-19 cases, testing also has increased however not in the similar proportion and thus by developed nation standard we are lagging. With increasing TPR and cases per million, Delhi is well on its way to surpass even Mumbai which till now has proven to be worst hit in this pandemic. An interesting finding is that of test per confirmed case which shows that every 6th person in Maharashtra and every 8th in Delhi is showing positive result of Covid-19 test. Given such an increase and unlocked India, Delhi might soon enter into the third stage of community transmission where source of 50 percent or more cases would be unknown. There has been an increase in the Covid-19 related health infrastructure with the public-private partnership which involved both private hospitals and lab joining hands to battle Covid-19, however, affordability still remains an issue. If experts are to be believed, pandemic is not over because we have unlocked. The worst is yet to come as Covid-19 is predicted to peak in mid-July to August in India. Thus, it would be advisable to not venture out unnecessarily just because restrictions have been lifted. Also, following the guidelines- hand-washing, avoiding public gathering, social distancing and covering nose and mouth has now become imperative.", "qid": 8, "docid": "po7wys3s", "rank": 41, "score": 0.8467607498168945}, {"content": "Title: Network structure of COVID-19 spread and the lacuna in India's testing strategy Content: We characterize the network of COVID-19 spread in India and find that the transmission rate is 0.43, with daily case growth driven by individuals who contracted the virus abroad. We explore the question of whether this represents exponentially decaying dynamics or is simply an artefact of India's testing strategy. Testing has largely been limited to individuals travelling from high-risk countries and their immediate contacts, meaning that the network reflects positive identifications from a biased testing sample. Given generally low levels of testing and an almost complete absence of testing for community spread, there is significant risk that we may be missing out on the actual nature of outbreak. India still has an apparently low current caseload, with possibly a small window of time to act, and should therefore aggressively and systematically expand random testing for community spread, including for asymptomatic cases. This will help understand true transmission characteristics and plan appropriately for the immediate future.", "qid": 8, "docid": "deuvq0wf", "rank": 42, "score": 0.8466289043426514}, {"content": "Title: Testing COVID-19 tests faces methodological challenges Content: In battling the COVID-19 pandemic, testing is essential. The detection of viral RNA allows the identification of infected persons, while the detection of antibodies may reveal a response to a previous infection. Tests for coronavirus should be rigorously evaluated in terms of their analytical and clinical performance. This poses not only logistic challenges, but also methodological ones. Some of these are generic for the diagnostic accuracy paradigm, while others are more specific for tests for viruses. Problematic for evaluations of the clinical performance of tests for viral RNA is the absence of an independent reference standard. Many studies lack rigor in terms of the recruitment of study participants. Study reports are often insufficiently informative, which makes it difficult to assess the applicability of study findings. Attempts to summarize the performance of these tests in terms of a single estimate of the clinical sensitivity fails to do justice to the identifiable sources of the large heterogeneity in mechanisms for generating false negative results.", "qid": 8, "docid": "6n35qvi8", "rank": 43, "score": 0.8463662266731262}, {"content": "Title: Low Utility of Repeat Real-Time PCR Testing for SARS-CoV-2 in Clinical Specimens Content: Abstract: In a multicenter cohort of 22,315 patients tested for COVID-19, 1676 (7.5%) had repeat testing via real-time PCR following an initial negative test. Of those retested within seven days of their first negative test, only 2.0% had a positive result. This suggests that repeat testing from the same source is unlikely to provide additional information.", "qid": 8, "docid": "urwn7bsu", "rank": 44, "score": 0.8459293842315674}, {"content": "Title: Serial Laboratory Testing for SARS-CoV-2 Infection Among Incarcerated and Detained Persons in a Correctional and Detention Facility \u2014 Louisiana, April\u2013May 2020 Content: Transmission of SARS-CoV-2, the virus that causes coronavirus disease 2019 (COVID-19), by asymptomatic and presymptomatic persons poses important challenges to controlling spread of the disease, particularly in congregate settings such as correctional and detention facilities (1). On March 29, 2020, a staff member in a correctional and detention facility in Louisiana developed symptoms\u2020 and later had a positive test result for SARS-CoV-2. During April 2-May 7, two additional cases were detected among staff members, and 36 cases were detected among incarcerated and detained persons at the facility; these persons were removed from dormitories and isolated, and the five dormitories that they had resided in before diagnosis were quarantined. On May 7, CDC and the Louisiana Department of Health initiated an investigation to assess the prevalence of SARS-CoV-2 infection among incarcerated and detained persons residing in quarantined dormitories. Goals of this investigation included evaluating COVID-19 symptoms in this setting and assessing the effectiveness of serial testing to identify additional persons with SARS-CoV-2 infection as part of efforts to mitigate transmission. During May 7-21, testing of 98 incarcerated and detained persons residing in the five quarantined dormitories (A-E) identified an additional 71 cases of SARS-CoV-2 infection; 32 (45%) were among persons who reported no symptoms at the time of testing, including three who were presymptomatic. Eighteen cases (25%) were identified in persons who had received negative test results during previous testing rounds. Serial testing of contacts from shared living quarters identified persons with SARS-CoV-2 infection who would not have been detected by symptom screening alone or by testing at a single time point. Prompt identification and isolation of infected persons is important to reduce further transmission in congregate settings such as correctional and detention facilities and the communities to which persons return when released.", "qid": 8, "docid": "73cfcubp", "rank": 45, "score": 0.8458837866783142}, {"content": "Title: A novel comprehensive metric to assess COVID-19 testing outcomes: Effects of geography, government, and policy response Content: Testing and case identification are key strategies in controlling the COVID-19 pandemic. Contact tracing and isolation are only possible if cases have been identified. The effectiveness of testing must be tracked, but a single comprehensive metric is not available to assess testing effectiveness, and no timely estimates of case detection rate are available globally, making inter-country comparisons difficult. The purpose of this paper was to propose a single, comprehensive metric, called the COVID-19 Testing Index (CovTI) scaled from 0 to 100, that incorporated several testing metrics. The index was based on case-fatality rate, test positivity rate, active cases, and an estimate of the detection rate. It used parsimonious modeling to estimate the true total number of COVID-19 cases based on deaths, testing, health system capacity, and government transparency. Publicly reported data from 188 countries and territories were included in the index. Estimates of detection rates aligned with previous estimates in literature (R2=0.97). As of June 3, 2020, the states with the highest CovTI included Iceland, Australia, New Zealand, Hong Kong, and Thailand, and some island nations. Globally, CovTI increased from April 20 ([x]=43.2) to June 3 ([x]=52.2) but declined in ca. 10% of countries. Bivariate analyses showed the average in countries with open public testing policies (59.7, 95% CI 55.6-63.8) were significantly higher than countries with no testing policy (30.2, 95% CI 18.1-42.3) (p<0.0001). A multiple linear regression model assessed the association of independent grouping variables with CovTI. Open public testing and extensive contact tracing were shown to significantly increase CovTI, after adjusting for extrinsic factors, including geographic isolation and centralized forms of government. This tool may be useful for policymakers to assess testing effectiveness, inform decisions, and identify model countries. It may also serve as a tool for researchers in analyses by combining it with other databases.", "qid": 8, "docid": "6ed3two6", "rank": 46, "score": 0.8456014394760132}, {"content": "Title: How much of SARS-CoV-2 Infections is India detecting? A model-based estimation Content: Background and Rationale: Amid SARS-CoV-2 outbreak, the low number of infections for a population size of 1.38 billion is widely discussed, but with no definite answers. Methods: We used the model proposed by Bommer and Vollmer to assess the quality of official case records. The infection fatality rates were taken from Verity et al (2020). Age distribution of the population for India and states are taken from the Census of India (2011). Reported number of deaths and SARS-CoV-2 confirmed cases from https://www.covid19india.org. The reported numbers of samples tests were collected from the reports of the Indian Council for Medical Research (ICMR). Results: The findings suggest that India is detecting just 3.6% of the total number of infections with a huge variation across its states. Among 13 states which have more than 100 COVID-19 cases, the detection rate varies from 81.9% (of 410 estimated infections) in Kerala to 0.8% (of 35487 estimated infections) in Madhya Pradesh and 2.4% (of 7431 estimated infections) in Gujarat. Conclusion: As the study reports a lower number of deaths and higher recovery rates in the states with a high detection rate, thus suggest that India must enhance its testing capacity and go for widespread testing. Late detection puts patients in greater need of mechanical ventilation and ICU care, which imposes greater costs on the health system. The country should also adopt population-level random testing to assess the prevalence of the infection.", "qid": 8, "docid": "c9bp9euw", "rank": 47, "score": 0.8455275297164917}, {"content": "Title: Diagnostic Performance of a Rapid Point of Care Test for SARS-CoV-2 in an Urban ED Setting Content: The ability to rapidly and accurately identify a patient's COVID-19 status has had significant impact on emergency departments (ED) and health systems globally. Since the identification of SARS-CoV-2 illness in the United States, there has been rapid development in patient testing capacity following initial challenges including sparse availability. This was made possible by increasing availability of diagnostic molecular tests in several formats, from laboratory based traditional, RT-PCR methods to near patient testing rapid point of care PCR tests.", "qid": 8, "docid": "onhiptn7", "rank": 48, "score": 0.845112681388855}, {"content": "Title: Serial Laboratory Testing for SARS-CoV-2 Infection Among Incarcerated and Detained Persons in a Correctional and Detention Facility - Louisiana, April-May 2020 Content: Transmission of SARS-CoV-2, the virus that causes coronavirus disease 2019 (COVID-19), by asymptomatic and presymptomatic persons poses important challenges to controlling spread of the disease, particularly in congregate settings such as correctional and detention facilities (1). On March 29, 2020, a staff member in a correctional and detention facility in Louisiana developed symptoms\u0086 and later had a positive test result for SARS-CoV-2. During April 2-May 7, two additional cases were detected among staff members, and 36 cases were detected among incarcerated and detained persons at the facility; these persons were removed from dormitories and isolated, and the five dormitories that they had resided in before diagnosis were quarantined. On May 7, CDC and the Louisiana Department of Health initiated an investigation to assess the prevalence of SARS-CoV-2 infection among incarcerated and detained persons residing in quarantined dormitories. Goals of this investigation included evaluating COVID-19 symptoms in this setting and assessing the effectiveness of serial testing to identify additional persons with SARS-CoV-2 infection as part of efforts to mitigate transmission. During May 7-21, testing of 98 incarcerated and detained persons residing in the five quarantined dormitories (A-E) identified an additional 71 cases of SARS-CoV-2 infection; 32 (45%) were among persons who reported no symptoms at the time of testing, including three who were presymptomatic. Eighteen cases (25%) were identified in persons who had received negative test results during previous testing rounds. Serial testing of contacts from shared living quarters identified persons with SARS-CoV-2 infection who would not have been detected by symptom screening alone or by testing at a single time point. Prompt identification and isolation of infected persons is important to reduce further transmission in congregate settings such as correctional and detention facilities and the communities to which persons return when released.", "qid": 8, "docid": "ghmvmkez", "rank": 49, "score": 0.8449406027793884}, {"content": "Title: Major testing issues in US Content: Delays and restrictions on who can be tested for the covid-19 virus in the US have raised the risk that it is spreading undetected, reports Colin Barras", "qid": 8, "docid": "dftnv7ez", "rank": 50, "score": 0.8449112176895142}, {"content": "Title: Evolu\u00e7\u00e3o da preval\u00eancia de infec\u00e7\u00e3o por COVID-19 no Rio Grande do Sul, Brasil: inqu\u00e9ritos sorol\u00f3gicos seriados./ Evolu\u00e7\u00e3o da preval\u00eancia de infec\u00e7\u00e3o por COVID-19 no Rio Grande do Sul, Brasil: inqu\u00e9ritos sorol\u00f3gicos seriados./ Trends in the prevalence of COVID-19 infection in Rio Grande do Sul, Brazil: repeated serological surveys Content: COVID-19, the disease produced by the virus SARS-CoV-2, has spread quickly throughout the world, leading the World Health Organization to first classify it as an international health emergency and, subsequently, declaring it pandemic. The number of confirmed cases, as April 11, surpassed 1,700,000, but this figure does not reflect the prevalence of COVID-19 in the population as, in many countries, tests are almost exclusively performed in people with symptoms, particularly severe cases. To properly assess the magnitude of the problem and to contribute to the design of evidence-based policies for fighting COVID-19, one must accurately estimate the population prevalence of infection. Our study is aimed at estimating the prevalence of infected individuals in the state of Rio Grande do Sul, Brazil, to document how fast the infection spreads, and to estimate the proportion of infected persons who present or presented symptoms, as well as the proportion of asymptomatic infections. Four repeated serological surveys will be conducted in probability samples of nine sentinel cities every two weeks. Tests will be performed in 4,500 participants in each survey, totaling18,000 interviews. Interviews and tests will be conducted at the participants' household. A rapid test for the detection of antibodies will be used; the test was validated prior to the beginning of the fieldwork.", "qid": 8, "docid": "73a9yes1", "rank": 51, "score": 0.8448116779327393}, {"content": "Title: Trends in the prevalence of COVID-19 infection in Rio Grande do Sul, Brazil: repeated serological surveys. Content: COVID-19, the disease produced by the virus SARS-CoV-2, has spread quickly throughout the world, leading the World Health Organization to first classify it as an international health emergency and, subsequently, declaring it pandemic. The number of confirmed cases, as April 11, surpassed 1,700,000, but this figure does not reflect the prevalence of COVID-19 in the population as, in many countries, tests are almost exclusively performed in people with symptoms, particularly severe cases. To properly assess the magnitude of the problem and to contribute to the design of evidence-based policies for fighting COVID-19, one must accurately estimate the population prevalence of infection. Our study is aimed at estimating the prevalence of infected individuals in the state of Rio Grande do Sul, Brazil, to document how fast the infection spreads, and to estimate the proportion of infected persons who present or presented symptoms, as well as the proportion of asymptomatic infections. Four repeated serological surveys will be conducted in probability samples of nine sentinel cities every two weeks. Tests will be performed in 4,500 participants in each survey, totaling18,000 interviews. Interviews and tests will be conducted at the participants' household. A rapid test for the detection of antibodies will be used; the test was validated prior to the beginning of the fieldwork.", "qid": 8, "docid": "1cdmsxu1", "rank": 52, "score": 0.8448116779327393}, {"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": 53, "score": 0.8447302579879761}, {"content": "Title: [Covid-19 diagnosis : clinical recommendations and performance of nasopharyngeal swab-PCR]. Content: The Covid-19 pandemic imposes new diagnostic strategies in order to optimize the medical care of our patients. The current biblio-graphy, although of low quality, shows a sensitivity of 56 to 83 % for the Covid-19 PCR. Even though one negative test can exclude a Covid-19 in the majority of cases, the NPV (Negative Predictive Value) decreases with increasing prevalence (pre-test probability). This finding suggests the need for strict auto-isolation of patients until the resolution of their symptoms. For patients that present with typical symptoms, who have a presumed Covid-19 prevalence of -40-50 %, a negative test should be interpreted with caution and a repeat test may be needed.", "qid": 8, "docid": "1mcmwe7f", "rank": 54, "score": 0.8447020053863525}, {"content": "Title: SARS-CoV-2 and the COVID-19 disease: a mini review on diagnostic methods Content: Coronavirus disease 2019 (COVID-19) is an infectious disease initially reported in China and currently worldwide dispersed caused by a new coronavirus (SARS-CoV-2 or 2019-nCoV) affecting more than seven million people around the world causing more than 400 thousand deaths (on June 8th, 2020). The diagnosis of COVID-19 is based on the clinical and epidemiological history of the patient. However, the gold standard for COVID-19 diagnosis is the viral detection through the amplification of nucleic acids. Although the quantitative Reverse-Transcription Polymerase Chain Reaction (RT-PCR) has been described as the gold standard for diagnosing COVID-19, there are several difficulties involving its use. Here we comment on RT-PCR and describe alternative tests developed for the diagnosis of COVID-19.", "qid": 8, "docid": "8vi60e0a", "rank": 55, "score": 0.8446638584136963}, {"content": "Title: Time Course of COVID-19 Cases in Austria Content: COVID-19 is an infectious disease caused by a novel coronavirus, which first appeared in China in late 2019, and reached pandemic distribution in early 2020. The first major outbreak in Europe occurred in Northern Italy where it spread to neighboring countries, notably to Austria, where skiing resorts served as a main transmission hub. Soon, the Austrian government introduced strict measures to curb the spread of the virus. Using publicly available data, we assessed the efficiency of the governmental measures. We assumed an average incubation period of one week and an average duration of infectivity of 10 days. One week after the introduction of strict measures, the increase in daily new cases was reversed, and the reproduction number dropped. The crude estimates tended to overestimate the reproduction rate in the early phase. Publicly available data provide a first estimate about the effectiveness of public health measures. However, more data are needed for an unbiased assessment.", "qid": 8, "docid": "cfk25vpu", "rank": 56, "score": 0.8446385860443115}, {"content": "Title: Dynamics of RT-qPCR SARS-CoV-2 Detection Rates Prior to and After Symptom Onset Content: Effective RT-qPCR testing for SARS-CoV-2 is essential for treatment, surveillance and control of the COVID-19 pandemic. A recent meta-analysis suggested that testing prior to the onset of symptoms is likely to miss the majority of infected individuals. These findings cast severe doubts on the effectiveness of mass screening efforts intended to detect SARS-CoV-2 prior to the onset of symptoms and decrease community transmissions from pre-/asymptomatic individuals. However, alternative analyses and additional data described herein refine these estimates and suggest that many SARS-CoV-2 infections could potentially be detected prior to symptom onset.", "qid": 8, "docid": "l2wxq1qm", "rank": 57, "score": 0.8443171977996826}, {"content": "Title: Estimating the global spread of COVID-19 Content: Limited and inconsistent testing and differences in age distribution, health care resources, social distancing, and policies have caused large variations in the extent and dynamics of the COVID-19 pandemic across nations, complicating the estimation of prevalence, the infection fatality rate (IFR), and other factors important to care providers and policymakers. Using data for all 84 countries with reliable testing data (spanning 4.75 billion people) we develop a dynamic epidemiological model integrating data on cases, deaths, excess mortality and other factors to estimate how asymptomatic transmission, disease acuity, hospitalization, and behavioral and policy responses to risk condition prevalence and IFR across nations and over time. For these nations we estimate IFR averages 0.68% (0.64%-0.7%). Cases and deaths through June 18, 2020 are estimated to be 11.8 and 1.48 times official reports, respectively, at 88.5 (85-95.3) million and 600 (586-622) thousand. Prevalence and IFR vary substantially, e.g., Ecuador (18%; 0.61%), Chile (15.5%; 0.57%), Mexico (8.8%; 0.69%), Iran (7.9%; 0.44%), USA (5.3%; 0.99%), UK (5.2%; 1.59%), Iceland (1.65%, 0.56%), New Zealand (0.1%, 0.64%), but all nations remain well below the level needed for herd immunity. By alerting the public earlier and reducing contacts, extensive testing when the pandemic was declared could have averted 35.3 (32.7-42.7) million cases and 197 (171-232) thousand deaths. However, future outcomes are less dependent on testing and more contingent on the willingness of communities and governments to reduce transmission. Absent breakthroughs in treatment or vaccination and with mildly improved responses we project 249 (186-586) million cases and 1.75 (1.40-3.67) million deaths in the 84 countries by Spring 2021.", "qid": 8, "docid": "837qlk8y", "rank": 58, "score": 0.8442156910896301}, {"content": "Title: Estimating the extent of true asymptomatic COVID-19 and its potential for community transmission: systematic review and meta-analysis Content: Background: The prevalence of true asymptomatic COVID-19 cases is critical to policy makers considering the effectiveness of mitigation measures against the SARS-CoV-2 pandemic. We aimed to synthesize all available research on the asymptomatic rates and transmission rates where possible. Methods: We searched PubMed, Embase, Cochrane COVID-19 trials, and European PMC for pre-print platforms such as MedRxiv. We included primary studies reporting on asymptomatic prevalence where: (a) the sample frame includes at-risk population, and (b) there was sufficiently long follow up to identify pre-symptomatic cases. Meta-analysis used fixed effect and random effects models. Results: We screened 571 articles and included five low risk-of-bias studies from three countries (China (2), USA (2), Italy (1)) that tested 9,242 at-risk people, of which 413 were positive and 65 were asymptomatic. Diagnosis in all studies was confirmed using a RT-qPCR test. The proportion of asymptomatic cases ranged from 6% to 41%. Meta-analysis (fixed effect) found that the proportion of asymptomatic cases was 16% (95% CI: 12% - 20%) overall; higher in non-aged care 19% (15% - 24%), and lower in long-term aged care 8% (4% - 14%). Two studies provided direct evidence of forward transmission of the infection by asymptomatic cases but suggested lower rates than symptomatic cases. Conclusion: Our estimates of the prevalence of asymptomatic COVID-19 cases are lower than many highly publicized studies, but still substantial. Further robust epidemiological evidence is urgently needed, including in sub-populations such as children, to better understand the importance of asymptomatic cases for driving spread of the pandemic.", "qid": 8, "docid": "li8kvzdh", "rank": 59, "score": 0.8441359996795654}, {"content": "Title: SARS-CoV-2 and the COVID-19 disease: a mini review on diagnostic methods Content: Coronavirus disease 2019 (COVID-19) is an infectious disease initially reported in China and currently worldwide dispersed caused by a new coronavirus (SARS-CoV-2 or 2019-nCoV) affecting more than seven million people around the world causing more than 400 thousand deaths (on June 8(th), 2020). The diagnosis of COVID-19 is based on the clinical and epidemiological history of the patient. However, the gold standard for COVID-19 diagnosis is the viral detection through the amplification of nucleic acids. Although the quantitative Reverse-Transcription Polymerase Chain Reaction (RT-PCR) has been described as the gold standard for diagnosing COVID-19, there are several difficulties involving its use. Here we comment on RT-PCR and describe alternative tests developed for the diagnosis of COVID-19.", "qid": 8, "docid": "f6p9i951", "rank": 60, "score": 0.8440496921539307}, {"content": "Title: Sniffing out the evidence; It's now time for public health bodies recognize the link between COVID-19 and smell and taste disturbance Content: Since the outbreak of the pandemic, anecdotal observations have been accumulating rapidly that sudden anosmia and dysgeusia are peculiar symptoms associated with the COVID-19 infection. Prof C. Hopkins, as President of British Rhinological Society, published a letter describing \"the loss of sense of smell as a marker of COVID-19 infection\" and proposed that adults presenting with anosmia but no other symptoms should self-isolate for seven days. The Hopkins team published the first case report and case series as well as other evidence that isolated sudden onset anosmia (ISOA), should be considered highly suspicious for SARS-CoV-2(1). Subsequently, a larger series of 2428 patients presenting with new onset anosmia during the COVID-19 pandemic has been reported, of whom 16% report loss of sense of smell as an isolated symptom. Only 51% reported the recognized symptoms of cough or fever. A major limitation of this series however, was a lack of access to testing to confirm the COVID-19 status of the patients(2); in the 80 who had been tested 74% were positive. In the same way, the American Academy of Otolaryngology-head and neck surgery (AA0-HNS) proposed \"that anosmia could be added to the list of screening tools for possible COVID-19 infection. More, they warrant serious consideration for self-isolation and testing those patients&quot;.", "qid": 8, "docid": "3xccfhd9", "rank": 61, "score": 0.843910813331604}, {"content": "Title: Management of COVID\u201019\u2010related paediatric blood samples in a clinical haematology laboratory Content: There is currently limited knowledge about the transmission risks of the SARS-CoV-2 virus and its associated disease COVID-19 from routine clinical specimens. The first study to be published on the initial 41 cases of COVID-19 infections admitted in Wuhan detected SARS-CoV-2 RNA in the blood of 6/41 (15%) of patients (Huang et. al., 2020) . However, another study conducted on 1070 clinical specimens collected from confirmed COVID-19 patients in China showed the highest positive rates of SARS-CoV-2 from rRT-PCR testing of respiratory specimens such as bronchoalveolar lavage, sputum and nasopharyngeal swabs (32% - 93%). In contrast, only 1% of blood specimens and none of the urine specimens tested positive (Wang et. al., 2020).", "qid": 8, "docid": "4650vwvy", "rank": 62, "score": 0.8437457084655762}, {"content": "Title: Redundancy in reporting on COVID\u201019 Content: Additional to the problems described very well by Dr. Ioannidis1 , there is another issue that became highlighted during this pandemic: redundancy in research and reporting. Redundant articles repeat already known information and are mostly published just for the sake of publishing. By searching through Pubmed, one can easily see that the number of publications related to COVID-19 is growing exponentially (Figure).", "qid": 8, "docid": "938nfrdp", "rank": 63, "score": 0.8435984253883362}, {"content": "Title: A Statistical Analysis Of CoV-19 Positive Test Frequency Data Indicates A Need For Greater Attention To CoV-19 Test Quality And Pre-Wuhan Cov-19 Prevalence Content: Increased attention to analysis of SARS-CoV-2 (CoV-19) positive test frequency data is essential for achievement of better knowledge of the natural history of the virus in human populations, improved accuracy of CoV-19 epidemiological data, and development of public response policies that are better crafted to address the current CoV-19-induced global crisis. A statistical analysis of currently available positive test frequency data reveals a surprisingly uniform relationship between the number of CoV-19 test performed and the number of positive tests obtained. The uniformity is particularly striking for United States CoV-19 test data. Such observations warrant closer evaluation of other factors, besides virus spread, that may also contribute to the nature of the coronavirus pandemic. These include indigenous CoV-19 and the quality of CoV-19 testing.", "qid": 8, "docid": "uyq45ryf", "rank": 64, "score": 0.8435130715370178}, {"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": 65, "score": 0.8431333303451538}, {"content": "Title: Towards reduction in bias in epidemic curves due to outcome misclassification through Bayesian analysis of time-series of laboratory test results: Case study of COVID-19 in Alberta, Canada and Philadelphia, USA Content: The aim of our work was to better understand misclassification errors in identification of true cases of COVID-19 and to study the impact of these errors in epidemic curves. We examined publically available time-series data of laboratory tests for SARS-CoV-2 viral infection, the causal agent for COVID-19, to try to explore, using a Bayesian approach, about the sensitivity and specificity of the PCR-based diagnostic test. Data originated from Alberta, Canada (available on 3/28/2020) and city of Philadelphia, USA (available on 3/31/2020). Our analysis revealed that the data were compatible with near-perfect specificity but it was challenging to gain information about sensitivity (prior and posterior largely overlapped). We applied these insights to uncertainty/bias analysis of epidemic curves into jurisdictions under the assumptions of both improving and degrading sensitivity. If the sensitivity improved from 60 to 95%, the observed and adjusted epidemic curves likely fall within the 95% confidence intervals of the observed counts. However, bias in the shape and peak of the epidemic curves can be pronounced, if sensitivity either degrades or remains poor in the 60\u201370% range. In the extreme scenario, hundreds of undiagnosed cases, even among tested, are possible, potentially leading to further unchecked contagion should these cases not self-isolate. The best way to better understand bias in the epidemic curves of COVID-19 due to errors in testing is to empirically evaluate misclassification of diagnosis in clinical settings and apply this knowledge to adjustment of epidemic curves, a task for which the Bayesian method we presented is well-suited.", "qid": 8, "docid": "qu9b07ea", "rank": 66, "score": 0.8430275917053223}, {"content": "Title: Sniffing out the evidence; It's now time for public health bodies recognize the link between COVID-19 and smell and taste disturbance. Content: Since the outbreak of the pandemic, anecdotal observations have been accumulating rapidly that sudden anosmia and dysgeusia are peculiar symptoms associated with the COVID-19 infection. Prof C. Hopkins, as President of British Rhinological Society, published a letter describing \"the loss of sense of smell as a marker of COVID-19 infection\" and proposed that adults presenting with anosmia but no other symptoms should self-isolate for seven days. The Hopkins team published the first case report and case series as well as other evidence that isolated sudden onset anosmia (ISOA), should be considered highly suspicious for SARS-CoV-2(1). Subsequently, a larger series of 2428 patients presenting with new onset anosmia during the COVID-19 pandemic has been reported, of whom 16% report loss of sense of smell as an isolated symptom. Only 51% reported the recognized symptoms of cough or fever. A major limitation of this series however, was a lack of access to testing to confirm the COVID-19 status of the patients(2); in the 80 who had been tested 74% were positive. In the same way, the American Academy of Otolaryngology-head and neck surgery (AA0-HNS) proposed \"that anosmia could be added to the list of screening tools for possible COVID-19 infection. More, they warrant serious consideration for self-isolation and testing those patients\".", "qid": 8, "docid": "6yl3oh6n", "rank": 67, "score": 0.8428785800933838}, {"content": "Title: [Covid-19 diagnosis : clinical recommendations and performance of nasopharyngeal swab-PCR] Content: The Covid-19 pandemic imposes new diagnostic strategies in order to optimize the medical care of our patients The current biblio-graphy, although of low quality, shows a sensitivity of 56 to 83 % for the Covid-19 PCR Even though one negative test can exclude a Covid-19 in the majority of cases, the NPV (Negative Predictive Value) decreases with increasing prevalence (pre-test probability) This finding suggests the need for strict auto-isolation of patients until the resolution of their symptoms For patients that present with typical symptoms, who have a presumed Covid-19 prevalence of -40-50 %, a negative test should be interpreted with caution and a repeat test may be needed", "qid": 8, "docid": "tz7kzcrt", "rank": 68, "score": 0.8428487777709961}, {"content": "Title: The Infection Rate of the Coronavirus Disease 2019 (COVID-19) in Wuhan, China Content: For the pandemic of COVID-19, the initial number of infections in Wuhan China has never been known or estimated properly. This data is critical to understand the current pandemic across the world, as well as to eliminate panic from overestimated fatality rate that has biased the public health policies of many countries. By our unique estimation with the data of a number of foreign government evacuations with thorough follow-up and etiological tests, it is safe to say that a large number of infections in Wuhan, China have not been diagnosed (the number of undiagnosed is much more than the final diagnosed number 50,333 to date).", "qid": 8, "docid": "bhpbsz6h", "rank": 69, "score": 0.842848002910614}, {"content": "Title: Epidemiology, diagnosis, treatment, and future perspectives concerning SARS-COV-2: a review article Content: The present study aimed to review the epidemiology, clinical manifestation, laboratory diagnosis, treatment, and future perspectives related to COVID-19 infections. The following electronic databases were used searched: MEDLINE, SCIELO, and LILACS. It became clear that COVID-19 infections occur through exposure to the virus, and both the immunosuppressed and healthy population appear susceptible. The clinical course of COVID-19 is still not clear, although the SARS-CoV-2 infection seems to develop with mild, influenza-like symptoms in the vast majority of subjects, i.e., 10%-15% of COVID-19 patients. Since rRT-PCR tests serve as the gold standard method to confirm a SARS-CoV-2 infection, false-negative results could hinder the prevention and control of the epidemic, particularly considering the test plays a key role in the decision for continued isolated medical observation or discharge. Our findings also indicate that a radical increase in the identification and isolation of currently undocumented infections would be needed to fully control SARS-CoV2.", "qid": 8, "docid": "elieuuuy", "rank": 70, "score": 0.842847466468811}, {"content": "Title: Epidemiology, diagnosis, treatment, and future perspectives concerning SARS-COV-2: a review article. Content: The present study aimed to review the epidemiology, clinical manifestation, laboratory diagnosis, treatment, and future perspectives related to COVID-19 infections. The following electronic databases were used searched: MEDLINE, SCIELO, and LILACS. It became clear that COVID-19 infections occur through exposure to the virus, and both the immunosuppressed and healthy population appear susceptible. The clinical course of COVID-19 is still not clear, although the SARS-CoV-2 infection seems to develop with mild, influenza-like symptoms in the vast majority of subjects, i.e., 10%-15% of COVID-19 patients. Since rRT-PCR tests serve as the gold standard method to confirm a SARS-CoV-2 infection, false-negative results could hinder the prevention and control of the epidemic, particularly considering the test plays a key role in the decision for continued isolated medical observation or discharge. Our findings also indicate that a radical increase in the identification and isolation of currently undocumented infections would be needed to fully control SARS-CoV2.", "qid": 8, "docid": "kzgjnpz9", "rank": 71, "score": 0.842847466468811}, {"content": "Title: How to Best Predict the Daily Number of New Infections of Covid-19 Content: Knowledge about the daily number of new infections of Covid-19 is important because it is the basis for political decisions resulting in lockdowns and urgent health care measures. We use Germany as an example to illustrate shortcomings of official numbers, which are, at least in Germany, disclosed only with several days of delay and severely underreported on weekends (more than 40%). These shortcomings outline an urgent need for alternative data sources. The other widely cited source provided by the Center for Systems Science and Engineering at Johns Hopkins University (JHU) also deviates for Germany on average by 79% from the official numbers. We argue that Google Search and Twitter data should complement official numbers. They predict even better than the original values from Johns Hopkins University and do so several days ahead. These two data sources could also be used in parts of the world where official numbers do not exist or are perceived to be unreliable.", "qid": 8, "docid": "ojhc7peo", "rank": 72, "score": 0.84270179271698}, {"content": "Title: Transmission risk of patients with COVID-19 meeting discharge criteria should be interpreted with caution Content: As of Apr. 22, 2020, the World Health Organization (2020) has reported over 2.4 million confirmed coronavirus disease 2019 (COVID-19) patients and 169 151 deaths. Recent articles have uncovered genomic characteristics and clinical features of COVID-19 (Chan et al., 2020; Chang et al., 2020; Guan et al., 2020; Zhu et al., 2020), while our understanding of COVID-19 is still limited. As suggested by guidelines promoted by the General Office of National Health Commission of the People's Republic of China (2020) (from Versions 1 to 6), discharged standards for COVID-19 were still dependent on viral real-time polymerase chain reaction (RT-PCR) tests of respiratory specimens, showing that recovered COVID-19 patients with twice negative RT-PCR could meet discharge criteria. Here, we examined two cases in which nucleic acid test results were inconsistent with clinical and radiological findings, leading to suboptimal care.", "qid": 8, "docid": "kugveoru", "rank": 73, "score": 0.8426315784454346}, {"content": "Title: Test sensitivity is secondary to frequency and turnaround time for COVID-19 surveillance Content: The COVID-19 pandemic has created a public health crisis. Because SARS-CoV-2 can spread from individuals with pre-symptomatic, symptomatic, and asymptomatic infections, the re-opening of societies and the control of virus spread will be facilitated by robust surveillance, for which virus testing will often be central. After infection, individuals undergo a period of incubation during which viral titers are usually too low to detect, followed by an exponential growth of virus, leading to a peak viral load and infectiousness, and ending with declining viral levels and clearance. Given the pattern of viral load kinetics, we model surveillance effectiveness considering test sensitivities, frequency, and sample-to-answer reporting time. These results demonstrate that effective surveillance, including time to first detection and outbreak control, depends largely on frequency of testing and the speed of reporting, and is only marginally improved by high test sensitivity. We therefore conclude that surveillance should prioritize accessibility, frequency, and sample-to-answer time; analytical limits of detection should be secondary.", "qid": 8, "docid": "q44yuued", "rank": 74, "score": 0.8425295352935791}, {"content": "Title: Testing COVID-19 tests faces methodological challenges Content: Abstract In battling the COVID-19 pandemic, testing is essential. The detection of viral RNA allows the identification of infected persons, while the detection of antibodies may reveal a response to a previous infection. Tests for coronavirus should be rigorously evaluated in terms of their analytical and clinical performance. This poses not only logistic challenges, but also methodological ones. Some of these are generic for the diagnostic accuracy paradigm, while others are more specific for tests for viruses. Problematic for evaluations of the clinical performance of tests for viral RNA is the absence of an independent reference standard. Many studies lack rigor in terms of the recruitment of study participants. Study reports are often insufficiently informative, which makes it difficult to assess the applicability of study findings. Attempts to summarize the performance of these tests in terms of a single estimate of the clinical sensitivity fails to do justice to the identifiable sources of the large heterogeneity in mechanisms for generating false negative results.", "qid": 8, "docid": "d4mqgesb", "rank": 75, "score": 0.8422956466674805}, {"content": "Title: COVID-19 Waves: Importance of Accumulative Mortality per Million Inhabitants Content: The reported number of new cases underestimates the real spread of COVID-19 pandemic because of non-tested asymptomatic people and limited global access to reliable diagnostic tests. In this context, COVID-19 mortality with confirmed diagnosis becomes an attractive source of information to be included in the analysis of perspectives and proposals. Objective data are required to calculate the capacity of resources provided by health systems. New strategies are needed to stabilize or minimize the mortality surge. However, we will not afford this goal until more alternatives were available. We still need an effective treatment, an affordable vaccine, or a collective achievement of sufficient immunity (reaching up to 70% of the whole population). At any time, the arriving waves of the pandemic are testing the capacity of governments. The health services struggle to keep the plateau in a steady-state below 100 deaths per million inhabitants. Therefore, it is necessary to increase the alternatives and supplies based on the current and near-future expected demands imposed by the number of deaths by COVID-19. Estimating COVID-19 mortality in various scenarios with the gradual release of social constraints will help predict the magnitude of those arriving waves.", "qid": 8, "docid": "acceu3l5", "rank": 76, "score": 0.8421750068664551}, {"content": "Title: COVID-19 Waves: Importance of Accumulative Mortality per Million Inhabitants. Content: The reported number of new cases underestimates the real spread of COVID-19 pandemic because of non-tested asymptomatic people and limited global access to reliable diagnostic tests. In this context, COVID-19 mortality with confirmed diagnosis becomes an attractive source of information to be included in the analysis of perspectives and proposals. Objective data are required to calculate the capacity of resources provided by health systems. New strategies are needed to stabilize or minimize the mortality surge. However, we will not afford this goal until more alternatives were available. We still need an effective treatment, an affordable vaccine, or a collective achievement of sufficient immunity (reaching up to 70% of the whole population). At any time, the arriving waves of the pandemic are testing the capacity of governments. The health services struggle to keep the plateau in a steady-state below 100 deaths per million inhabitants. Therefore, it is necessary to increase the alternatives and supplies based on the current and near-future expected demands imposed by the number of deaths by COVID-19. Estimating COVID-19 mortality in various scenarios with the gradual release of social constraints will help predict the magnitude of those arriving waves.", "qid": 8, "docid": "qdxccgea", "rank": 77, "score": 0.8421750068664551}, {"content": "Title: Detecting the Emergent or Re-Emergent COVID-19 Pandemic in a Country: Modelling Study of Combined Primary Care and Hospital Surveillance Content: Aims: We aimed to determine the effectiveness of surveillance using testing for SARS-CoV-2 to identify an outbreak arising from a single case of border control failure at a country level. Methods: A stochastic version of the SEIR model CovidSIM v1.1 designed specifically for COVID-19 was utilised. It was seeded with New Zealand (NZ) population data and relevant parameters sourced from the NZ and international literature. Results: For what we regard as the most plausible scenario with an effective reproduction number of 2.0, the results suggest that 95% of outbreaks from a single imported case would be detected in the period up to day 33 after introduction. At the time point of detection, there would be a median number of 6 infected cases in the community (95%UI: 1-68). To achieve this level of detection, an on-going programme of 7,800 tests per million people per week for the NZ population would be required. The vast majority of this testing (96%) would be of symptomatic cases in primary care settings and the rest in hospitals. Despite the large number of tests required, there are plausible strategies to enhance testing yield and cost-effectiveness eg, (i) adjusting the eligibility criteria via symptom profiles; (ii) and pooling of test samples. Conclusions: This model-based analysis suggests that a surveillance system with a very high level of routine testing is probably required to detect an emerging or re-emerging SARS-CoV-2 outbreak within one month of a border control failure in a nation.", "qid": 8, "docid": "yigdvc1q", "rank": 78, "score": 0.8421052098274231}, {"content": "Title: Laboratory preparedness for SARS-CoV-2 testing in India: Harnessing a network of Virus Research & Diagnostic Laboratories Content: BACKGROUND & OBJECTIVES: An outbreak of respiratory illness of unknown aetiology was reported from Hubei province of Wuhan, People's Republic of China, in December 2019. The outbreak was attributed to a novel coronavirus (CoV), named as severe acute respiratory syndrome (SARS)-CoV-2 and the disease as COVID-19. Within one month, cases were reported from 25 countries. In view of the novel viral strain with reported high morbidity, establishing early countrywide diagnosis to detect imported cases became critical. Here we describe the role of a countrywide network of VRDLs in early diagnosis of COVID-19. METHODS: The Indian Council of Medical Research (ICMR)-National Institute of Virology (NIV), Pune, established screening as well as confirmatory assays for SARS-CoV-2. A total of 13 VRDLs were provided with the E gene screening real-time reverse transcription-polymerase chain reaction (rRT-PCR) assay. VRDLs were selected on the basis of their presence near an international airport/seaport and their past performance. The case definition for testing included all individuals with travel history to Wuhan and symptomatic individuals with travel history to other parts of China. This was later expanded to include symptomatic individuals returning from Singapore, Japan, Hong Kong, Thailand and South Korea. RESULTS: Within a week of standardization of the test at NIV, all VRDLs could initiate testing for SARS-CoV-2. Till February 29, 2020, a total of 2,913 samples were tested. This included both 654 individuals quarantined in the two camps and others fitting within the case definition. The quarantined individuals were tested twice - at days 0 and 14. All tested negative on both occasions. Only three individuals belonging to different districts in Kerala were found to be positive. INTERPRETATION & CONCLUSIONS: Sudden emergence of SARS-CoV-2 and its potential to cause a pandemic posed an unsurmountable challenge to the public health system of India. However, concerted efforts of various arms of the Government of India resulted in a well-coordinated action at each level. India has successfully demonstrated its ability to establish quick diagnosis of SARS-CoV-2 at NIV, Pune, and the testing VRDLs.", "qid": 8, "docid": "1bjskqyg", "rank": 79, "score": 0.8420873880386353}, {"content": "Title: Laboratory preparedness for SARS-CoV-2 testing in India: Harnessing a network of Virus Research & Diagnostic Laboratories Content: Background & objectives: An outbreak of respiratory illness of unknown aetiology was reported from Hubei province of Wuhan, People's Republic of China, in December 2019. The outbreak was attributed to a novel coronavirus (CoV), named as severe acute respiratory syndrome (SARS)-CoV-2 and the disease as COVID-19. Within one month, cases were reported from 25 countries. In view of the novel viral strain with reported high morbidity, establishing early countrywide diagnosis to detect imported cases became critical. Here we describe the role of a countrywide network of VRDLs in early diagnosis of COVID-19. Methods: The Indian Council of Medical Research (ICMR)-National Institute of Virology (NIV), Pune, established screening as well as confirmatory assays for SARS-CoV-2. A total of 13 VRDLs were provided with the E gene screening real-time reverse transcription-polymerase chain reaction (rRT-PCR) assay. VRDLs were selected on the basis of their presence near an international airport/seaport and their past performance. The case definition for testing included all individuals with travel history to Wuhan and symptomatic individuals with travel history to other parts of China. This was later expanded to include symptomatic individuals returning from Singapore, Japan, Hong Kong, Thailand and South Korea. Results: Within a week of standardization of the test at NIV, all VRDLs could initiate testing for SARS-CoV-2. Till February 29, 2020, a total of 2,913 samples were tested. This included both 654 individuals quarantined in the two camps and others fitting within the case definition. The quarantined individuals were tested twice - at days 0 and 14. All tested negative on both occasions. Only three individuals belonging to different districts in Kerala were found to be positive. Interpretation & conclusions: Sudden emergence of SARS-CoV-2 and its potential to cause a pandemic posed an unsurmountable challenge to the public health system of India. However, concerted efforts of various arms of the Government of India resulted in a well-coordinated action at each level. India has successfully demonstrated its ability to establish quick diagnosis of SARS-CoV-2 at NIV, Pune, and the testing VRDLs.", "qid": 8, "docid": "nl8lvzo7", "rank": 80, "score": 0.8420873880386353}, {"content": "Title: Data-driven Identification of Number of Unreported Cases for COVID-19: Bounds and Limitations Content: Accurate forecasts for COVID-19 are necessary for better preparedness and resource management. Specifically, deciding the response over months or several months requires accurate long-term forecasts which is particularly challenging as the model errors accumulate with time. A critical factor that can hinder accurate long-term forecasts, is the number of unreported/asymptomatic cases. While there have been early serology tests to estimate this number, more tests need to be conducted for more reliable results. To identify the number of unreported/asymptomatic cases, we take an epidemiology data-driven approach. We show that we can identify lower bounds on this ratio or upper bound on actual cases as a factor of reported cases. To do so, we propose an extension of our prior heterogeneous infection rate model, incorporating unreported/asymptomatic cases. We prove that the number of unreported cases can be reliably estimated only from a certain time period of the epidemic data. In doing so, we construct an algorithm called Fixed Infection Rate method, which identifies a reliable bound on the learned ratio. We also propose two heuristics to learn this ratio and show their effectiveness on simulated data. We use our approaches to identify the upper bounds on the ratio of actual to reported cases for New York City and several US states. Our results demonstrate with high confidence that the actual number of cases cannot be more than 35 times in New York, 40 times in Illinois, 38 times in Massachusetts and 29 times in New Jersey, than the reported cases.", "qid": 8, "docid": "bm7q56mp", "rank": 81, "score": 0.8419860005378723}, {"content": "Title: Public health measures to slow community spread of COVID-19 ;The Journal of Infectious Diseases ;Oxford Academic Content: COVID-19 was initially identified in an outbreak of viral pneumonia in Wuhan in December 2019, and has now been recognized in 77 countries with over 90,000 laboratory-confirmed cases and over 3,000 deaths as of 3 March 2020 [1] The epidemiology of COVID-19 has recently become clearer as incident cases continue to rise and researchers refine estimates of the severity, transmissibility, and populations affected Based on available data, COVID-19 is efficiently transmitted in the community, and the proportion of infections leading to severe illness is particularly high among adults \u226550 years of age and among individuals with comorbid health conditions Although rare, severe cases have also been reported among younger individuals Thus far, the estimated basic reproductive number (R0) of COVID-19 is higher than that of influenza [2], as is the case fatality risk for adults and older individuals An estimated 80% of COVID-19 cases are mild [1] This is not a glass half full statistic, as 20% of infections result in clinically severe cases that have the potential to overwhelm already overburdened health facilities Given the lack of vaccines and effective antivirals, nonpharmaceutical interventions (NPIs) are the most effective available interventions for local and global control and mitigation of COVID-19 To date, measures aimed at slowing introduction of infection globally have included travel restrictions, isolation of confirmed cases, and quarantine of exposed persons In the United States, NPIs have reduced the number of infected persons entering the country, but recent outbreaks in multiple US states make it clear that these measures have delayed but not prevented community transmission In 2009, NPIs were able to delay large epidemic waves of pandemic influenza A(H1N1)pdm09 in some locations until after the summer, since influenza transmission tends to be reduced by higher temperatures and humidity It is unclear whether COVID-19 transmission will be heavily affected by seasonal weather variation, given that transmission is now occurring in multiple tropical and sub-tropical locations", "qid": 8, "docid": "lu9mum1d", "rank": 82, "score": 0.841788113117218}, {"content": "Title: Early trends for SARS-CoV-2 infection in central and north Texas and impact on other circulating respiratory viruses Content: Introduction: Rapid diagnosis and isolation are key to containing the rapid spread of a pandemic agent like SARS-CoV-2, which has spread globally since its initial outbreak in Wuhan province in China. SARS-CoV-2 is novel to most parts of the world including USA and the effect on normally prevalent viruses is just becoming apparent. We present our initial data on the prevalence of respiratory viruses in the month of March, 2020. Methods: This is a retrospective cohort study post launching of SARS-CoV-2 testing at BSWH, Temple TX. Testing for SARS-CoV-2 was performed by real-time RT-PCR assay and results were shared with State public health officials for immediate interventions. Results: More than 3500 tests were performed during the first two weeks of testing for SARS-CoV-2 and identified 168 (4.7%) positive patients. Sixty-two (3.2%) of the 1,912 ambulatory patients and 106 (6.3%) of the 1,659 ED/inpatients were tested positive. Higher rate of infection (6.9%) were noted in the patients belonging to age group 25-34 years and least number of positive cases were noted in <25 years old (2%) group. The TX State county specific patient demographic information was shared with respective public health departments for epidemiological interventions. Incidentally, this study showed that there was a sudden decrease in the occurrence of other infections due to seasonal viruses, perhaps due to increased epidemiological awareness, about SARS-CoV-2, among general public. Authors would also like to share a small study on SARS-CoV-2 serological assay for the detection of IgG antibodies. Conclusions: This study was intended to provide an initial experience of dealing with a pandemic and the role of laboratories in crisis management. Epidemiological interventions depend on timely availability of accurate diagnostic tests and throughput capacity of such systems during large outbreaks like SARS-CoV-2.", "qid": 8, "docid": "5fz8ef4f", "rank": 83, "score": 0.8417870402336121}, {"content": "Title: Asymptomatic patients and asymptomatic phases of Coronavirus Disease 2019 (COVID-19): a population-based surveillance study Content: In this population-based study, we identified 307 confirmed COVID-19 cases from massive surveillance, including 129,551 individuals screened at fever clinics or returning from Hubei and 3710 close contacts of confirmed COVID-19 patients. Among them, 17 patients were asymptomatic at initial clinical assessment. These asymptomatic patients on admission accounted for a small proportion of all patients (5.54%) with relatively weak transmissibility, and the detection rate was 0.35 per 100 close contacts. Moreover, the dynamics of symptoms of the 307 patients showed that the interval from symptom remission to the final negativity of viral nucleic acid was 5.0 days (IQR 2.0 to 11.0 days), with 14 patients (4.56%) having re-detectable viral RNA after discharge. Together, our findings suggested asymptomatic carriers and presymptomatic patients only accounted for a small proportion of COVID-19. Also, the asymptomatic phase in during recovery of COVID-19 urged that negativity in viral RNA is necessary as de-isolation criteria and follow-up is recommended.", "qid": 8, "docid": "l4n9hwcx", "rank": 84, "score": 0.8417108058929443}, {"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": 85, "score": 0.8415688276290894}, {"content": "Title: Estimating cases of COVID-19 from Daily Death Data in Italy Content: COVID-19 is an emerging infectious disease which has been declared a pan- demic by the World Health Organisation. Due to limited testing capacity for this new virus, variable symptomatology the majority of infected showing non-specific mild or no symptoms it is likely current prevalence data is an underestimate. Methods: We present an estimate of the number of cases of COVID-19 com- pared to the number of confirmed case in Italy based on the daily reported deaths and information about the incubation period, time from symptom on- set to death and reported case fatality rate. Results: Our model predicts that on the 31st of January 2020 when the first 3 infected cases had been identified by Italian authorise there were already nearly 30 cases in Italy, and by the 24th of February 2020 only 0.5% cases had been detected and confirmed by Italian authorities. While official statistics had 132 confirmed case we believe a more accurate estimate would be closer to 26000. With a case-doubling period of about 2.5 days.", "qid": 8, "docid": "ao93c31w", "rank": 86, "score": 0.8407672643661499}, {"content": "Title: Global prediction of unreported SARS-CoV2 infection from observed COVID-19 cases Content: Summary: Estimation of infectiousness and fatality of the SARS-CoV-2 virus in the COVID-19 global pandemic is complicated by ascertainment bias resulting from incomplete and non-representative samples of infected individuals. We developed a strategy for overcoming this bias to obtain more plausible estimates of the true values of key epidemiological variables. We fit mechanistic Bayesian latent-variable SIR models to confirmed COVID-19 cases, deaths, and recoveries, for all regions (countries and US states) independently. Bayesian averaging over models, we find that the raw infection incidence rate underestimates the true rate by a factor, the case ascertainment ratio CARt that depends upon region, and show how CARt changes over time. At the regional onset of COVID-19, the predicted global median for each case confirmed was 13 infections unreported (CARt = 0.07 C.I. (0.02, 0.4)). As the infection spread, the median CARt rose to 9 unreported cases for every one diagnosed as of April 15, 2020 (CARt = 0.1 C.I. (0.02, 0.5)). We also estimate that the median global initial reproduction number R0 is 3.3 (C.I (1.5, 8.3)) and the total infection fatality rate near the onset is 0.17% (C.I. (0.05%, 0.9%)). However the time-dependent reproduction number Rt and infection fatality rate as of April 15 were 1.2 (C.I. (0.6, 2.5)) and 0.8% (C.I. (0.2%,4%)), respectively. We find that there is great variability between country- and state-level values. Our estimates are consistent with recent serological estimates of cumulative infections for the state of New York, but inconsistent with claims that very large fractions of the population have already been infected in most other regions. For most regions, our estimates imply a great deal of uncertainty about the current state and trajectory of the epidemic.", "qid": 8, "docid": "wkfhngq0", "rank": 87, "score": 0.8405476212501526}, {"content": "Title: Projection of COVID-19 Pandemic in Uganda Content: COVID-19 (Corona Virus) is caused by Severe Acute Respiratory Syndrome Corona Virus 2 (SARS-COV-2). The virus that was first discovered in China Wuhan Province about 3 months ago (first cases were reported in Wuhan on December 31st, 2019) has spread world wide. The six (6) top countries (excluding China) most affected so far include; USA, Italy, Spain, Germany, France, and Iran. With Italy showing the highest death toll. In Uganda where it was discovered on 19/3/2020 with one (01) case has just in nine (9) days, increased to thirty (30) infected individuals. This model is a wake-up call over the rate at which COVID-19 is likely to spread throughout the country. Thus it is a guide for policymakers and planners to benchmark on for solutions to this deadly virus.", "qid": 8, "docid": "co4ckyp9", "rank": 88, "score": 0.8404191732406616}, {"content": "Title: Test, test, test for COVID-19 antibodies: the importance of sensitivity, specificity and predictive powers Content: Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) antibody tests of varying specificity and sensitivity are now available. For informing individuals whether they have had coronavirus disease 2019 (COVID-19), they need to be very accurate. For measuring population prevalence of past infection, the numbers of false positives and negatives need to be roughly equal. With a series of worked examples for a notional population of 100,000 people, we show that even test systems with a high specificity can yield a large number of false positive results, especially where the population prevalence is low. For example, at a true population prevalence of 5%, using a test with 99% sensitivity and specificity, 16% of positive results will be false and thus 950 people will be incorrectly informed they have had the infection. Further confirmatory testing may be needed. Giving false reassurance on which personal or societal decisions might be based could be harmful for individuals, undermine public confidence and foster further outbreaks.", "qid": 8, "docid": "hzi3kvw5", "rank": 89, "score": 0.8402634859085083}, {"content": "Title: Burden of COVID-19 pandemic in India: Perspectives from Health Infrastructure Content: The coronavirus (COVID-19) is spreading rapidly across the country but testing regime of India is far from the global standards. It is important to identify the states where testing needs expansion and the magnitudes of active COVID cases are higher focusing on current health infrastructure to meet the pandemic. The data on COVID-19 was extracted from the Application Programming Interface. Test positive rate, test per confirmed case, recovery rate, case fatality rate, and percent distribution of active cases were computed. Availability of hospitals, hospital beds, intensive care unit and ventilators per lakh population was also computed by public and private sector. The result revealed that, Maharashtra constitutes more than one-third positive cases in the country. More than a quarter of the active cases in India belonged to the Mumbai district of Maharashtra, followed by the Chennai district (9.4%) and Ahmedabad district (9.1%). Further, about 40 percent of the active cases in India belonged to the 11 districts of Maharashtra. The increased test positive rate in Maharashtra and Gujarat to almost double in last one month is a concern. In order to bring the states and the country in right track, the test positive rate need to be brought down to below 2 percent. The procurement of higher number of high throughput machine, the Cobas 6800 testing machine, is need of the hour. Only few states have adequate health infrastructure. The priority should be the laid on expansion of more laboratories and hospitals, storage of PPE kit, testing kit, and indigenously developed vaccines.", "qid": 8, "docid": "7t31dkjj", "rank": 90, "score": 0.8402001261711121}, {"content": "Title: The misleading illusion of COVID-19 confirmed case data: alternative estimates and a monitoring tool Content: Confirmed Case Data have been widely cited during the current COVID-19 pandemic as an estimate of the spread of the SARS-CoV-2 virus. However, their central role in media, official reports and decision-making may be undeserved and misleading. Previously published Infection Fatality Rates were weighted by age structure in the 50 countries with more reported deaths to obtain country-specific rates. For each country, the number of infections up to the Infection Date (23 days ago = Incubation Period + Onset to Death period) and the present percentage of immune population were estimated using Infection Fatality Rate, the number of reported deaths (which is less prone to undersampling), and projecting back to Infection Date. We then estimated a Detection Index for each country as the percentage of estimated infections that confirmed cases represent. Assuming that detection remains constant after Infection Date, we estimated the number of deaths and the estimated percentage of the population of each country expected to be immune up to 23 days into the future. Estimated Infection Fatality Rates are higher in Europe. In most countries, confirmed cases currently represent less than 30% of estimated infections on Infection Date, and this value decreases with time. Countries with flat curves throughout the pandemic show the lowest immunity percentages and these values seem unlikely to change in the near future, suggesting that they remain vulnerable to new outbreaks. Estimates for some countries with low Infection Fatality Rates suggest a still steep increase in the number of casualties in the next three weeks. Countries that did not control initial outbreaks seem to have reached higher immunity percentages, although mostly still under 5%. We provide the code to monitor the trajectories of these estimates in 178 countries throughout the COVID-19 pandemic.", "qid": 8, "docid": "z9r5i0ky", "rank": 91, "score": 0.8401393890380859}, {"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": 92, "score": 0.8401058912277222}, {"content": "Title: Scrutinising the COVID-19 data on 590.000 cases. A retrospective, population-based descriptive study for data quality surveillance and a review at 4.540.000 cases. Content: Reports on the detected positive patients with COVID-19 are as per today the best estimation of a country spread of the pandemic. In order to evaluate the early indicators for true lethality and recovery time, the data where the model is built must be quality checked. Each country sets different procedures and criteria for fatality count due to COVID-19 and the health system is stressed by having insufficient testing, untracked patients and premature discharge. In this paper the dynamics behind such data quality issues are discussed throughout the disease course to support better modeling and decision-making processes in a stressed healthcare system. From 593.291 cases in the sample, and its 7 representative groups, the recovery time and the local CFR are negatively correlated, having the highest fatality rates (21%, Spain) the countries with shorter recovery time (11 days, Spain). Also, CFR can be an indicator of Infection inconsistencies (i.e. South Korea, CFR 1%, Time to recovery 25 days). At the review part, focus is made on the inconsistencies detected in Germany and South Korea datasets as well as the potential misfits on China and Spain. Overall, the Time to Fatality ranges between 4 and 8 days, and the mean is of 6 days (South Korea, 7 days; Japan, 6days). Only Germany and France are detecting earlier than other countries and admit 10 days before fatality occurs. One simple explanation for the local CFR and Recovery time correlation is to define such rate as a measure of the healthcare system overload. Anomalous CFR indexes point to a stressed healthcare system. The higher the overload, the more focus on critical cases and hence the higher local CFR. The COVID-19 intrinsic CFR is unlikely to change by a factor of 10x from countries with similar lifestyle, GDP per capita and health services (i.e. the Mediterranean Basin, Northern Europe, etc.). Because of this fact, early CFR measured before Healthcare system overwhelming (COVID-19 free flow) are considered to be more accurate than the measured CFR while the outbreak is still ongoing, Finally, the synthetic Infection indexes may be a helpful indirect measure of the real population infection rate and also used for data quality audit. Any model built upon inconsistent data will be complex to explain and justify.", "qid": 8, "docid": "n1j8b1gw", "rank": 93, "score": 0.8400660157203674}, {"content": "Title: Dynamic of SARS-CoV-2 RT-PCR positivity and seroprevalence among high-risk health care workers and hospital staff Content: Staff members from Covid-19 highly exposed units were invited to participate in a six month study of SARS-CoV-2 carriage and seroprevalence. The results of Day 1 and Day 15 visits show that 41 SARS-CoV-2 infections were confirmed by RT-PCR and/or serology in 326 participants (overall infection rate=12.6%). Having co-morbidity or symptoms at the time of collection was a risk factor for infection but not working as a physician/nurse. This universal screening in high-risk units irrespective of symptoms allowed asymptomatic and potentially contagious infected workers to be self-isolated during 7 days.", "qid": 8, "docid": "is8n1m3g", "rank": 94, "score": 0.8396605253219604}, {"content": "Title: Guidelines for Laboratory Diagnosis of Coronavirus Disease 2019 (COVID-19) in Korea Content: The outbreak of coronavirus disease 2019 (COVID-19), which began in December 2019, is still ongoing in Korea, with &gt;9,000 confirmed cases as of March 25, 2020 COVID-19 is a severe acute respiratory syndrome Coronavirus 2 (SARS-CoV-2) infection, and real-time reverse transcription-PCR is currently the most reliable diagnostic method for COVID-19 around the world Korean Society for Laboratory Medicine and the Korea Centers for Disease Prevention and Control propose guidelines for diagnosing COVID-19 in clinical laboratories in Korea These guidelines are based on other related domestic and international guidelines, as well as expert opinions and include the selection of test subjects, selection of specimens, diagnostic methods, interpretation of test results, and biosafety", "qid": 8, "docid": "jv3b0r15", "rank": 95, "score": 0.8396208882331848}, {"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": 96, "score": 0.8394988775253296}, {"content": "Title: Prevalence of SARS-CoV-2 among workers returning to Bihar gives snapshot of COVID across India Content: India has reported the fourth highest number of confirmed SARS-CoV-2 cases worldwide. Because there is little community testing for COVID, this case count is likely an underestimate. When India partially exited from lockdown on May 4, 2020, millions of daily laborers left cities for their rural family homes. RNA testing on a near-random sample of laborers returning to the state of Bihar is used to estimate positive testing rate for COVID across India for a 6-week period immediately following the initial lifting of India's lockdown. Positive testing rates among returning laborers are only moderately correlated with, and 21% higher than, Indian states' official reports, which are not based on random sampling. Higher prevalence among returning laborers may also reflect greater COVID spread in crowded poor communities such as slums.", "qid": 8, "docid": "qyxko730", "rank": 97, "score": 0.8394085764884949}, {"content": "Title: Co-detection of respiratory pathogens in patients hospitalized with Coronavirus viral disease-2019 pneumonia. Content: Clinical, laboratory and imaging characteristics of Coronavirus disease 2019 (Covid-19) and risk factors associated with poor outcomes have been reported in various studies.1-2 Nevertheless, information on whether other respiratory pathogens (RP) were co-detected in patients in these series was not provided, despite the fact that coinfections with RP have been reported to occur in this clinical setting.3-6 This article is protected by copyright. All rights reserved.", "qid": 8, "docid": "cf0d0pdx", "rank": 98, "score": 0.8393620848655701}, {"content": "Title: Contact tracing: Unearthing key epidemiological features of COVID-19 Content: COVID-19 is an emerging global pandemic with a steady rise in both morbidity and mortality over the past few months. Contact tracing of COVID-19 patients is an essential task to mitigate the spread. The following case was one of the initial patients reported from India and details the importance of contact tracing, timely testing and adequate quarantine/isolation in disease control.", "qid": 8, "docid": "tkfpcowf", "rank": 99, "score": 0.8392930030822754}, {"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": 8, "docid": "tujxlve3", "rank": 100, "score": 0.8391257524490356}]}
{"query": "how has COVID-19 affected Canada", "hits": [{"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": 1, "score": 0.8714016675949097}, {"content": "Title: Health-related concerns and precautions during the COVID-19 pandemic: A comparison of Canadians with and without underlying health conditions Content: BACKGROUND: The risk of experiencing adverse outcomes from the coronavirus disease 2019 (COVID-19), such as hospitalization, admission to intensive care units and death, is elevated for older individuals and those with certain underlying health conditions including diabetes, chronic conditions affecting lungs, heart or kidneys, and a compromised immune system. DATA AND METHODS: Data collected between March 29 and April 3, 2020 from the Canadian Perspectives Survey Series 1: Impacts of COVID-19 (n=4,627) were used to estimate the prevalence of underlying health conditions, health concerns and precautionary behaviours among Canadians aged 15 or older living in the provinces. Multivariate analyses examined associations between these variables after accounting for age, sex and education. RESULTS: Close to 1 in 4 Canadians (24%) had an underlying health condition that increased their risk of adverse outcomes from COVID-19. Overall, 36% of the population were very or extremely concerned about the impact of COVID-19 on their own health. Individuals with underlying health conditions had higher odds (odds ratio: 2.0, 95% confidence interval: 1.6 to 2.5) of being highly concerned than those without these conditions, after adjustment for demographic characteristics. High percentages of Canadians took precautions to reduce the risk of infection regardless of whether or not they had underlying health conditions. DISCUSSION: Health status was associated with higher levels of concern for one's own health in the early period of the COVID-19 pandemic. Most Canadians were taking precautions recommended by public health authorities to protect themselves and others.", "qid": 9, "docid": "in2edn29", "rank": 2, "score": 0.8681085109710693}, {"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": 3, "score": 0.8672904372215271}, {"content": "Title: COVID-19 Pandemic: Global Impact and Potential Implications for Cardiovascular Disease in Canada Content: BACKGROUND: Literature indicates that cardiovascular disease (CVD, including stroke), older age, and availability of healthcare resources impact COVID-19 case fatality rates (CFR). The cumulative effect of COVID-19 CFR in global CVD populations and the extrapolated impact on access to healthcare services in the CVD population in Canada are not fully known. This study explored the relationships of factors that may impact COVID-19 CFR and estimated the potential indirect impact of COVID-19 on Canadian healthcare resources. METHODS: Country-level epidemiological data were analyzed to study the correlation, main effect, and interaction between COVID-19 CFR and: a) proportion of the population with CVD, b) proportion of the population \u2265 65 years, and c) availability of essential health services as defined by the World Health Organization Universal Health Coverage (UHC) index. For indirect implications on healthcare resources, estimates of the volume of postponed coronary artery bypass grafting (CABG), percutaneous coronary intervention (PCI) and valve surgeries in Ontario were calculated. RESULTS: Positive correlations were found between COVID-19 CFR and a) proportion of the population with CVD (\u03c1=0.40, p=0.001), b) proportion of the population \u2265 65 years (\u03c1=0.43, p=0.0005) and c) UHC index (\u03c1=0.27, p=0.03). For every 1% increase in proportion of the population \u2265 65 years or proportion of the population with CVD, COVID-19 CFR was 9% and 19% higher, respectively. Approximately 1,252 procedures would be postponed monthly in Ontario due to current public health measures. CONCLUSIONS: Countries with more prevalent CVD reported higher COVID-19 CFR. Strain on healthcare resources is likely in Canada.", "qid": 9, "docid": "el11o2cg", "rank": 4, "score": 0.8638644814491272}, {"content": "Title: Health-related concerns and precautions during the COVID-19 pandemic: A comparison of Canadians with and without underlying health conditions. Content: BACKGROUND The risk of experiencing adverse outcomes from the coronavirus disease 2019 (COVID-19), such as hospitalization, admission to intensive care units and death, is elevated for older individuals and those with certain underlying health conditions including diabetes, chronic conditions affecting lungs, heart or kidneys, and a compromised immune system. DATA AND METHODS Data collected between March 29 and April 3, 2020 from the Canadian Perspectives Survey Series 1: Impacts of COVID-19 (n=4,627) were used to estimate the prevalence of underlying health conditions, health concerns and precautionary behaviours among Canadians aged 15 or older living in the provinces. Multivariate analyses examined associations between these variables after accounting for age, sex and education. RESULTS Close to 1 in 4 Canadians (24%) had an underlying health condition that increased their risk of adverse outcomes from COVID-19. Overall, 36% of the population were very or extremely concerned about the impact of COVID-19 on their own health. Individuals with underlying health conditions had higher odds (odds ratio: 2.0, 95% confidence interval: 1.6 to 2.5) of being highly concerned than those without these conditions, after adjustment for demographic characteristics. High percentages of Canadians took precautions to reduce the risk of infection regardless of whether or not they had underlying health conditions. DISCUSSION Health status was associated with higher levels of concern for one's own health in the early period of the COVID-19 pandemic. Most Canadians were taking precautions recommended by public health authorities to protect themselves and others.", "qid": 9, "docid": "06v5bf01", "rank": 5, "score": 0.8600313663482666}, {"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": 6, "score": 0.8599727153778076}, {"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": 7, "score": 0.8538594841957092}, {"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": 8, "score": 0.8515729904174805}, {"content": "Title: A national cross-sectional survey of public perceptions, knowledge, and behaviors during the COVID-19 pandemic Content: Introduction: Efforts to mitigate the global spread of the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) have largely relied on broad compliance with public health recommendations, yet navigating the high volume of evolving information and misinformation related to SARS-CoV-2 can be challenging. We assessed national public perceptions (e.g., severity, concerns, health), knowledge (e.g., transmission, information sources), and behaviors (e.g., physical distancing) related to COVID-19 in Canada to understand public perspectives and inform future public health initiatives. Methods: We administered a national online survey with the goal of obtaining responses from 2000 adults residing in Canada. Respondent sampling was stratified by age, sex, and region. We used descriptive statistics to summarize respondent characteristics and tested for significant overall regional differences using chi-squared tests and t-tests, as appropriate. Results: We collected 1,996 eligible questionnaires between April 26th and May 1st, 2020. One-fifth (20%) of respondents knew someone diagnosed with COVID-19, but few had tested positive themselves (0.6%). Negative impacts of pandemic conditions were evidenced in several areas, including concerns about healthcare (e.g. sufficient equipment, 52%), pandemic stress (45%), and worsening social (49%) and mental/emotional (39%) health. Most respondents (88%) felt they had good to excellent knowledge of virus transmission, and predominantly accessed (74%) and trusted (60%) Canadian news television, newspapers/magazines, or non-government news websites for COVID-19 information. We found high compliance with distancing measures (80% either self-isolating or always physical distancing). We identified regional differences in perceptions, knowledge, and behaviors related to COVID-19. Discussion: We found that knowledge about COVID-19 is largely acquired through domestic news sources, which may explain high self-reported compliance with prevention measures. The results highlight the broader impact of a pandemic on the general public's overall health and wellbeing, outside of personal infection. The study findings should be used to inform public health communications during COVID-19 and future pandemics.", "qid": 9, "docid": "2pmpa7n0", "rank": 9, "score": 0.8481729030609131}, {"content": "Title: COVID-19 and Long-Term Care Policy for Older People in Canada Content: Older people are especially vulnerable to COVID-19, including and especially people living in long-term care facilities. In this Perspective, we discuss the impact of the COVID-19 pandemic on long-term care policy in Canada. More specifically, we use the example of recent developments in Quebec, where a tragedy in a specific facility is acting as a dramatic \"focusing event\". It draws attention to the problems facing long-term care facilities, considering existing policy legacies and the opening of a \"policy window\" that may facilitate comprehensive reforms in the wake of the COVID-19 pandemic.", "qid": 9, "docid": "ulav1vcf", "rank": 10, "score": 0.8468960523605347}, {"content": "Title: COVOID-19 and Long-Term Care Policy for Older People in Canada. Content: Older people are especially vulnerable to COVID-19, including and especially people living in long-term care facilities. In this Perspective, we discuss the impact of the COVID-19 pandemic on long-term care policy in Canada. More specifically, we use the example of recent developments in Quebec, where a tragedy in a specific facility is acting as a dramatic \"focusing event\". It draws attention to the problems facing long-term care facilities, considering existing policy legacies and the opening of a \"policy window\" that may facilitate comprehensive reforms in the wake of the COVID-19 pandemic.", "qid": 9, "docid": "scjui91o", "rank": 11, "score": 0.8468960523605347}, {"content": "Title: Understanding the Perceived Mental Health of Canadians During the COVID-19 Pandemic Content: BACKGROUND: While the physical health implications of the COVID-19 pandemic are regularly publicly available, the mental health toll on Canadians is unknown. This article examines the self-perceived mental health of Canadians during the COVID-19 pandemic and explores associations with various concerns after accounting for socioeconomic and health factors. DATA: The cross-sectional Canadian Perspectives Survey Series 1 collected information related to COVID-19 in late March and early April 2020 concerning labour market participation, behaviours, and health for the Canadian population 15 years and older living in the 10 provinces. METHODS: Socioeconomic and health characteristics of respondents as well as concerns about the impact of COVID-19 were examined to determine differences in experiencing excellent or very good compared to good, fair or poor perceived mental health. RESULTS: Just over half of Canadians aged 15 and older (54%) reported excellent or very good mental health during the COVID-19 pandemic. Several concerns were also associated with mental health. Notably, after considering the effects of socioeconomic and health characteristics, women, youth, individuals with a physical health condition and those who were very or extremely concerned with family stress from confinement were less likely to report excellent or very good mental health. DISCUSSION: These findings point to particular risks for lower perceived mental health during the COVID-19 pandemic. Results highlight various concerns of Canadians which may be associated with mental health, in particular, family stress in the home.", "qid": 9, "docid": "90t0jmwf", "rank": 12, "score": 0.8464633226394653}, {"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": 13, "score": 0.8459715247154236}, {"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": 0.8457305431365967}, {"content": "Title: Laboratory-confirmed COVID-19 in children and youth in Canada, January 15-April 27, 2020 Content: Understanding the epidemiology of COVID-19 among children and youth in Canada will help to inform public health measures in settings where children gather. As of April 27, 2020, provinces and territories provided the Public Health Agency of Canada with detailed information on 24,079 cases, of which 3.9% (n=938) were younger than 20 years of age. The detection rate per 100,000 population was lower in this age group (11.9 per 100,000), compared with those aged 20-59 years (72.4 per 100,000) and 60 and older (113.6 per 100,000). The median age among those younger than 20 years of age was 13 years, and cases were distributed equally across male and female genders. Among provinces and territories with more than 100 cases, 1.6% to 9.8% of cases were younger than 20 years of age. Cases in this age group were more likely to be asymptomatic: 10.7% compared with 2.4% in those aged 20-59 years and 4.1% in those aged 60 and older. Children and youth experienced severe outcomes less often, but 2.2% (n=15/672) of cases within this age group were severe enough to require hospitalization. Based on available exposure information, 11.3% (n=59/520) of cases aged younger than 20 years had no known contact with a case. Canadian findings align with those of other countries.", "qid": 9, "docid": "bvujapf5", "rank": 15, "score": 0.8434982895851135}, {"content": "Title: Laboratory-confirmed COVID-19 in children and youth in Canada, January 15-April 27, 2020. Content: Understanding the epidemiology of COVID-19 among children and youth in Canada will help to inform public health measures in settings where children gather. As of April 27, 2020, provinces and territories provided the Public Health Agency of Canada with detailed information on 24,079 cases, of which 3.9% (n=938) were younger than 20 years of age. The detection rate per 100,000 population was lower in this age group (11.9 per 100,000), compared with those aged 20-59 years (72.4 per 100,000) and 60 and older (113.6 per 100,000). The median age among those younger than 20 years of age was 13 years, and cases were distributed equally across male and female genders. Among provinces and territories with more than 100 cases, 1.6% to 9.8% of cases were younger than 20 years of age. Cases in this age group were more likely to be asymptomatic: 10.7% compared with 2.4% in those aged 20-59 years and 4.1% in those aged 60 and older. Children and youth experienced severe outcomes less often, but 2.2% (n=15/672) of cases within this age group were severe enough to require hospitalization. Based on available exposure information, 11.3% (n=59/520) of cases aged younger than 20 years had no known contact with a case. Canadian findings align with those of other countries.", "qid": 9, "docid": "xzoleks8", "rank": 16, "score": 0.8434982895851135}, {"content": "Title: Temporal estimates of case-fatality rate for COVID-19 outbreaks in Canada and the United States Content: BACKGROUND: Estimates of the case-fatality rate (CFR) associated with coronavirus disease 2019 (COVID-19) vary widely in different population settings. We sought to estimate and compare the COVID-19 CFR in Canada and the United States while adjusting for 2 potential biases in crude CFR. METHODS: We used the daily incidence of confirmed COVID-19 cases and deaths in Canada and the US from Jan. 31 to Apr. 22, 2020. We applied a statistical method to minimize bias in the crude CFR by accounting for the survival interval as the lag time between disease onset and death, while considering reporting rates of COVID-19 cases less than 50% (95% confidence interval 10%-50%). RESULTS: Using data for confirmed cases in Canada, we estimated the crude CFR to be 4.9% on Apr. 22, 2020, and the adjusted CFR to be 5.5% (credible interval [CrI] 4.9%-6.4%). After we accounted for various reporting rates less than 50%, the adjusted CFR was estimated at 1.6% (CrI 0.7%-3.1%). The US crude CFR was estimated to be 5.4% on Apr. 20, 2020, with an adjusted CFR of 6.1% (CrI 5.4%-6.9%). With reporting rates of less than 50%, the adjusted CFR for the US was 1.78 (CrI 0.8%-3.6%). INTERPRETATION: Our estimates suggest that, if the reporting rate is less than 50%, the adjusted CFR of COVID-19 in Canada is likely to be less than 2%. The CFR estimates for the US were higher than those for Canada, but the adjusted CFR still remained below 2%. Quantification of case reporting can provide a more accurate measure of the virulence and disease burden of severe acute respiratory syndrome coronavirus 2.", "qid": 9, "docid": "9hbgn66l", "rank": 17, "score": 0.8423703908920288}, {"content": "Title: Understanding the Perceived Mental Health of Canadians During the COVID-19 Pandemic. Content: BACKGROUND While the physical health implications of the COVID-19 pandemic are regularly publicly available, the mental health toll on Canadians is unknown. This article examines the self-perceived mental health of Canadians during the COVID-19 pandemic and explores associations with various concerns after accounting for socioeconomic and health factors. DATA The cross-sectional Canadian Perspectives Survey Series 1 collected information related to COVID-19 in late March and early April 2020 concerning labour market participation, behaviours, and health for the Canadian population 15 years and older living in the 10 provinces. METHODS Socioeconomic and health characteristics of respondents as well as concerns about the impact of COVID-19 were examined to determine differences in experiencing excellent or very good compared to good, fair or poor perceived mental health. RESULTS Just over half of Canadians aged 15 and older (54%) reported excellent or very good mental health during the COVID-19 pandemic. Several concerns were also associated with mental health. Notably, after considering the effects of socioeconomic and health characteristics, women, youth, individuals with a physical health condition and those who were very or extremely concerned with family stress from confinement were less likely to report excellent or very good mental health. DISCUSSION These findings point to particular risks for lower perceived mental health during the COVID-19 pandemic. Results highlight various concerns of Canadians which may be associated with mental health, in particular, family stress in the home.", "qid": 9, "docid": "lf5xg8p3", "rank": 18, "score": 0.8416064977645874}, {"content": "Title: Food security and Canada's agricultural system challenged by COVID\u201019 Content: The effect of COVID\u201019 on Canadian food security is examined from two different perspectives. COVID\u201019 creates a unique \u201cincome shock\u201d that is expected to increase the prevalence of household food insecurity. This food insecurity can be measured by utilizing the Canadian Community Health Survey (CCHS). More fundamentally, COVID\u201019 heightens household concern about the capacity of the Canadian food system to ensure food availability. Despite surges in demand and supply chain disruptions, we currently do not observe broad, rapid appreciation in food prices. This suggests that there is an adequate supply of food for the near term. There is less certainty over intermediate and longer time periods because so many factors are in flux, particularly the rate of increases in sicknesses and deaths across the country and globally. Data on these health factors and elements of the food supply chain are needed to predict beyond a short time frame. In this regard, we discuss three ongoing considerations\u2014ease of capital flows, international exchange, and maintaining transportation\u2014that will help ensure food availability in the longer run.", "qid": 9, "docid": "tz5jajeb", "rank": 19, "score": 0.8403575420379639}, {"content": "Title: Potential magnitude of COVID-19-induced healthcare resource depletion in Ontario, Canada Content: Background: The global spread of coronavirus disease 2019 (COVID-19) continues in several jurisdictions, causing significant strain to healthcare systems. The purpose of our study is to predict the impact of the COVID-19 pandemic on patient outcomes and the healthcare system in Ontario, Canada. Methods: We developed an individual-level simulation to model the flow of COVID-19 patients through the Ontario healthcare system. We simulated different combined scenarios of epidemic trajectory and healthcare capacity. Outcomes include numbers of patients needing admission to the ward, Intensive Care Unit (ICU), and requiring ventilation; days to resource depletion; and numbers of patients awaiting resources and deaths associated with limited access to resources. Findings: We demonstrate that with effective early public health measures system resources need not be depleted. For scenarios considering late or ineffective implementation of physical distancing, health system resources would be depleted within 14-26 days. Resource depletion was also avoided or delayed with aggressive measures to rapidly increase ICU, ventilator, and acute care hospital capacity. Interpretation: We found that without aggressive physical distancing measures the Ontario healthcare system would have been inadequately equipped to manage the expected number of patients with COVID-19, despite the rapid capacity increase. This overall lack of resources would have led to an increase in mortality. By slowing the spread of the disease via ongoing public health measures and having increased healthcare capacity, Ontario may have avoided catastrophic stresses to its health care system.", "qid": 9, "docid": "u2upcaod", "rank": 20, "score": 0.8400919437408447}, {"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": 21, "score": 0.8389241695404053}, {"content": "Title: Temporal estimates of case-fatality rate for COVID-19 outbreaks in Canada and the United States. Content: BACKGROUND Estimates of the casefatality rate (CFR) associated with coronavirus disease 2019 (COVID-19) vary widely in different population settings. We sought to estimate and compare the COVID-19 CFR in Canada and the United States while adjusting for 2 potential biases in crude CFR. METHODS We used the daily incidence of confirmed COVID-19 cases and deaths in Canada and the US from Jan. 31 to Apr. 22, 2020. We applied a statistical method to minimize bias in the crude CFR by accounting for the survival interval as the lag time between disease onset and death, while considering reporting rates of COVID-19 cases less than 50% (95% confidence interval 10%-50%). RESULTS Using data for confirmed cases in Canada, we estimated the crude CFR to be 4.9% on Apr. 22, 2020, and the adjusted CFR to be 5.5% (credible interval [CrI] 4.9%-6.4%). After we accounted for various reporting rates less than 50%, the adjusted CFR was estimated at 1.6% (CrI 0.7%-3.1%). The US crude CFR was estimated to be 5.4% on Apr. 20, 2020, with an adjusted CFR of 6.1% (CrI 5.4%-6.9%). With reporting rates of less than 50%, the adjusted CFR for the US was 1.78 (CrI 0.8%-3.6%). INTERPRETATION Our estimates suggest that, if the reporting rate is less than 50%, the adjusted CFR of COVID-19 in Canada is likely to be less than 2%. The CFR estimates for the US were higher than those for Canada, but the adjusted CFR still remained below 2%. Quantification of case reporting can provide a more accurate measure of the virulence and disease burden of severe acute respiratory syndrome coronavirus 2.", "qid": 9, "docid": "glah2z2m", "rank": 22, "score": 0.8373674750328064}, {"content": "Title: Economic thoughts on COVID\u201019 for Canadian food processors Content: In this paper, I explore the potential effects of the COVID\u201019 pandemic on Canadian food processors. First, COVID\u201019 may have an impact on food processing economic activities because of supply and demand shocks. Second, the impact of COVID\u201019 on food processing may depend on the type of products and the size of the processors. The effects of measures taken by the government to flatten the epidemiological curve on the economic activities of the food processing sector are uncertain.", "qid": 9, "docid": "qunw5hhy", "rank": 23, "score": 0.8371813297271729}, {"content": "Title: Determinants of self-reported symptoms and testing for COVID-19 in Canada using a nationally representative survey Content: In April 2020, a nationally representative sample of 4, 240 Canadians age 18 years and older were polled about COVID experience in March, early in the epidemic. We examined determinants of COVID symptoms, defined as fever plus difficulty breathing/shortness of breath, dry cough so severe that it disrupts sleep, and/or loss of sense of smell; and testing for SARS-CoV-2 by respondents and/or household members. About 8% of Canadians reported that they and/or one or more household members experienced COVID symptoms. Symptoms were more common in younger than older adults, and among visible minorities. Overall, 3% of respondents and/or household members had been tested for SARS-CoV-2. Being tested was associated with having COVID symptoms, being of Indigenous identity, and living in Quebec. Periodic nationally representative surveys, including high-risk older populations, of symptoms, as well as SARS-CoV-2 antibodies, are needed to understand the course of the Canadian epidemic and prepare for the future.", "qid": 9, "docid": "u54kja4g", "rank": 24, "score": 0.8370280861854553}, {"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": 9, "docid": "6ngsyo8o", "rank": 25, "score": 0.8368093371391296}, {"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": 9, "docid": "4q1j6g44", "rank": 26, "score": 0.8368093371391296}, {"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": 27, "score": 0.834667444229126}, {"content": "Title: Public health measures to slow community spread of COVID-19 ;The Journal of Infectious Diseases ;Oxford Academic Content: COVID-19 was initially identified in an outbreak of viral pneumonia in Wuhan in December 2019, and has now been recognized in 77 countries with over 90,000 laboratory-confirmed cases and over 3,000 deaths as of 3 March 2020 [1] The epidemiology of COVID-19 has recently become clearer as incident cases continue to rise and researchers refine estimates of the severity, transmissibility, and populations affected Based on available data, COVID-19 is efficiently transmitted in the community, and the proportion of infections leading to severe illness is particularly high among adults \u226550 years of age and among individuals with comorbid health conditions Although rare, severe cases have also been reported among younger individuals Thus far, the estimated basic reproductive number (R0) of COVID-19 is higher than that of influenza [2], as is the case fatality risk for adults and older individuals An estimated 80% of COVID-19 cases are mild [1] This is not a glass half full statistic, as 20% of infections result in clinically severe cases that have the potential to overwhelm already overburdened health facilities Given the lack of vaccines and effective antivirals, nonpharmaceutical interventions (NPIs) are the most effective available interventions for local and global control and mitigation of COVID-19 To date, measures aimed at slowing introduction of infection globally have included travel restrictions, isolation of confirmed cases, and quarantine of exposed persons In the United States, NPIs have reduced the number of infected persons entering the country, but recent outbreaks in multiple US states make it clear that these measures have delayed but not prevented community transmission In 2009, NPIs were able to delay large epidemic waves of pandemic influenza A(H1N1)pdm09 in some locations until after the summer, since influenza transmission tends to be reduced by higher temperatures and humidity It is unclear whether COVID-19 transmission will be heavily affected by seasonal weather variation, given that transmission is now occurring in multiple tropical and sub-tropical locations", "qid": 9, "docid": "lu9mum1d", "rank": 28, "score": 0.8338488340377808}, {"content": "Title: Failing our Most Vulnerable: COVID-19 and Long-Term Care Facilities in Ontario Content: Background: The COVID-19 epidemic has taken a fearsome toll on individuals residing in long-term care facilities (LTC). As of April 10, 2020 half COVID-19 deaths in Canada had occurred in LTC. We sought to better understand trends and risk factors for COVID-19 death in LTC in Ontario. Methods: We analyzed a COVID-19 outbreak database created by the Ontario Ministry of Health, for the period March 29-April 7, 2020. Mortality incidence rate ratios for LTC were calculated with community living Ontarians aged > 69 used as the comparator group. Count-based regression methods were used to model temporal trends and identify associations between infection risk in staff and residents, and subsequent LTC resident death. Results: Confirmed or suspected cases of COVID-19 were identified in 272/627 LTC by April 7, 2020. The incidence rate ratio for COVID-19 death was 13.1 (9.9-17.3) relative to community living adults over 69. Incidence rate ratio increased over time and was 87.28 (90% CrI 9.98 to 557.08) by April 7, 2020. Lagged infection in staff was a strong predictor of death in residents (e.g., adjusted IRR for death per infected staff member 1.17, 95% CI 1.11 to 1.26 at a 6-day lag). Interpretation: Mortality risk in elders in Ontario is currently concentrated in LTC, and this risk has increased sharply over a short period of time. Early identification of risk requires a focus on testing and provision of personal protective equipment to staff, and restructuring the LTC workforce to prevent movement of COVID-19 between LTC.", "qid": 9, "docid": "pz8hpuya", "rank": 29, "score": 0.833641529083252}, {"content": "Title: Estimation of COVID-19-induced depletion of hospital resources in Ontario, Canada Content: BACKGROUND: The global spread of coronavirus disease 2019 (COVID-19) continues in several jurisdictions, causing substantial strain to health care systems. The purpose of our study was to predict the effect of the COVID-19 pandemic on patient outcomes and use of hospital resources in Ontario, Canada. METHODS: We developed an individual-level simulation to model the flow of patients with COVID-19 through the hospital system in Ontario. We simulated different combined scenarios of epidemic trajectory and hospital health care capacity. Our outcomes included the number of patients who needed admission to the ward or to the intensive care unit (ICU) with or without the need for mechanical ventilation, number of days to resource depletion, number of patients awaiting resources and number of deaths. RESULTS: We found that with effective early public health measures, hospital system resources would not be depleted. For scenarios with late or ineffective implementation of physical distancing, hospital resources would be depleted within 14-26 days, and in the worst case scenario, 13 321 patients would die while waiting for needed resources. Resource depletion would be avoided or delayed with aggressive measures to increase ICU, ventilator and acute care hospital capacities. INTERPRETATION: We found that without aggressive physical distancing measures, the Ontario hospital system would have been inadequately equipped to manage the expected number of patients with COVID-19 despite a rapid increase in capacity. This lack of hospital resources would have led to an increase in mortality. By slowing the spread of the disease using public health measures and by increasing hospital capacity, Ontario may have avoided catastrophic stresses to its hospitals.", "qid": 9, "docid": "h6g65f9w", "rank": 30, "score": 0.833387017250061}, {"content": "Title: Asymmetric nexus between temperature and COVID-19 in the top ten affected provinces of China: A current application of quantile-on-quantile approach Content: Abstract The present study examines the asymmetrical effect of temperature on COVID-19 (Coronavirus Disease) from 22 January 2020 to 31 March 2020 in the 10 most affected provinces in China. This study used the Sim & Zhou' quantile-on-quantile (QQ) approach to analyze how the temperature quantities affect the different quantiles of COVID-19. Daily COVID-19 and, temperature data collected from the official websites of the Chinese National Health Commission and Weather Underground Company (WUC) respectively. Empirical results have shown that the relationship between temperature and COVID-19 is mostly positive for Hubei, Hunan, and Anhui, while mostly negative for Zhejiang and Shandong provinces. The remaining five provinces Guangdong, Henan, Jiangxi, Jiangsu, and Heilongjiang are showing the mixed trends. These differences among the provinces can be explained by the differences in the number of COVID-19 cases, temperature, and the province's overall hospital facilitations. The study concludes that maintaining a safe and comfortable atmosphere for patients while COVID-19 is being treated may be rational.", "qid": 9, "docid": "p86gf179", "rank": 31, "score": 0.8332920670509338}, {"content": "Title: Asymmetric nexus between temperature and COVID-19 in the top ten affected provinces of China: A current application of quantile-on-quantile approach Content: The present study examines the asymmetrical effect of temperature on COVID-19 (Coronavirus Disease) from 22 January 2020 to 31 March 2020 in the 10 most affected provinces in China. This study used the Sim & Zhou' quantile-on-quantile (QQ) approach to analyze how the temperature quantities affect the different quantiles of COVID-19. Daily COVID-19 and, temperature data collected from the official websites of the Chinese National Health Commission and Weather Underground Company (WUC) respectively. Empirical results have shown that the relationship between temperature and COVID-19 is mostly positive for Hubei, Hunan, and Anhui, while mostly negative for Zhejiang and Shandong provinces. The remaining five provinces Guangdong, Henan, Jiangxi, Jiangsu, and Heilongjiang are showing the mixed trends. These differences among the provinces can be explained by the differences in the number of COVID-19 cases, temperature, and the province's overall hospital facilitations. The study concludes that maintaining a safe and comfortable atmosphere for patients while COVID-19 is being treated may be rational.", "qid": 9, "docid": "3tow59gc", "rank": 32, "score": 0.8317948579788208}, {"content": "Title: Differential COVID-19-attributable mortality and BCG vaccine use in countries Content: While mortality attributable to COVID-19 has devastated global health systems and economies, striking regional differences have been observed. The Bacille Calmette Guerin (BCG) vaccine has previously been shown to have non-specific protective effects on infections, as well as long-term efficacy against tuberculosis. Using publicly available data we built a simple log-linear regression model to assess the association of BCG use and COVID-19-attributable mortality per 1 million population after adjusting for confounders including country economic status (GDP per capita), and proportion of elderly among the population. The timing of country entry into the pandemic epidemiological trajectory was aligned by plotting time since the 100th reported case. Countries with economies classified as lower-middle-income, upper-middle-income and high-income countries (LMIC, UMIC, HIC) had median crude COVID-19 log-mortality of 0.4 (Interquartile Range (IQR) 0.1, 0.4), 0.7 (IQR 0.2, 2.2) and 5.5 (IQR 1.6, 13.9), respectively. COVID-19-attributable mortality among BCG-using countries was 5.8 times lower [95% CI 1.8-19.0] than in non BCG-using countries. Notwithstanding limitations due to testing constraints in LMICs, case ascertainment bias and a plausible rise of cases as countries progress along the epidemiological trajectory, these analyses provide intriguing observations that urgently warrant mobilization of resources for prospective randomized interventional studies and institution of systematic disease surveillance, particularly in LMICs.", "qid": 9, "docid": "1n96pz86", "rank": 33, "score": 0.8317935466766357}, {"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": 9, "docid": "1u2d4m49", "rank": 34, "score": 0.8314391374588013}, {"content": "Title: Factors associated with country-variation in COVID-19 morbidity and mortality worldwide: an observational geographic study Content: Background: The world is threatened by the outbreak of coronavirus disease 19 (COVID-19) since December 2019. The number of cases and deaths increased dramatically in some countries from March 2020. The objective of our study was to examine potential associated factors with country-variation in COVID-19 morbidity and mortality in the world. Methods: We performed a retrospective geographic study including all countries with the most recent available data on free access on the web. We analyzed univariate and multivariable correlation between both the number of reported cases and deaths by country and demographic, socioeconomic characteristics, lockdown as major control measure, average annual temperature and relative humidity. We performed simple linear regression, independent t test and ANOVA test for univariate analyses and negative binomial regression model for multivariable analyses. Results: We analyzed data of 186 countries from all world regions. As of 13th April 2020, a total of 1 804 302 COVID-19 cases and 113 444 deaths were reported. The reported number of COVID-19 cases and deaths by countries was associated with the number of days between the first case and lockdown, the number of cases at lockdown, life expectancy at birth, average annual temperature and the socio-economic level. Countries which never implemented BCG vaccination reported higher mortality than others. Conclusions: The pandemic is still ongoing and poses a global health threat as there is no effective antiviral treatment or vaccines. Thus, timing of control measure implementation is a crucial factor in determining the spread of the epidemic. It should be a lesson for this pandemic and for the future.", "qid": 9, "docid": "9a6v7898", "rank": 35, "score": 0.8312694430351257}, {"content": "Title: Covid-19 outbreak and perspective in morocco Content: Coronavirus disease 2019 (COVID-19) is a respiratory illness that can spread from person to person. The virus that causes COVID-19 is a novel coronavirus that was first identified during an investigation into an outbreak in Wuhan, China and rapidly spread across the world to become the first pandemic caused by a coronavirus. As of 26 March 2020, there are 275 cases affected by COVID-19 announced by the Moroccan government, and it possible to limit the spread of this serious disease, with the cooperation of all the citizens in respect of the measures of containment and individual protection. Also, with the announce yesterday by the Moroccan government of the authorization of use of chloroquine in treatment of COVID-19 pneumonia, COVID-19 will be soon eradicated from Morocco and hopefully from all over the world.", "qid": 9, "docid": "8yr41aa8", "rank": 36, "score": 0.8311026692390442}, {"content": "Title: Testing lags and emerging COVID-19 outbreaks in federal penitentiaries in Canada Content: Objectives: To provide the first known comprehensive analysis of COVID-19 outcomes in a federal penitentiary system. We examined the following COVID-19 outcomes within federal penitentiaries and contrasted them with the overall population in the penitentiaries' respective provincial jurisdictions: testing, prevalence, the proportion recovered, and fatality. Methods: Data for prisons were obtained from the Correctional Service of Canada and, for the general population, from COVID-19 Esri Canadian Outbreak Tracking Hub. Data were retrieved between March 30 and April 21, 2020, and are accurate to this date. Penitentiary-, province- and sex-specific frequency statistics for each outcome were calculated. Results: Data on 50 of 51 penitentiaries (98%) were available. Of these, 72% of penitentiaries reported fewer tests per 1000 population than the Canadian general population average (16 tests/1000 population), and 24% of penitentiaries reported zero tests. Penitentiaries with high levels of testing were those that already had elevated COVID-19 prevalence. Five penitentiaries reported an outbreak (at least one case). Hardest hit penitentiaries were those in Quebec and British Columbia, with some prisons reporting COVID-19 prevalence of 30% to 40%. Of these, two were women's prisons. Female prisoners were over-represented among cases (31% of cases overall, despite representing 5% of the total prison population). Conclusion: Increased sentinel or universal testing may be appropriate given the confined nature of prison populations. This, along with rigorous infection prevention control practices and the potential release of prisoners, will be needed to curb current outbreaks and those likely to come.", "qid": 9, "docid": "qrywrn7m", "rank": 37, "score": 0.829885721206665}, {"content": "Title: Projection of COVID-19 Pandemic in Uganda Content: COVID-19 (Corona Virus) is caused by Severe Acute Respiratory Syndrome Corona Virus 2 (SARS-COV-2). The virus that was first discovered in China Wuhan Province about 3 months ago (first cases were reported in Wuhan on December 31st, 2019) has spread world wide. The six (6) top countries (excluding China) most affected so far include; USA, Italy, Spain, Germany, France, and Iran. With Italy showing the highest death toll. In Uganda where it was discovered on 19/3/2020 with one (01) case has just in nine (9) days, increased to thirty (30) infected individuals. This model is a wake-up call over the rate at which COVID-19 is likely to spread throughout the country. Thus it is a guide for policymakers and planners to benchmark on for solutions to this deadly virus.", "qid": 9, "docid": "co4ckyp9", "rank": 38, "score": 0.8294544219970703}, {"content": "Title: Estimation of COVID-19-induced depletion of hospital resources in Ontario, Canada. Content: BACKGROUND The global spread of coronavirus disease 2019 (COVID-19) continues in several jurisdictions, causing substantial strain to health care systems. The purpose of our study was to predict the effect of the COVID-19 pandemic on patient outcomes and use of hospital resources in Ontario, Canada. METHODS We developed an individuallevel simulation to model the flow of patients with COVID-19 through the hospital system in Ontario. We simulated different combined scenarios of epidemic trajectory and hospital health care capacity. Our outcomes included the number of patients who needed admission to the ward or to the intensive care unit (ICU) with or without the need for mechanical ventilation, number of days to resource depletion, number of patients awaiting resources and number of deaths. RESULTS We found that with effective early public health measures, hospital system resources would not be depleted. For scenarios with late or ineffective implementation of physical distancing, hospital resources would be depleted within 14-26 days, and in the worst case scenario, 13 321 patients would die while waiting for needed resources. Resource depletion would be avoided or delayed with aggressive measures to increase ICU, ventilator and acute care hospital capacities. INTERPRETATION We found that without aggressive physical distancing measures, the Ontario hospital system would have been inadequately equipped to manage the expected number of patients with COVID-19 despite a rapid increase in capacity. This lack of hospital resources would have led to an increase in mortality. By slowing the spread of the disease using public health measures and by increasing hospital capacity, Ontario may have avoided catastrophic stresses to its hospitals.", "qid": 9, "docid": "gpxxdebo", "rank": 39, "score": 0.8292936086654663}, {"content": "Title: COVID-19: Stroke Admissions, Emergency Department Visits, and Prevention Clinic Referrals Content: We assessed the impact of the coronavirus disease 19 (COVID-19) pandemic on code stroke activations in the emergency department, stroke unit admissions, and referrals to the stroke prevention clinic at London's regional stroke center, serving a population of 1.8 million in Ontario, Canada. We found a 20% drop in the number of code strokes in 2020 compared to 2019, immediately after the first cases of COVID-19 were officially confirmed. There were no changes in the number of stroke admissions and there was a 22% decrease in the number of clinic referrals, only after the provincial lockdown. Our findings suggest that the decrease in code strokes was mainly driven by patient-related factors such as fear to be exposed to the SARS-CoV-2, while the reduction in clinic referrals was largely explained by hospital policies and the Government lockdown.", "qid": 9, "docid": "oek9ud99", "rank": 40, "score": 0.8292289972305298}, {"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": 41, "score": 0.8290739059448242}, {"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": 42, "score": 0.8286235332489014}, {"content": "Title: Impact of COVID-19 on Canadian Radiology Residency Training Programs Content: PURPOSE: The novel coronavirus disease (COVID-19) pandemic has swept the globe, with a domino effect on medical education and training. In this study, we surveyed Canadian radiology residents to understand the impact of the pandemic on their residency training, strategies utilized by the residency programs in mitigating those impacts, and factors important to residents in the selection of educational resources on COVID-19. METHODS: A 10-item questionnaire was distributed to 460 resident members of the Canadian Association of Radiologists. The survey was open for 2 weeks, with a reminder sent at half-way mark. RESULTS: We received 96 responses (response rate: 20.9%). The 4 highest affected domains of training were daytime case volumes (92.4%), daytime schedules (87.4%), internal and external assessments (86.5%), and vacation/travel (83.3%). Virtual teaching rounds (91.7%), change in schedules to allow staying home (78.1%), and virtual/phone readouts (72.9%) were the most utilized strategies by the Canadian radiology residency programs. Overall stress of exposure to the disease was moderate to low (86.5%). A minority of the residents were redeployed (6.2%), although most (68.8%) were on standby for redeployment. Residents preferred published society guidelines (92.3%), review papers (79.3%), video lectures (79.3%), and web tools (76.9%) for learning about COVID-19 imaging manifestations. CONCLUSION: The COVID-19 pandemic has had a significant impact on various domains of the Canadian radiology residency programs, which has been mitigated by several strategies employed by the training programs.", "qid": 9, "docid": "12eny1vl", "rank": 43, "score": 0.8273658752441406}, {"content": "Title: COVID-19: Stroke Admissions, Emergency Department Visits, and Prevention Clinic Referrals Content: We assessed the impact of the coronavirus disease 19 (COVID-19) pandemic on code stroke activations in the emergency department, stroke unit admissions, and referrals to the stroke prevention clinic at London\u2019s regional stroke center, serving a population of 1.8 million in Ontario, Canada. We found a 20% drop in the number of code strokes in 2020 compared to 2019, immediately after the first cases of COVID-19 were officially confirmed. There were no changes in the number of stroke admissions and there was a 22% decrease in the number of clinic referrals, only after the provincial lockdown. Our findings suggest that the decrease in code strokes was mainly driven by patient-related factors such as fear to be exposed to the SARS-CoV-2, while the reduction in clinic referrals was largely explained by hospital policies and the Government lockdown.", "qid": 9, "docid": "7g2kg2tz", "rank": 44, "score": 0.8269048929214478}, {"content": "Title: Will the COVID-19 pandemic slow down in the Northern hemisphere by the onset of summer? An epidemiological hypothesis Content: The COVID-19 pandemic has affected most countries of the world. As corona viruses are highly prevalent in the cold season, the question remains whether or not the pandemic will improve with increasing temperatures in the Northern hemisphere. We use data from a primary care registry of almost 15,000 patients over 20 years to retrieve information on viral respiratory infection outbreaks. Our analysis suggests that the severity of the pandemic will be softened by the seasonal change to summer.", "qid": 9, "docid": "iztm1z6g", "rank": 45, "score": 0.8267295360565186}, {"content": "Title: Social stigma in the time of Coronavirus Content: The COVID-19 pandemic has dramatically changed the lives of people around the globe since it appeared in Wuhan, China, at the beginning of December 2019. The burden of disease and its death toll have had an unprecedented impact on the healthcare, economic, and financial systems of low-, middle-, and high-income countries [1\u20133]. Peoples\u2019 lives have been disrupted and negatively impacted by COVID-19-related suffering and lockdowns at community and household level.", "qid": 9, "docid": "bhmt5l8y", "rank": 46, "score": 0.8264674544334412}, {"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": 47, "score": 0.8260213732719421}, {"content": "Title: Correlation between universal BCG vaccination policy and reduced morbidity and mortality for COVID-19: an epidemiological study Content: COVID-19 has spread to most countries in the world. Puzzlingly, the impact of the disease is different in different countries. These differences are attributed to differences in cultural norms, mitigation efforts, and health infrastructure. Here we propose that national differences in COVID-19 impact could be partially explained by the different national policies respect to Bacillus Calmette-Guerin (BCG) childhood vaccination. BCG vaccination has been reported to offer broad protection to respiratory infections. We compared large number of countries BCG vaccination policies with the morbidity and mortality for COVID-19. We found that countries without universal policies of BCG vaccination (Italy, Nederland, USA) have been more severely affected compared to countries with universal and long-standing BCG policies. Countries that have a late start of universal BCG policy (Iran, 1984) had high mortality, consistent with the idea that BCG protects the vaccinated elderly population. We also found that BCG vaccination also reduced the number of reported COVID-19 cases in a country. The combination of reduced morbidity and mortality makes BCG vaccination a potential new tool in the fight against COVID-19.", "qid": 9, "docid": "35meen0h", "rank": 48, "score": 0.8257768154144287}, {"content": "Title: Covid-19 nephropathy; an emerging condition caused by novel coronavirus infection Content: Implication for health policy/practice/research/medical education: COVID-19, a pandemic caused by a novel coronavirus, has become a major public health problem worldwide. It principally affects the upper and lower respiratory tract in the majority of cases. In severe cases, it may involve multiple organs including the kidneys. Kidney involvement has been reported to be around 3-9% and the most common presentation is with acute kidney injury (AKI); however, the data is still preliminary. Data regarding COVID-19 virus affecting patients with prior kidney diseases are still rudimentary. Further research is needed to understand the full spectrum of COVID-19 infection on kidney health.", "qid": 9, "docid": "jh4g5brk", "rank": 49, "score": 0.8252052068710327}, {"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": 9, "docid": "ete5n5pw", "rank": 50, "score": 0.8250484466552734}, {"content": "Title: BCG vaccination and socioeconomic variables vs Covid-19 global features: clearing up a controversial issue Content: Background: The Covid-19 pandemic is characterized by extreme variability in the outcome distribution and mortality rates across different countries. Some recent studies suggested an inverse correlation with BCG vaccination at population level, while others denied this hypothesis. In order to address this controversial issue, we performed a strict epidemiological study collecting data available on a global scale, considering additional variables such as cultural-political factors and adherence to other vaccination coverages. Methods: Data on 121 countries, accounting for about 99% of Covid-19 cases and deaths globally, were from John's Hopkins Coronavirus Resource Center, World Bank, International Monetary Fund, United Nations, Human Freedom Report, and BCG Atlas. Statistical models used were Ordinary Least Squares, Tobit and Fractional Probit, implemented on Stata/MP16 software. Results: Based on our results, countries where BCG vaccination is or has been mandated in the last decades have seen a drastic reduction in Covid-19 diffusion (-80% on average) and mortality (-50% on average), even controlling for relative wealth of countries and their governmental health expenditure. A significant contribution to this reduction (respectively -50% and -13% on average) was also associated to the outbreak onset during summer, suggesting a possible influence of seasonality. Other variables turned out to be associated, though to a lesser extent. Conclusions: Relying on a very large dataset and a wide array of control variables, our study confirms a strong and robust association between Covid-19 diffusion and mortality with BCG vaccination and a set socio-economic factors, opening new perspectives for clinical speculations and public health policies.", "qid": 9, "docid": "fpmd9nzf", "rank": 51, "score": 0.8249056339263916}, {"content": "Title: An Epidemiological Study on COVID-19: A Rapidly Spreading Disease Content: Background The outbreak of the novel coronavirus disease in 2019 (COVID-19) caused a major public health crisis worldwide and challenged healthcare systems across the six continents. The high infectivity of the disease led many governments to adopt strict regulations and measures with the aim of containing its spread. The purpose of this study is to assess the incidence, severity, and territorial expansion of COVID-19. Methods Data from the World Health Organization was screened, and COVID-19 situation reports were extracted from January 21 up till March 14 (inclusive). Our data included the total number of cases, total number of new cases, total number of cured cases, and total number of related deaths. Percentage change of cases over the days of our study were calculated using the Joinpoint regression, with a significance level set at greater than 0.05. Results The total number of COVID-19 cases reached 156,622, with 5,845 subsequent deaths. China, Italy, and Iran have the highest number of cases worldwide. During the first 22 days, the incidence rate of COVID-19 increased significantly to reach 1.81 cases per million persons (p<0.001). That was followed by a significant decrease over the next 11 days (p<0.001) to reach 0.071 cases per million persons. A steady rise then followed, which saw a significant increase in incidence rate to 1.429 cases per million persons (p<0.001). Percentages of death and cured cases varied across the different countries; nevertheless, death percentages have generally been decreasing since the start of the crisis. Conclusion Adopting precautionary regulations such as social isolation, increasing sanitation, and employing strict quarantine measures have proved to be beneficial in containing the virus. Further research needs to be conducted to help discover therapeutic modalities and improve outcomes.", "qid": 9, "docid": "52c7myio", "rank": 52, "score": 0.8248378038406372}, {"content": "Title: TB infection and BCG vaccination: are we protected from COVID-19? Content: OBJECTIVES: The incidence of emerging coronavirus disease 2019 (COVID-19) disease is variable across the different parts of the world. Apart from travel patterns, other factors determining this difference may include host immune response. The aim of this study was to assess the effect of tuberculosis (TB) endemicity and Bacille Calmette-Guerin (BCG) coverage on COVID-19. STUDY DESIGN: This was a cross-sectional study. METHODS: We reviewed available data regarding TB incidence, BCG coverage (as per the World Health Organization), and COVID-19 incidence of 174 countries. We divided the countries into four cohorts depending on annual TB incidence and BCG coverage. RESULTS: Countries with high TB incidence had lower COVID-19 than countries with low TB incidence. Similarly, countries with high BCG coverage had lower incidence of COVID-19, suggesting some protective mechanisms in TB-endemic areas. However, the ecological differences and different testing strategies between countries could not be accounted for in this analysis. CONCLUSION: Higher TB incidence and BCG coverage were found to be associated with lesser incidence of COVID-19. This outcome paves the way for further research into pathogenesis and immune response in COVID-19.", "qid": 9, "docid": "wasb9u88", "rank": 53, "score": 0.8247849345207214}, {"content": "Title: Surveillance of persons-who tested negative for COVID-19 in Ontario, January 22-February 22, 2020 Content: As of January 22, 2020, \"disease caused by a novel coronavirus\" became a reportable disease of public health significance in Ontario. Public health units were provided with guidance on the entry of patients tested for severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2), the virus causing 2019 coronavirus disease (COVID-19), into the provincial public health information system. Between January 22 and February 22, 2020, there were 359 individuals who had a negative test result recorded and three confirmed cases of COVID-19. Of those who tested negative, 51% were female and 71% were under 50 years of age. The most common symptoms reported were cough (55%), fever (37%) and sore throat (35%). The majority were tested within three days of symptom onset, but over one-quarter tested more than seven days after symptom onset. Over the first month of reportability, reported travel history shifted from China to an increasing proportion with travel outside of China.", "qid": 9, "docid": "cgk8dxv5", "rank": 54, "score": 0.8247764706611633}, {"content": "Title: Surveillance of persons-who tested negative for COVID-19 in Ontario, January 22-February 22, 2020. Content: As of January 22, 2020, \"disease caused by a novel coronavirus\" became a reportable disease of public health significance in Ontario. Public health units were provided with guidance on the entry of patients tested for severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2), the virus causing 2019 coronavirus disease (COVID-19), into the provincial public health information system. Between January 22 and February 22, 2020, there were 359 individuals who had a negative test result recorded and three confirmed cases of COVID-19. Of those who tested negative, 51% were female and 71% were under 50 years of age. The most common symptoms reported were cough (55%), fever (37%) and sore throat (35%). The majority were tested within three days of symptom onset, but over one-quarter tested more than seven days after symptom onset. Over the first month of reportability, reported travel history shifted from China to an increasing proportion with travel outside of China.", "qid": 9, "docid": "z2zt4fs2", "rank": 55, "score": 0.8247764706611633}, {"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": 56, "score": 0.8247112035751343}, {"content": "Title: Lack of coordination and medical disinformation in Canadian self-assessment tools for COVID-19 Content: As SARS-CoV-2 threatens to overwhelm health systems in Canada, it is imperative that provinces are able to plan and manage an effective and reduced risk response. For this response to be most effective, it must reflect an evidence-based, pan-Canadian response. We designed four different prototypical patients with a combination of common COVID-19 symptoms and opportunities for exposure who were made to self-assess using the 10 provincial COVID-19 self-assessment tools on 1 April. These tools were developed to allow individuals to self-triage, allowing health systems direct capacity to testing and care. We assessed the consistency of the self-assessment tools and of the guidance provided to the patients. While the tools generally screen in three areas, the scope of included COVID-19 associated symptoms as well as the opportunities for exposure, and therefore transmission, vary between provinces such that no two provinces screened in the same way. This was, in turn, reflected in the inconsistency in guidance found. A patient with cough who had travelled abroad or had close contact with a confirmed case within 14 days received the most consistent guidance, with remaining patients receiving guidance ranging from mandatory quarantine or self-isolation to being told they did not have COVID-19 symptoms, guidance at odds with medical evidence. Thus, there is not a single, evidence-based Canadian standard of care simply for self-assessment. Without consistency in public health guidance, Canadians cannot appropriately self-isolate to mitigate community transmission, nor can the necessary valid and reliable data be collected to inform critical epidemiological models that help guide pandemic response. If federal and provincial governments are unable to coordinate a response, Parliament must use its available jurisdiction to legislate a duty on both to follow national standards, so as to improve coordination on COVID-19 in coming months.", "qid": 9, "docid": "idg60ids", "rank": 57, "score": 0.8245612382888794}, {"content": "Title: Economic Consequences of the COVID-19 Outbreak: the Need for Epidemic Preparedness Content: COVID-19 is not only a global pandemic and public health crisis; it has also severely affected the global economy and financial markets. Significant reductions in income, a rise in unemployment, and disruptions in the transportation, service, and manufacturing industries are among the consequences of the disease mitigation measures that have been implemented in many countries. It has become clear that most governments in the world underestimated the risks of rapid COVID-19 spread and were mostly reactive in their crisis response. As disease outbreaks are not likely to disappear in the near future, proactive international actions are required to not only save lives but also protect economic prosperity.", "qid": 9, "docid": "1ts0734u", "rank": 58, "score": 0.8242048025131226}, {"content": "Title: The negative impact of COVID-19 on contraception and sexual and reproductive health: Could immediate postpartum LARCs be the solution? Content: The COVID-19 pandemic has taken much of the world by surprise. With over 4 700 000 infections to date across 188 countries and more than 310 000 deaths worldwide over the course of just 5 months, we were remarkably unprepared.[1] Although the focus has rightly been on the provision of adequate health care for those falling ill from the virus and the search for a cure or vaccine, we must be aware that looming in the background are the usual health issues that millions of people face every day, and that these will not go away during the pandemic.", "qid": 9, "docid": "oejq1su0", "rank": 59, "score": 0.8241354823112488}, {"content": "Title: Climatic factors influence COVID-19 outbreak as revealed by worldwide mortality Content: The COVID-19 outbreak is triggering a global crisis that is challenging governments, health systems and the scientific community worldwide. A central question in the COVID-19 pandemic is whether climatic factors modulate its progression. This information is key to epidemiologists and healthcare decision-makers for improving their management plans. Previous attempts to assess the impact of climatic parameters have yielded ambiguous results, either because they were using geographically or temporally restricted data, or because they were comparing infection rates across countries, which were measured differently depending on local screening strategies. In March 2020, the spread of COVID-19 dramatically increased the number of countries recording deaths, providing an opportunity to use mortality rate, which is measured more homogeneously across countries than infection rates, as a descriptor of the COVID-19 outbreak over a large latitudinal range. Here, using data recorded in 208 territories from 88 countries, we show that mortality rate is negatively influenced by warmer air temperature and positively affected by higher relative humidity. Each additional Celsius degree decreases mortality rate by ~4%, while a 1% increase in relative humidity raises mortality rate by ~2%. Temperature is positively correlated with UV-index, for which one unit of increase results in a ~15% decrease in the mortality rate. We also show that other factors contribute to the dynamics of the COVID-19 outbreak, such as the proportion of vulnerable age classes in the population, access to a non-overwhelmed health system, as well as governmental travel restrictions for controlling the spread of the disease. All of them are critical factors impacting the mortality rate of COVID-19. The influence of climatic factors is a warning to all southern hemisphere countries where winter is coming soon. Northern hemisphere countries should also be warned that climatic factors alone will likely not be sufficient to contain the disease.", "qid": 9, "docid": "eob22inx", "rank": 60, "score": 0.8238551020622253}, {"content": "Title: Effect of underlying comorbidities on the infection and severity of COVID-19 in South Korea Content: ABSTRACT Background: The coronavirus disease (COVID-19) pandemic is an emerging threat worldwide. It is still unclear how comorbidities affect the risk of infection and severity of COVID-19. Methods: A nationwide retrospective case-control study of 65,149 individuals, aged 18 years or older, whose medical cost for COVID-19 testing were claimed until April 8, 2020. The diagnosis of COVID-19 and severity of COVID-19 infection were identified from the reimbursement data using diagnosis codes and based on whether respiratory support was used, respectively. Odds ratios were estimated using multiple logistic regression, after adjusting for age, sex, region, healthcare utilization, and insurance status. Results: The COVID-19 group (5,172 of 65,149) was younger and showed higher proportion of females. 5.6% (293 of 5,172) of COVID-19 cases were severe. The severe COVID-19 group had older patients and a higher male ratio than the non-severe group. Cushing syndrome (Odds ratio range (ORR) 2.059-2.358), chronic renal disease (ORR 1.292-1.604), anemia (OR 1.132), bone marrow dysfunction (ORR 1.471-1.645), and schizophrenia (ORR 1.287-1.556) showed significant association with infection of COVID-19. In terms of severity, diabetes (OR 1.417, 95% CI 1.047-1.917), hypertension (OR 1.378, 95% CI 1.008-1.883), heart failure (ORR 1.562-1.730), chronic lower respiratory disease (ORR 1.361-1.413), non-infectious lower digestive system disease (ORR 1.361-1.418), rheumatoid arthritis (ORR 1.865-1.908), substance use (ORR 2.790-2.848), and schizophrenia (ORR 3.434-3.833) were related with severe COVID-19. Conclusions: We identified several comorbidities associated with COVID-19. Health care workers should be more careful when diagnosing and treating COVID-19 when the patient has the above-mentioned comorbidities. Keywords: COVID-19, SARS-CoV-2, Comorbidity, Risk factor, Severity", "qid": 9, "docid": "dyuw4kbm", "rank": 61, "score": 0.8235121965408325}, {"content": "Title: Leveraging the COVID-19 response to improve emergency care systems in the Eastern Mediterranean Region Content: The COVID-19 pandemic began as a cluster of reported cases of acute respiratory illness in China on 31 December 2019 and went on to spread with exponential growth across the globe. By the time it was characterized as a global pandemic on 11 March 2020, 17 of 22 countries in the Eastern Mediterranean Region (EMR) had reports of infected persons. EMR countries are particularly susceptible to such outbreaks due to the presence of globally interconnected markets; complex emergencies in more than half of the countries; religious mass gatherings that draw tens of millions of pilgrims annually; and variation in emergency care systems capacity and health systems performance within and between countries.", "qid": 9, "docid": "fimq65ul", "rank": 62, "score": 0.8233078122138977}, {"content": "Title: Leveraging the COVID-19 response to improve emergency care systems in the Eastern Mediterranean Region. Content: The COVID-19 pandemic began as a cluster of reported cases of acute respiratory illness in China on 31 December 2019 and went on to spread with exponential growth across the globe. By the time it was characterized as a global pandemic on 11 March 2020, 17 of 22 countries in the Eastern Mediterranean Region (EMR) had reports of infected persons. EMR countries are particularly susceptible to such outbreaks due to the presence of globally interconnected markets; complex emergencies in more than half of the countries; religious mass gatherings that draw tens of millions of pilgrims annually; and variation in emergency care systems capacity and health systems performance within and between countries.", "qid": 9, "docid": "8npfs26s", "rank": 63, "score": 0.8233077526092529}, {"content": "Title: Lifestyle at Time of COVID-19: How Could Quarantine Affect Cardiovascular Risk Content: COVID-19 is causing a global pandemic with a high number of deaths and infected people. To contain the diffusion of COVID-19 virus, governments have enforced restrictions on outdoor activities or even collective quarantine on the population. Quarantine carries some long-term effects on cardiovascular disease, mainly related to unhealthy lifestyle and anxiety.", "qid": 9, "docid": "pigamjae", "rank": 64, "score": 0.8231756687164307}, {"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": 9, "docid": "0a371595", "rank": 65, "score": 0.8229594230651855}, {"content": "Title: Ramping Up the Delivery of Cardiac Surgery During the COVID-19 Pandemic: A Guidance Statement from the Canadian Society of Cardiac Surgeons Content: Abstract The coronavirus disease 2019 (COVID-19) has had a profound global impact. Its rapid transmissibility has forced whole countries to adopt strict measures to contain its spread. As part of necessary pandemic planning, the majority of Canadian cardiac surgical programs have prioritized and delayed elective procedures in an effort to reduce the burden on the health care system and to mobilize resources in the event of a pandemic surge. While the number of COVID-19 cases continue to increase worldwide, new cases have begun to decline in many jurisdictions. This \u201cflattening of the curve\u201d has inevitably prompted discussions around re-opening of the economy, relaxing some public health restrictions and resuming non-urgent health care delivery.", "qid": 9, "docid": "xtudcufl", "rank": 66, "score": 0.8228721618652344}, {"content": "Title: Current perspectives on Coronavirus 2019 (COVID-19) and cardiovascular disease: A white paper by the JAHA editors. Content: Coronavirus Disease 2019 (COVID-19), caused by the Severe Acute Respiratory Syndrome Coronavirus-2 (SARS-CoV-2), has infected more than 3.0 million people worldwide and killed more than 200,000 as of April 27, 2020, making it the most lethal pandemic since the Spanish flu of 1918.1, 2 COVID-19 may preferentially infect individuals with cardiovascular conditions, is more severe in subjects with cardiovascular comorbidities, may directly or indirectly affect the heart and may interact with cardiovascular medications.3 In addition, the widespread effects of the pandemic on the global healthcare system affects the routine and emergency cardiac care for patients who are, may be, or are not infected with COVID-19.", "qid": 9, "docid": "tr5whji0", "rank": 67, "score": 0.8226903676986694}, {"content": "Title: The Impact of COVID-19 on Physical Activity Behavior and Well-Being of Canadians Content: A global pandemic caused by the novel coronavirus (COVID-19) resulted in restrictions to daily living for Canadians, including social distancing and closure of city and provincial recreation facilities, national parks and playgrounds. The objective of this study was to assess how these preemptive measures impacted physical activity behaviour and well-being of Canadians. An online survey was utilized to measure participant physical activity behavior, nature exposure, well-being and anxiety levels. Results indicate that while 40.5% of inactive individuals became less active, only 22.4% of active individuals became less active. Comparatively, 33% of inactive individuals became more active while 40.3% of active individuals became more active. There were significant differences in well-being outcomes in the inactive population between those who were more active, the same or less active (p < 0.001) but this was not seen in the active population. Inactive participants who spent more time engaged in outdoor physical activity had lower anxiety than those who spent less time in outdoor physical activity. Public health measures differentially affected Canadians who were active and inactive and physical activity was strongly associated with well-being outcomes in inactive individuals. This suggests that health promoting measures directed towards inactive individuals may be essential to improving well-being.", "qid": 9, "docid": "4v0qgfat", "rank": 68, "score": 0.8225420713424683}, {"content": "Title: Disease and age-related inequalities in paediatric research, funding and communication: lessons from the COVID-19 pandemic Content: COVID-19 has already caused millions of infections, thousands of deaths and countless indirect and poorly estimated consequences on other diseases and the global economy. All ages are potentially susceptible, but the virus has had a lower direct impact on children, with fewer severe cases and low mortality rates. However, the reasons for this are still unclear and we cannot rule out children's role in transmitting the disease. The serious impact that restrictive measures have had on children's lives have not been fully considered. Because children are less affected by COVID-19, the scientific community, health agencies and governments have not focused much attention on them during this pandemic.", "qid": 9, "docid": "w3hgmfzb", "rank": 69, "score": 0.8224437236785889}, {"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": 9, "docid": "huyl21vz", "rank": 70, "score": 0.8223899602890015}, {"content": "Title: Severe acute respiratory syndrome-coronavirus 2 and novel coronavirus disease 2019: An extraordinary pandemic Content: COVID-19 has emerged as one of the most significant illnesses of the current century. It is caused by severe acute respiratory syndrome coronavirus 2. The world was initially viewing it as a localized outbreak in Wuhan city of China; however, it started spreading quickly to other parts of the world. Globally, half-hearted containment measures and a false sense of safety against this novel coronavirus led to the dissemination of disease. Currently, no effective therapy or vaccine is available to manage this illness. After learning a huge lesson, global efforts would hopefully lead to effective control of this pandemic.", "qid": 9, "docid": "i8opdley", "rank": 71, "score": 0.8223565220832825}, {"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": 9, "docid": "reigmh19", "rank": 72, "score": 0.8218562602996826}, {"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": 9, "docid": "9mjyu55i", "rank": 73, "score": 0.8213160037994385}, {"content": "Title: Supporting individuals with intellectual and developmental disability during the first 100 days of the COVID-19 outbreak in the USA Content: BACKGROUND: It is unknown how the novel Coronavirus SARS-CoV-2, the cause of the current acute respiratory illness COVID-19 pandemic that has infected millions of people, affects people with intellectual and developmental disability (IDD). The aim of this study is to describe how individuals with IDD have been affected in the first 100 days of the COVID-19 pandemic. METHODS: Shortly after the first COVID-19 case was reported in the USA, our organisation, which provides continuous support for over 11 000 individuals with IDD, assembled an outbreak committee composed of senior leaders from across the health care organisation. The committee led the development and deployment of a comprehensive COVID-19 prevention and suppression strategy, utilising current evidence-based practice, while surveilling the global and local situation daily. We implemented enhanced infection control procedures across 2400 homes, which were communicated to our employees using multi-faceted channels including an electronic resource library, mobile and web applications, paper postings in locations, live webinars and direct mail. Using custom-built software applications enabling us to track patient, client and employee cases and exposures, we leveraged current public health recommendations to identify cases and to suppress transmission, which included the use of personal protective equipment. A COVID-19 case was defined as a positive nucleic acid test for SARS-CoV-2 RNA. RESULTS: In the 100-day period between 20 January 2020 and 30 April 2020, we provided continuous support for 11 540 individuals with IDD. Sixty-four per cent of the individuals were in residential, community settings, and 36% were in intermediate care facilities. The average age of the cohort was 46 \u00b1 12 years, and 60% were male. One hundred twenty-two individuals with IDD were placed in quarantine for exhibiting symptoms and signs of acute infection such as fever or cough. Sixty-six individuals tested positive for SARS-CoV-2, and their average age was 50. The positive individuals were located in 30 different homes (1.3% of total) across 14 states. Fifteen homes have had single cases, and 15 have had more than one case. Fifteen COVID-19-positive individuals were hospitalised. As of 30 April, seven of the individuals hospitalised have been discharged back to home and are recovering. Five remain hospitalised, with three improving and two remaining in intensive care and on mechanical ventilation. There have been three deaths. We found that among COVID-19-positive individuals with IDD, a higher number of chronic medical conditions and male sex were characteristics associated with a greater likelihood of hospitalisation. CONCLUSIONS: In the first 100 days of the COVID-19 outbreak in the USA, we observed that people with IDD living in congregate care settings can benefit from a coordinated approach to infection control, case identification and cohorting, as evidenced by the low relative case rate reported. Male individuals with higher numbers of chronic medical conditions were more likely to be hospitalised, while most younger, less chronically ill individuals recovered spontaneously at home.", "qid": 9, "docid": "p1hm0g7h", "rank": 74, "score": 0.821129322052002}, {"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": 9, "docid": "828ubhzi", "rank": 75, "score": 0.8210856318473816}, {"content": "Title: Preparing a neurology department for SARS-CoV-2 (COVID-19): Early experiences at Columbia University Irving Medical Center and the New York Presbyterian Hospital in New York City. Content: Beginning in December 2019, a novel coronavirus, SARS-CoV-2 (COVID-19), began spreading rapidly throughout China and now is a global pandemic with cases reported in over 192 countries and territories worldwide. Clinically, COVID-19 ranges from a mild, self-limiting respiratory illness to severe progressive pneumonia and multiorgan failure. The first COVID-19 case was reported at the beginning of March in New York City (NYC), and now just three weeks later, NYC and its suburbs have over 5% of global cases. Worldwide, there is a rapid increase in the number of cases daily, including the number of patients requiring hospitalization and intensive care support.", "qid": 9, "docid": "h661u7t6", "rank": 76, "score": 0.821008026599884}, {"content": "Title: The Role of Data Registries in the Time of COVID-19. Content: On April 1, 2020, the confirmed global burden of COVID-19 was more than 900,000 with 46,413 deaths. Despite worldwide calls for social distancing and containment, the incidence of the disease continues to increase. COVID-19 is a respiratory tract infection caused by the novel coronavirus (SARS-CoV2). Preliminary analyses from the Chinese Center for Disease Control and Prevention indicated an overall case fatality rate (CFR) of 2.3%; however the CFR was higher in older adults (14.8% in those 80\u00b1 years) and 49% of all critical cases. Those with preexisting conditions (cardiovascular disease (CVD), diabetes, chronic respiratory disease, hypertension, and cancer) also had higher CRFs. In the United States, 116 million adults have hypertension, 26 million US adults have diabetes mellitus, 9% have preexisting CVD and may therefore be at greater risk of complications or adverse health outcomes from COVID-19 infection.", "qid": 9, "docid": "2tlbeqvb", "rank": 77, "score": 0.820865273475647}, {"content": "Title: Review of published systematic reviews and meta-analyses on COVID-19 Content: Purpose: The rapid spread of the COVID-19 pandemic has prompted researchers from all over the world to share their experience. The results were numerous reports with variable quality. The latter has provided an impetus to examine all published meta-analyses and systematic reviews on COVID-19 to date to examine available evidence. Methods: Using predefined selection criteria, a literature search identified 43 eligible meta-analyses and/or systematic reviews. Results: Most (N=17) studies addressed clinical manifestations and associated comorbidity, 6 studies addressed clinical manifestations in pregnant women and younger individuals, 8 studies addressed diagnostic data, 9 studies addressed various interventions, and 9 studies addressed prevention and control. The number of studies included in the various systemic reviews and meta-analyses ranged from 2 to 89. While there were some similarities and consistency for some findings, e.g. the relation between comorbidities and disease severity, we also noted occasionally conflicting data. Conclusion: As more data are collected from patients infected with COVID-19 all over the world, more studies will undoubtedly be published and attention to scientific accuracy in the performance of trials must be exercised to inform clinical decision-making and treatment guidelines.", "qid": 9, "docid": "w170rm6q", "rank": 78, "score": 0.8204046487808228}, {"content": "Title: COVID stress syndrome: Concept, structure, and correlates Content: BACKGROUND: Research shows that the COVID Stress Scales have a robust multifactorial structure, representing five correlated facets of COVID-19-related distress: (a) Fear of the dangerousness of COVID-19, which includes fear of coming into contact with fomites potentially contaminated with SARSCoV2, (b) worry about socioeconomic costs of COVID-19 (e.g., worry about personal finances and disruption in the supply chain), (c) xenophobic fears that foreigners are spreading SARSCoV2, (d) traumatic stress symptoms associated with direct or vicarious traumatic exposure to COVID-19 (nightmares, intrusive thoughts, or images related to COVID-19), and (e) COVID-19-related compulsive checking and reassurance seeking. These factors cohere to form a COVID stress syndrome, which we sought to further delineate in the present study. METHODS: A population-representative sample of 6,854 American and Canadian adults completed a self-report survey comprising questions about current mental health and COVID-19-related experiences, distress, and coping. RESULTS: Network analysis revealed that worry about the dangerousness of COVID-19 is the central feature of the syndrome. Latent class analysis indicated that the syndrome is quasi-dimensional, comprising five classes differing in syndrome severity. Sixteen percent of participants were in the most severe class and possibly needing mental health services. Syndrome severity was correlated with preexisting psychopathology and with excessive COVID-19-related avoidance, panic buying, and coping difficulties during self-isolation. CONCLUSION: The findings provide new information about the structure and correlates of COVID stress syndrome. Further research is needed to determine whether the syndrome will abate once the pandemic has passed or whether, for some individuals, it becomes a chronic condition.", "qid": 9, "docid": "nku9xqoy", "rank": 79, "score": 0.8203257322311401}, {"content": "Title: The need for neurologists in the care of COVID\u201019 patients Content: Coronavirus disease 2019 (COVID-19) is an infectious disease caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) resulting in severe acute respiratory syndrome in a substantial number of patients. Approximately 5% to 10% of patients need intensive care unit (ICU) admission and mechanical ventilation [1]. The primary symptoms of COVID-19 include fever, dry cough and fatigue [2]. However, a recent report from Shandong, China, disclosed that a subset of patients did not suffer from respiratory symptoms but had neurologic signs and symptoms [3]. Moreover, in a retrospective study from Wuhan, China, neurologic symptoms were observed in 36.4% of the hospitalized patients with COVID-19 infection and pertained to both the central and peripheral nervous system [4].", "qid": 9, "docid": "l21fin9q", "rank": 80, "score": 0.8202724456787109}, {"content": "Title: Will helminth co-infection modulate COVID-19 severity in endemic regions? Content: As COVID-19 spreads through the world, most cases to date are in middle- and high-income nations. The impact on resource-poor nations remains unknown. Amongst many factors likely to affect the impact of COVID-19 in these areas, co-infections need to be considered. Here, we discuss whether the immunomodulatory effects of helminth infections may affect COVID-19 severity.", "qid": 9, "docid": "rku20ctp", "rank": 81, "score": 0.8199598789215088}, {"content": "Title: Initial evidence of higher morbidity and mortality due to SARS-CoV-2 in regions with lower air quality Content: COVID-19 has spread in all continents in a span of just over three months, escalating into a pandemic that poses several humanitarian as well as scientific challenges. We here investigated the geographical expansion of the infection and correlate it with the annual indexes of air quality observed from the Sentinel-5 satellite orbiting around China, Italy and the U.S.A. Controlling for population size, we find more viral infections in those areas afflicted by Carbon Monoxide (CO) and Nitrogen Dioxide (NO2). Higher mortality was also correlated with poor air quality, namely with high PM2.5, CO and NO2 values. In Italy, the correspondence between poor air quality and SARS-CoV-2 appearance and induced mortality was the starkest. Similar to smoking, people living in polluted areas are more vulnerable to SARS-CoV-2 infections and induced mortality. This further suggests the detrimental impact climate change will have on the trajectory of future epidemics.", "qid": 9, "docid": "7edmbp1o", "rank": 82, "score": 0.8199273347854614}, {"content": "Title: Effect of Underlying Comorbidities on the Infection and Severity of COVID-19 in Korea: a Nationwide Case-Control Study Content: BACKGROUND: The coronavirus disease 2019 (COVID-19) pandemic is an emerging threat worldwide. It remains unclear how comorbidities affect the risk of infection and severity of COVID-19. METHODS: This is a nationwide retrospective case-control study of 219,961 individuals, aged 18 years or older, whose medical costs for COVID-19 testing were claimed until May 15, 2020. COVID-19 diagnosis and infection severity were identified from reimbursement data using diagnosis codes and on the basis of respiratory support use, respectively. Odds ratios (ORs) were estimated using multiple logistic regression, after adjusting for age, sex, region, healthcare utilization, and insurance status. RESULTS: The COVID-19 group (7,341 of 219,961) was young and had a high proportion of female. Overall, 13.0% (954 of 7,341) of the cases were severe. The severe COVID-19 group had older patients and a proportion of male ratio than did the non-severe group. Diabetes (odds ratio range [ORR], 1.206\u20131.254), osteoporosis (ORR, 1.128\u20131.157), rheumatoid arthritis (ORR, 1.207\u20131.244), substance use (ORR, 1.321\u20131.381), and schizophrenia (ORR, 1.614\u20131.721) showed significant association with COVID-19. In terms of severity, diabetes (OR, 1.247; 95% confidential interval, 1.009\u20131.543), hypertension (ORR, 1.245\u20131.317), chronic lower respiratory disease (ORR, 1.216\u20131.233), chronic renal failure, and end-stage renal disease (ORR, 2.052\u20132.178) were associated with severe COVID-19. CONCLUSION: We identified several comorbidities associated with COVID-19. Health care workers should be more careful while diagnosing and treating COVID-19 when patients have the abovementioned comorbidities.", "qid": 9, "docid": "n64t89pn", "rank": 83, "score": 0.8198891282081604}, {"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": 9, "docid": "2r0a357c", "rank": 84, "score": 0.8198357820510864}, {"content": "Title: Effect of Underlying Comorbidities on the Infection and Severity of COVID-19 in Korea: a Nationwide Case-Control Study Content: BACKGROUND: The coronavirus disease 2019 (COVID-19) pandemic is an emerging threat worldwide. It remains unclear how comorbidities affect the risk of infection and severity of COVID-19. METHODS: This is a nationwide retrospective case-control study of 219,961 individuals, aged 18 years or older, whose medical costs for COVID-19 testing were claimed until May 15, 2020. COVID-19 diagnosis and infection severity were identified from reimbursement data using diagnosis codes and on the basis of respiratory support use, respectively. Odds ratios (ORs) were estimated using multiple logistic regression, after adjusting for age, sex, region, healthcare utilization, and insurance status. RESULTS: The COVID-19 group (7,341 of 219,961) was young and had a high proportion of female. Overall, 13.0% (954 of 7,341) of the cases were severe. The severe COVID-19 group had older patients and a proportion of male ratio than did the non-severe group. Diabetes (odds ratio range [ORR], 1.206-1.254), osteoporosis (ORR, 1.128-1.157), rheumatoid arthritis (ORR, 1.207-1.244), substance use (ORR, 1.321-1.381), and schizophrenia (ORR, 1.614-1.721) showed significant association with COVID-19. In terms of severity, diabetes (OR, 1.247; 95% confidential interval, 1.009-1.543), hypertension (ORR, 1.245-1.317), chronic lower respiratory disease (ORR, 1.216-1.233), chronic renal failure, and end-stage renal disease (ORR, 2.052-2.178) were associated with severe COVID-19. CONCLUSION: We identified several comorbidities associated with COVID-19. Health care workers should be more careful while diagnosing and treating COVID-19 when patients have the abovementioned comorbidities.", "qid": 9, "docid": "1exvjxwx", "rank": 85, "score": 0.8193690180778503}, {"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": 9, "docid": "6w8jun1e", "rank": 86, "score": 0.819164514541626}, {"content": "Title: COVID-19: protecting our ENT workforce. Content: As we write at the end of March 2020, the coronavirus disease 19 (COVID-19) pandemic is posing an urgent and significant threat to global health. It has become clear that the healthcare worker army that forms the front line are also at increased risk of exposure to the SARS-CoV-2 virus that causes this disease. In China 3.8% of all cases of COVID-19 were in healthcare workers, but 14.8% of those had severe or critical disease.1.", "qid": 9, "docid": "yt4phdyb", "rank": 87, "score": 0.8189049959182739}, {"content": "Title: Epidemiological Determinants of Acute Respiratory Syndrome Coronavirus-2 Disease Pandemic and The Role of the Bacille-Calmette-Guerin Vaccine in Reducing Morbidity and Mortality Content: This study analyzed the determinants of morbidity, mortality, and case fatality rate (CFR) of the ongoing pandemic of severe acute respiratory syndrome coronavirus-2 disease 2019 (COVID-19) Data for 210 countries and territories available in public domains were analyzed in relation to mandatory vaccination with Bacille-Calmette-Guerin (BCG), population density, median age of the country population, health care expenditure per capita, life expectancy at birth, healthy life expectancy, literacy rate, per capita gross domestic production adjusted to purchasing power (PPP), burden of tuberculosis (TB), acquired immunodeficiency disease caused by human immunodeficiency virus (HI V-AIDS), malaria, cardiovascular disease (CVD), neoplasm, diabetes, deaths due to energy-protein (food) deficiency (EPD), and per capita government spending on safe water and sanitation Mandatory BCG vaccination showed a highly significant (p&lt;0 0001) negative correlation with COVID-19 morbidity (r = -0 62) and mortality (r = -0 58) rates, but no significant correlation with CFR The median age of the nation showed a significant (p&lt;0 0001) positive correlation with COVID-19 morbidity (r= 0 40) and mortality (r = 0 34) rates, but no significant correlation with CFR The pandemic resulted in higher morbidity (r= 0 47, p&lt;0 0001) and mortality (r= 0 25, p = 0 01) rates in countries with a higher PPP than in those with a lower PPP COVID-19 CFR and morbidity and mortality rates showed no significant correlation with population density, the burden of malaria or diabetes, or the level of spending on safe water and sanitation Only the burden of TB showed a positive correlation with CFR (r = 0 17, p = 0 05) However, COVID-19 morbidity showed a significant (p =0 05) negative correlation with the burden of TB, HI V-AIDS, CVD, and EPD Mortality and morbidity in COVID-19 patients showed a positive correlation with per capita health expenditure, life expectancy, the burden of neoplasia, and PPP", "qid": 9, "docid": "4bnje5un", "rank": 88, "score": 0.8186525702476501}, {"content": "Title: Demographic and Socio-Economic Factors, and Healthcare Resource Indicators Associated with the Rapid Spread of COVID-19 in Northern Italy: An Ecological Study Content: Background: COVID-19 rapidly escalated into a pandemic, threatening 213 countries, areas, and territories the world over. We aimed to identify potential province-level socioeconomic determinants of the virus's dissemination, and explain between-province differences in the speed of its spread, based on data from 36 provinces of Northern Italy. Methods: This is an ecological study. We included all confirmed cases of SARS-CoV-2 reported between February 24th and March 30th, 2020. For each province, we calculated the trend of contagion as the relative increase in the number of individuals infected between two time endpoints, assuming an exponential growth. Pearson's test was used to correlate the trend of contagion with a set of healthcare-associated, economic, and demographic parameters by province. The virus's spread was input as a dependent variable in a stepwise OLS regression model to test the association between rate of spread and province-level indicators. Findings: Multivariate analysis showed that the spread of COVID-19 was correlated negatively with aging index (p-value=0.003), and positively with public transportation per capita (p-value=0.012), the % of private long-term care hospital beds and, to a lesser extent (p-value=0.070), the % of private acute care hospital beds (p-value=0.006). Interpretation: Demographic and socioeconomic factors, and healthcare organization variables were found associated with a significant difference in the rate of COVID-19 spread in 36 provinces of Northern Italy. An aging population seemed to naturally contain social contacts. The availability of healthcare resources and their coordination could play an important part in spreading infection.", "qid": 9, "docid": "vkbnjw14", "rank": 89, "score": 0.8185781240463257}, {"content": "Title: Is BCG vaccination causally related to reduced COVID-19 mortality? Content: The ongoing severe acute respiratory sickness coronavirus 2 (SARS-CoV-2) pandemic has resulted in more than 3,600,000 detected cases of COVID-19 illness and nearly 260,000 deaths worldwide as of May 6, 2020. Recently, BCG vaccination was shown to correlate with reduced COVID-19 case fatality rates (preprint: Miller et al, 2020; preprint: Sala & Miyakawa, 2020; https://www.jsatonotes.com/2020/03/if-i-were-north-americaneuropeanaustral.html). The most recent data from publicly available resources also indicate that both COVID-19 incidence and total deaths are strongly associated with the presence or absence of national mandatory BCG vaccination programs. As seen in Table 1, seven of eight countries with very low numbers of total deaths (< 40 per 1 million population) adopted a mandatory BCG vaccination program using one of a set of 6 separate BCG strains (Table 1). In contrast, COVID-19 mortality was markedly higher in countries where BCG vaccination is not widely administered or is given only to high-risk groups. COVID-19 mortality was also higher in countries where widespread BCG vaccination was discontinued more than 20 years ago and in countries that used the BCG Denmark strain regularly or temporarily. This raises the question of whether BCG vaccination and reduced COVID-19 mortality are causally related. An additional question is why different BCG strains may be variably associated with mortality.", "qid": 9, "docid": "qy79ybat", "rank": 90, "score": 0.8185526132583618}, {"content": "Title: Healthcare Worker COVID-19 Cases in Ontario, Canada: A Cross-sectional Study Content: Background: Our objectives were to describe and compare healthcare worker (HCW) and non-HCW COVID-19 cases in Ontario, as well as the frequency of COVID-19 among HCWs household members. Methods: Using reportable disease data at Public Health Ontario which captures COVID-19 cases in Ontario, we conducted a cross-sectional study comparing demographic, exposure, and clinical variables between HCWs and non-HCWs with COVID-19 as of 14 May 2020. We calculated rates of infections over time and determined the frequency of within household transmissions using natural language processing. Results: There were 4,230 (17.5%) HCW COVID-19 cases in Ontario, of whom 20.2% were nurses, 2.3% were physicians, and the remaining 77.4% other specialties. HCWs were more likely to be between 30-60 years of age and female. HCWs were more likely to present asymptomatically (8.1% versus 7.0%, p=0.010) or with atypical symptoms (17.8% versus 10.5%, p<0.001). The mortality among HCWs was 0.2% compared to 10.5% of non-HCWs. HCWs commonly had exposures to a confirmed case or outbreak (74.1%), however only 3.1% were confirmed to be nosocomial. The rate of new infections was 5.5 times higher in HCWs than non-HCWs, but mirrored the epidemic curve. We identified 391 (9.8%) probable secondary household transmissions. Interpretation: HCWs represent a disproportionate number of COVID-19 cases in Ontario but with low confirmed numbers of nosocomial transmission. The data support substantial testing bias and under-ascertainment of general population cases. Protecting HCWs through appropriate personal protective equipment and physician distancing from colleagues is paramount.", "qid": 9, "docid": "4rutnzbu", "rank": 91, "score": 0.8182188272476196}, {"content": "Title: Outdoor Air Pollutant Concentration and COVID-19 Infection in Wuhan, China Content: COVID-19 infection, first reported in Wuhan, China in December 2019, has become a global pandemic, causing significantly high infections and mortalities in Italy, the UK, the US, and other parts of the world. Based on the statistics reported by John Hopkins University, 4.7M people worldwide and 84,054 people in China have been confirmed positive and infected with COVID-19, as of 18 May 2020. Motivated by the previous studies which show that the exposures to air pollutants may increase the risk of influenza infection, our study examines if such exposures will also affect Covid-19 infection. To the best of our understanding, we are the first group in the world to rigorously explore the effects of outdoor air pollutant concentrations, meteorological conditions and their interactions, and lockdown interventions, on Covid-19 infection in China. Since the number of confirmed cases is likely to be under-reported due to the lack of testing capacity, the change in confirmed case definition, and the undiscovered and unreported asymptotic cases, we use the rate of change in the daily number of confirmed infection cases instead as our dependent variable. Even if the number of reported infections is under-reported, the rate of change will still accurately reflect the relative change in infection, provided that the trend of under-reporting remains the same. In addition, the rate of change in daily infection cases can be distorted by the government imposed public health interventions, including the lockdown policy, inter-city and intra-city mobility, and the change in testing capacity and case definition. Hence, the effects of the lockdown policy and the inter-city and intra-city mobility, and the change in testing capacity and case definition are all taken into account in our statistical modelling. Furthermore, we adopt the generalized linear regression models covering both the Negative Binomial Regression and the Poisson Regression. These two regression models, when combined with different time-lags (to reflect the COVID-19 incubation period and delay due to official confirmation) in air pollutant exposure (PM2.5), are used to fit the COVID-19 infection model. Our statistical study has shown that higher PM2.5 concentration is significantly correlated with a higher rate of change in the daily number of confirmed infection cases in Wuhan, China (p < 0.05). We also determine that a higher dew point interacting with a higher PM2.5 concentration is correlated with a higher rate of change in the daily number of confirmed infection cases, while a higher UV index and a higher PM2.5 concentration are correlated with a lower rate of change. Furthermore, we find that PM2.5 concentration eight days ago has the strongest predictive power for COVID-19 Infection. Our study bears significance to the understanding of the effect of air pollutant (PM2.5) on COVID-19 infection, the interaction effects of both the air pollutant concentration (PM2.5) and the meteorological conditions on the rate of change in infection, as well as the insights into whether lockdown should have an effect on COVID-19 infection.", "qid": 9, "docid": "6i6b3f4j", "rank": 92, "score": 0.8178374171257019}, {"content": "Title: Globalized low-income countries may experience higher COVID-19 mortality rates Content: Understanding the factors underpinning COVID-19 infection and mortality rates is essential in order to implement actions that help mitigate the current pandemia. Here we evaluate how a suit of 15 climatic and socio-economic variables influence COVID-19 exponential growth-phase infection and mortality rates across 36 countries. We found that imports of goods and services, international tourism and the number of published scientific papers are good predictors of COVID-19 infection rates, indicating that more globalized countries may have experienced multiple and recurrent introductions of the virus. However, high-income countries showed lower mortality rates, suggesting that the consequences of the current pandemia will be worse for globalized low-income countries. International aid agencies could use this information to help mitigate the consequences of the current pandemia in the most vulnerable countries.", "qid": 9, "docid": "1ntplgl6", "rank": 93, "score": 0.8177348375320435}, {"content": "Title: A longitudinal study on the mental health of general population during the COVID-19 epidemic in China Content: In addition to being a public physical health emergency, Coronavirus disease 2019 (COVID-19) affected global mental health, as evidenced by panic-buying worldwide as cases soared. Little is known about changes in levels of psychological impact, stress, anxiety and depression during this pandemic. This longitudinal study surveyed the general population twice - during the initial outbreak, and the epidemic's peak four weeks later, surveying demographics, symptoms, knowledge, concerns, and precautionary measures against COVID-19. There were 1738 respondents from 190 Chinese cities (1210 first-survey respondents, 861 s-survey respondents; 333 respondents participated in both). Psychological impact and mental health status were assessed by the Impact of Event Scale-Revised (IES-R) and the Depression, Anxiety and Stress Scale (DASS-21), respectively. IES-R measures PTSD symptoms in survivorship after an event. DASS -21 is based on tripartite model of psychopathology that comprise a general distress construct with distinct characteristics. This study found that there was a statistically significant longitudinal reduction in mean IES-R scores (from 32.98 to 30.76, p < 0.01) after 4 weeks. Nevertheless, the mean IES-R score of the first- and second-survey respondents were above the cut-off scores (>24) for PTSD symptoms, suggesting that the reduction in scores was not clinically significant. During the initial evaluation, moderate-to-severe stress, anxiety and depression were noted in 8.1%, 28.8% and 16.5%, respectively and there were no significant longitudinal changes in stress, anxiety and depression levels (p > 0.05). Protective factors included high level of confidence in doctors, perceived survival likelihood and low risk of contracting COVID-19, satisfaction with health information, personal precautionary measures. As countries around the world brace for an escalation in cases, Governments should focus on effective methods of disseminating unbiased COVID-19 knowledge, teaching correct containment methods, ensuring availability of essential services/commodities, and providing sufficient financial support.", "qid": 9, "docid": "7uw8k8cq", "rank": 94, "score": 0.8176263570785522}, {"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": 9, "docid": "eiek6olk", "rank": 95, "score": 0.8174805045127869}, {"content": "Title: Response to Covid-19: An ethical imperative to build a resilient health system in India Content: China reported cases of a severe form of pneumonia in December 2019 from Wuhan city, Hubei province. The virus causing this illness was identified as the novel Coronavirus 2019, which has now been christened Covid-19. The illness is characterised by fever, cough, body pain and in a few cases, progression to acute respiratory distress syndrome (ARDS) which marks very serious damage to the lungs (1-4). Apart from Wuhan, China, the virus has spread to 26 other countries as on February 18, 2020. Of these 26 countries, the cases of Covid-19 have been exported directly from China in 23 of them. As on February 23, 2020, a total of 78,811 confirmed cases, 2445 deaths have been reported globally. The World Health Organization declared this as a Public Health Emergency of International Concern (PHEIC) on January 30, 2020 (5).", "qid": 9, "docid": "hpx1eby0", "rank": 96, "score": 0.8173625469207764}, {"content": "Title: Response to Covid-19: An ethical imperative to build a resilient health system in India. Content: China reported cases of a severe form of pneumonia in December 2019 from Wuhan city, Hubei province. The virus causing this illness was identified as the novel Coronavirus 2019, which has now been christened Covid-19. The illness is characterised by fever, cough, body pain and in a few cases, progression to acute respiratory distress syndrome (ARDS) which marks very serious damage to the lungs (1-4). Apart from Wuhan, China, the virus has spread to 26 other countries as on February 18, 2020. Of these 26 countries, the cases of Covid-19 have been exported directly from China in 23 of them. As on February 23, 2020, a total of 78,811 confirmed cases, 2445 deaths have been reported globally. The World Health Organization declared this as a Public Health Emergency of International Concern (PHEIC) on January 30, 2020 (5).", "qid": 9, "docid": "mwxy0yt4", "rank": 97, "score": 0.8173625469207764}, {"content": "Title: Climate effect on COVID-19 spread rate: an online surveillance tool Content: Background: COVID-19 outbreak poses an unprecedented challenge for societies, healthcare organizations and economies. In the present analysis we coupled climate data with COVID-19 spread rates worldwide, and in a single country (USA). Methods: Data of confirmed COVID-19 cases was derived from the COVID-19 Global Cases by the CSSE at Johns Hopkins University up to March 19, 2020. We assessed disease spread by two measures: replication rate (RR), the slope of the logarithmic curve of confirmed cases, and the rate of spread (RoS), the slope of the linear regression of the logarithmic curve. Results: Based on predefined criteria, the mean COVID-19 RR was significantly lower in warm climate countries (0.12\u00b1 0.02) compared with cold countries (0.24\u00b1 0.01), (P<0.0001). Similarly, RoS was significantly lower in warm climate countries 0.12\u00b1 0.02 vs. 0.25\u00b1 0.01 than in cold climate countries (P<0.001). In all countries (independent of climate classification) both RR and RoS displayed a moderate negative correlation with temperature R= -0.69, 95% confidence interval [CI], -0.87 to -0.36; P<0.001 and R= -0.72, 95% confidence interval [CI], -0.87 to -0.36; P<0.001, respectively. We identified a similar moderate negative correlation with the dew point temperature. Additional climate variables did not display a significant correlation with neither RR nor RoS. Finally, in an ancillary analysis, COVID-19 intra-country model using an inter-state analysis of the USA did not identify yet correlation between climate parameters and RR or RoS as of March, 19, 2020. Conclusions: Our analysis suggests a plausible negative correlation between warmer climate and COVID-19 spread rate as defined by RR and RoS worldwide. This initial correlation should be interpreted cautiously and be further validated over time, the pandemic is at different stages in various countries as well as in regions within these countries. As such, some associations may be more affected by local transmission patterns rather than by climate. Importantly, we provide an online surveillance dashboard (https://covid19.net.technion.ac.il/) to further assess the association between climate parameters and outbreak dynamics worldwide as time goes by", "qid": 9, "docid": "mdyojac2", "rank": 98, "score": 0.8172725439071655}, {"content": "Title: Significantly Improved COVID-19 Outcomes in Countries with Higher BCG Vaccination Coverage: A Multivariable Analysis Content: COVID-19 started in Hubei province in China and has spread to 210 countries within 3 months. The statistic of COVID-19 across the world is reported daily, providing a dynamic perspective for each country. We tested the hypothesis that the vaccination against tuberculosis with BCG correlates with better outcomes for COVID-19 patients. To this end, we combined the information on demography, economy, major chronic diseases, and immunization policies with the COVID-19 outcomes. We filtered out at a fixed date all countries that were below a predetermined value for population size and number of COVID-19 deaths per million (DPM). Altogether, 55 countries, covering 62.9% of the world population, met our criteria and were analyzed. To allow a reliable comparison between countries, each was aligned to a critical alignment threshold date (0.5 DPM). We found that the years of BCG admission are negatively correlated with DPM at varying times post alignment. Results from multivariable regression tests with 22 quantitative properties of each country and its population substantiate the dominant contribution of BCG admission years to the COVID-19 outcomes. Analyzing countries according to an age group partition across several time-points, reveals that the strongest correlation is attributed to the coverage in BCG vaccination of the young population (<25 years), to a lesser degree the middle age group (25-64 years), while BCG coverage status of the elderly (>65 years) was insignificant. More specifically, the signal is attributed to recent immunizations (last 15 years) rather than past policies. We propose that BCG immunization coverage, especially among the most recently vaccinated, may contribute to attenuation of the COVID-19 spread and severity.", "qid": 9, "docid": "j060e7de", "rank": 99, "score": 0.8172217011451721}, {"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": 100, "score": 0.8171954154968262}]}
{"query": "are patients taking Angiotensin-converting enzyme inhibitors (ACE) at increased risk for COVID-19?", "hits": [{"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": 1, "score": 0.9387636780738831}, {"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": 2, "score": 0.9363096356391907}, {"content": "Title: Inflammation Level Severity and Death in Patients With COVID-19: A Rapid Systematic Review and Meta-Analysis Content: Background: An association among the use of angiotensin-converting-enzyme(ACE) inhibitors and angiotensin-receptor blockers(ARBs) with the clinical outcomes of coronavirus disease 2019 (COVID-19) is unclear. Methods: PubMed, EMBASE, and the preprint databases MedRxiv and BioRxiv were searched for relevant studies that assessed the association among inflammation level, application of ACEI/ARB, infection severity and death in patients with COVID-19. Odd risks(OR) and 95% confidence interval (CI) were combined using random-effects or fixed models depending on heterogeneity. Results: Eleven studies were included with a total of 33,483 patients. Our review showed ACEI/ARB therapy might be associated with the reduced inflammatory factor (interleukin-6) and elevated level of immune cells(CD3, CD8). Meta-analysis showed no significant increase in the risk of COVID-19 infection(OR:0.95, 95%CI:0.89-1.05) in patients receiving ACEI/ARB therapy, and ACEI/ARB therapy was associated with a decreased risk of severe COVID-19 (OR:0.75, 95%CI: 0.59-0.96) and mortality (OR:0.52, 95%CI: 0.35-0.79). Subgroup analyses showed that, among the general population, application of ACEI/ARB therapy was associated with reduced risks of all-cause death(OR:0.31, 95%CI: 0.13-0.75), and the risk of severe COVID-19(OR:0.79, 95%CI: 0.60-1.05) infection and COVID-19 infection(OR:0.85, 95% CI: 0.66-1.08) were not increased. Among patients with hypertension, the use of an ACEI/ARB was associated with a lower severity of COVID-19(OR:0.73, 95%CI: 0.51-1.03) and lower mortality(OR:0.57, 95%CI: 0.37-0.87), without evidence of an increased risk of COVID-19 infection(OR:1.00, 95%CI: 0.90-1.12). Conclusion: On the basis of the available evidence, this is the first meta-analysis showed that, in general population, the use of ACEI/ARB therapy was safe without an increased risk of COVID-19 infection and with a decreasing trend of severe COVID-19 infection and lower mortality. In patients with hypertension, the use of ACEI/ARB therapy should be encouraged, without increased risk of COVID-19 inflection, and better prognosis (a decreasing trends of severe COVID-19 and reduced all-cause death). Overall, ACEI/ARB therapy should be continued in patients who are at risk for, or have COVID-19, either in general population or hypertension patients. Our results need to be interpreted with caution considering the potential for residual confounders, and more well-designed studies that control the clinical confounders are necessary to confirm our findings. Key Words COVID-19; ACEI/ARB; SARS-COV-2; pneumonia; infectious disease; lung, hypertension", "qid": 20, "docid": "93hgg2py", "rank": 3, "score": 0.9218415021896362}, {"content": "Title: Association Between ACEIs or ARBs Use and Clinical Outcomes in COVID-19 Patients: A Systematic Review and Meta-analysis Content: Importance: There is a controversy regarding whether or not to continue angiotensin-converting enzyme inhibitors (ACEIs) and angiotensin receptor blockers (ARBs) in patients with coronavirus disease 2019 (COVID-19). Objective: To evaluate the association between ACEIs or ARBs use and clinical outcomes in COVID-19 patients. Data Sources: Systematic search of the PubMed, Embase, Scopus, Web of Science, and Cochrane Central Register of Controlled Trials from database inception to May 31, 2020. We also searched the preprint servers medRxiv and SSNR for additional studies. Study Selection: Observational studies and randomized controlled trials reporting the effect of ACEIs or ARBs use on clinical outcomes of adult patients with COVID-19. Data Extraction and Synthesis: Risk of bias of observational studies were evaluated using the Newcastle-Ottawa Scale. Meta-analyses were performed using a random-effects models and effects expressed as Odds ratios (OR) and mean differences with their 95% confidence interval (95%CI). If available, adjusted effects were pooled. Main Outcomes and Measures: The primary outcome was all-cause mortality and secondary outcomes were COVID-19 severity, hospital discharge, hospitalization, intensive care unit admission, mechanical ventilation, length of hospital stay, and troponin, creatinine, procalcitonin, C-reactive protein (CRP), interleukin-6 (IL-6), and D-dimer levels. Results: 40 studies (21 cross-sectional, two case-control, and 17 cohorts) involving 50615 patients were included. ACEIs or ARBs use was not associated with all-cause mortality overall (OR 1.11, 95%CI 0.77-1.60, p=0.56), in subgroups by study design and using adjusted effects. ACEI or ARB use was independently associated with lower COVID-19 severity (aOR 0.56, 95%CI 0.37-0.87, p<0.01). No significant associations were found between ACEIs or ARBs use and hospital discharge, hospitalization, mechanical ventilation, length of hospital stay, and biomarkers. Conclusions and Relevance: ACEIs or ARBs use was not associated with higher all-cause mortality in COVID-19. However, ACEI or ARB use was independently associated with lower COVID-19 severity. Our results support the current international guidelines to continue the use of ACEIs and ARBs in COVID-19 patients with hypertension.", "qid": 20, "docid": "ub718jpv", "rank": 4, "score": 0.9217898845672607}, {"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": 5, "score": 0.9213458895683289}, {"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": 6, "score": 0.918554425239563}, {"content": "Title: Angiotensin Converting Enzyme Inhibitor and Angiotensin II Receptor Blocker Use Among Outpatients Diagnosed with COVID-19 Content: Coronavirus disease 2019 (COVID-19) is a viral pandemic precipitated by the severe acute respiratory syndrome coronavirus 2. Since previous reports suggested that viral entry into cells may involve angiotensin converting enzyme 2, there has been growing concern that angiotensin converting enzyme inhibitor (ACEI) and angiotensin II receptor blocker (ARB) use may exacerbate the disease severity. In this retrospective, single-center US study of adult patients diagnosed with COVID-19, we evaluated the association of ACEI/ARB use with hospital admission. Secondary outcomes included: ICU admission, mechanical ventilation, length of hospital stay, use of inotropes, and all-cause mortality. Propensity score matching was performed to account for potential confounders. Among 590 unmatched patients diagnosed with COVID-19, 78 patients were receiving ACEI/ARB (median age 63 years and 59.7% male) and 512 patients were non-users (median age 42 years and 47.1% male). In the propensity matched population, multivariate logistic regression analysis adjusting for age, gender and comorbidities demonstrated that ACEI/ARB use was not associated with hospital admission (OR 1.2, 95% CI 0.5-2.7, p = 0.652). CAD and CKD/ESRD remained independently associated with admission to hospital. All-cause mortality, ICU stay, need for ventilation, and inotrope use was not significantly different between the 2 study groups. In conclusion, among patients who were diagnosed with COVID-19, ACEI/ARB use was not associated with increased risk of hospital admission.", "qid": 20, "docid": "ps9xawlp", "rank": 7, "score": 0.9185311794281006}, {"content": "Title: Association of Angiotensin-Converting Enzyme Inhibitor or Angiotensin Receptor Blocker Use With COVID-19 Diagnosis and Mortality Content: Importance: It has been hypothesized that angiotensin-converting enzyme inhibitors (ACEIs)/angiotensin receptor blockers (ARBs) may make patients more susceptible to coronavirus disease 2019 (COVID-19) and to worse outcomes through upregulation of the functional receptor of the virus, angiotensin-converting enzyme 2. Objective: To examine whether use of ACEI/ARBs was associated with COVID-19 diagnosis and worse outcomes in patients with COVID-19. Design, Setting, and Participants: To examine outcomes among patients with COVID-19, a retrospective cohort study using data from Danish national administrative registries was conducted. Patients with COVID-19 from February 22 to May 4, 2020, were identified using ICD-10 codes and followed up from day of diagnosis to outcome or end of study period (May 4, 2020). To examine susceptibility to COVID-19, a Cox regression model with a nested case-control framework was used to examine the association between use of ACEI/ARBs vs other antihypertensive drugs and the incidence rate of a COVID-19 diagnosis in a cohort of patients with hypertension from February 1 to May 4, 2020. Exposures: ACEI/ARB use was defined as prescription fillings 6 months prior to the index date. Main Outcomes and Measures: In the retrospective cohort study, the primary outcome was death, and a secondary outcome was a composite outcome of death or severe COVID-19. In the nested case-control susceptibility analysis, the outcome was COVID-19 diagnosis. Results: In the retrospective cohort study, 4480 patients with COVID-19 were included (median age, 54.7 years [interquartile range, 40.9-72.0]; 47.9% men). There were 895 users (20.0%) of ACEI/ARBs and 3585 nonusers (80.0%). In the ACEI/ARB group, 18.1% died within 30 days vs 7.3% in the nonuser group, but this association was not significant after adjustment for age, sex, and medical history (adjusted hazard ratio [HR], 0.83 [95% CI, 0.67-1.03]). Death or severe COVID-19 occurred in 31.9% of ACEI/ARB users vs 14.2% of nonusers by 30 days (adjusted HR, 1.04 [95% CI, 0.89-1.23]). In the nested case-control analysis of COVID-19 susceptibility, 571 patients with COVID-19 and prior hypertension (median age, 73.9 years; 54.3% men) were compared with 5710 age- and sex-matched controls with prior hypertension but not COVID-19. Among those with COVID-19, 86.5% used ACEI/ARBs vs 85.4% of controls; ACEI/ARB use compared with other antihypertensive drugs was not significantly associated with higher incidence of COVID-19 (adjusted HR, 1.05 [95% CI, 0.80-1.36]). Conclusions and Relevance: Prior use of ACEI/ARBs was not significantly associated with COVID-19 diagnosis among patients with hypertension or with mortality or severe disease among patients diagnosed as having COVID-19. These findings do not support discontinuation of ACEI/ARB medications that are clinically indicated in the context of the COVID-19 pandemic.", "qid": 20, "docid": "hn6wni8d", "rank": 8, "score": 0.9184021949768066}, {"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": 9, "score": 0.917771577835083}, {"content": "Title: ACEI/ARB use and risk of infection or severity or mortality of COVID-19: A systematic review and meta-analysis Content: The effects of angiotensin-converting enzyme inhibitors (ACEIs) and angiotensin receptor blockers (ARBs) on the risk of COVID-19 infection and disease progression are yet to be investigated. The relationship between ACEI/ARB use and COVID-19 infection was systematically reviewed. To identify relevant studies that met predetermined inclusion criteria, unrestricted searches of the PubMed, Embase, and Cochrane Library databases were conducted. The search strategy included clinical date published until May 9, 2020. Twelve articles involving more than 19,000 COVID-19 cases were included. To estimate overall risk, random-effects models were adopted. Our results showed that ACEI/ARB exposure was not associated with a higher risk of COVID-19 infection (OR = 0.99; 95 % CI, 0-1.04; P = 0.672). Among those with COVID-19 infection, ACEI/ARB exposure was also not associated with a higher risk of having severe infection (OR = 0.98; 95 % CI, 0.87-1.09; P = 0.69) or mortality (OR = 0.73, 95 %CI, 0.5-1.07; P = 0.111). However, ACEI/ARB exposure was associated with a lower risk of mortality compared to those on non-ACEI/ARB antihypertensive drugs (OR = 0.48, 95 % CI, 0.29-0.81; P = 0.006). In conclusion, current evidence did not confirm the concern that ACEI/ARB exposure is harmful in patientswith COVID-19 infection. This study supports the current guidelines that discourage discontinuation of ACEIs or ARBs in COVID-19 patients and the setting of the COVID-19 pandemic.", "qid": 20, "docid": "v8tfxd6a", "rank": 10, "score": 0.9175949096679688}, {"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": 20, "docid": "bwg3tzx8", "rank": 11, "score": 0.9171057939529419}, {"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": 12, "score": 0.916811466217041}, {"content": "Title: Association of Use of Angiotensin-Converting Enzyme Inhibitors and Angiotensin II Receptor Blockers With Testing Positive for Coronavirus Disease 2019 (COVID-19) Content: Importance: The role of angiotensin-converting enzyme inhibitors (ACEI) and angiotensin II receptor blockers (ARB) in the setting of the coronavirus disease 2019 (COVID-19) pandemic is hotly debated. There have been recommendations to discontinue these medications, which are essential in the treatment of several chronic disease conditions, while, in the absence of clinical evidence, professional societies have advocated their continued use. Objective: To study the association between use of ACEIs/ARBs with the likelihood of testing positive for COVID-19 and to study outcome data in subsets of patients taking ACEIs/ARBs who tested positive with severity of clinical outcomes of COVID-19 (eg, hospitalization, intensive care unit admission, and requirement for mechanical ventilation). Design, Setting, and Participants: Retrospective cohort study with overlap propensity score weighting was conducted at the Cleveland Clinic Health System in Ohio and Florida. All patients tested for COVID-19 between March 8 and April 12, 2020, were included. Exposures: History of taking ACEIs or ARBs at the time of COVID-19 testing. Main Outcomes and Measures: Results of COVID-19 testing in the entire cohort, number of patients requiring hospitalizations, intensive care unit admissions, and mechanical ventilation among those who tested positive. Results: A total of 18\u00e2\u0080\u00af472 patients tested for COVID-19. The mean (SD) age was 49 (21) years, 7384 (40%) were male, and 12\u00e2\u0080\u00af725 (69%) were white. Of 18\u00e2\u0080\u00af472 patients who underwent COVID-19 testing, 2285 (12.4%) were taking either ACEIs or ARBs. A positive COVID-19 test result was observed in 1735 of 18\u00e2\u0080\u00af472 patients (9.4%). Among patients who tested positive, 421 (24.3%) were admitted to the hospital, 161 (9.3%) were admitted to an intensive care unit, and 111 (6.4%) required mechanical ventilation. Overlap propensity score weighting showed no significant association of ACEI and/or ARB use with COVID-19 test positivity (overlap propensity score-weighted odds ratio, 0.97; 95% CI, 0.81-1.15). Conclusions and Relevance: This study found no association between ACEI or ARB use and COVID-19 test positivity. These clinical data support current professional society guidelines to not discontinue ACEIs or ARBs in the setting of the COVID-19 pandemic. However, further study in larger numbers of hospitalized patients receiving ACEI and ARB therapy is needed to determine the association with clinical measures of COVID-19 severity.", "qid": 20, "docid": "v10tfut9", "rank": 13, "score": 0.9166941046714783}, {"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": 14, "score": 0.9161627292633057}, {"content": "Title: ACEI/ARB Use and Risk of Infection or Severity or Mortality of COVID-19: A Systematic Review and Meta-analysis Content: We have sparse knowledge of the effects of angiotensin-converting enzyme inhibitors (ACEIs) and angiotensin receptor blockers (ARBs) on the risk of COVID-19 infection and the progression of this disease. We systematically assessed these relationships. Unrestricted searches of the PubMed, Embase, and Cochrane Library databases were conducted, with an end date of May 9, 2020, to identify relevant studies that met predetermined inclusion criteria. Random-effects models were adopted to estimate the overall relative risk. Fourteen articles involving more than 19000 COVID-19 cases were included. Our results showed that ACEI/ARB exposure is not associated with a higher risk of COVID-19 infection (OR = 0.99; 95% CI, 0.95-1.04; P = 0.672). Among those with COVID-19 infection, ACEI/ARB exposure is not associated with a higher risk of severity (OR = 0.98; 95%CI 0.87-1.09; P = 0.69) or mortality (OR = 0.73, 95%CI 0.5-1.07; P = 0.111). However, ACEI/ARB exposure was associated with a lower risk of mortality compared those with non-ACEI/ARB antihypertensive drugs (OR = 0.48, 95% CI 0.29-0.81; P = 0.006). In conclusion, current evidence did not confirm previous concern regarding a harmful role of ACEI/ARB in COVID-19 patients. The present study support current professional society guidelines to not discontinue ACEIs or ARBs in the setting of the COVID-19 pandemic or COVID-19 patients.", "qid": 20, "docid": "cvj1t0gi", "rank": 15, "score": 0.9148290753364563}, {"content": "Title: Renin-angiotensin-aldosterone system inhibitors and COVID-19 infection or hospitalization: a cohort study Content: There are plausible mechanisms by which angiotensin-converting enzyme inhibitors (ACEIs) and angiotensin receptor blockers (ARBs) may increase the risk of COVID-19 infection or affect disease severity. To examine the association between these medications and COVID-19 infection or hospitalization, we conducted a retrospective cohort study within a US integrated healthcare system. Among people aged [\u2265]18 years enrolled in the health plan for at least 4 months as of 2/29/2020, current ACEI and ARB use was identified from pharmacy data, and the estimated daily dose was calculated and standardized across medications. COVID-19 infections were identified through 6/14/2020 from laboratory and hospitalization data. We used logistic regression to estimate adjusted odds ratios (ORs) and 95% confidence intervals. Among 322,044 individuals, 720 developed COVID-19 infection. Among people using ACEI/ARBs, 183/56,105 developed COVID-19 (3.3 per 1000 individuals) compared with 537/265,939 without ACEI/ARB use (2.0 per 1000), yielding an adjusted OR of 0.94 (95% CI 0.75-1.16). For use of < 1 defined daily dose vs. nonuse, the adjusted OR for infection was 0.89 (95% CI 0.62-1.26); for 1 to < 2 defined daily doses, 0.97 (95% CI 0.71-1.31); and for [\u2265]2 defined daily doses, 0.94 (95% CI 0.72-1.23). The OR was similar for ACEIs and ARBs and in subgroups by age and sex. 29% of people with COVID-19 infection were hospitalized; the adjusted OR for hospitalization in relation to ACEI/ARB use was 0.92 (95% CI 0.54-1.57), and there was no association with dose. These findings support current recommendations that individuals on these medications continue their use.", "qid": 20, "docid": "01xdd8zf", "rank": 16, "score": 0.9141939878463745}, {"content": "Title: Association of Angiotensin-Converting Enzyme Inhibitor or Angiotensin Receptor Blocker Use With COVID-19 Diagnosis and Mortality. Content: Importance It has been hypothesized that angiotensin-converting enzyme inhibitors (ACEIs)/angiotensin receptor blockers (ARBs) may make patients more susceptible to coronavirus disease 2019 (COVID-19) and to worse outcomes through upregulation of the functional receptor of the virus, angiotensin-converting enzyme 2. Objective To examine whether use of ACEI/ARBs was associated with COVID-19 diagnosis and worse outcomes in patients with COVID-19. Design, Setting, and Participants To examine outcomes among patients with COVID-19, a retrospective cohort study using data from Danish national administrative registries was conducted. Patients with COVID-19 from February 22 to May 4, 2020, were identified using ICD-10 codes and followed up from day of diagnosis to outcome or end of study period (May 4, 2020). To examine susceptibility to COVID-19, a Cox regression model with a nested case-control framework was used to examine the association between use of ACEI/ARBs vs other antihypertensive drugs and the incidence rate of a COVID-19 diagnosis in a cohort of patients with hypertension from February 1 to May 4, 2020. Exposures ACEI/ARB use was defined as prescription fillings 6 months prior to the index date. Main Outcomes and Measures In the retrospective cohort study, the primary outcome was death, and a secondary outcome was a composite outcome of death or severe COVID-19. In the nested case-control susceptibility analysis, the outcome was COVID-19 diagnosis. Results In the retrospective cohort study, 4480 patients with COVID-19 were included (median age, 54.7 years [interquartile range, 40.9-72.0]; 47.9% men). There were 895 users (20.0%) of ACEI/ARBs and 3585 nonusers (80.0%). In the ACEI/ARB group, 18.1% died within 30 days vs 7.3% in the nonuser group, but this association was not significant after adjustment for age, sex, and medical history (adjusted hazard ratio [HR], 0.83 [95% CI, 0.67-1.03]). Death or severe COVID-19 occurred in 31.9% of ACEI/ARB users vs 14.2% of nonusers by 30 days (adjusted HR, 1.04 [95% CI, 0.89-1.23]). In the nested case-control analysis of COVID-19 susceptibility, 571 patients with COVID-19 and prior hypertension (median age, 73.9 years; 54.3% men) were compared with 5710 age- and sex-matched controls with prior hypertension but not COVID-19. Among those with COVID-19, 86.5% used ACEI/ARBs vs 85.4% of controls; ACEI/ARB use compared with other antihypertensive drugs was not significantly associated with higher incidence of COVID-19 (adjusted HR, 1.05 [95% CI, 0.80-1.36]). Conclusions and Relevance Prior use of ACEI/ARBs was not significantly associated with COVID-19 diagnosis among patients with hypertension or with mortality or severe disease among patients diagnosed as having COVID-19. These findings do not support discontinuation of ACEI/ARB medications that are clinically indicated in the context of the COVID-19 pandemic.", "qid": 20, "docid": "kc6dls2z", "rank": 17, "score": 0.9141367673873901}, {"content": "Title: Treatment with ACE-inhibitors is associated with less severe disease with SARS-Covid-19 infection in a multi-site UK acute Hospital Trust Content: Abstract: Background: The SARS-Cov2 virus binds to the ACE2 receptor for cell entry. It has been suggested that ACE-inhibitors, which are commonly used in patients with hypertension or diabetes and which raise ACE2 levels, may increase the risk of severe COVID-19 infection. Methods: We evaluated this hypothesis in an early cohort of 205 acute inpatients with COVID-19 at King's College Hospital and Princess Royal University Hospital, London, UK with the primary endpoint being death or transfer to a critical care unit for organ support within 7-days of symptom onset. Findings: 53 patients out of 205 patients reached the primary endpoint. Contrary to the hypothesis, treatment with ACE-inhibitors was associated with a reduced risk of rapidly deteriorating severe disease. There was a lower rate of death or transfer to a critical care unit within 7 days in patients on an ACE-inhibitor OR 0.29 (CI 0.10-0.75, p<0.01), adjusting for age, gender, comorbidities (hypertension, diabetes mellitus, ischaemic heart disease and heart failure). Interpretation: Although a small sample size, we do not see evidence for ACE-inhibitors increasing the short-term severity of COVID-19 disease and patients on treatment with ACE-inhibitors should continue these drugs during their COVID-19 illness. A potential beneficial effect needs to be explored as more data becomes available.", "qid": 20, "docid": "60wcvkbn", "rank": 18, "score": 0.9135732054710388}, {"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": 19, "score": 0.9135340452194214}, {"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": 20, "score": 0.9135308861732483}, {"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": 21, "score": 0.9134543538093567}, {"content": "Title: Risks and Impact of Angiotensin-Converting Enzyme Inhibitors or Angiotensin-Receptor Blockers on SARS-CoV-2 Infection in Adults: A Living Systematic Review Content: BACKGROUND: The role of angiotensin-converting enzyme inhibitors (ACEIs) and angiotensin-receptor blockers (ARBs) in COVID-19 disease susceptibility, severity, and treatment is unclear. PURPOSE: To evaluate, on an ongoing basis, whether use of ACEIs or ARBs either increases risk for severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection or is associated with worse COVID-19 disease outcomes, and to assess the efficacy of these medications for COVID-19 treatment. DATA SOURCES: MEDLINE (Ovid) and Cochrane Database of Systematic Reviews from 2003 to 4 May 2020, with planned ongoing surveillance for 1 year; the World Health Organization database of COVID-19 publications and medRxiv.org through 17 April 2020; and ClinicalTrials.gov to 24 April 2020, with planned ongoing surveillance. STUDY SELECTION: Observational studies and trials in adults that examined associations and effects of ACEIs or ARBs on risk for SARS-CoV-2 infection and COVID-19 disease severity and mortality. DATA EXTRACTION: Single-reviewer abstraction confirmed by another reviewer, independent evaluation by 2 reviewers of study quality, and collective assessment of certainty of evidence. DATA SYNTHESIS: Two retrospective cohort studies found that ACEI and ARB use was not associated with a higher likelihood of receiving a positive SARS-CoV-2 test result, and 1 case\u2013control study found no association with COVID-19 illness in a large community (moderate-certainty evidence). Fourteen observational studies, involving a total of 23 565 adults with COVID-19, showed consistent evidence that neither medication was associated with more severe COVID-19 illness (high-certainty evidence). Four registered randomized trials plan to evaluate ACEIs and ARBs for treatment of COVID-19. LIMITATION: Half the studies were small and did not adjust for important confounding variables. CONCLUSION: High-certainty evidence suggests that ACEI or ARB use is not associated with more severe COVID-19 disease, and moderate-certainty evidence suggests no association between use of these medications and positive SARS-CoV-2 test results among symptomatic patients. Whether these medications increase the risk for mild or asymptomatic disease or are beneficial in COVID-19 treatment remains uncertain. PRIMARY FUNDING SOURCE: None. (PROSPERO: registration number pending)", "qid": 20, "docid": "z22a5yzo", "rank": 22, "score": 0.9129887819290161}, {"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": 23, "score": 0.9124047160148621}, {"content": "Title: Risks and Impact of Angiotensin-Converting Enzyme Inhibitors or Angiotensin-Receptor Blockers on SARS-CoV-2 Infection in Adults Content: BACKGROUND: The role of angiotensin-converting enzyme inhibitors (ACEIs) and angiotensin-receptor blockers (ARBs) in COVID-19 disease susceptibility, severity, and treatment is unclear. PURPOSE: To evaluate, on an ongoing basis, whether use of ACEIs or ARBs either increases risk for severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection or is associated with worse COVID-19 disease outcomes, and to assess the efficacy of these medications for COVID-19 treatment. DATA SOURCES: MEDLINE (Ovid) and Cochrane Database of Systematic Reviews from 2003 to 4 May 2020, with planned ongoing surveillance for 1 year; the World Health Organization database of COVID-19 publications and medRxiv.org through 17 April 2020; and ClinicalTrials.gov to 24 April 2020, with planned ongoing surveillance. STUDY SELECTION: Observational studies and trials in adults that examined associations and effects of ACEIs or ARBs on risk for SARS-CoV-2 infection and COVID-19 disease severity and mortality. DATA EXTRACTION: Single-reviewer abstraction confirmed by another reviewer, independent evaluation by 2 reviewers of study quality, and collective assessment of certainty of evidence. DATA SYNTHESIS: Two retrospective cohort studies found that ACEI and ARB use was not associated with a higher likelihood of receiving a positive SARS-CoV-2 test result, and 1 case-control study found no association with COVID-19 illness in a large community (moderate-certainty evidence). Fourteen observational studies, involving a total of 23 565 adults with COVID-19, showed consistent evidence that neither medication was associated with more severe COVID-19 illness (high-certainty evidence). Four registered randomized trials plan to evaluate ACEIs and ARBs for treatment of COVID-19. LIMITATION: Half the studies were small and did not adjust for important confounding variables. CONCLUSION: High-certainty evidence suggests that ACEI or ARB use is not associated with more severe COVID-19 disease, and moderate-certainty evidence suggests no association between use of these medications and positive SARS-CoV-2 test results among symptomatic patients. Whether these medications increase the risk for mild or asymptomatic disease or are beneficial in COVID-19 treatment remains uncertain. PRIMARY FUNDING SOURCE: None. (PROSPERO: registration number pending).", "qid": 20, "docid": "0nwmoua3", "rank": 24, "score": 0.9121494293212891}, {"content": "Title: Association of Use of Angiotensin-Converting Enzyme Inhibitors and Angiotensin II Receptor Blockers With Testing Positive for Coronavirus Disease 2019 (COVID-19). Content: Importance The role of angiotensin-converting enzyme inhibitors (ACEI) and angiotensin II receptor blockers (ARB) in the setting of the coronavirus disease 2019 (COVID-19) pandemic is hotly debated. There have been recommendations to discontinue these medications, which are essential in the treatment of several chronic disease conditions, while, in the absence of clinical evidence, professional societies have advocated their continued use. Objective To study the association between use of ACEIs/ARBs with the likelihood of testing positive for COVID-19 and to study outcome data in subsets of patients taking ACEIs/ARBs who tested positive with severity of clinical outcomes of COVID-19 (eg, hospitalization, intensive care unit admission, and requirement for mechanical ventilation). Design, Setting, and Participants Retrospective cohort study with overlap propensity score weighting was conducted at the Cleveland Clinic Health System in Ohio and Florida. All patients tested for COVID-19 between March 8 and April 12, 2020, were included. Exposures History of taking ACEIs or ARBs at the time of COVID-19 testing. Main Outcomes and Measures Results of COVID-19 testing in the entire cohort, number of patients requiring hospitalizations, intensive care unit admissions, and mechanical ventilation among those who tested positive. Results A total of 18 472 patients tested for COVID-19. The mean (SD) age was 49 (21) years, 7384 (40%) were male, and 12 725 (69%) were white. Of 18 472 patients who underwent COVID-19 testing, 2285 (12.4%) were taking either ACEIs or ARBs. A positive COVID-19 test result was observed in 1735 of 18 472 patients (9.4%). Among patients who tested positive, 421 (24.3%) were admitted to the hospital, 161 (9.3%) were admitted to an intensive care unit, and 111 (6.4%) required mechanical ventilation. Overlap propensity score weighting showed no significant association of ACEI and/or ARB use with COVID-19 test positivity (overlap propensity score-weighted odds ratio, 0.97; 95% CI, 0.81-1.15). Conclusions and Relevance This study found no association between ACEI or ARB use and COVID-19 test positivity. These clinical data support current professional society guidelines to not discontinue ACEIs or ARBs in the setting of the COVID-19 pandemic. However, further study in larger numbers of hospitalized patients receiving ACEI and ARB therapy is needed to determine the association with clinical measures of COVID-19 severity.", "qid": 20, "docid": "pn4cz2bf", "rank": 25, "score": 0.9121400117874146}, {"content": "Title: Impact of angiotensin-converting enzyme inhibitors and angiotensin receptor blockers on COVID-19 in a western population. CARDIOVID registry Content: INTRODUCTION AND OBJECTIVES: Coronavirus disease (COVID-19) has been designated a global pandemic by the World Health Organization. It is unclear whether previous treatment with angiotensin-converting enzyme inhibitors (ACEI) and angiotensin receptor blockers (ARB) affects the prognosis of COVID-19 patients. The aim of this study was to evaluate the clinical implications of previous treatment with ACEI/ARB on the prognosis of patients with COVID-19 infection. METHODS: Single-center, retrospective, observational cohort study based on all the inhabitants of our health area. Analyses of main outcomes (mortality, heart failure, hospitalization, intensive care unit [ICU] admission, and major acute cardiovascular events [a composite of mortality and heart failure]) were adjusted by multivariate logistic regression and propensity score matching models. RESULTS: Of the total population, 447 979 inhabitants, 965 patients (0.22%) were diagnosed with COVID-19 infection, and 210 (21.8%) were under ACEI or ARB treatment at the time of diagnosis. Treatment with ACEI/ARB (combined and individually) had no effect on mortality (OR, 0.62; 95%CI, 0.17-2.26; P=.486), heart failure (OR, 1.37; 95%CI, 0.39-4.77; P=.622), hospitalization rate (OR, 0.85; 95%CI, 0.45-1.64; P=.638), ICU admission (OR, 0.87; 95%CI, 0.30-2.50; P=.798), or major acute cardiovascular events (OR, 1.06; 95%CI, 0.39-2.83; P=.915). This neutral effect remained in a subgroup analysis of patients requiring hospitalization. CONCLUSIONS: Previous treatment with ACEI/ARB in patients with COVID-19 had no effect on mortality, heart failure, requirement for hospitalization, or ICU admission. Withdrawal of ACEI/ARB in patients testing positive for COVID-19 would not be justified, in line with current recommendations of scientific societies and government agencies.", "qid": 20, "docid": "6kzrc2ud", "rank": 26, "score": 0.9120092391967773}, {"content": "Title: Inhibitors of the renin-angiotensin system: The potential role in the pathogenesis of COVID-19 Content: Coronavirus disease 2019 (COVID-19), which initially began in China, has spread to other countries of Asia, Europe, America, Africa and Oceania, with the number of confirmed cases and suspected cases increasing each day. According to recently published research, it was found that the majority of the severe cases were elderly, and many of them had at least one chronic disease, especially cardiovascular diseases. Angiotensin-converting enzyme inhibitors/angiotensin receptor blockers (ACEIs/ARBs) are the most widely used drugs for cardiovascular diseases. The clinical effect of ACEIs/ARBs on patients with COVID-19 is still uncertain. This paper describes their potential role in the pathogenesis of COVID-19, which may provide useful in the advice of cardiologists and physicians.", "qid": 20, "docid": "g4d4bdw0", "rank": 27, "score": 0.9118149280548096}, {"content": "Title: Inhibitors of the renin-angiotensin system: The potential role in the pathogenesis of COVID-19. Content: Coronavirus disease 2019 (COVID-19), which initially began in China, has spread to other countries of Asia, Europe, America, Africa and Oceania, with the number of confirmed cases and suspected cases increasing each day. According to recently published research, it was found that the majority of the severe cases were elderly, and many of them had at least one chronic disease, especially cardiovascular diseases. Angiotensin-converting enzyme inhibitors/angiotensin receptor blockers (ACEIs/ARBs) are the most widely used drugs for cardiovascular diseases. The clinical effect of ACEIs/ARBs on patients with COVID-19 is still uncertain. This paper describes their potential role in the pathogenesis of COVID-19, which may provide useful in the advice of cardiologists and physicians.", "qid": 20, "docid": "5a2zi2xp", "rank": 28, "score": 0.9118149280548096}, {"content": "Title: Impact of angiotensin-converting enzyme inhibitors and angiotensin receptor blockers on COVID-19 in a western population. CARDIOVID registry Content: ABSTRACT Introduction and objectives: Coronavirus disease (COVID-19) has been designated a global pandemic by the World Health Organization. It is unclear whether previous treatment with angiotensin-converting enzyme inhibitors (ACEI) and angiotensin receptor blockers (ARB) affects the prognosis of COVID-19 patients. The aim of this study was to evaluate the clinical implications of previous treatment with ACEI/ARB on the prognosis of patients with COVID-19 infection. Methods: Single-center, retrospective, observational cohort study based on all the inhabitants of our health area. Analyses of main outcomes (mortality, heart failure, hospitalization, intensive care unit [ICU] admission, and major acute cardiovascular events [a composite of mortality and heart failure]) were adjusted by multivariate logistic regression and propensity score matching models. Results: Of the total population, 447 979 inhabitants, 965 patients (0.22%) were diagnosed with COVID-19 infection, and 210 (21.8%) were under ACEI or ARB treatment at the time of diagnosis. Treatment with ACEI/ARB (combined and individually) had no effect on mortality (OR, 0.62; 95%CI, 0.17-2.26; P = .486), heart failure (OR, 1.37; 95%CI, 0.39-4.77; P = .622), hospitalization rate (OR, 0.85; 95%CI, 0.45-1.64; P = .638), ICU admission (OR, 0.87; 95%CI, 0.30-2.50; P = .798), or major acute cardiovascular events (OR, 1.06; 95%CI, 0.39-2.83; P = .915). This neutral effect remained in a subgroup analysis of patients requiring hospitalization. Conclusions: Previous treatment with ACEI/ARB in patients with COVID-19 had no effect on mortality, heart failure, requirement for hospitalization, or ICU admission. Withdrawal of ACEI/ARB in patients testing positive for COVID-19 would not be justified, in line with current recommendations of scientific societies and government agencies.", "qid": 20, "docid": "utgnwox8", "rank": 29, "score": 0.9111510515213013}, {"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": 30, "score": 0.9081456661224365}, {"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": 31, "score": 0.9071716070175171}, {"content": "Title: Compliance of Antihypertensive Medication and Risk of Coronavirus Disease 2019: a Cohort Study Using Big Data from the Korean National Health Insurance Service Content: BACKGROUND: There is a controversy whether it is safe to continue renin-angiotensin system blockers in patients with coronavirus disease 2019 (COVID-19). We analyzed big data to investigate whether angiotensin-converting enzyme inhibitors and/or angiotensin II receptor blockers have any significant effect on the risk of COVID-19. Population-based cohort study was conducted based on the prescription data from nationwide health insurance records. METHODS: We investigated the 1,374,381 residents aged \u2265 40 years living in Daegu, the epicenter of the COVID-19 outbreak, between February and March 2020. Prescriptions of antihypertensive medication during the year before the outbreak were extracted from the National Health Insurance Service registry. Medications were categorized by types and stratified by the medication possession ratios (MPRs) of antihypertensive medications after controlling for the potential confounders. The risk of COVID-19 was estimated using a difference in difference analysis. RESULTS: Females, older individuals, low-income earners, and recently hospitalized patients had a higher risk of infection. Patients with higher MPRs of antihypertensive medications had a consistently lower risk of COVID-19 than those with lower MPRs of antihypertensive medications and non-users. Among patients who showed complete compliance, there was a significantly lower risk of COVID-19 for those prescribed angiotensin II receptor blockers (relative risk [RR], 0.751; 95% confidence interval [CI], 0.587\u20130.960) or calcium channel blockers (RR, 0.768; 95% CI, 0.601\u20130.980). CONCLUSION: Renin-angiotensin system blockers or other antihypertensive medications do not increase the risk of COVID-19. Patients should not stop antihypertensive medications, including renin-angiotensin system blockers, because of concerns of COVID-19.", "qid": 20, "docid": "pnk1tt3w", "rank": 32, "score": 0.907120943069458}, {"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": 20, "docid": "wxpfg25n", "rank": 33, "score": 0.9068661332130432}, {"content": "Title: Compliance of Antihypertensive Medication and Risk of Coronavirus Disease 2019: a Cohort Study Using Big Data from the Korean National Health Insurance Service Content: BACKGROUND: There is a controversy whether it is safe to continue renin-angiotensin system blockers in patients with coronavirus disease 2019 (COVID-19). We analyzed big data to investigate whether angiotensin-converting enzyme inhibitors and/or angiotensin II receptor blockers have any significant effect on the risk of COVID-19. Population-based cohort study was conducted based on the prescription data from nationwide health insurance records. METHODS: We investigated the 1,374,381 residents aged &#8805; 40 years living in Daegu, the epicenter of the COVID-19 outbreak, between February and March 2020. Prescriptions of antihypertensive medication during the year before the outbreak were extracted from the National Health Insurance Service registry. Medications were categorized by types and stratified by the medication possession ratios (MPRs) of antihypertensive medications after controlling for the potential confounders. The risk of COVID-19 was estimated using a difference in difference analysis. RESULTS: Females, older individuals, low-income earners, and recently hospitalized patients had a higher risk of infection. Patients with higher MPRs of antihypertensive medications had a consistently lower risk of COVID-19 than those with lower MPRs of antihypertensive medications and non-users. Among patients who showed complete compliance, there was a significantly lower risk of COVID-19 for those prescribed angiotensin II receptor blockers (relative risk [RR], 0.751; 95% confidence interval [CI], 0.587-0.960) or calcium channel blockers (RR, 0.768; 95% CI, 0.601-0.980). CONCLUSION: Renin-angiotensin system blockers or other antihypertensive medications do not increase the risk of COVID-19. Patients should not stop antihypertensive medications, including renin-angiotensin system blockers, because of concerns of COVID-19.", "qid": 20, "docid": "7xzlcsbv", "rank": 34, "score": 0.9068100452423096}, {"content": "Title: Use of angiotensin-converting enzyme inhibitors and angiotensin II receptor blockers in context of COVID-19 outbreak: a retrospective analysis Content: The possible effects of angiotensin-converting enzyme inhibitors (ACEIs) or angiotensin II receptor blockers (ARBs) on COVID-19 disease severity have generated considerable debate. We performed a single-center, retrospective analysis of hospitalized adult COVID-19 patients in Wuhan, China, who had definite clinical outcome (dead or discharged) by February 15, 2020. Patients on anti-hypertensive treatment with or without ACEI/ARB were compared on their clinical characteristics and outcomes. The medical records from 702 patients were screened. Among the 101 patients with a history of hypertension and taking at least one anti-hypertensive medication, 40 patients were receiving ACEI/ARB as part of their regimen, and 61 patients were on antihypertensive medication other than ACEI/ARB. We observed no statistically significant differences in percentages of in-hospital mortality (28% vs. 34%, P = 0.46), ICU admission (20% vs. 28%, P = 0.37) or invasive mechanical ventilation (18% vs. 26%, P = 0.31) between patients with or without ACEI/ARB treatment. Further multivariable adjustment of age and gender did not provide evidence for a significant association between ACEI/ARB treatment and severe COVID-19 outcomes. Our findings confirm the lack of an association between chronic receipt of renin-angiotensin system antagonists and severe outcomes of COVID-19. Patients should continue previous anti-hypertensive therapy until further evidence is available.", "qid": 20, "docid": "hfnqcw5d", "rank": 35, "score": 0.9065664410591125}, {"content": "Title: A systematic review and meta-analysis to evaluate the clinical outcomes in COVID-19 patients on angiotensin-converting enzyme inhibitors or angiotensin receptor blockers Content: INTRODUCTION: Angiotensin-converting enzyme inhibitors (ACEIs) and angiotensin receptor blockers (ARBs) share their target receptor site with the SARS-CoV-2 virus, that may cause ACE2 receptor up-regulation 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 a need for an updated systematic review and meta-analysis of the latest clinical studies. METHODS AND RESULTS: 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 ACEIs and/or ARBs, and a meta-analysis was performed. A total of 16 studies were included for the review and meta-analysis. There were conflicting findings reported in the rates of severity and mortality in several studies. In a pooled analysis of four studies, there was a statistically non-significant association of ACEI/ARB use with lower odds of developing severe disease vs. non-users [odds ratio (OR) = 0.81, 95% confidence interval (CI): 0.41\u20131.58, I(2)=50.52, P-value = 0.53). In a pooled analysis of six studies, there was a statistically non-significant association of ACEI/ARB use with lower odds of mortality as compared with non-users (OR = 0.86, 95% CI = 0.53\u20131.41, I(2) = 79.12, P-value = 0.55). CONCLUSION: It is concluded that ACEIs and ARBs should be continued in COVID-19 patients, reinforcing the recommendations made by several medical societies. Additionally, the individual patient factors such as ACE2 polymorphisms which might confer higher risk of adverse outcomes need to be evaluated further.", "qid": 20, "docid": "s4ty52kb", "rank": 36, "score": 0.9060146808624268}, {"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": 37, "score": 0.9060083627700806}, {"content": "Title: A systematic review and meta-analysis to evaluate the clinical outcomes in COVID-19 patients on angiotensin-converting enzyme inhibitors or angiotensin receptor blockers Content: INTRODUCTION: Angiotensin-converting enzyme inhibitors (ACEIs) and angiotensin receptor blockers (ARBs) share their target receptor site with the SARS-CoV-2 virus, that may cause ACE2 receptor up-regulation 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 a need for an updated systematic review and meta-analysis of the latest clinical studies. METHODS AND RESULTS: 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 ACEIs and/or ARBs, and a meta-analysis was performed. A total of 16 studies were included for the review and meta-analysis. There were conflicting findings reported in the rates of severity and mortality in several studies. In a pooled analysis of four studies, there was a statistically non-significant association of ACEI/ARB use with lower odds of developing severe disease vs. non-users [odds ratio (OR) = 0.81, 95% confidence interval (CI): 0.41-1.58, I2=50.52, P-value = 0.53). In a pooled analysis of six studies, there was a statistically non-significant association of ACEI/ARB use with lower odds of mortality as compared with non-users (OR = 0.86, 95% CI = 0.53-1.41, I2 = 79.12, P-value = 0.55). CONCLUSION: It is concluded that ACEIs and ARBs should be continued in COVID-19 patients, reinforcing the recommendations made by several medical societies. Additionally, the individual patient factors such as ACE2 polymorphisms which might confer higher risk of adverse outcomes need to be evaluated further.", "qid": 20, "docid": "lk7vkbav", "rank": 38, "score": 0.9058003425598145}, {"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": 39, "score": 0.9050172567367554}, {"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": 40, "score": 0.9049906730651855}, {"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": 41, "score": 0.9047350287437439}, {"content": "Title: The effect of RAS blockers on the clinical characteristics of COVID-19 patients with hypertension Content: Background: Coronavirus disease 2019 (COVID-19), caused by a novel coronavirus (designated as SARS-CoV-2) has become a pandemic worldwide. Based on the current reports, hypertension may be associated with increased risk of sever condition in hospitalized COVID-19 patients. Angiotensin-converting enzyme 2 (ACE2) was recently identified to functional receptor of SARS-CoV-2. Previous experimental data revealed ACE2 level was increased following treatment with ACE inhibitors (ACEIs) and angiotensin receptor blockers (ARBs). Currently doctors concern whether these commonly used renin-angiotensin system (RAS) blockers-ACEIs/ARBs may increase the severity of COVID-19. Methods: We extracted data regarding 50 hospitalized hypertension patients with laboratory confirmed COVID-19 in the Renmin Hospital of Wuhan University from Feb 7 to Mar 03, 2020. These patients were grouped into RAS blockers group (Group A, n=20) and non-RAS blockers group (Group B, n=30) according to the basic blood pressure medications. All patients continued to use pre-admission antihypertensive drugs. Clinical severity (symptoms, laboratory and chest CT findings, etc.), clinical course, and short time outcome were analyzed after hospital admission. Results: Ten (50%) and seventeen (56.7%) of the Group A and Group B participants were males (P=0.643), and the average age was 52.65\u00b113.12 and 67.77\u00b112.84 years (P=0.000), respectively. The blood pressure of both groups was under effective control. There was no significant difference in clinical severity, clinical course and in-hospital mortality between Group A and Group B. Serum cardiac troponin I (cTnI) (P=0.03), and N-terminal (NT)-pro hormone BNP (NT-proBNP) (P=0.04) showed significant lower level in Group A than in Group B. But the patients with more than 0.04ng/mL or elevated NT-proBNP level had no statistical significance between the two groups. In patients over 65 years or under 65 years, cTnI or NT-proBNP level showed no difference between the two groups. Conclusions: We observed there was no obvious difference in clinical characteristics between RAS blockers and non-RAS blockers groups. These data suggest ACEIs/ARBs may have few effects on increasing the clinical severe conditions of COVID-19.", "qid": 20, "docid": "gm9564re", "rank": 42, "score": 0.9040608406066895}, {"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": 43, "score": 0.9032812118530273}, {"content": "Title: Review of evidence on using ACEi and ARBs in patients with hypertension and COVID-19 Content: COVID-19 has recently become a major pandemic with associated socioeconomic dimensions. Mortality statistics suggest that COVID-19 is more lethal in aged patients with comorbid conditions including hypertension. There is ongoing debate about whether the use of angiotensin converting enzyme (ACE) inhibitors (ACEi) and angiotensin receptor blockers (ARBs) are useful or hazardous in patients with COVID-19, with both narratives supported by researchers with different hypotheses. The researchers supporting the use of these medications believe ACE2 functional blockers may block cellular entry of the SARS-CoV-2 virus and thus improve patient outcomes. The counter viewpoint argues that continuous use of these drugs results in hyperexpression of ACE2 receptors on respiratory epithelium allowing easier SARS-CoV-2 intracellular entry, resulting in enhanced viral replication and tissue damage. This short review discusses the available research on the subject with the objective to consolidate data to allow formulation of recommendations on their use or otherwise. Moreover, the authors also suggest areas for future research on the subject.", "qid": 20, "docid": "2jiu9v0o", "rank": 44, "score": 0.903264045715332}, {"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": 45, "score": 0.9031087160110474}, {"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": 46, "score": 0.902435302734375}, {"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": 47, "score": 0.9016399383544922}, {"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": 48, "score": 0.9016247987747192}, {"content": "Title: Association of Renin Angiotensin System Blockers with Outcomes in Patients with Covid-19: A Systematic Review and Meta-analysis Content: Background: Patients with cardiovascular disease are at increased risk of critical illness and mortality from Covid-19 disease. Conflicting findings have raised concerns regarding the association of angiotensin converting enzyme inhibitors (ACEI) and angiotensin receptor blockers (ARBs) use with likelihood or severity of infection during this pandemic. Objective: To study the cumulative evidence for association of ACEI/ARB use with outcomes among patients with confirmed Covid-19. Methods: The MEDLINE and EMBASE databases were thoroughly searched from November 01, 2019 to May 15, 2020 for studies reporting on outcomes based on ACEI/ARB use in patients with confirmed Covid-19. Preferred reporting items for systematic review and meta-analysis guidelines were used for the present study. Relevant data was collected and pooled odds ratios (OR) with 95% confidence intervals (CI) were calculated using random-effects model. Main Outcome measures: In-hospital mortality was the primary end of interest. Second end-point was severe or critical illness defined as either need for intensive care unit, invasive mechanical ventilation, or mortality. Results: Fifteen studies with total of 23,822 patients (N ACEI/ARB=6,650) were included in the present analysis. Overall, prevalence of ACEI/ARB use ranged from 7.7% to 46.2% across studies. Among 10 studies, patients using ACEI/ARB had similar odds of mortality [OR 1.03 (0.69-1.55)] and severe or critical illness [1.18 (0.91-1.54)] compared to those not on ACEI/ARB. In an analysis restricted to patients with hypertension, ACEI/ARB use was associated with significantly lower mortality [0.64 (0.45-0.89)], while the odds of severe/critical illness [0.76(0.52-1.12); p=0.16] remained non-significant compared with non-ACEI/ARB users. Conclusion: There is no evidence for increased risk of severe illness or mortality in patients using ACEI/ARB compared with non-users. In patients with hypertension, ACE/ARB use might be associated with reduced mortality, however these findings need to be confirmed in prospective randomized controlled trials.", "qid": 20, "docid": "6vajr6w7", "rank": 49, "score": 0.9013198614120483}, {"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": 50, "score": 0.9011178016662598}, {"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": 51, "score": 0.9008442163467407}, {"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": 52, "score": 0.9006444215774536}, {"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": 53, "score": 0.9004377722740173}, {"content": "Title: Evidence for Use or Disuse of Renin-Angiotensin System Modulators in Patients Having COVID-19 With an Underlying Cardiorenal Disorder Content: Coronavirus disease 19 (COVID-19) originated in Wuhan, China, in December 2019 has been declared pandemic by World Health Organization due to an exponential rise in the number of infected and deceased persons across the globe. Emerging reports suggest that susceptibility and mortality rates are higher in patients with certain comorbidities when compared to the average population. Cardiovascular diseases and diabetes are important risk factors for a lethal outcome of COVID-19. Extensive research ensuing the outbreak of coronavirus-related severe acute respiratory syndrome in the year 2003, and COVID-19 recently revealed a role of renin-angiotensin system (RAS) components in the entry of coronavirus wherein angiotensin-converting enzyme 2 (ACE2) had garnered the significant attention. This raises the question whether the use of RAS inhibitors, the backbone of treatment of cardiovascular, neurovascular, and kidney diseases could increase the susceptibility for coronavirus infection or unfortunate outcomes of COVID-19. Thus, currently, there is a lack of consensus regarding the effects of RAS inhibitors in such patients. Moreover, expert bodies like American Heart Association, American College of Cardiology, and so on have now released official statements that RAS inhibitors must be continued, unless suggested otherwise by a physician. In this brief review, we will elaborate on the role of RAS and ACE2 in pathogenesis of COVID-19. Moreover, we will discuss the potential effect of the use and disuse of RAS inhibitors in patients having COVID-19 with cardiometabolic comorbidities.", "qid": 20, "docid": "lhwkthzx", "rank": 54, "score": 0.900323212146759}, {"content": "Title: Evidence for Use or Disuse of Renin-Angiotensin System Modulators in Patients Having COVID-19 With an Underlying Cardiorenal Disorder. Content: Coronavirus disease 19 (COVID-19) originated in Wuhan, China, in December 2019 has been declared pandemic by World Health Organization due to an exponential rise in the number of infected and deceased persons across the globe. Emerging reports suggest that susceptibility and mortality rates are higher in patients with certain comorbidities when compared to the average population. Cardiovascular diseases and diabetes are important risk factors for a lethal outcome of COVID-19. Extensive research ensuing the outbreak of coronavirus-related severe acute respiratory syndrome in the year 2003, and COVID-19 recently revealed a role of renin-angiotensin system (RAS) components in the entry of coronavirus wherein angiotensin-converting enzyme 2 (ACE2) had garnered the significant attention. This raises the question whether the use of RAS inhibitors, the backbone of treatment of cardiovascular, neurovascular, and kidney diseases could increase the susceptibility for coronavirus infection or unfortunate outcomes of COVID-19. Thus, currently, there is a lack of consensus regarding the effects of RAS inhibitors in such patients. Moreover, expert bodies like American Heart Association, American College of Cardiology, and so on have now released official statements that RAS inhibitors must be continued, unless suggested otherwise by a physician. In this brief review, we will elaborate on the role of RAS and ACE2 in pathogenesis of COVID-19. Moreover, we will discuss the potential effect of the use and disuse of RAS inhibitors in patients having COVID-19 with cardiometabolic comorbidities.", "qid": 20, "docid": "cjrji0ev", "rank": 55, "score": 0.9003231525421143}, {"content": "Title: Angiotensin II Receptor Blockers and Angiotensin-Converting Enzyme Inhibitors Usage is Associated with Improved Inflammatory Status and Clinical Outcomes in COVID-19 Patients With Hypertension Content: With the capability of inducing elevated expression of ACE2, the cellular receptor for SARS-CoV-2, angiotensin II receptor blockers or angiotensin-converting enzyme inhibitors (ARBs/ACEIs) treatment may have a controversial role in both facilitating virus infection and reducing pathogenic inflammation. We aimed to evaluate the correlation of ARBs/ACEIs usage with the pathogenesis of COVID-19 in a retrospective, single-center study. 126 COVID-19 patients with preexisting hypertension at Hubei Provincial Hospital of Traditional Chinese Medicine (HPHTCM) in Wuhan from January 5 to February 22, 2020 were retrospectively allocated to ARBs/ACEIs group (n=43) and non-ARBs/ACEIs group (n=83) according to their antihypertensive medication. 125 age- and sex-matched COVID-19 patients without hypertension were randomly selected as non-hypertension controls. In addition, the medication history of 1942 hypertension patients that were admitted to HPHTCM from November 1 to December 31, 2019 before 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/ACEIs usage in hypertension patients with or without COVID-19 were comparable. Among COVID-19 patients with hypertension, those received either ARBs/ACEIs or non-ARBs/ACEIs had comparable blood pressure. However, ARBs/ACEIs group had significantly lower concentrations of CRP (p=0.049) and procalcitonin (PCT, p=0.008). Furthermore, much lower proportion of critical patients (9.3% vs 22.9%; p=0.061), and a lower death rate (4.7% vs 13.3%; p=0.216) were observed in ARBs/ACEIs group than non-ARBs/ACEIs group, although these differences failed to reach statistical significance. Our findings thus support the use of ARBs/ACEIs in COVID-19 patients with preexisting hypertension.", "qid": 20, "docid": "mwttkclk", "rank": 56, "score": 0.8997520804405212}, {"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": 57, "score": 0.899560272693634}, {"content": "Title: COVID-19 and Angiotensin-Converting Enzyme Inhibitor/Angiotensin-Receptor Blocker Therapy Content: Mackey and colleagues reported a systematic review that found high-certainty evidence that angiotensin-converting enzyme inhibitors and angiotensin-receptor blockers are not associated with greater illness severity in patients with COVID-19. The editorialist discusses the findings and emphasizes that, unless further data show otherwise, clinicians should continue to prescribe these drugs for their standard indications in patients with COVID-19.", "qid": 20, "docid": "7ae0galy", "rank": 58, "score": 0.8995414972305298}, {"content": "Title: ARB/ACEI use and severe COVID-19: a nationwide case-control study Content: Background: Angiotensin receptor blockers (ARBs) and angiotensin converting enzyme inhibitors (ACEIs) have anti-inflammatory effects. Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) uses the membrane protein angiotensin-converting enzyme 2 (ACE2), which is increased by ARB/ACEI treatment, as a cell entry receptor. Therefore, the use of ARBs/ACEIs for COVID-19 remains controversial. Methods: A retrospective case-control study was conducted using COVID-19 patients previously diagnosed with hypertension before COVID-19 onset. The primary outcome was severe infection or all-cause mortality. Cases included ARB/ACEI use for 30 days or longer during the 6 months before COVID-19 onset. Primary controls included antihypertensive use other than ARBs/ACEIs (narrow control); secondary controls included all other hypertension patients (broad control). We investigated ARB/ACEI association with outcomes in general and by subgroups (age, sex, and presence of diabetes) using logistic regression models with propensity score matching. Findings: Of 234427 suspected COVID-19 patients we screened, 1585 hypertension patients were analyzed. In the 892 cases, 428 narrow controls, and 693 broad controls, severe infection or death occurred in 8.6%, 22.2%, and 16.7%, respectively. ARB/ACEI use was associated with a reduced risk of severe infection or death relative to the narrow control group (adjusted odds ratio [aOR] 0.43, 95% confidence interval [CI] 0.28-0.65) and broad control group (aOR 0.49, 95% CI 0.33-0.71). The association was smaller for newly diagnosed hypertension patients (aOR 0.11, 95% CI 0.03-0.42 compared to narrow control group). ARB/ACEI protective effects against severe infection or death were significantly observed in male and diabetic patients. Interpretation: ARB/ACEI use was associated with a lower risk of severe infection or mortality compared to other antihypertensives or ARB/ACEI nonuse.", "qid": 20, "docid": "vla7tt6s", "rank": 59, "score": 0.8993216753005981}, {"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": 60, "score": 0.8989928960800171}, {"content": "Title: Effects Of ARBs And ACEIs On Virus Infection, Inflammatory Status And Clinical Outcomes In COVID-19 Patients With Hypertension: A Single Center Retrospective Study. Content: With the capability of inducing elevated expression of ACE2, the cellular receptor for SARS-CoV-2, angiotensin II receptor blockers or angiotensin-converting enzyme inhibitors (ARBs/ACEIs) treatment may have a controversial role in both facilitating virus infection and reducing pathogenic inflammation. We aimed to evaluate the effects of ARBs/ACEIs on COVID-19 in a retrospective, single-center study. 126 COVID-19 patients with preexisting hypertension at Hubei Provincial Hospital of Traditional Chinese Medicine (HPHTCM) in Wuhan from January 5 to February 22, 2020 were retrospectively allocated to ARBs/ACEIs group (n=43) and non-ARBs/ACEIs group (n=83) according to their antihypertensive medication. 125 age- and sex-matched COVID-19 patients without hypertension were randomly selected as non-hypertension controls. In addition, the medication history of 1942 hypertension patients that were admitted to HPHTCM from November 1 to December 31, 2019 before 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/ACEIs usage in hypertension patients with or without COVID-19 were comparable. Among COVID-19 patients with hypertension, those received either ARBs/ACEIs or non-ARBs/ACEIs had comparable blood pressure. However, ARBs/ACEIs group had significantly lower concentrations of CRP (p=0.049) and procalcitonin (PCT, p=0.008). Furthermore, a lower proportion of critical patients (9.3% vs 22.9%; p=0.061), and a lower death rate (4.7% vs 13.3%; p=0.216) were observed in ARBs/ACEIs group than non-ARBs/ACEIs group, although these differences failed to reach statistical significance. Our findings thus support the use of ARBs/ACEIs in COVID-19 patients with preexisting hypertension.", "qid": 20, "docid": "yomcxz43", "rank": 61, "score": 0.8988396525382996}, {"content": "Title: O Efeito da Doen\u00e7a de Coronav\u00edrus 2019 nas Doen\u00e7as Cardiovasculares./ O Efeito da Doen\u00e7a de Coronav\u00edrus 2019 nas Doen\u00e7as Cardiovasculares./ The Effect of Coronavirus Disease 2019 on Cardiovascular Diseases Content: Coronavirus disease 2019 (COVID-19) is a global pandemic affecting the world, seen in more than 1,300,000 patients. COVID-19 acts through the angiotensin-converting enzyme 2 (ACE2) receptor. Cardiovascular comorbidities are more common with COVID-19, and nearly 10% of cases develop myocarditis (22% of critical patients). Further research is needed to continue or discontinue ACE inhibitors and angiotensin receptor blockers, which are essential in hypertension and heart failure in COVID-19. Intensive research is promising for the treatment and prevention of COVID-19.", "qid": 20, "docid": "uzmj8zki", "rank": 62, "score": 0.8977863788604736}, {"content": "Title: The Effect of Coronavirus Disease 2019 on Cardiovascular Diseases. Content: Coronavirus disease 2019 (COVID-19) is a global pandemic affecting the world, seen in more than 1,300,000 patients. COVID-19 acts through the angiotensin-converting enzyme 2 (ACE2) receptor. Cardiovascular comorbidities are more common with COVID-19, and nearly 10% of cases develop myocarditis (22% of critical patients). Further research is needed to continue or discontinue ACE inhibitors and angiotensin receptor blockers, which are essential in hypertension and heart failure in COVID-19. Intensive research is promising for the treatment and prevention of COVID-19.", "qid": 20, "docid": "a30ryzkj", "rank": 63, "score": 0.8977863788604736}, {"content": "Title: Association between renin-angiotensin system inhibitors and COVID-19 complications Content: AIMS: To describe the characteristics of patients hospitalized with COVID-19 (including their long-term at-home medication use), and compare them with regard to the course of the disease. To assess the association between renin-angiotensin system inhibitors (RASIs) and disease progression and critical outcomes. METHODS AND RESULTS: All consecutive hospitalized patients with laboratory-confirmed COVID-19 in a university hospital in Amiens (France) were included in this study. The primary composite endpoint was admission to an intensive care unit (ICU) or death before ICU admission. Univariable and multivariable logistic regression models were used to identify factors associated with the composite endpoint. Between 28 February 2020 and 30 March 2020, a total of 499 local patients tested positive for SARS-CoV-2. Of these, 231 were not hospitalized {males 33%; median [interquartile range (IQR)] age: 44 (32-54)}, and 268 were hospitalized [males 58%; median (IQR) age: 73 (61-84)]. A total of 116 patients met the primary endpoint: 47 died before ICU admission, and 69 were admitted to the ICU. Patients meeting the primary endpoint were more likely than patients not meeting the primary endpoint to have coronary heart disease and to have been taking RASIs; however, the two subsets of patients did not differ with regard to median age. After adjustment for other associated variables, the risk of meeting the composite endpoint was 1.73 times higher (odds ratio 1.73, 95% confidence interval 1.02-2.93) in patients treated at baseline with a RASI than in patients not treated with this drug class. This association was confirmed when the analysis was restricted to patients treated with antihypertensive agents. CONCLUSIONS: We highlighted a potential safety signal for RASIs, the long-term use of which was independently associated with a higher risk of severe COVID-19 and a poor outcome. Due to the widespread use of this important drug class, formal proof based on clinical trials is needed to better understand the association between RASIs and complications of COVID-19.", "qid": 20, "docid": "t8bryhs7", "rank": 64, "score": 0.897309422492981}, {"content": "Title: The use of renin angiotensin system inhibitor on mortality in patients with coronavirus disease 2019 (COVID-19): A systematic review and meta-analysis Content: BACKGROUND: and Aims; To investigate the association between use of angiotensin-converting enzyme inhibitor (ACEI)/angiotensin-receptor blocker (ARB) and outcomes of hypertensive COVID-19 patients, a systematic review and meta-analysis were performed. METHODS: We systematically searched PubMed, EuropePMC, ProQuest, and Cochrane Central Databases using the terms \"(COVID-19 OR SARS-CoV-2) AND (angiotensin converting enzyme OR angiotensin receptor blocker)\". The primary and second outcomes were mortality (non-survivor) and severe COVID-19, respectively. RESULTS: Totally, 7410 patients were included from 15 studies. Pooled analysis showed that the use of ACEI/ARB was not associated with mortality (OR 0.73 [0.38, 1.40], p = 0.34; I2: 81%) and severity (OR 1.03 [0.73, 1.45], p = 0.87; I2: 65%). Pooled adjusted OR showed no risk/benefit associated with ACEI/ARB use in terms of mortality (OR 0.83 [0.54, 1.27], p = 0.38; I2: 0%). Subgroup analysis showed that the use of ARB was associated with reduced mortality (OR 0.51 [0.29, 0.90], p = 0.02; I2: 22%) but not ACEI subgroup (OR 0.68 [0.39, 1.17], p = 0.16; I2: 0%). Meta-regression showed that the association between ACEI/ARB use and mortality in patients with COVID-19 do not varies by gender (p = 0.104). GRADE showed a very low certainty of evidence for effect of ACEI/ARB on mortality and severity. The certainty of evidence was very low for both ACEI and ARB subgroups. CONCLUSION: Administration of a renin angiotensin system (RAS) inhibitor, was not associated with increased mortality or severity of COVID-19 in patients with hypertension. Specifically, ARB and not ACEI use, was associated with lower mortality.", "qid": 20, "docid": "kfhfwq5e", "rank": 65, "score": 0.8972328901290894}, {"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": 20, "docid": "pknvtj3q", "rank": 66, "score": 0.897175669670105}, {"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": 67, "score": 0.897022008895874}, {"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": 68, "score": 0.8967994451522827}, {"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": 69, "score": 0.8966777324676514}, {"content": "Title: The use of renin angiotensin system inhibitor on mortality in patients with coronavirus disease 2019 (COVID-19): A systematic review and meta-analysis Content: BACKGROUND: and Aims; To investigate the association between use of angiotensin-converting enzyme inhibitor (ACEI)/angiotensin-receptor blocker (ARB) and outcomes of hypertensive COVID-19 patients, a systematic review and meta-analysis were performed. METHODS: We systematically searched PubMed, EuropePMC, ProQuest, and Cochrane Central Databases using the terms \u201c(COVID-19 OR SARS-CoV-2) AND (angiotensin converting enzyme OR angiotensin receptor blocker)\u201d. The primary and second outcomes were mortality (non-survivor) and severe COVID-19, respectively. RESULTS: Totally, 7410 patients were included from 15 studies. Pooled analysis showed that the use of ACEI/ARB was not associated with mortality (OR 0.73 [0.38, 1.40], p = 0.34; I(2): 81%) and severity (OR 1.03 [0.73, 1.45], p = 0.87; I(2): 65%). Pooled adjusted OR showed no risk/benefit associated with ACEI/ARB use in terms of mortality (OR 0.83 [0.54, 1.27], p = 0.38; I(2): 0%). Subgroup analysis showed that the use of ARB was associated with reduced mortality (OR 0.51 [0.29, 0.90], p = 0.02; I(2): 22%) but not ACEI subgroup (OR 0.68 [0.39, 1.17], p = 0.16; I(2): 0%). Meta-regression showed that the association between ACEI/ARB use and mortality in patients with COVID-19 do not varies by gender (p = 0.104). GRADE showed a very low certainty of evidence for effect of ACEI/ARB on mortality and severity. The certainty of evidence was very low for both ACEI and ARB subgroups. CONCLUSION: Administration of a renin angiotensin system (RAS) inhibitor, was not associated with increased mortality or severity of COVID-19 in patients with hypertension. Specifically, ARB and not ACEI use, was associated with lower mortality.", "qid": 20, "docid": "ax5gd3fq", "rank": 70, "score": 0.8965859413146973}, {"content": "Title: Antihypertensive medication uses and serum ACE2 levels: ACEIs/ARBs treatment does not raise serum levels of ACE2 Content: IMPORTANCE: Recent reports have shown that hypertension is the most common comorbidity associated with mortality in the current coronavirus disease 2019 (COVID-19). This has been related to the use of angiotensin-converting enzyme inhibitors (ACEIs) and angiotensin II receptor blockers (ARBs) as animal studies indicate that these medications increase levels of ACE2, the cellular entry point for the coronavirus SARS-CoV-2. This has prompted clinicians to recommend discontinuing ACEIs and ARBs. OBJECTIVE: To examine the effect of ACEIs or ARBs treatment on serum levels of ACE2 and other key enzymes in the renin-angiotensin system (RAS). DESIGN, SETTING, AND PARTICIPANTS: A single center population-based study of 5457 Icelanders from the Age, Gene/Environment Susceptibility Reykjavik Study (AGES-RS) of the elderly (mean age 75\u00b16 years) stratified by ACEIs (N = 699) or ARBs (N = 753) treatment. MAIN OUTCOMES AND MEASURES: The AGES-RS study population was stratified by ACEIs and ARBs medication use and compared for age, body mass index (BMI) (kg/m(2)), hypertension and type 2 diabetes (T2D) as well as serum levels of renin, ACE and ACE2. RESULTS: While renin and ACE levels were significantly raised in serum of individuals on ACEIs or ARBs treatments, the ACE2 levels remained unaffected. CONCLUSIONS AND RELEVANCE: Treatment with ACEIs or ARBs does not raise ACE2 levels in serum. Therefore, the present study does not support the proposed discontinuation of these medications among patients affected with COVID-19.", "qid": 20, "docid": "d6arv0nl", "rank": 71, "score": 0.8962979316711426}, {"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": 72, "score": 0.8957955837249756}, {"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": 73, "score": 0.895659327507019}, {"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": 74, "score": 0.8955230712890625}, {"content": "Title: Treatment with ACE inhibitors or ARBs and risk of severe/lethal COVID-19: a meta-analysis Content: OBJECTIVE: It has been hypothesised that the use of ACE inhibitors and angiotensin receptor blockers (ARBs) might either increase or reduce the risk of severe or lethal COVID-19. The findings from the available observational studies varied, and summary estimates are urgently needed to elucidate whether these drugs should be suspended during the pandemic, or patients and physicians should be definitely reassured. This meta-analysis of adjusted observational data aimed to summarise the existing evidence on the association between these medications and severe/lethal COVID-19. METHODS: We searched MedLine, Scopus and preprint repositories up to 8 June 2020 to retrieve cohort or case-control studies comparing the risk of severe/fatal COVID-19 (either mechanical ventilation, intensive care unit admission or death), among hypertensive subjects treated with: (1) ACE inhibitors, (2) ARBs and (3) both, versus untreated subjects. Data were combined using a random-effect generic inverse variance approach. RESULTS: Ten studies, enrolling 9890 hypertensive subjects were included in the analyses. Compared with untreated subjects, those using either ACE inhibitors or ARBs showed a similar risk of severe or lethal COVID-19 (summary OR: 0.90; 95% CI 0.65 to 1.26 for ACE inhibitors; 0.92; 95% CI 0.75 to 1.12 for ARBs). The results did not change when both drugs were considered together, when death was the outcome and excluding the studies with significant, divergent results. CONCLUSION: The present meta-analysis strongly supports the recommendation of several scientific societies to continue ARBs or ACE inhibitors for all patients, unless otherwise advised by their physicians who should thus be reassured.", "qid": 20, "docid": "lbp6fquk", "rank": 75, "score": 0.8953066468238831}, {"content": "Title: Association between renin\u2013angiotensin system inhibitors and COVID-19 complications Content: AIMS: To describe the characteristics of patients hospitalized with COVID-19 (including their long-term at-home medication use), and compare them with regard to the course of the disease. To assess the association between renin\u2013angiotensin system inhibitors (RASIs) and disease progression and critical outcomes. METHODS AND RESULTS: All consecutive hospitalized patients with laboratory-confirmed COVID-19 in a university hospital in Amiens (France) were included in this study. The primary composite endpoint was admission to an intensive care unit (ICU) or death before ICU admission. Univariable and multivariable logistic regression models were used to identify factors associated with the composite endpoint. Between 28 February 2020 and 30 March 2020, a total of 499 local patients tested positive for SARS-CoV-2. Of these, 231 were not hospitalized {males 33%; median [interquartile range (IQR)] age: 44 (32\u201354)}, and 268 were hospitalized [males 58%; median (IQR) age: 73 (61\u201384)]. A total of 116 patients met the primary endpoint: 47 died before ICU admission, and 69 were admitted to the ICU. Patients meeting the primary endpoint were more likely than patients not meeting the primary endpoint to have coronary heart disease and to have been taking RASIs; however, the two subsets of patients did not differ with regard to median age. After adjustment for other associated variables, the risk of meeting the composite endpoint was 1.73 times higher (odds ratio 1.73, 95% confidence interval 1.02\u20132.93) in patients treated at baseline with a RASI than in patients not treated with this drug class. This association was confirmed when the analysis was restricted to patients treated with antihypertensive agents. CONCLUSIONS: We highlighted a potential safety signal for RASIs, the long-term use of which was independently associated with a higher risk of severe COVID-19 and a poor outcome. Due to the widespread use of this important drug class, formal proof based on clinical trials is needed to better understand the association between RASIs and complications of COVID-19.", "qid": 20, "docid": "xf39pfa9", "rank": 76, "score": 0.8948967456817627}, {"content": "Title: ACE\u2010inhibitors and Angiotensin\u20102 Receptor Blockers are not associated with severe SARS\u2010COVID19 infection in a multi\u2010site UK acute Hospital Trust Content: AIMS: The SARS\u2010Cov2 virus binds to the ACE2 receptor for cell entry. It has been suggested that ACE\u2010inhibitors (ACEi) and Angiotensin\u20102 Blockers (ARB), which are commonly used in patients with hypertension or diabetes and may raise tissue ACE2 levels, could increase the risk of severe COVID19 infection. METHODS AND RESULTS: We evaluated this hypothesis in a consecutive cohort of 1200 acute inpatients with COVID19 at two hospitals with a multi\u2010ethnic catchment population in London (UK). The mean age was 68 \u00b1 17 years (57% male) and 74% of patients had at least 1 comorbidity. 415 patients (34.6%) reached the primary endpoint of death or transfer to a critical care unit for organ support within 21\u2010days of symptom onset. 399 patients (33.3%) were taking ACEi or ARB. Patients on ACEi/ARB were significantly older and had more comorbidities. The odds ratio (OR) for the primary endpoint in patients on ACEi and ARB, after adjustment for age, sex and co\u2010morbidities, was 0.63 (CI 0.47\u20130.84, p < 0.01). CONCLUSIONS: There was no evidence for increased severity of COVID19 disease 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\u2010analyses and randomised clinical trials. This article is protected by copyright. All rights reserved.", "qid": 20, "docid": "akancd4c", "rank": 77, "score": 0.8947708606719971}, {"content": "Title: Estimation of RAAS-Inhibitor effect on the COVID-19 outcome: A Meta-analysis Content: BACKGROUND AND RATIONALE: Some studies of hospitalized patients suggested that the risk of death and/or severe illness due to COVID-19 is not associated with the use of angiotensin-converting enzyme inhibitors (ACEIs) and/or angiotensin II receptor type 1 blockers (ARBs). Nevertheless, some controversy still exists and there is limited information of the ACEIs/ARBs effect size on COVID-19 prognosis. AIM AND METHODS: We aimed to measure the effect of ACEIs and/or ARBs on COVID-19 severe clinical illness by a meta-analysis. Literature search included all studies published since the COVID-19 outbreak began (December 2019) until May 9, 2020. We analyzed information from studies that included tested COVID-19 patients with arterial hypertension as comorbidity prior to hospital admission and history of taking ACEIs, ARBs, or ACEIs/ARBs. RESULTS: We included 16 studies that involved 24,676 COVID-19 patients, and we compared patients with critical (n = 4134) vs. non-critical (n = 20,542) outcomes. The overall assessment by estimating random effects shows that the use of ACEIs/ARBs is not associated with higher risk of in-hospital-death and/or severe illness among hypertensive patients with COVID-19 infection. On the contrary, effect estimate shows an overall protective effect of RAAS inhibitors/blockers (ACEIs, ARBs, and/or ACEIs/ARBs) with \u223c 23 % reduced risk f death and/or critical disease (OR: 0.768, 95%CI: 0.651-0.907, p=0.0018). The use of ACEIs (OR:0.652, 95%CI:0.478-0.891, p=0.0072) but not ACEIs/ARBs (OR:0.867, 95%CI:0.638-1.179, p =NS) or ARBs alone (OR:0.810, 95%CI:0.629-1.044, p=NS) may explain the overall protection displayed by RAAS intervention combined. CONCLUSION: RAAS inhibitors might be associated with better COVID-19 prognosis.", "qid": 20, "docid": "npzzycis", "rank": 78, "score": 0.8947250247001648}, {"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": 79, "score": 0.8939086198806763}, {"content": "Title: Estimation of Renin-Angiotensin-Aldosterone-System (RAAS)-Inhibitor effect on COVID-19 outcome: A Meta-analysis Content: BACKGROUND AND RATIONALE: Some studies of hospitalized patients suggested that the risk of death and/or severe illness due to COVID-19 is not associated with the use of angiotensin-converting enzyme inhibitors (ACEIs) and/or angiotensin II receptor type 1 blockers (ARBs). Nevertheless, some controversy still exists and there is limited information of the ACEIs/ARBs effect size on COVID-19 prognosis. AIM AND METHODS: We aimed to measure the effect of ACEIs and/or ARBs on COVID-19 severe clinical illness by a meta-analysis. Literature search included all studies published since the COVID-19 outbreak began (December 2019) until May 9, 2020. We analyzed information from studies that included tested COVID-19 patients with arterial hypertension as comorbidity prior to hospital admission and history of taking ACEIs, ARBs, or ACEIs/ARBs. RESULTS: We included 16 studies that involved 24,676 COVID-19 patients, and we compared patients with critical (n\u00e2\u0080\u00af=\u00e2\u0080\u00af4134) vs. non-critical (n\u00e2\u0080\u00af=\u00e2\u0080\u00af20,542) outcomes. The overall assessment by estimating random effects shows that the use of ACEIs/ARBs is not associated with higher risk of in-hospital-death and/or severe illness among hypertensive patients with COVID-19 infection. On the contrary, effect estimate shows an overall protective effect of RAAS inhibitors/blockers (ACEIs, ARBs, and/or ACEIs/ARBs) with \u00e2\u0088\u00bc 23 % reduced risk of death and/or critical disease (OR: 0.768, 95%CI: 0.651-0.907, p=0.0018). The use of ACEIs (OR:0.652, 95%CI:0.478-0.891, p=0.0072) but not ACEIs/ARBs (OR:0.867, 95%CI:0.638-1.179, p =NS) or ARBs alone (OR:0.810, 95%CI:0.629-1.044, p=NS) may explain the overall protection displayed by RAAS intervention combined. CONCLUSION: RAAS inhibitors might be associated with better COVID-19 prognosis.", "qid": 20, "docid": "1edsm58s", "rank": 80, "score": 0.8938660621643066}, {"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": 81, "score": 0.8935869336128235}, {"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": 82, "score": 0.8932861685752869}, {"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": 83, "score": 0.8932861685752869}, {"content": "Title: Could anti-hypertensive drug therapy affect the clinical prognosis of hypertensive patients with COVID-19 infection? Data from centers of southern Italy. Content: Background Coronavirus-19 (COVID-19) is the cause of a pandemic disease, with severe acute respiratory syndrome by binding target epithelial lung cells through angiotensin converting enzyme 2 (ACE2) in humans. Thus, hypertensive patients with COVID-19 could have worse prognosis. Indeed, angiotensin converting enzyme (ACEi) inhibitors and/or angiotensin receptor blockers (ARBs) may interfere with ACE2 expression/activity. Thus, hypertensive patients undergoing ACEi and/or ARBs drug therapy may be at a higher risk of contracting a serious COVID-19 infection and should be monitored. Moreover, in the present study we investigated the effects of ACEi vs. ARBs vs. calcium channel blockers on clinical outcomes as mechanical ventilation, Intensive Care Unit (ICU) admissions, heart injury and death in 62 hypertensive patients hospitalized for COVID-19 infection. Methods and Results The multicenter study was prospectively conducted at Department of Infectious Diseases of Sant'Anna Hospital of Caserta, and of University of Campania \"Luigi Vanvitelli\" of Naples, at Department of Advanced Surgical and Medical Sciences of University of Campania \"Luigi Vanvitelli\", Naples, and at General Medical Assistance Unit \"FIMG\", Naples, Italy. Lowest values of left ventricle ejection fraction predicted deaths (1.142; [1.008-1.294], p <0.05), while highest values of interleukin 6 (IL6) predicted the admission to ICU (1.617; [1.094-2.389]), mechanical ventilation (1.149; [1.082-1.219]), heart injuries (1.367; [1.054-1.772]) and deaths (4.742; [1.788-8.524]). ConclusionsAnti-hypertensive drugs didn't affect the prognosis in COVID-19 patients. Consequently, tailored anti-inflammatory and immune therapies in addition to chronic antihypertensive therapy, could prevent a worse prognosis, as well as improve the clinical outcomes in hypertensive patients with COVID-19 infection.", "qid": 20, "docid": "rbi4kg69", "rank": 84, "score": 0.8930611610412598}, {"content": "Title: Could anti-hypertensive drug therapy affect the clinical prognosis of hypertensive patients with COVID-19 infection? Data from centers of southern Italy Content: Background Coronavirus-19 (COVID-19) is the cause of a pandemic disease, with severe acute respiratory syndrome by binding target epithelial lung cells through angiotensin converting enzyme 2 (ACE2) in humans. Thus, hypertensive patients with COVID-19 could have worse prognosis. Indeed, angiotensin converting enzyme (ACEi) inhibitors and/or angiotensin receptor blockers (ARBs) may interfere with ACE2 expression/activity. Thus, hypertensive patients undergoing ACEi and/or ARBs drug therapy may be at a higher risk of contracting a serious COVID-19 infection and should be monitored. Moreover, in the present study we investigated the effects of ACEi vs. ARBs vs. calcium channel blockers on clinical outcomes as mechanical ventilation, Intensive Care Unit (ICU) admissions, heart injury and death in 62 hypertensive patients hospitalized for COVID-19 infection. Methods and Results The multicenter study was prospectively conducted at Department of Infectious Diseases of Sant'Anna Hospital of Caserta, and of University of Campania \"Luigi Vanvitelli\" of Naples, at Department of Advanced Surgical and Medical Sciences of University of Campania \"Luigi Vanvitelli\", Naples, and at General Medical Assistance Unit \"FIMG\", Naples, Italy. Lowest values of left ventricle ejection fraction predicted deaths (1.142; [1.008-1.294], p <0.05), while highest values of interleukin 6 (IL6) predicted the admission to ICU (1.617; [1.094-2.389]), mechanical ventilation (1.149; [1.082-1.219]), heart injuries (1.367; [1.054-1.772]) and deaths (4.742; [1.788-8.524]). ConclusionsAnti-hypertensive drugs didn't affect the prognosis in COVID-19 patients. Consequently, tailored anti-inflammatory and immune therapies in addition to chronic antihypertensive therapy, could prevent a worse prognosis, as well as improve the clinical outcomes in hypertensive patients with COVID-19 infection.", "qid": 20, "docid": "75apu1m4", "rank": 85, "score": 0.893061101436615}, {"content": "Title: The Lung, the Heart, the Novel Coronavirus, and the Renin-Angiotensin System; The Need for Clinical Trials Content: Angiotensin-converting enzyme 2 (ACE2) is the receptor for COVID-19 (SARs-CoV-2). ACE2 protects the lung and heart from acute respiratory distress syndrome (ARDS) and acute myocarditis and arrhythmias, because it breaks down Angiotensin II, which has inflammatory effects in the lung and heart as well as in the kidney. When SARS-CoV-2 binds to ACE2, it suppresses it, so this protective action of ACE2 is lost. Death from COVID-19 is due to ARDS and also heart failure and acute cardiac injury. Drugs that prevent the inflammatory actions of Angiotensin II (i.e., Angiotensin receptor blockers, ARBs) prevent acute lung injury caused by SARS-CoV. Clinical trials are underway to test the risks and benefits of ARBs and angiotensin-converting enzyme inhibitors (ACEIs) in COVID-19 patients requiring hospitalization. Other potential treatments are also discussed.", "qid": 20, "docid": "tj7z3ocr", "rank": 86, "score": 0.8928602933883667}, {"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": 87, "score": 0.8926651477813721}, {"content": "Title: Renin-angiotensin system inhibitors improve the clinical outcomes of COVID-19 patients with hypertension Content: The dysfunction of the renin-angiotensin system (RAS) has been observed in coronavirus infection disease (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 clinical outcomes remains unknown. COVID-19 patients with hypertension were enrolled to evaluate the effect of RAS inhibitors. We observed that patients receiving ACEI or ARB therapy had a lower rate of severe diseases and a trend toward a lower level of IL-6 in peripheral blood. In addition, ACEI or ARB therapy increased CD3 and CD8 T cell counts in peripheral blood and decreased the peak viral load compared to other antihypertensive drugs. This evidence supports the benefit of using ACEIs or ARBs to potentially contribute to the improvement of clinical outcomes of COVID-19 patients with hypertension.", "qid": 20, "docid": "wz28xxhn", "rank": 88, "score": 0.8925665616989136}, {"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": 0.8921552896499634}, {"content": "Title: Use of inhibitors of the renin angiotensin system and COVID-19 prognosis: a systematic review and meta-analysis Content: Background: controversy has arisen in the scientific community on whether the use of renin angiotensin system (RAS) inhibitors in the context of COVID-19 would be of benefit or harmful. A meta-analysis of eligible studies comparing the occurrence of severe and fatal COVID-19 in infected patients who were under treatment with angiotensin converting enzyme inhibitors (ACEI) or angiotensin receptor blockers (ARB) vs no treatment or other antihypertensives was conducted. Methods: PubMed, Google Scholar, the Cochrane Library, MedRxiv and BioRxiv were searched for relevant studies. Fixed-effect models or random-effect models were used depending on the heterogeneity between estimates. Results: a total of fifteen studies with 21,614 patients were included. The use of RAS inhibitors was associated with a non-significant 20% decreased risk of the composite outcome (death, admission to intensive care unit, mechanical ventilation requirement or progression to severe or critical pneumonia): RR 0.81 (95%CI: 0.63-1.04), p=0.10, I2=82%. In a subgroup analysis that included hypertensive subjects only, ACEI/ARB were associated with a 27% significant decrease in the risk of the composite outcome (RR 0.73 (95%CI: 0.56-0.96), p=0.02, I2=65%). Conclusion: the results of this pooled analysis suggest that the use of ACEI/ARB does not worsen the prognosis, and could even be protective in hypertensive subjects. Patients should continue these drugs during their COVID-19 illness.", "qid": 20, "docid": "lboa7rtn", "rank": 90, "score": 0.8921042680740356}, {"content": "Title: Treatment with ACE inhibitors or ARBs and risk of severe/lethal COVID-19: a meta-analysis. Content: OBJECTIVE It has been hypothesised that the use of ACE inhibitors and angiotensin receptor blockers (ARBs) might either increase or reduce the risk of severe or lethal COVID-19. The findings from the available observational studies varied, and summary estimates are urgently needed to elucidate whether these drugs should be suspended during the pandemic, or patients and physicians should be definitely reassured. This meta-analysis of adjusted observational data aimed to summarise the existing evidence on the association between these medications and severe/lethal COVID-19. METHODS We searched MedLine, Scopus and preprint repositories up to 8 June 2020 to retrieve cohort or case-control studies comparing the risk of severe/fatal COVID-19 (either mechanical ventilation, intensive care unit admission or death), among hypertensive subjects treated with: (1) ACE inhibitors, (2) ARBs and (3) both, versus untreated subjects. Data were combined using a random-effect generic inverse variance approach. RESULTS Ten studies, enrolling 9890 hypertensive subjects were included in the analyses. Compared with untreated subjects, those using either ACE inhibitors or ARBs showed a similar risk of severe or lethal COVID-19 (summary OR: 0.90; 95% CI 0.65 to 1.26 for ACE inhibitors; 0.92; 95% CI 0.75 to 1.12 for ARBs). The results did not change when both drugs were considered together, when death was the outcome and excluding the studies with significant, divergent results. CONCLUSION The present meta-analysis strongly supports the recommendation of several scientific societies to continue ARBs or ACE inhibitors for all patients, unless otherwise advised by their physicians who should thus be reassured.", "qid": 20, "docid": "9vywrvw3", "rank": 91, "score": 0.892015278339386}, {"content": "Title: Interactions of coronaviruses with ACE2, angiotensin II, and RAS inhibitors\u2014lessons from available evidence and insights into COVID-19 Content: The rapid spread of a novel coronavirus, severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), has led to an ongoing pandemic of coronavirus disease 2019 (COVID-19). Recently, angiotensin-converting enzyme 2 (ACE2) has been shown to be a functional receptor for SARS-CoV-2 to enter host target cells. Given that angiotensin receptor blockers (ARBs) and an ACE inhibitor (ACEI) upregulated ACE2 expression in animal studies, the concern might arise regarding whether ARBs and ACEIs would increase the morbidity and mortality of COVID-19. On the other hand, animal data suggested a potential protective effect of ARBs against COVID-19 pneumonia because an ARB prevented the aggravation of acute lung injury in mice infected with SARS-CoV, which is closely related to SARS-CoV-2. Importantly, however, there is no clinical or experimental evidence supporting that ARBs and ACEIs either augment the susceptibility to SARS-CoV-2 or aggravate the severity and outcomes of COVID-19 at present. Until further data are available, it is recommended that ARB and ACEI medications be continued for the treatment of patients with cardiovascular disease and hypertension, especially those at high risk, according to guideline-directed medical therapy based on the currently available evidence.", "qid": 20, "docid": "6u623i0w", "rank": 92, "score": 0.8918906450271606}, {"content": "Title: Interactions of coronaviruses with ACE2, angiotensin II, and RAS inhibitors-lessons from available evidence and insights into COVID-19 Content: The rapid spread of a novel coronavirus, severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), has led to an ongoing pandemic of coronavirus disease 2019 (COVID-19). Recently, angiotensin-converting enzyme 2 (ACE2) has been shown to be a functional receptor for SARS-CoV-2 to enter host target cells. Given that angiotensin receptor blockers (ARBs) and an ACE inhibitor (ACEI) upregulated ACE2 expression in animal studies, the concern might arise regarding whether ARBs and ACEIs would increase the morbidity and mortality of COVID-19. On the other hand, animal data suggested a potential protective effect of ARBs against COVID-19 pneumonia because an ARB prevented the aggravation of acute lung injury in mice infected with SARS-CoV, which is closely related to SARS-CoV-2. Importantly, however, there is no clinical or experimental evidence supporting that ARBs and ACEIs either augment the susceptibility to SARS-CoV-2 or aggravate the severity and outcomes of COVID-19 at present. Until further data are available, it is recommended that ARB and ACEI medications be continued for the treatment of patients with cardiovascular disease and hypertension, especially those at high risk, according to guideline-directed medical therapy based on the currently available evidence.", "qid": 20, "docid": "i5i2owvv", "rank": 93, "score": 0.8918905258178711}, {"content": "Title: ACE inhibitors, AT1 receptor blockers and COVID-19: clinical epidemiology evidences for a continuation of treatments. The ACER-COVID study Content: Aims: The question of interactions between the renin angiotensin aldosterone system drugs and the incidence and prognosis of COVID-19 infection has been raised by the medical community. We hypothesised that if patients treated with ACE inhibitors (ACEI) or AT1 receptor blockers (ARB) were more prone to SARS-CoV2 infection and had a worse prognosis than untreated patients, the prevalence of consumption of these drugs would be higher in patients with COVID-19 compared to the general population. Methods and results: We used a clinical epidemiology approach based on the estimation of standardised prevalence ratio (SPR) of consumption of ACEI and ARB in four groups of patients (including 187 COVID-19 positive) with increasing severity referred to the University hospital of Lille and in three French reference samples (the exhaustive North population (n=1,569,968), a representative sample of the French population (n=414,046), a random sample of Lille area (n=1,584)). The SPRs of ACEI and ARB did not differ as the severity of the COVID-19 patients increased, being similar to the regular consumption of these drugs in the North of France population with the same non-significant increase for both treatment (1.17 [0.83-1.67]). A statistically significant increase in the SPR of ARB (1.56 [1.02-2.39]) was observed in intensive care unit patients only. After stratification on obesity, this increase was limited to the high risk subgroup of obese patients. Conclusions: Our results strongly support the recommendation that ACEI and ARB should be continued in the population and in COVID-19 positive patients, reinforcing the position of several scientific societies.", "qid": 20, "docid": "6baw4hmt", "rank": 94, "score": 0.8906742334365845}, {"content": "Title: Currently prescribed drugs in the UK that could up or downregulate ACE2 in COVID-19 disease: A systematic review Content: Objective: To review evidence on routinely prescribed drugs in the UK that could up or downregulate Angiotensin Converting Enzyme 2 (ACE2) and potentially affect COVID-19 disease Design: Systematic review Data source: MEDLINE, EMBASE, CINAHL, the Cochrane Library and Web of Science Study selection: Any design with animal or human models examining a currently prescribed UK drug compared to a control, placebo or sham group, and reporting an effect on ACE2 level, activity or gene expression. Data extraction and synthesis: MEDLINE, EMBASE, CINAHL, the Cochrane Library, Web of Science and OpenGrey from inception to 1st April 2020. Methodological quality was assessed using the SYRCLE's risk of bias tool for animal studies and Cochrane risk of bias tool for human studies. Results: We screened 3,360 titles and included 112 studies with 21 different drug classes identified as influencing ACE2 activity. Ten studies were in humans and 102 were in animal models None examined ACE2 in human lungs. The most frequently examined drugs were Angiotensin Receptor Blockers (ARBs) (n= 55) and Angiotensin-Converting Enzyme- Inhibitors (ACE-I) (n= 22). More studies reported upregulation than downregulation with ACE-I (n=22), ARBs (n=55), insulin (n=8), thiazolidinedione (n=7) aldosterone agonists (n=3), statins (n=5), oestrogens (n=5) calcium channel-blockers (n=3) GLP-1 agonists (n=2) and NSAIDs (n=2). Conclusions: There is an abundance of academic literature and media reports on the potential of drugs that could attenuate or exacerbate COVID-19 disease. This is leading to trials of repurposed drugs and uncertainty amongst patients and clinicians concerning continuation or cessation of prescribed medications. Our review indicates that the impact of currently prescribed drugs on ACE2 has been poorly studied in-vivo, particularly in human lungs where the SARS-CoV-2 virus appears to enact its pathogenic effects. We found no convincing evidence to justify starting or stopping currently prescribed drugs to influence outcomes of COVID-19 disease.", "qid": 20, "docid": "nkc5dxw5", "rank": 95, "score": 0.8906005620956421}, {"content": "Title: Is the ACE2 Overexpression a Risk Factor for COVID-19 Infection? Content: In the recent coronavirus disease (COVID-19) outbreak, a higher proportion of patients with severe disease were found in older persons with comorbidities. This observation has been related to the use of drugs that can increase the cellular expression of angiotensin-converting enzyme 2 (ACE2) that has been recognized as target to which the virus bind to cells. Although this hypothesis is possible, it may also have other explanations which are discussed.", "qid": 20, "docid": "9iitpj8u", "rank": 96, "score": 0.890143632888794}, {"content": "Title: The ACE-2 in COVID-19: Foe or Friend? Content: COVID-19 is a rapidly spreading outbreak globally. Emerging evidence demonstrates that older individuals and people with underlying metabolic conditions of diabetes mellitus, hypertension, and hyperlipidemia are at higher risk of morbidity and mortality. The SARS-CoV-2 infects humans through the angiotensin converting enzyme (ACE-2) receptor. The ACE-2 receptor is a part of the dual system renin-angiotensin-system (RAS) consisting of ACE-Ang-II-AT (1) R axis and ACE-2-Ang-(1\u20137)-Mas axis. In metabolic disorders and with increased age, it is known that there is an upregulation of ACE-Ang-II-AT (1) R axis with a downregulation of ACE-2-Ang-(1\u20137)-Mas axis. The activated ACE-Ang-II-AT1R axis leads to pro-inflammatory and pro-fibrotic effects in respiratory system, vascular dysfunction, myocardial fibrosis, nephropathy, and insulin secretory defects with increased insulin resistance. On the other hand, the ACE-2-Ang-(1\u20137)-Mas axis has anti-inflammatory and antifibrotic effects on the respiratory system and anti-inflammatory, antioxidative stress, and protective effects on vascular function, protects against myocardial fibrosis, nephropathy, pancreatitis, and insulin resistance. In effect, the balance between these two axes may determine the prognosis. The already strained ACE-2-Ang-(1\u20137)-Mas in metabolic disorders is further stressed due to the use of the ACE-2 by the virus for entry, which affects the prognosis in terms of respiratory compromise. Further evidence needs to be gathered on whether modulation of the renin angiotensin system would be advantageous due to upregulation of Mas activation or harmful due to the concomitant ACE-2 receptor upregulation in the acute management of COVID-19.", "qid": 20, "docid": "ggx4v0bz", "rank": 97, "score": 0.8900065422058105}, {"content": "Title: Predictors of severe or lethal COVID-19, including Angiotensin Converting Enzyme inhibitors and Angiotensin II Receptor Blockers, in a sample of infected Italian citizens Content: AIMS: This retrospective case-control study was aimed at identifying potential independent predictors of severe/lethal COVID-19, including the treatment with Angiotensin-Converting Enzyme inhibitors (ACEi) and/or Angiotensin II Receptor Blockers (ARBs). METHODS AND RESULTS: All adults with SARS-CoV-2 infection in two Italian provinces were followed for a median of 24 days. ARBs and/or ACEi treatments, and hypertension, diabetes, cancer, COPD, renal and major cardiovascular diseases (CVD) were extracted from clinical charts and electronic health records, up to two years before infection. The sample consisted of 1603 subjects (mean age 58.0y; 47.3% males): 454 (28.3%) had severe symptoms, 192 (12.0%) very severe or lethal disease (154 deaths; mean age 79.3 years; 70.8% hypertensive, 42.2% with CVD). The youngest deceased person aged 44 years. Among hypertensive subjects (n = 543), the proportion of those treated with ARBs or ACEi were 88.4%, 78.7% and 80.6% among patients with mild, severe and very severe/lethal disease, respectively. At multivariate analysis, no association was observed between therapy and disease severity (Adjusted OR for very severe/lethal COVID-19: 0.87; 95% CI: 0.50\u20131.49). Significant predictors of severe disease were older age (with AORs largely increasing after 70 years of age), male gender (AOR: 1.76; 1.40\u20132.23), diabetes (AOR: 1.52; 1.05\u20132.18), CVD (AOR: 1.88; 1.32\u20132.70) and COPD (AOR: 1.88; 1.11\u20133.20). Only gender, age and diabetes also predicted very severe/lethal disease. CONCLUSION: No association was found between COVID-19 severity and treatment with ARBs and/or ACEi, supporting the recommendation to continue medication for all patients unless otherwise advised by their physicians.", "qid": 20, "docid": "a0bcmjkn", "rank": 98, "score": 0.8899561166763306}, {"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": 99, "score": 0.8899351358413696}, {"content": "Title: Renin-Angiotensin-Aldosterone Inhibitors and COVID-19 Content: The Corona Virus Disease 2019 (COVID-19) outbreak has rapidly spread throughout the world, accounting for significant morbidity and mortality. There is a concern that renin-angiotensin-aldosterone inhibitors increase susceptibility to COVID-19. Currently there are no clinical data demonstrating beneficial or adverse effects of these medications on COVID-19 outcomes. Renin-angiotensin-aldosterone inhibitors should be continued in patients in otherwise stable conditions who are at risk for or having COVID-19.", "qid": 20, "docid": "sew2sx9v", "rank": 100, "score": 0.8896191716194153}]}
{"query": "what are the mortality rates overall and in specific populations", "hits": [{"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": 1, "score": 0.8228667974472046}, {"content": "Title: Why Do COVID-19 Fatality Rates Differ Across Countries? An Explorative Cross-country Study Based on Select Indicators Content: In this article, we analyse the factors that determine the fatality rates across 29 economies spread across both the developing and developed world. Recent emerging literature and expert opinions in popular media have indicated various factors that may explain cross-country difference in fatality rates. These factors range from access to public health infrastructure, BCG vaccination policies, demographic structure, restrictive policy interventions and the weather. In addition, articles are examining different kinds of fatality rates that can be explained. Progressing beyond fragmented databases and anecdotal evidence, we have developed a database for such factors, have explored various econometric models to test the explanatory power of these factors in explaining several kinds of fatality rates. Based on available data, our study reveals that factors such as public health system, population age structure, poverty level and BCG vaccination are powerful contributory factors in determining fatality rates. Interactions between factors such as poverty level and BCG vaccination provide interesting insights into the complex interplay of factors. Our analysis suggests that poor citizens\u2019 access to the public healthcare system are worse in many countries irrespective of whether they are developed or developing countries.", "qid": 21, "docid": "98n6ycwe", "rank": 2, "score": 0.8026467561721802}, {"content": "Title: Non\u2010parametric estimation of the case fatality ratio with competing risks data: an application to Severe Acute Respiratory Syndrome (SARS) Content: For diseases with some level of associated mortality, the case fatality ratio measures the proportion of diseased individuals who die from the disease. In principle, it is straightforward to estimate this quantity from individual follow\u2010up data that provides times from onset to death or recovery. In particular, in a competing risks context, the case fatality ratio is defined by the limiting value of the sub\u2010distribution function, F (1)(t) = Pr(T \u2a7dt and J = 1), associated with death, as t \u2192 \u221e, where T denotes the time from onset to death (J = 1) or recovery (J = 2). When censoring is present, however, estimation of F (1)(\u221e) is complicated by the possibility of little information regarding the right tail of F (1), requiring use of estimators of F (1)(t(*)) or F (1)(t (*))/(F (1)(t (*))+F (2)(t (*))) where t (*) is large, with F (2)(t) = Pr(T \u2a7dt and J = 2) being the analogous sub\u2010distribution function associated with recovery. With right censored data, the variability of such estimators increases as t (*) increases, suggesting the possibility of using estimators at lower values of t (*) where bias may be increased but overall mean squared error be smaller. These issues are investigated here for non\u2010parametric estimators of F (1) and F (2). The ideas are illustrated on case fatality data for individuals infected with Severe Acute Respiratory Syndrome (SARS) in Hong Kong in 2003. Copyright \u00a9 2006 John Wiley & Sons, Ltd.", "qid": 21, "docid": "y20azr7b", "rank": 3, "score": 0.7896754741668701}, {"content": "Title: Simple Compartmental Models for Disease Transmission Content: Communicable diseases that are endemic (always present in a population ) cause many deaths). For example, in 2011 tuberculosis caused an estimated 1,400,000 deaths and HIV/AIDS caused an estimated 1,200,000 deaths worldwide. According to the World Health Organization there were 627,000 deaths caused by malaria, but other estimates put the number of malaria deaths at 1,2000,000. Measles, which is easily treated in the developed world, caused 160,000 deaths in 2011, but in 1980 there were 2,600,000 measles deaths. The striking reduction in measles deaths is due to the availability of a measles vaccine. Other diseases such as typhus, cholera, schistosomiasis, and sleeping sickness are endemic in many parts of the world. The effects of high disease mortality on mean life span and of disease debilitation and mortality on the economy in afflicted countries are considerable. Most of these disease deaths are in less developed countries, especially in Africa, where endemic diseases are a huge barrier to development.", "qid": 21, "docid": "msohpcoy", "rank": 4, "score": 0.7891638278961182}, {"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": 5, "score": 0.7879906892776489}, {"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": 21, "docid": "03q86e1d", "rank": 6, "score": 0.7875410318374634}, {"content": "Title: Estimating Absolute and Relative Case Fatality Ratios from Infectious Disease Surveillance Data Content: Knowing which populations are most at risk for severe outcomes from an emerging infectious disease is crucial in deciding the optimal allocation of resources during an outbreak response. The case fatality ratio (CFR) is the fraction of cases that die after contracting a disease. The relative CFR is the factor by which the case fatality in one group is greater or less than that in a second group. Incomplete reporting of the number of infected individuals, both recovered and dead, can lead to biased estimates of the CFR. We define conditions under which the CFR and the relative CFR are identifiable. Furthermore, we propose an estimator for the relative CFR that controls for time-varying reporting rates. We generalize our methods to account for elapsed time between infection and death. To demonstrate the new methodology, we use data from the 1918 influenza pandemic to estimate relative CFRs between counties in Maryland. A simulation study evaluates the performance of the methods in outbreak scenarios. An R software package makes the methods and data presented here freely available. Our work highlights the limitations and challenges associated with estimating absolute and relative CFRs in practice. However, in certain situations, the methods presented here can help identify vulnerable subpopulations early in an outbreak of an emerging pathogen such as pandemic influenza.", "qid": 21, "docid": "s3xoti17", "rank": 7, "score": 0.7871780395507812}, {"content": "Title: A Comparison of Generalized Stochastic Milevsky-Promislov Mortality Models with Continuous Non-Gaussian Filters Content: The ability to precisely model mortality rates [Formula: see text] plays an important role from the economic point of view in healthcare. The aim of this article is to propose a comparison of the estimation of the mortality rates based on a class of stochastic Milevsky-Promislov mortality models. We assume that excitations are modeled by second, fourth and sixth order polynomials of outputs from a linear non-Gaussian filter. To estimate the model parameters we use the first and second moments of [Formula: see text]. The theoretical values obtained in both cases were compared with theoretical [Formula: see text] based on a classical Lee-Carter model. The obtained results confirm the usefulness of the switched model based on the continuous non-Gaussian processes used for modeling [Formula: see text].", "qid": 21, "docid": "bvgzy7yq", "rank": 8, "score": 0.7871109247207642}, {"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": 21, "docid": "yjt2g95o", "rank": 9, "score": 0.7864806652069092}, {"content": "Title: Strict Lower Bound on the COVID-19 Fatality Rate in Overwhelmed Healthcare Systems Content: The Infection Fatality Rate (IFR) for COVID-19 is a poorly known, yet crucial, aspect of the disease. Counting only current deaths in a region and assuming everyone in that region is infected provides an absolute lower bound on the IFR. Using this estimator for New York City, Lombardy and Madrid yields strong bounds on the average IFR in overwhelmed health systems. Their combined 35,152 deaths implies IFR > 0.14% averaged over 25.1 million people. This is the best-case scenario and conclusively demonstrates that COVID-19 is more deadly than influenza. The actual value of the average COVID-19 IFR is likely to be higher than this bound.", "qid": 21, "docid": "cmjzst9v", "rank": 10, "score": 0.7859923839569092}, {"content": "Title: The true case fatality of COVID19: An analytical solution Content: The exact risk of dying from COVID-19 has remained elusive and a topic of debate. The observed case fatality rates of 46 different countries are hypothesized to be dependent on their testing rates. An analytical test to this hypothesis suggests that the case fatality rate of COVID-19 could be consistent to a certain degree across all countries and states. The current global fatality rate is estimated to be around 1% and expected to converge between 1-3% when the pandemic ends. This model can be helpful to estimate the true infection rate for individual countries.", "qid": 21, "docid": "2zf9rmbf", "rank": 11, "score": 0.7859011888504028}, {"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": 21, "docid": "0falsc4z", "rank": 12, "score": 0.7850310802459717}, {"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": 13, "score": 0.7823789715766907}, {"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": 14, "score": 0.7794570326805115}, {"content": "Title: Worldwide differences in COVID-19-related mortality Content: Mortality statistics due to COVID-19 worldwide are compared, by adjusting for the size of the population and the stage of the pandemic. Data from the European Centre for Disease Control and Prevention, and Our World in Data websites were used. Analyses are based on number of deaths per one million inhabitants. In order to account for the stage of the pandemic, the baseline date was defined as the day in which the 10th death was reported. The analyses included 78 countries and territories which reported 10 or more deaths by April 9. On day 10, India had 0.06 deaths per million, Belgium had 30.46 and San Marino 618.78. On day 20, India had 0.27 deaths per million, China had 0.71 and Spain 139.62. On day 30, four Asian countries had the lowest mortality figures, whereas eight European countries had the highest ones. In Italy and Spain, mortality on day 40 was greater than 250 per million, whereas in China and South Korea, mortality was below 4 per million. Mortality on day 10 was moderately correlated with life expectancy, but not with population density. Asian countries presented much lower mortality figures as compared to European ones. Life expectancy was found to be correlated with mortality.", "qid": 21, "docid": "xwpqae0r", "rank": 15, "score": 0.7790642976760864}, {"content": "Title: Worldwide differences in COVID-19-related mortality. Content: Mortality statistics due to COVID-19 worldwide are compared, by adjusting for the size of the population and the stage of the pandemic. Data from the European Centre for Disease Control and Prevention, and Our World in Data websites were used. Analyses are based on number of deaths per one million inhabitants. In order to account for the stage of the pandemic, the baseline date was defined as the day in which the 10th death was reported. The analyses included 78 countries and territories which reported 10 or more deaths by April 9. On day 10, India had 0.06 deaths per million, Belgium had 30.46 and San Marino 618.78. On day 20, India had 0.27 deaths per million, China had 0.71 and Spain 139.62. On day 30, four Asian countries had the lowest mortality figures, whereas eight European countries had the highest ones. In Italy and Spain, mortality on day 40 was greater than 250 per million, whereas in China and South Korea, mortality was below 4 per million. Mortality on day 10 was moderately correlated with life expectancy, but not with population density. Asian countries presented much lower mortality figures as compared to European ones. Life expectancy was found to be correlated with mortality.", "qid": 21, "docid": "inhxonsk", "rank": 16, "score": 0.7790642976760864}, {"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": 17, "score": 0.7788377404212952}, {"content": "Title: Serology-informed estimates of SARS-COV-2 infection fatality risk in Geneva, Switzerland Content: The infection fatality risk (IFR) is the average number of deaths per infection by a pathogen and is key to characterizing the severity of infection across the population and for specific demographic groups. To date, there are few empirical estimates of IFR published due to challenges in measuring infection rates. Outside of closed, closely surveilled populations where infection rates can be monitored through viral surveillance, we must rely on indirect measures of infection, like specific antibodies. Representative seroprevalence studies provide an important avenue for estimating the number of infections in a community, and when combined with death counts can lead to robust estimates of the IFR. We estimated overall and age-specific IFR for the canton of Geneva, Switzerland using age-stratified daily case and death incidence reports combined with five weekly population-based seroprevalence estimates. From February 24th to June 2nd there were 5'039 confirmed cases and 286 reported deaths within Geneva (population of 506'765). We inferred age-stratified (5-9, 10-19, 20-49, 50-65 and 65+) IFRs by linking the observed number of deaths to the estimated number of infected individuals from each serosurvey. We account for the delays between infection and seroconversion as well as between infection and death. Inference is drawn in a Bayesian framework that incorporates uncertainty in seroprevalence estimates (supplement). Of the 286 reported deaths caused by SARS-CoV-2, the youngest person to die was 31 years old. Infected individuals younger than 50 years experienced statistically similar IFRs (range 0.00032-0.0016%), which increases to 0.14% (95% CrI 0.096-0.19) for those 50-64 years old to 5.6% (95% CrI 4.3-7.4) for those 65 years and older (supplement). After accounting for demography and age-specific seroprevalence, we estimate a population-wide IFR of 0.64% (95% CrI 0.38-0.98). Our results are subject to two notable limitations. Among the 65+ age group that died of COVID-19 within Geneva, 50% were reported among residents of assisted care facilities, where around 0.8% of the Geneva population resides. While the serosurvey protocol did not explicitly exclude these individuals, they are likely to have been under-represented. This would lead to an overestimation of the IFR in the 65+ age group if seroprevalence in this institutionalized population was higher than in the general population (supplement). Further, our IFR estimates are based on current evidence regarding post-infection antibody kinetics, which may differ between severe and mild infections. If mild infections have significantly lower and short-lived antibody responses, our estimates of IFR may be biased upwards. Estimates of IFR are key for understanding the true pandemic burden and for weighing different risk reduction strategies. The IFR is not solely determined by host and pathogen biology, but also by the capacity of health systems to treat severe cases. Despite having among the highest per capita incidence in Switzerland, Geneva's health system accommodated the influx of cases needing intensive care (peak of 80/110 ICU-beds including surge capacity) while maintaining care quality standards. As such, our IFR estimates can be seen as a best-case scenario with respect to health system capacity. Our results reveal that population-wide estimates of IFR mask great heterogeneity by age and point towards the importance of age-targeted interventions to reduce exposures among those at highest risk of death.", "qid": 21, "docid": "zr74ec1u", "rank": 18, "score": 0.776619553565979}, {"content": "Title: Incidence and Mortality Rates of Disasters and Mass Casualty Incidents in Korea: A Population-Based Cross-Sectional Study, 2000-2009 Content: The objective of study was to evaluate the incidence and mortality rates of disasters and mass casualty incidents (MCIs) over the past 10 yr in the administrative system of Korea administrative system and to examine their relationship with population characteristics. This was a population-based cross-sectional study. We calculated the nationwide incidence, as well as the crude mortality and injury incidence rates, of disasters and MCIs. The data were collected from the administrative database of the National Emergency Management Agency (NEMA) and from provincial fire departments from January 2000 to December 2009. A total of 47,169 events were collected from the NEMA administrative database. Of these events, 115 and 3,079 cases were defined as disasters and MCIs that occurred in Korea, respectively. The incidence of technical disasters/MCIs was approximately 12.7 times greater than that of natural disasters/MCIs. Over the past 10 yr, the crude mortality rates for disasters and MCIs were 2.36 deaths per 100,000 persons and 6.78 deaths per 100,000 persons, respectively. The crude injury incidence rates for disasters and MCIs were 25.47 injuries per 100,000 persons and 152 injuries per 100,000 persons, respectively. The incidence and mortality of disasters/MCIs in Korea seem to be low compared to that of trend around the world.", "qid": 21, "docid": "ysyz3grd", "rank": 19, "score": 0.7755800485610962}, {"content": "Title: COVID-19, Australia: Epidemiology Report 12 (Reporting week to 23:59 AEST 19 April 2020) Content: Confirmed cases in Australia notified up to 19 April 2020: notifications = 6,606; deaths = 69. The reduction in international travel and domestic movement, social distancing measures and public health action have likely slowed the spread of the disease. Notifications in Australia remain predominantly among people with recent overseas travel, with some locally-acquired cases being detected. Most locally-acquired cases can be linked back to a confirmed case, with a small portion unable to be epidemiologically linked. The distribution of overseas-acquired cases to locally-acquired cases varies by jurisdiction. The crude case fatality rate (CFR) in Australia remains low (1.0%) compared to the World Health Organization's globally-reported rate (6.8%) and to other comparable high-income countries such as the United States of America (4.7%) and the United Kingdom (13.5%). The low CFR is likely reflective of high case ascertainment including detection of mild cases. High case ascertainment enables public health response and reduction of disease transmission. Internationally, cases continue to increase. The rates of increase have started to slow in several regions, although it is too soon to tell whether this trend will be sustained. Interpretation of international epidemiology should be conducted with caution as it differs from country to country depending not only on the disease dynamics, but also on differences in case detection, testing and implemented public health measures.", "qid": 21, "docid": "4i1rygij", "rank": 20, "score": 0.7753812074661255}, {"content": "Title: COVID-19, Australia: Epidemiology Report 12 (Reporting week to 23:59 AEST 19 April 2020). Content: Confirmed cases in Australia notified up to 19 April 2020: notifications = 6,606; deaths = 69. The reduction in international travel and domestic movement, social distancing measures and public health action have likely slowed the spread of the disease. Notifications in Australia remain predominantly among people with recent overseas travel, with some locally-acquired cases being detected. Most locally-acquired cases can be linked back to a confirmed case, with a small portion unable to be epidemiologically linked. The distribution of overseas-acquired cases to locally-acquired cases varies by jurisdiction. The crude case fatality rate (CFR) in Australia remains low (1.0%) compared to the World Health Organization's globally-reported rate (6.8%) and to other comparable high-income countries such as the United States of America (4.7%) and the United Kingdom (13.5%). The low CFR is likely reflective of high case ascertainment including detection of mild cases. High case ascertainment enables public health response and reduction of disease transmission. Internationally, cases continue to increase. The rates of increase have started to slow in several regions, although it is too soon to tell whether this trend will be sustained. Interpretation of international epidemiology should be conducted with caution as it differs from country to country depending not only on the disease dynamics, but also on differences in case detection, testing and implemented public health measures.", "qid": 21, "docid": "u56qs6yq", "rank": 21, "score": 0.7753811478614807}, {"content": "Title: Global Burden of Infectious Diseases Content: Systematic efforts to quantify and monitor the burden of specific health conditions in populations, at the national level, started in the mid-1950s for malaria, poliomyelitis, and influenza in the United States. Comprehensive surveillance of morbidity and mortality for dozens of conditions has since been well established in the United States and in other industrialized countries. However, despite the clear need for epidemiological data to inform health policies, reliable and comprehensive health statistics are not available in many developing countries. International efforts to assess and monitor the burden of certain diseases have been limited in the past to a small number of infectious diseases in the context of global eradication programs \u2013 smallpox, poliomyelitis, guinea worm, and, more recently, HIV/AIDS, severe acute respiratory syndrome (SARS), and avian flu influenza A (H5N1). The Global Burden of Disease Study (GBD), published in 1996, filled an important gap in our knowledge of population health status. It created a common metric, the disability-adjusted life year (DALY), to estimate morbidity and mortality for eight regions that collectively span the world\u2019s population, generating comparable information on incidence and prevalence in global health. However, patterns of disease, disability, and risk factors have since changed significantly and new data on their distribution are available. Furthermore, the unprecedented money and attention now pouring into international health has made an accurate assessment of global health patterns a matter of utmost urgency. The new Global Burden of Diseases, Injuries, and Risk Factors (GBD 2005) project, which began in 2007, represents the first major effort at a systematic revision of estimates in health for every region in the world comprehensively, and will ensure that that the global health community bases its research and policies on complete, valid, and reliable information. Burden of disease estimates provided in this article are for 2001 \u2013 the year for which the most recent estimates of the global burden of disease and risk factors are currently available. Causes of deaths were categorized into three main groups: group I (infectious diseases and maternal, perinatal, and nutritional conditions), group II (noncommunicable diseases), and group III (injuries). Accordingly, estimates of the global burden of infectious diseases are provided in the context of the overall burden from other conditions, diseases, and injuries. The relative importance of the burden of infectious diseases was forecasted to change by 2020. As the epidemiological transition progresses worldwide, a decline in the burden of infectious diseases is expected as the burden of noncommunicable diseases and injuries gradually increases. The pace of the epidemiological transition, however, varies greatly among regions so that the projected decreases in the burden of infectious diseases are expected to vary between regions. Trends in the global burden due to specific infectious diseases projected to 2020 also vary among specific conditions. The global burden of HIV/AIDS, for instance, is expected to greatly increase, whereas the global burden due to respiratory infections and diarrheal diseases is expected to decrease. Contrary to expectations, the global burden of malaria has increased in recent years.", "qid": 21, "docid": "kzlo48b0", "rank": 22, "score": 0.7750407457351685}, {"content": "Title: Methods for Estimating the Case Fatality Ratio for a Novel, Emerging Infectious Disease Content: During the course of an epidemic of a potentially fatal disease, it is important that the case fatality ratio be well estimated. The authors propose a novel method for doing so based on the Kaplan-Meier survival procedure, jointly considering two outcomes (death and recovery), and evaluate its performance by using data from the 2003 epidemic of severe acute respiratory syndrome in Hong Kong, People's Republic of China. They compare this estimate obtained at various points in the epidemic with the case fatality ratio eventually observed; with two commonly quoted, na\u00efve estimates derived from cumulative incidence and mortality statistics at single time points; and with estimates in which a parametric mixture model is used. They demonstrate the importance of patient characteristics regarding outcome by analyzing subgroups defined by age at admission to the hospital.", "qid": 21, "docid": "4us84ol1", "rank": 23, "score": 0.7741855382919312}, {"content": "Title: A comparison study of realtime fatality rates: severe acute respiratory syndrome in Hong Kong, Singapore, Taiwan, Toronto and Beijing, China Content: Summary. In an outbreak of a completely new infectious disease like severe acute respiratory syndrome (SARS), estimation of the fatality rate over the course of the epidemic is of clinical and epidemiological importance. In contrast with the constant case fatality rate, a new measure, termed the \u2018realtime\u2019 fatality rate, is proposed for monitoring the new emerging epidemic at a population level. A competing risk model implemented via a counting process is used to estimate the realtime fatality rate in an epidemic of SARS. It can capture and reflect the time\u2010varying nature of the fatality rate over the course of the outbreak in a timely and accurate manner. More importantly, it can provide information on the efficacy of a certain treatment and management policy for the disease. The method has been applied to the SARS data from the regions affected, namely Hong Kong, Singapore, Toronto, Taiwan and Beijing. The magnitudes and patterns of the estimated fatalities are virtually the same except in Beijing, which has a lower rate. It is speculated that the effect is linked to the different treatment protocols that were used. The standard estimate of the case fatality rate that was used by the World Health Organization has been shown to be unable to provide useful information to monitor the time\u2010varying fatalities that are caused by the epidemic.", "qid": 21, "docid": "7mrxym8k", "rank": 24, "score": 0.774025559425354}, {"content": "Title: Occupational Deaths among Healthcare Workers Content: Recent experiences with severe acute respiratory syndrome and the US smallpox vaccination program have demonstrated the vulnerability of healthcare workers to occupationally acquired infectious diseases. However, despite acknowledgment of risk, the occupational death rate for healthcare workers is unknown. In contrast, the death rate for other professions with occupational risk, such as police officer or firefighter, has been well defined. With available information from federal sources and calculating the additional number of deaths from infection by using data on prevalence and natural history, we estimate the annual death rate for healthcare workers from occupational events, including infection, is 17\u201357 per 1 million workers. However, a much more accurate estimate of risk is needed. Such information could inform future interventions, as was seen with the introduction of safer needle products. This information would also heighten public awareness of this often minimized but essential aspect of patient care.", "qid": 21, "docid": "93m011gz", "rank": 25, "score": 0.773064911365509}, {"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": 26, "score": 0.7728716135025024}, {"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": 27, "score": 0.7727925181388855}, {"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": 21, "docid": "o72xreym", "rank": 28, "score": 0.7727919220924377}, {"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": 21, "docid": "xw244riy", "rank": 29, "score": 0.772791862487793}, {"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": 30, "score": 0.7725389003753662}, {"content": "Title: Pathogen Genomics and the Potential for Understanding Diseases in the Developing World Content: Approximately 46% and 32% of deaths among children under five globally occur in sub-Saharan Africa and South Asia, respectively. Over 80% of the 4.2 million child deaths in Africa are caused by infectious diseases, sharply contrasted to Europe where 39% of the 0.15 million child deaths are attributable to infectious diseases (Fig. 5.1) (Black et al. 2010). Hence, despite the remarkable public health advancements in hygiene, sanitation, antimicrobial drugs and vaccine strategies of the twenty-first century, the burden of infectious diseases remains unacceptably high in the developing world.", "qid": 21, "docid": "h62e6ils", "rank": 31, "score": 0.7723376750946045}, {"content": "Title: Epidemiology of Viral Infections Content: Viruses survive in nature only if they are able to pass from one host to another, whether of the same or another species. Viral epidemiology is the study of the factors that determine the frequency and distribution of viral diseases in an animal population. In the broadest sense, epidemiology may be viewed as a part of population biology, involving not only environmental factors but also genetic factors in both the virus and the host. The terms incidence and prevalence are used to describe quantitative aspects of the occurrence of infections in populations. The incidence of infection is defined as the proportion of a population contracting that infection during a specified period, whereas prevalence refers to the proportion infected at a particular point in time. The comparisons of incidence and prevalence at different times and places are made by relating the appropriate numerator to a denominator that may be as general as the total population of the animal species concerned or may be specified as the susceptible population at risk. A disease is said to be enzootic when there are continuous chains of transmission in the region involved; epizootics are peaks in disease incidence. The size of the peak required to constitute an epizootic is arbitrary and is related to the background enzootic rate, the morbidity, and the anxiety that the disease arouses.", "qid": 21, "docid": "1lra8dfz", "rank": 32, "score": 0.7718357443809509}, {"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": 33, "score": 0.7714080810546875}, {"content": "Title: Explaining national differences in the mortality of Covid-19: individual patient simulation model to investigate the effects of testing policy and other factors on apparent mortality. Content: There has been extensive speculation on the apparent differences in mortality between countries reporting on the confirmed cases and deaths due to Covid-19. A number of explanations have been suggested, but there is no clear evidence about how apparent fatality rates may be expected to vary with the different testing regimes, admission policies and other variables. An individual patient simulation model was developed to address this question. Parameters and sensitivity analysis based upon recent international data sources for Covid-19 and results were averaged over 100 iterations for a simulated cohort of over 500,000 patients. Different testing regimes for Covid-19 were considered; testing admitted patients only, various rates of community testing of symptomatic cases and active contact-tracing and screening. In the base case analysis, apparent mortality ranged from 10.5% under a policy of testing only admitted patients to 0.4% with intensive contact tracing and community testing. These findings were sensitive to assumptions regarding admission rates and the rate of spread, with more selective admission policies and suppression of spread increasing the apparent mortality and the potential for apparent mortality rates to exceed 18% under some circumstances. Under all scenarios the proportion of patients tested in the community had the greatest impact on apparent mortality. Whilst differences in mortality due to health service and demographic factors cannot be excluded, the current international differences in reported mortality are all consistent with differences in practice regarding screening, community testing and admission policies.", "qid": 21, "docid": "gkd1h8yi", "rank": 34, "score": 0.7712454795837402}, {"content": "Title: What does and does not correlate with COVID-19 death rates Content: We correlate county-level COVID-19 death rates with key variables using both linear regression and negative binomial mixed models, although we focus on linear regression models. We include four sets of variables: socio-economic variables, county-level health variables, modes of commuting, and climate and pollution patterns. Our analysis studies daily death rates from April 4, 2020 to May 27, 2020. We estimate correlation patterns both across states, as well as within states. For both models, we find higher shares of African American residents in the county are correlated with higher death rates. However, when we restrict ourselves to correlation patterns within a given state, the statistical significance of the correlation of death rates with the share of African Americans, while remaining positive, wanes. We find similar results for the share of elderly in the county. We find that higher amounts of commuting via public transportation, relative to telecommuting, is correlated with higher death rates. The correlation between driving into work, relative to telecommuting, and death rates is also positive across both models, but statistically significant only when we look across states and counties. We also find that a higher share of people not working, and thus not commuting either because they are elderly, children or unemployed, is correlated with higher death rates. Counties with higher home values, higher summer temperatures, and lower winter temperatures have higher death rates. Contrary to past work, we do not find a correlation between pollution and death rates. Also importantly, we do not find that death rates are correlated with obesity rates, ICU beds per capita, or poverty rates. Finally, our model that looks within states yields estimates of how a given state's death rate compares to other states after controlling for the variables included in our model; this may be interpreted as a measure of how states are doing relative to others. We find that death rates in the Northeast are substantially higher compared to other states, even when we control for the four sets of variables above. Death rates are also statistically significantly higher in Michigan, Louisiana, Iowa, Indiana, and Colorado. California's death rate is the lowest across all states.", "qid": 21, "docid": "flkd7u9u", "rank": 35, "score": 0.7712066769599915}, {"content": "Title: Basic Reproduction Rate and Case Fatality Rate of COVID-19: Application of Meta-analysis Content: Abstract Background: The outbreak of novel coronavirus disease of 2019 (COVID-19) has a wider geographical spread than other previous viruses such as Ebola and H1N1. The onset of disease and its transmission and severity has become a global concern. The policymakers have a serious concern for containing the spread and minimising the risk of death. Aim: This study aims to provide the estimates of basic reproduction rate (R0) and case fatality rate (CFR) which applies to a generalised population. Methods: A systematic review was carried out to retrieve the published estimates of reproduction rate and case fatality rate in peer-reviewed articles from PubMed MEDLINE database with defined inclusion and exclusion criteria in the period 15 December 2019 to 3 May 2020. The systematic review led to the selection of 24 articles for R0 and 17 articles for CFR. These studies used data from China and its provinces, other Asian countries such as Japan, Korea, the Philippines, and countries from other parts of the world such as Nigeria, Iran, Italy, Europe as a whole, France, Latin America, Turkey, the United Kingdom (UK), and the United States of America (USA). These selected articles gave an output of 30 counts of R0 and 29 counts of CFR which were used in a meta-analysis. A meta-analysis, with the inverse variance method, fixed- and random-effects model and the Forest plot, was performed to estimate the mean effect size or mean value of basic reproduction rate and case fatality rate. The Funnel plot is used to comprehend the publication bias. Results: We estimated the robust estimate of R0 at 3.11 (2.49-3.71) persons and the robust estimate of CFR at 2.56 (2.06-3.05) per cent after accounting for heterogeneity among studies, using the random-effects model. The regional subgroup analysis in a meta-analysis was significant for R0 but was not significant for CFR. The R0 values varied from 1.90 (1.06-2.74) persons to 3.83 (2.44-5.22) persons across the regions. The Funnel plot confirms that the selected studies are significant at one per cent level of significance. Conclusion: We found that one person is likely to infect two to three persons in the absence of any control measures, and around three per cent of the population are at the risk of death within one-and-a-half months from the onset of disease COVID-19 in a generalised population. The emergence of SARS-CoV-2 varies across regions, but the risk of death remains the same. Contribution: The estimates of R0 and CFR are independent of data from a particular region or time or a homogeneous population. These estimates are applicable to a generalised population. Therefore, the estimates of R0 and CFR are unequivocally applicable to developing country like India and its states or districts, in ambivalence. The assessments of R0 and CFR values across the developed nations make all of us aware of consequences of COVID-19, and hence these estimates are of crucial importance for government authorities for the practical implementation of strategies and control measures to contain the disease. Keywords: Covid-19, SARS-CoV-2, Reproduction Rate, Case Fatality Rate, Systematic Review, Meta-analysis", "qid": 21, "docid": "hps2ompw", "rank": 36, "score": 0.7696611285209656}, {"content": "Title: Mortality, morbidity and health in developed societies: a review of data sources Content: The purpose of this paper is to review the major sources of data on mortality, morbidity and health in Europe and in other developed regions in order to examine their potential for analysing mortality and morbidity levels and trends. The review is primarily focused on routinely collected information covering a whole country. No attempt is made to draw up an inventory of sources by country; the paper deals instead with the pros and cons of each source for mortality and morbidity studies in demography. While each source considered separately can already yield useful, though partial, results, record linkage among data sources can significantly improve the analysis. Record linkage can also lead to the detection of possible causal associations that could eventually be confirmed. More generally, Big Data can reveal changing mortality and morbidity trends and patterns that could lead to preventive measures being taken rather than more costly curative ones.", "qid": 21, "docid": "cs9zddms", "rank": 37, "score": 0.7692650556564331}, {"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": 38, "score": 0.7691608667373657}, {"content": "Title: A Method to Identify the Missing COVID-19 Cases in the U.S. and Results for mid-April 2020 Content: I use the COVID-19 death rate in South Korea and a method relating the ratio of death rates in a U.S. state to its share of cumulative positive tests to estimate the total cases of COVID-19 in the U.S. and to estimate the extent of infection and the unidentified share of the infected population in each of the lower-48 states and in New York City in mid-April, 2020. I identify a logarithmic relationship between the cumulative death rate in a state and its cumulative positive share of tests. Using this relationship, I find that 4.3-5.4 million people, 1.4-1.7% of the U.S. population, were infected, with rates of infection that ranged from 0.1% in more rural states to 8-10% in New York state and 11-13% in New York City. Only 16-20% of these infected individuals were identified later through testing.", "qid": 21, "docid": "rkqerpfb", "rank": 39, "score": 0.7690998315811157}, {"content": "Title: The sociospatial factors of death: Analyzing effects of geospatially-distributed variables in a Bayesian mortality model for Hong Kong Content: Human mortality is in part a function of multiple socioeconomic factors that differ both spatially and temporally. Adjusting for other covariates, the human lifespan is positively associated with household wealth. However, the extent to which mortality in a geographical region is a function of socioeconomic factors in both that region and its neighbors is unclear. There is also little information on the temporal components of this relationship. Using the districts of Hong Kong over multiple census years as a case study, we demonstrate that there are differences in how wealth indicator variables are associated with longevity in (a) areas that are affluent but neighbored by socially deprived districts versus (b) wealthy areas surrounded by similarly wealthy districts. We also show that the inclusion of spatially-distributed variables reduces uncertainty in mortality rate predictions in each census year when compared with a baseline model. Our results suggest that geographic mortality models should incorporate nonlocal information (e.g., spatial neighbors) to lower the variance of their mortality estimates, and point to a more in-depth analysis of sociospatial spillover effects on mortality rates.", "qid": 21, "docid": "x35haoyb", "rank": 40, "score": 0.7685233354568481}, {"content": "Title: Correspondence regarding recently published editorial: \u2018Will children reveal their secret? The coronavirus dilemma\u2019 Content: When individuals without prior immunity are considered, case fatality ratios are typically higher in adults than in children for most infectious diseases, with few exceptions.", "qid": 21, "docid": "bfq66x1c", "rank": 41, "score": 0.7681469917297363}, {"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": 21, "docid": "v76ech81", "rank": 42, "score": 0.7675378918647766}, {"content": "Title: Global patterns of mortality in international migrants: a systematic review and meta-analysis. Content: BACKGROUND 258 million people reside outside their country of birth; however, to date no global systematic reviews or meta-analyses of mortality data for these international migrants have been done. We aimed to review and synthesise available mortality data on international migrants. METHODS In this systematic review and meta-analysis, we searched MEDLINE, Embase, the Cochrane Library, and Google Scholar databases for observational studies, systematic reviews, and randomised controlled trials published between Jan 1, 2001, and March 31, 2017, without language restrictions. We included studies reporting mortality outcomes for international migrants of any age residing outside their country of birth. Studies that recruited participants exclusively from intensive care or high dependency hospital units, with an existing health condition or status, or a particular health exposure were excluded. We also excluded studies limited to maternal or perinatal outcomes. We screened studies using systematic review software and extracted data from published reports. The main outcomes were all-cause and International Classification of Diseases, tenth revision (ICD-10) cause-specific standardised mortality ratios (SMRs) and absolute mortality rates. We calculated summary estimates using random-effects models. This study is registered with PROSPERO, number CRD42017073608. FINDINGS Of the 12 480 articles identified by our search, 96 studies were eligible for inclusion. The studies were geographically diverse and included data from all global regions and for 92 countries. 5464 mortality estimates for more than 15\u00b72 million migrants were included, of which 5327 (97%) were from high-income countries, 115 (2%) were from middle-income countries, and 22 (<1%) were from low-income countries. Few studies included mortality estimates for refugees (110 estimates), asylum seekers (144 estimates), or labour migrants (six estimates). The summary estimate of all-cause SMR for international migrants was lower than one when compared with the general population in destination countries (0\u00b770 [95% CI 0\u00b765-0\u00b776]; I2=99\u00b78%). All-cause SMR was lower in both male migrants (0\u00b772 [0\u00b763-0\u00b781]; I2=99\u00b78%) and female migrants (0\u00b775 [0\u00b767-0\u00b784]; I2=99\u00b78%) compared with the general population. A mortality advantage was evident for refugees (SMR 0\u00b750 [0\u00b746-0\u00b754]; I2=89\u00b78%), but not for asylum seekers (1\u00b705 [0\u00b789-1\u00b724]; I2=54\u00b74%), although limited data was available on these groups. SMRs for all causes of death were lower in migrants compared with the general populations in the destination country across all 13 ICD-10 categories analysed, with the exception of infectious diseases and external causes. Heterogeneity was high across the majority of analyses. Point estimates of all-cause age-standardised mortality in migrants ranged from 420 to 874 per 100 000 population. INTERPRETATION Our study showed that international migrants have a mortality advantage compared with general populations, and that this advantage persisted across the majority of ICD-10 disease categories. The mortality advantage identified will be representative of international migrants in high-income countries who are studying, working, or have joined family members in these countries. However, our results might not reflect the health outcomes of more marginalised groups in low-income and middle-income countries because little data were available for these groups, highlighting an important gap in existing research. Our results present an opportunity to reframe the public discourse on international migration and health in high-income countries. FUNDING Wellcome Trust, National Institute for Health Research, Medical Research Council, Alliance for Health Policy and Systems Research, Department for International Development, Fogarty International Center, Grand Challenges Canada, International Development Research Centre Canada, Inter-American Institute for Global Change Research, National Cancer Institute, National Heart, Lung and Blood Institute, National Institute of Mental Health, Swiss National Science Foundation, World Diabetes Foundation, UK National Institute for Health Research Imperial Biomedical Research Centre, Imperial College Healthcare Charity, and European Society for Clinical Microbiology and Infectious Diseases (ESCMID) Study Group Research Funding for the ESCMID Study Group for Infections in Travellers and Migrants.", "qid": 21, "docid": "ppwviewr", "rank": 43, "score": 0.7674286961555481}, {"content": "Title: Global, regional, and national disability-adjusted life-years (DALYs) for 333 diseases and injuries and healthy life expectancy (HALE) for 195 countries and territories, 1990-2016: a systematic analysis for the Global Burden of Disease Study 2016. Content: BACKGROUND Measurement of changes in health across locations is useful to compare and contrast changing epidemiological patterns against health system performance and identify specific needs for resource allocation in research, policy development, and programme decision making. Using the Global Burden of Diseases, Injuries, and Risk Factors Study 2016, we drew from two widely used summary measures to monitor such changes in population health: disability-adjusted life-years (DALYs) and healthy life expectancy (HALE). We used these measures to track trends and benchmark progress compared with expected trends on the basis of the Socio-demographic Index (SDI). METHODS We used results from the Global Burden of Diseases, Injuries, and Risk Factors Study 2016 for all-cause mortality, cause-specific mortality, and non-fatal disease burden to derive HALE and DALYs by sex for 195 countries and territories from 1990 to 2016. We calculated DALYs by summing years of life lost and years of life lived with disability for each location, age group, sex, and year. We estimated HALE using age-specific death rates and years of life lived with disability per capita. We explored how DALYs and HALE differed from expected trends when compared with the SDI: the geometric mean of income per person, educational attainment in the population older than age 15 years, and total fertility rate. FINDINGS The highest globally observed HALE at birth for both women and men was in Singapore, at 75\u00b72 years (95% uncertainty interval 71\u00b79-78\u00b76) for females and 72\u00b70 years (68\u00b78-75\u00b71) for males. The lowest for females was in the Central African Republic (45\u00b76 years [42\u00b70-49\u00b75]) and for males was in Lesotho (41\u00b75 years [39\u00b70-44\u00b70]). From 1990 to 2016, global HALE increased by an average of 6\u00b724 years (5\u00b797-6\u00b748) for both sexes combined. Global HALE increased by 6\u00b704 years (5\u00b774-6\u00b727) for males and 6\u00b749 years (6\u00b708-6\u00b777) for females, whereas HALE at age 65 years increased by 1\u00b778 years (1\u00b761-1\u00b793) for males and 1\u00b796 years (1\u00b769-2\u00b713) for females. Total global DALYs remained largely unchanged from 1990 to 2016 (-2\u00b73% [-5\u00b79 to 0\u00b79]), with decreases in communicable, maternal, neonatal, and nutritional (CMNN) disease DALYs offset by increased DALYs due to non-communicable diseases (NCDs). The exemplars, calculated as the five lowest ratios of observed to expected age-standardised DALY rates in 2016, were Nicaragua, Costa Rica, the Maldives, Peru, and Israel. The leading three causes of DALYs globally were ischaemic heart disease, cerebrovascular disease, and lower respiratory infections, comprising 16\u00b71% of all DALYs. Total DALYs and age-standardised DALY rates due to most CMNN causes decreased from 1990 to 2016. Conversely, the total DALY burden rose for most NCDs; however, age-standardised DALY rates due to NCDs declined globally. INTERPRETATION At a global level, DALYs and HALE continue to show improvements. At the same time, we observe that many populations are facing growing functional health loss. Rising SDI was associated with increases in cumulative years of life lived with disability and decreases in CMNN DALYs offset by increased NCD DALYs. Relative compression of morbidity highlights the importance of continued health interventions, which has changed in most locations in pace with the gross domestic product per person, education, and family planning. The analysis of DALYs and HALE and their relationship to SDI represents a robust framework with which to benchmark location-specific health performance. Country-specific drivers of disease burden, particularly for causes with higher-than-expected DALYs, should inform health policies, health system improvement initiatives, targeted prevention efforts, and development assistance for health, including financial and research investments for all countries, regardless of their level of sociodemographic development. The presence of countries that substantially outperform others suggests the need for increased scrutiny for proven examples of best practices, which can help to extend gains, whereas the presence of underperforming countries suggests the need for devotion of extra attention to health systems that need more robust support. FUNDING Bill & Melinda Gates Foundation.", "qid": 21, "docid": "kzz677r2", "rank": 44, "score": 0.7669532895088196}, {"content": "Title: Potential Biases in Estimating Absolute and Relative Case-Fatality Risks during Outbreaks Content: Estimating the case-fatality risk (CFR)\u2014the probability that a person dies from an infection given that they are a case\u2014is a high priority in epidemiologic investigation of newly emerging infectious diseases and sometimes in new outbreaks of known infectious diseases. The data available to estimate the overall CFR are often gathered for other purposes (e.g., surveillance) in challenging circumstances. We describe two forms of bias that may affect the estimation of the overall CFR\u2014preferential ascertainment of severe cases and bias from reporting delays\u2014and review solutions that have been proposed and implemented in past epidemics. Also of interest is the estimation of the causal impact of specific interventions (e.g., hospitalization, or hospitalization at a particular hospital) on survival, which can be estimated as a relative CFR for two or more groups. When observational data are used for this purpose, three more sources of bias may arise: confounding, survivorship bias, and selection due to preferential inclusion in surveillance datasets of those who are hospitalized and/or die. We illustrate these biases and caution against causal interpretation of differential CFR among those receiving different interventions in observational datasets. Again, we discuss ways to reduce these biases, particularly by estimating outcomes in smaller but more systematically defined cohorts ascertained before the onset of symptoms, such as those identified by forward contact tracing. Finally, we discuss the circumstances in which these biases may affect non-causal interpretation of risk factors for death among cases.", "qid": 21, "docid": "o8aosx2q", "rank": 45, "score": 0.7667986750602722}, {"content": "Title: Why case fatality ratios can be misleading: individual- and population-based mortality estimates and factors influencing them Content: Different ways of calculating mortality during epidemics have yielded very different results, particularly during the current COVID-19 pandemic. For example, the \"CFR\" has been interchangeably called the case fatality ratio, case fatality rate, and case fatality risk, often without standard mathematical definitions. The most commonly used CFR is thecase fatality ratio, typically constructed using the estimated number of deaths to date divided by the estimated total number of confirmed infected cases to date. How does this CFR relate to an infected individual's probability of death? To explore such issues, we formulate both a survival probability model and an associated infection duration-dependent SIR model to define individual- and population-based estimates of dynamic mortality measures to show that neither of these are directly represented by the case fatality ratio. The key parameters that affect the dynamics of different mortality estimates are the incubation period and the time individuals were infected before confirmation of infection. Using data on the recent SARS-CoV-2 outbreaks, we estimate and compare the different dynamic mortality estimates and highlight their differences. Informed by our modeling, we propose more systematic methods to determine mortality during epidemic outbreaks and discuss sensitivity to confounding effects and uncertainties in the data such as undertesting and heterogeneous populations.", "qid": 21, "docid": "zf0bboc1", "rank": 46, "score": 0.7666260004043579}, {"content": "Title: Audit of intensive care: a 30 month experience using the Apache II severity of disease classification system Content: 608 patients admitted to a general Intensive Care Unit (ICU) over a 30 month period were analyzed according to the Apache II Severity of Disease Classification System on day one of admission. Hospital outcome details were available on 583 patients in the series. The mean Apache II scores for survivors (396) and non-survivors (187) were 13 (SD 7) and 24 (SD 9), and their Risk of Death were 16 (SD 16) and 47 (SD 27) respectively (p(0.001 for both). The majority of deaths (75%: 141/187) in our series came from those with chronic ill health (55%: 103/187), of whom 37% (38/103) were in endstage disease, and those with \u201cold\u201d trauma (18%: 34/187) often with incipient sepsis transferred from other hospitals after a mean delay of 9 days. Our higher than predicted mortality (mortality ratio 1.2) in comparison with centres in the United States of America (US) may be partly explained by the high proportion of our population from these unfavourable groups, by our use of the best Glasgow Coma Scale in the first 24 h following admission, and the major differences between our patient population and that of the US upon which the Apache II was based. The presence of these large unfavourable groups indicates a change in our admission policy is warranted.", "qid": 21, "docid": "hmctkbl1", "rank": 47, "score": 0.7665256261825562}, {"content": "Title: Chapter 6 Real-Time Estimation of the Case Fatality Ratio and Risk Factors of Death Content: Abstract During the course of an epidemic, estimating the risk of death and identifying risk factors of death are of utmost importance for public health assessment of the severity of infection. The real-time estimation involves a number of important statistical problems to consider, and this chapter comprehensively describes commonly used estimation methods and their pitfalls. When estimating the case fatality risk (CFR) during the course of an epidemic, the data are right-censored because of the time delay from illness onset to death. A conventional survival analysis technique is employed for addressing right censoring. Identification of risk factors of death also requires the care for censored nature of the data, and we have devised a method that combines the survival analysis and logistic regression. Ascertainment bias is always a practical issue in interpreting the absolute value of the CFR or comparing CFR between different groups, and recent studies have shown that observational effort including seroepidemiological survey has to be made to overcome this bias.", "qid": 21, "docid": "ipxu977x", "rank": 48, "score": 0.7662416100502014}, {"content": "Title: A Novel Approach for Estimating the Final Outcome of Global Diseases Like COVID-19 Content: The existence of a universal law which maps the bell curve of daily cases to a sigmoid curve for cumulative ones is used for making robust estimations about the final outcome of a disease. Computations of real time effective reproduction rate are presented and its limited usefulness is derived. After using methods ESE and EDE we are able to find the inflection point of the cumulative curve under consideration and study its time evolution. Since mortality processes tend to follow a Gompertz distribution, we apply the properties of it and introduce novel estimations for both the time remaining after inflection time and the capacity of the curve. Special properties of sigmoid curves are used for assessing the quality of estimation and as indices for the cycle completion. Application is presented for COVID-19 evolution for most affected countries and the World.", "qid": 21, "docid": "2xk2p9a8", "rank": 49, "score": 0.7656921148300171}, {"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": 50, "score": 0.7655017375946045}, {"content": "Title: Global between-countries variance in SARS-CoV-2 mortality is driven by reported prevalence, age distribution, and case detection rate Content: Objective: To explain the global between-countries variance in number of deaths per million citizens (nDpm) and case fatality rate (CFR) due to severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection. Design: Systematic analysis. Data sources: Worldometer, European Centre for Disease Prevention and Control, United Nations Main outcome measures: The explanators of nDpm and CFR were mathematically hypothesised and tested on publicly-available data from 88 countries with linear regression models on May 1st 2020. The derived explanators - age-adjusted infection fatality rate (IFRadj) and case detection rate (CDR) - were estimated for each country based on a SARS-CoV-2 model of China. The accuracy and agreement of the models with observed data was assessed with R2 and Bland-Altman plots, respectively. Sensitivity analyses involved removal of outliers and testing the models at five retrospective and two prospective time points. Results: Globally, IFRadj estimates varied between countries, ranging from below 0.2% in the youngest nations, to above 1.3% in Portugal, Greece, Italy, and Japan. The median estimated global CDR of SARS-CoV-2 infections on April 16th 2020 was 12.9%, suggesting that most of the countries have a much higher number of cases than reported. At least 93% and up to 99% of the variance in nDpm was explained by reported prevalence expressed as cases per million citizens (nCpm), IFRadj, and CDR. IFRadj and CDR accounted for up to 97% of the variance in CFR, but this model was less reliable than the nDpm model, being sensitive to outliers (R2 as low as 67.5%). Conclusions: The current differences in SARS-CoV-2 mortality between countries are driven mainly by reported prevalence of infections, age distribution, and CDR. The nDpm might be a more stable estimate than CFR in comparing mortality burden between countries.", "qid": 21, "docid": "i6ozygkp", "rank": 51, "score": 0.7654340267181396}, {"content": "Title: Excess mortality in mental health service users during the COVID-19 pandemic described by ethnic group: South London and Maudsley data Content: The COVID-19 pandemic in the UK was accompanied by excess all-cause mortality at a national level, only part of which was accounted for by known infections. Excess mortality has previously been described in people who had received care from the South London and Maudsley NHS Foundation Trust (SLaM), a large mental health service provider for 1.2m residents in south London. The SLaM Clinical Record Interactive Search (CRIS) data resource receives 24-hourly updates from its full electronic health record, including regularly sourced national mortality on all past and present SLaM service users. The SLaM urban catchment has high levels of deprivation and is ethnically diverse, so the objective of the descriptive analyses reported in this manuscript was to compare mortality in SLaM service users from 16th March to 15th May 2020 to that for the same period in 2019 within specific ethnic groups: i) White British, ii) Other White, iii) Black African/Caribbean, iv) South Asian, v) Other, and vi) missing/not stated. For Black African/Caribbean patients (the largest minority ethnic group) this ratio was 3.33, compared to 2.47 for White British patients. Considering premature mortality (restricting to deaths below age 70), these ratios were 2.74 and 1.96 respectively. Ratios were also high for those from Other ethnic groups (2.63 for all mortality, 3.07 for premature mortality).", "qid": 21, "docid": "rw4np4z3", "rank": 52, "score": 0.7651711702346802}, {"content": "Title: Morbidity and mortality in homeless individuals, prisoners, sex workers, and individuals with substance use disorders in high-income countries: a systematic review and meta-analysis. Content: BACKGROUND Inclusion health focuses on people in extremely poor health due to poverty, marginalisation, and multimorbidity. We aimed to review morbidity and mortality data on four overlapping populations who experience considerable social exclusion: homeless populations, individuals with substance use disorders, sex workers, and imprisoned individuals. METHODS For this systematic review and meta-analysis, we searched MEDLINE, Embase, and the Cochrane Library for studies published between Jan 1, 2005, and Oct 1, 2015. We included only systematic reviews, meta-analyses, interventional studies, and observational studies that had morbidity and mortality outcomes, were published in English, from high-income countries, and were done in populations with a history of homelessness, imprisonment, sex work, or substance use disorder (excluding cannabis and alcohol use). Studies with only perinatal outcomes and studies of individuals with a specific health condition or those recruited from intensive care or high dependency hospital units were excluded. We screened studies using systematic review software and extracted data from published reports. Primary outcomes were measures of morbidity (prevalence or incidence) and mortality (standardised mortality ratios [SMRs] and mortality rates). Summary estimates were calculated using a random effects model. FINDINGS Our search identified 7946 articles, of which 337 studies were included for analysis. All-cause standardised mortality ratios were significantly increased in 91 (99%) of 92 extracted datapoints and were 11\u00b786 (95% CI 10\u00b742-13\u00b730; I2=94\u00b71%) in female individuals and 7\u00b788 (7\u00b703-8\u00b774; I2=99\u00b71%) in men. Summary SMR estimates for the International Classification of Diseases disease categories with two or more included datapoints were highest for deaths due to injury, poisoning, and other external causes, in both men (7\u00b789; 95% CI 6\u00b740-9\u00b737; I2=98\u00b71%) and women (18\u00b772; 13\u00b773-23\u00b771; I2=91\u00b75%). Disease prevalence was consistently raised across the following categories: infections (eg, highest reported was 90% for hepatitis C, 67 [65%] of 103 individuals for hepatitis B, and 133 [51%] of 263 individuals for latent tuberculosis infection), mental health (eg, highest reported was 9 [4%] of 227 individuals for schizophrenia), cardiovascular conditions (eg, highest reported was 32 [13%] of 247 individuals for coronary heart disease), and respiratory conditions (eg, highest reported was 9 [26%] of 35 individuals for asthma). INTERPRETATION Our study shows that homeless populations, individuals with substance use disorders, sex workers, and imprisoned individuals experience extreme health inequities across a wide range of health conditions, with the relative effect of exclusion being greater in female individuals than male individuals. The high heterogeneity between studies should be explored further using improved data collection in population subgroups. The extreme health inequity identified demands intensive cross-sectoral policy and service action to prevent exclusion and improve health outcomes in individuals who are already marginalised. FUNDING Wellcome Trust, National Institute for Health Research, NHS England, NHS Research Scotland Scottish Senior Clinical Fellowship, Medical Research Council, Chief Scientist Office, and the Central and North West London NHS Trust.", "qid": 21, "docid": "h9gfyeb8", "rank": 53, "score": 0.7649357318878174}, {"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": 54, "score": 0.7647169232368469}, {"content": "Title: Online estimation of the case fatality rate using a run-off triangle data approach: An application to the Korean MERS outbreak in 2015. Content: This work is motivated by the recent Korean Middle East respiratory syndrome outbreak. We propose an easy online estimation procedure for the case fatality rate, ie, the proportion of deaths among the total cases during the course of an epidemic disease, which is an important indicator of the severity of a disease. The key step in our procedure is representing the data with the run-off triangle, which simultaneously takes into account two time axes, namely, the calendar and disease-duration times. We restructure the original data into run-off triangle data, where the cells contain the numbers of cured patients, deceased patients, and patients still having the disease at a given combination of calendar and disease-duration times. Based on the restructured run-off triangle data, we propose an online estimator of the case fatality rate. We numerically show the advantages of the proposed estimator compared to the existing estimators in the literature. Finally, we apply our procedure to the 2015 Korean Middle East respiratory syndrome outbreak data.", "qid": 21, "docid": "g9q2l3qp", "rank": 55, "score": 0.764438271522522}, {"content": "Title: Estimates of COVID-19 case-fatality risk from individual-level data Content: When calculated from aggregate data on confirmed cases and deaths, the case-fatality risk (CFR) is a simple ratio between the former and the latter, which is prone to numerous biases. With individual-level data, the CFR can be estimated as a true measure of risk as the proportion of incidence for the disease. We present the first estimates of the CFR for COVID-19 by age and sex based on event history modelling of the risk of dying among confirmed positive individuals in the Canadian province of Ontario, which maintains one of the few individual-level datasets on COVID-19 in the world.", "qid": 21, "docid": "fgjhli0p", "rank": 56, "score": 0.7639681100845337}, {"content": "Title: Age effects in monetary valuation of reduced mortality risks: the relevance of age-specific hazard rates Content: This paper highlights the relevance of age-specific hazard rates in explaining the age variation in \u201cvalue of statistical life\u201d (VSL) figures. The analysis\u2014which refers to a stated preference framework\u2014contributes to the ongoing discussion of whether benefits resulting from reduced mortality risk should be valued differently depending on the age of the beneficiaries. By focussing on a life-threatening environmental phenomenon I show that the consideration of the individual\u2019s age-specific hazard rate is important. If a particular risk affects all individuals regardless of their age so that their hazard rate is age-independent, VSL is rather constant for people at different age; if hazard rate varies with age, VSL estimates are sensitive to age. The results provide an explanation for the mixed outcomes in empirical studies and illustrate in which cases an adjustment to age may or may not be justified. Efficient provision of live-saving measures requires that such differences to be taken into account.", "qid": 21, "docid": "um9kefk4", "rank": 57, "score": 0.7638736963272095}, {"content": "Title: Global, regional, and national estimates of levels of preterm birth in 2014: a systematic review and modelling analysis. Content: BACKGROUND Preterm birth is the leading cause of death in children younger than 5 years worldwide. Although preterm survival rates have increased in high-income countries, preterm newborns still die because of a lack of adequate newborn care in many low-income and middle-income countries. We estimated global, regional, and national rates of preterm birth in 2014, with trends over time for some selected countries. METHODS We systematically searched for data on preterm birth for 194 WHO Member States from 1990 to 2014 in databases of national civil registration and vital statistics (CRVS). We also searched for population-representative surveys and research studies for countries with no or limited CRVS data. For 38 countries with high-quality data for preterm births in 2014, data are reported directly. For countries with at least three data points between 1990 and 2014, we used a linear mixed regression model to estimate preterm birth rates. We also calculated regional and global estimates of preterm birth for 2014. FINDINGS We identified 1241 data points across 107 countries. The estimated global preterm birth rate for 2014 was 10\u00b76% (uncertainty interval 9\u00b70-12\u00b70), equating to an estimated 14\u00b784 million (12\u00b765 million-16\u00b773 million) live preterm births in 2014. 12\u00b7 0 million (81\u00b71%) of these preterm births occurred in Asia and sub-Saharan Africa. Regional preterm birth rates for 2014 ranged from 13\u00b74% (6\u00b73-30\u00b79) in North Africa to 8\u00b77% (6\u00b73-13\u00b73) in Europe. India, China, Nigeria, Bangladesh, and Indonesia accounted for 57\u00b79 million (41\u00d74%) of 139\u00b79 million livebirths and 6\u00b76 million (44\u00d76%) of preterm births globally in 2014. Of the 38 countries with high-quality data, preterm birth rates have increased since 2000 in 26 countries and decreased in 12 countries. Globally, we estimated that the preterm birth rate was 9\u00d78% (8\u00d73-10\u00d79) in 2000, and 10\u00d76% (9\u00d70-12\u00d70) in 2014. INTERPRETATION Preterm birth remains a crucial issue in child mortality and improving quality of maternal and newborn care. To better understand the epidemiology of preterm birth, the quality and volume of data needs to be improved, including standardisation of definitions, measurement, and reporting. FUNDING WHO and the March of Dimes.", "qid": 21, "docid": "4f2wkjgj", "rank": 58, "score": 0.7637572288513184}, {"content": "Title: Global, regional, and national incidence, prevalence, and years lived with disability for 328 diseases and injuries for 195 countries, 1990-2016: a systematic analysis for the Global Burden of Disease Study 2016. Content: BACKGROUND As mortality rates decline, life expectancy increases, and populations age, non-fatal outcomes of diseases and injuries are becoming a larger component of the global burden of disease. The Global Burden of Diseases, Injuries, and Risk Factors Study 2016 (GBD 2016) provides a comprehensive assessment of prevalence, incidence, and years lived with disability (YLDs) for 328 causes in 195 countries and territories from 1990 to 2016. METHODS We estimated prevalence and incidence for 328 diseases and injuries and 2982 sequelae, their non-fatal consequences. We used DisMod-MR 2.1, a Bayesian meta-regression tool, as the main method of estimation, ensuring consistency between incidence, prevalence, remission, and cause of death rates for each condition. For some causes, we used alternative modelling strategies if incidence or prevalence needed to be derived from other data. YLDs were estimated as the product of prevalence and a disability weight for all mutually exclusive sequelae, corrected for comorbidity and aggregated to cause level. We updated the Socio-demographic Index (SDI), a summary indicator of income per capita, years of schooling, and total fertility rate. GBD 2016 complies with the Guidelines for Accurate and Transparent Health Estimates Reporting (GATHER). FINDINGS Globally, low back pain, migraine, age-related and other hearing loss, iron-deficiency anaemia, and major depressive disorder were the five leading causes of YLDs in 2016, contributing 57\u00b76 million (95% uncertainty interval [UI] 40\u00b78-75\u00b79 million [7\u00b72%, 6\u00b70-8\u00b73]), 45\u00b71 million (29\u00b70-62\u00b78 million [5\u00b76%, 4\u00b70-7\u00b72]), 36\u00b73 million (25\u00b73-50\u00b79 million [4\u00b75%, 3\u00b78-5\u00b73]), 34\u00b77 million (23\u00b70-49\u00b76 million [4\u00b73%, 3\u00b75-5\u00b72]), and 34\u00b71 million (23\u00b75-46\u00b70 million [4\u00b72%, 3\u00b72-5\u00b73]) of total YLDs, respectively. Age-standardised rates of YLDs for all causes combined decreased between 1990 and 2016 by 2\u00b77% (95% UI 2\u00b73-3\u00b71). Despite mostly stagnant age-standardised rates, the absolute number of YLDs from non-communicable diseases has been growing rapidly across all SDI quintiles, partly because of population growth, but also the ageing of populations. The largest absolute increases in total numbers of YLDs globally were between the ages of 40 and 69 years. Age-standardised YLD rates for all conditions combined were 10\u00b74% (95% UI 9\u00b70-11\u00b78) higher in women than in men. Iron-deficiency anaemia, migraine, Alzheimer's disease and other dementias, major depressive disorder, anxiety, and all musculoskeletal disorders apart from gout were the main conditions contributing to higher YLD rates in women. Men had higher age-standardised rates of substance use disorders, diabetes, cardiovascular diseases, cancers, and all injuries apart from sexual violence. Globally, we noted much less geographical variation in disability than has been documented for premature mortality. In 2016, there was a less than two times difference in age-standardised YLD rates for all causes between the location with the lowest rate (China, 9201 YLDs per 100 000, 95% UI 6862-11943) and highest rate (Yemen, 14 774 YLDs per 100 000, 11 018-19 228). INTERPRETATION The decrease in death rates since 1990 for most causes has not been matched by a similar decline in age-standardised YLD rates. For many large causes, YLD rates have either been stagnant or have increased for some causes, such as diabetes. As populations are ageing, and the prevalence of disabling disease generally increases steeply with age, health systems will face increasing demand for services that are generally costlier than the interventions that have led to declines in mortality in childhood or for the major causes of mortality in adults. Up-to-date information about the trends of disease and how this varies between countries is essential to plan for an adequate health-system response. 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": "dte78dra", "rank": 59, "score": 0.7632604837417603}, {"content": "Title: Perspectives on the basic reproductive ratio. Content: The basic reproductive ratio, R0, is defined as the expected number of secondary infections arising from a single individual during his or her entire infectious period, in a population of susceptibles. This concept is fundamental to the study of epidemiology and within-host pathogen dynamics. Most importantly, R0 often serves as a threshold parameter that predicts whether an infection will spread. Related parameters which share this threshold behaviour, however, may or may not give the true value of R0. In this paper we give a brief overview of common methods of formulating R0 and surrogate threshold parameters from deterministic, non-structured models. We also review common means of estimating R0 from epidemiological data. Finally, we survey the recent use of R0 in assessing emerging diseases, such as severe acute respiratory syndrome and avian influenza, a number of recent livestock diseases, and vector-borne diseases malaria, dengue and West Nile virus.", "qid": 21, "docid": "212x5waa", "rank": 60, "score": 0.7630609273910522}, {"content": "Title: Introduction: A Prelude to Mathematical Epidemiology Content: Recorded history continuously documents the invasion of populations by infectious agents, some causing many deaths before disappearing, others reappearing in invasions some years later in populations that have acquired some degree of immunity, due to prior exposure to related infectious pathogens. The \u201cSpanish\u201d flu epidemic of 1918\u20131919 exemplifies the devastating impact of relatively rare pandemics; this one was responsible for about 50,000,000 deaths worldwide, while on the mild side of the spectrum we experience annual influenza seasonal epidemics that cause roughly 35,000 deaths in the USA each year.", "qid": 21, "docid": "35rx2yav", "rank": 61, "score": 0.7629982829093933}, {"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": 62, "score": 0.7629716396331787}, {"content": "Title: Monitoring trends and differences in COVID-19 case fatality rates using decomposition methods: Contributions of age structure and age-specific fatality Content: The population-level case fatality rate (CFR) associated with COVID-19 varies substantially, both across countries and within countries over time. We analyze the contribution of two key determinants of the variation in the observed CFR: the age-structure of diagnosed infection cases and age-specific case-fatality rates. We use data on diagnosed COVID-19 cases and death counts attributable to COVID-19 by age for China, France, Germany, Italy, South Korea, Spain, and the United States. We calculate the CFR for each country at the latest data point and for Italy also over time. We use demographic decomposition to break the difference between CFRs into unique contributions arising from the age-structure of confirmed cases and the age-specific case-fatality. CFRs vary from 0.7% in Germany and 1.6% in South Korea to 8.6% in Spain and 10.6% in Italy. The age-structure of detected cases can explain a substantial proportion of cross-country variation in the CFR. For example, 57% of Spain's difference with respect to South Korea is explained by the observed cases being older. In Italy, the CFR increased from 4.2% to 10.6% between March 9 and March 29, 2020, and more than 95% of the change was due to increasing age-specific case fatality rates. The importance of the age-structure of infected cases likely reflects several factors, including different testing regimes and differences in transmission trajectories; while increasing age-specific case fatality rates indicate the worsening health outcomes of those infected with COVID-19. Our findings lend support to recommendations for data to be disaggregated by age, and potentially other variables, to facilitate a better understanding of population-level differences in CFRs. They also show the need for well designed seroprevalence studies to ascertain the extent to which differences in testing regimes drive differences in the age-structure of detected cases.", "qid": 21, "docid": "6ub9yh27", "rank": 63, "score": 0.7628421783447266}, {"content": "Title: Understanding the asymmetric spread and case fatality rate (CFR) for COVID-19 among countries Content: The severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infections are rising rapidly every day in the world, causing the disease COVID-19 with around 2 million people infected and more than 100,000 people died so far, in more than 200 countries. One of the baffling aspects of this pandemic is the asymmetric increase in cases and case fatality rate (CFR) among countries. We analyze the time series of the infection and fatality numbers and found two interesting aspects. Firstly, the rate of spread in a region is directly connected to the population density of the region where the virus is spreading. For example, the high rate of increase in cases in the United States of America (USA) is related to the high population density of New York City. This is shown by scaling the cumulative number of cases with a measure of the population density of the affected region in countries such as Italy, Spain, Germany, and the USA and we see that the curves are coinciding. Secondly, we analyzed the CFR number as a function of the number of days, since the first death, and we found that there are two clear categories among countries: one category with high CFR numbers (around 10%) and the other category with low CFR numbers (2% to 4%). When we analyzed the results, we see that countries with lower CFR numbers more or less tend to have implemented active control measures such as aggressive testing, tracking down possible infections, effective quarantine measures, etc. Moreover, we did not see any convincing correlation between mortality rates and the median age of the population.", "qid": 21, "docid": "pughsygu", "rank": 64, "score": 0.7628055810928345}, {"content": "Title: The Impact of Population Growth on the Epidemiology and Evolution of Infectious Diseases Content: It is generally expected that in developing countries the epidemiological transition, with improved health and lower mortality rates, will eventually lead to a demographic transition with lower fertility rates. The reductions in mortality characterising the epidemiological transition are often associated with controlling the infectious diseases within populations, which leaves the chronic diseases associated with old age, cancer and heart disease dominating the causes of death. However, if the demographic transition does not occur quickly, populations can grow rapidly, creating an increased potential for spread of infectious disease. These infectious diseases could, in turn, increase death rates amongst young people and reverse the epidemiological transition. The relationship between population growth, size and infection depends upon the changes in contact pattern associated with there being more people. If facilities can keep pace with growth, then the increase in contact rates can be kept to a minimum, and the potential reversal in the epidemic transition prevented. This makes development a crucial adjunct to population growth if the global community is not to be increasingly exposed to pandemics of infectious disease. Here we review the epidemiological and demographic theory which relates population growth and infectious disease.", "qid": 21, "docid": "61norte8", "rank": 65, "score": 0.7627441883087158}, {"content": "Title: Staphylococcus aureus Colonization and Long-Term Risk for Death, United States. Content: To examine the association of colonization by Staphylococcus aureus and general population mortality, we followed 10,598 adults for 8.5 years on average. Methicillin-susceptible S. aureus colonization was not associated with death. Methicillin-resistant S. aureus carriage predicted death in a crude analysis but not after adjustment for socioeconomic status and co-morbidities.", "qid": 21, "docid": "pzdssyiu", "rank": 66, "score": 0.7623851895332336}, {"content": "Title: Risk for Death among Children with Pneumonia, Afghanistan. Content: In Afghanistan, childhood deaths from pneumonia are high. Among 639 children at 1 hospital, the case-fatality rate was 12.1%, and 46.8% of pneumococcal serotypes detected were covered by the 13-valent vaccine. Most deaths occurred within 2 days of hospitalization; newborns and malnourished children were at risk. Vaccination could reduce pneumonia and deaths.", "qid": 21, "docid": "hljb6cv0", "rank": 67, "score": 0.7623413801193237}, {"content": "Title: Ecology of Increasing Diseases: Population Growth and Environmental Degradation Content: The World Health Organization (WHO) and other organizations report that the prevalence of human diseases during the past decade is rapidly increasing. Population growth and the pollution of water, air, and soil are contributing to the increasing number of human diseases worldwide. Currently an estimated 40% of world deaths are due to environmental degradation. The ecology of increasing diseases has complex factors of environmental degradation, population growth, and the current malnutrition of about 3.7 billion people in the world.", "qid": 21, "docid": "eq1hp6a7", "rank": 68, "score": 0.7620371580123901}, {"content": "Title: Predicting the mortality due to Covid-19 by the next month for Italy, Iran and South Korea; a simulation study Content: AIM: To estimate the number of confirmed cases and the rate of death and also to investigate the cause of death in Italy, Iran and South Korea in the next month. BACKGROUND: Growing number of confirmed and deaths cases from the coronavirus worldwide, particularly in Italy, Iran and South Korea, has resulted concerns about the future of these countries and their deterioration. Also the European region is likely to face more casualties due to the delay in the virus reaching most of its regions and, of course, as the trend continues. METHODS: We conducted a simulation in both current and ideal situation for the next month to predict the death rate and examine the reason for the difference in Italy, Iran and South Korea individually. If we assume the cultural and political factors and age pyramids distribution are similar across regions, the differences are mainly due either to the heavier health-care burden owing to the larger population or to the medical facilities diversities. RESULTS: Our results for Italy showed higher death number, but the rate would be more for Iran. South Korea is also expected to have a smaller increase in the number of confirmed cases and deaths compared to Iran and Italy by the next month. CONCLUSION: Given the prevailing conditions around the world and the increasing number of casualties, it is essential that all countries, especially those with fewer days of involvement, shall do their best to avoid major losses and damages.", "qid": 21, "docid": "qdoseeyv", "rank": 69, "score": 0.7615758776664734}, {"content": "Title: Predicting the mortality due to Covid-19 by the next month for Italy, Iran and South Korea; A simulation study Content: Aim: To estimate the number of confirmed cases and the rate of death and also to investigate the cause of death in Italy, Iran and South Korea in the next month. Background: Growing number of confirmed and deaths cases from the coronavirus worldwide, particularly in Italy, Iran and South Korea, has resulted concerns about the future of these countries and their deterioration. Also the European region is likely to face more casualties due to the delay in the virus reaching most of its regions and, of course, as the trend continues. Methods: We conducted a simulation in both current and ideal situation for the next month to predict the death rate and examine the reason for the difference in Italy, Iran and South Korea individually. If we assume the cultural and political factors and age pyramids distribution are similar across regions, the differences are mainly due either to the heavier health-care burden owing to the larger population or to the medical facilities diversities. Results: Our results for Italy showed higher death number, but the rate would be more for Iran. South Korea is also expected to have a smaller increase in the number of confirmed cases and deaths compared to Iran and Italy by the next month. Conclusion: Given the prevailing conditions around the world and the increasing number of casualties, it is essential that all countries, especially those with fewer days of involvement, shall do their best to avoid major losses and damages.", "qid": 21, "docid": "ap03onq3", "rank": 70, "score": 0.7615758776664734}, {"content": "Title: Aetiology-Specific Estimates of the Global and Regional Incidence and Mortality of Diarrhoeal Diseases Commonly Transmitted through Food Content: BACKGROUND: Diarrhoeal diseases are major contributors to the global burden of disease, particularly in children. However, comprehensive estimates of the incidence and mortality due to specific aetiologies of diarrhoeal diseases are not available. The objective of this study is to provide estimates of the global and regional incidence and mortality of diarrhoeal diseases caused by nine pathogens that are commonly transmitted through foods. METHODS AND FINDINGS: We abstracted data from systematic reviews and, depending on the overall mortality rates of the country, applied either a national incidence estimate approach or a modified Child Health Epidemiology Reference Group (CHERG) approach to estimate the aetiology-specific incidence and mortality of diarrhoeal diseases, by age and region. The nine diarrhoeal diseases assessed caused an estimated 1.8 billion (95% uncertainty interval [UI] 1.1\u20133.3 billion) cases and 599,000 (95% UI 472,000\u2013802,000) deaths worldwide in 2010. The largest number of cases were caused by norovirus (677 million; 95% UI 468\u20131,153 million), enterotoxigenic Escherichia coli (ETEC) (233 million; 95% UI 154\u2013380 million), Shigella spp. (188 million; 95% UI 94\u2013379 million) and Giardia lamblia (179 million; 95% UI 125\u2013263); the largest number of deaths were caused by norovirus (213,515; 95% UI 171,783\u2013266,561), enteropathogenic E. coli (121,455; 95% UI 103,657\u2013143,348), ETEC (73,041; 95% UI 55,474\u201396,984) and Shigella (64,993; 95% UI 48,966\u201392,357). There were marked regional differences in incidence and mortality for these nine diseases. Nearly 40% of cases and 43% of deaths caused by these nine diarrhoeal diseases occurred in children under five years of age. CONCLUSIONS: Diarrhoeal diseases caused by these nine pathogens are responsible for a large disease burden, particularly in children. These aetiology-specific burden estimates can inform efforts to reduce diarrhoeal diseases caused by these nine pathogens commonly transmitted through foods.", "qid": 21, "docid": "a8qr7nl6", "rank": 71, "score": 0.7612495422363281}, {"content": "Title: How Many Lives Has Lockdown Saved in the UK? Content: We compare the trajectory of deaths (both in hospitals and care homes) on a daily basis in Sweden and England and Wales (which constitute 90 per cent of the UK population) from 11 March to 12 June 2020, the latest date at which the relevant data is available for England and Wales. Deaths in both Sweden and England and Wales peaked on 8 April. The build up to the peak was very similar in both. Given the time lag between infection and death, the lockdown would have had little effect on the peak number of deaths. By 12 June, the deaths are virtually the same in both. However, from early May the decline in England and Wales has been much sharper. We estimate that to 12 June, lockdown saved just under 6,000 lives in England and Wales, or around 6,500 extrapolating to a UK level.", "qid": 21, "docid": "pl6t82lr", "rank": 72, "score": 0.7609279155731201}, {"content": "Title: Inferring the effective fraction of the population infected with Covid-19 from the behaviour of Lombardy, Madrid and London relative to the remainder of Italy, Spain and England Content: I use a very simple deterministic model for the spread of Covid-19 in a large population. Using this to compare the relative decay of the number of deaths per day between different regions in Italy, Spain and England, each applying in principle the same social distancing procedures across the whole country, I obtain an estimate of the total fraction of the population which had already become infected by April 10th. In the most heavily affected regions, Lombardy, Madrid and London, this fraction is higher than expected, i.e. $\\approx 0.3$. This result can then be converted to a determination of the infection fatality rate $ifr$, which appears to be $ifr \\approx 0.0025-0.005$, and even smaller in London, somewhat lower than usually assumed. Alternatively, the result can also be interpreted as an effectively larger fraction of the population than simple counting would suggest if there is a variation in susceptibility to infection with a variance of up to a value of about 2. The implications are very similar for either interpretation or for a combination of effects.", "qid": 21, "docid": "1qfo701c", "rank": 73, "score": 0.7607781887054443}, {"content": "Title: Methods for estimating disease transmission rates: Evaluating the precision of Poisson regression and two novel methods Content: Precise estimates of disease transmission rates are critical for epidemiological simulation models. Most often these rates must be estimated from longitudinal field data, which are costly and time-consuming to conduct. Consequently, measures to reduce cost like increased sampling intervals or subsampling of the population are implemented. To assess the impact of such measures we implement two different SIS models to simulate disease transmission: A simple closed population model and a realistic dairy herd including population dynamics. We analyze the accuracy of different methods for estimating the transmission rate. We use data from the two simulation models and vary the sampling intervals and the size of the population sampled. We devise two new methods to determine transmission rate, and compare these to the frequently used Poisson regression method in both epidemic and endemic situations. For most tested scenarios these new methods perform similar or better than Poisson regression, especially in the case of long sampling intervals. We conclude that transmission rate estimates are easily biased, which is important to take into account when using these rates in simulation models.", "qid": 21, "docid": "dp9w2b9t", "rank": 74, "score": 0.7605171203613281}, {"content": "Title: Childhood Infectious Diseases: Overview Content: Of the annual burden of 10 million deaths among children under 5 years, a large proportion is associated with infectious diseases. These include 36% of the 4 million newborn deaths due to sepsis, pneumonia, diarrhea, and tetanus. Among the postneonatal deaths due to infections, estimates and uncertainty bounds include: 22% of deaths attributed to diarrhea (14\u201330%), 21% to pneumonia (14\u201324%), 9% to malaria (6\u201313%), and 1% to measles (1\u20139%). Some 42 countries alone account for almost 90% of the global burden of child mortality. There is now sufficient evidence available on evidence-based interventions that can make a difference. It is estimated that almost two-thirds of these deaths are potentially preventable if interventions can be delivered at scale. Newborn infections and related mortality can be reduced by maternal tetanus toxoid vaccination, clean delivery, cord hygiene, exclusive and early breast-feeding, and prompt diagnosis and therapy. Diarrheal deaths can be prevented by adequate attention to breast-feeding, hand-washing and sanitation strategies, rota virus vaccine, adequate treatment including oral rehydration, appropriate dietary therapy, and oral zinc administration. Similarly, the global burden of pneumonia deaths can be reduced by vaccination strategies for measles, Hib, and pneumococcal disease, timely case detection, and treatment with appropriate antibiotics.", "qid": 21, "docid": "rm8d8fyj", "rank": 75, "score": 0.7597935199737549}, {"content": "Title: Predicting the mortality due to Covid-19 by the next month for Italy, Iran and South Korea; a simulation study. Content: Aim To estimate the number of confirmed cases and the rate of death and also to investigate the cause of death in Italy, Iran and South Korea in the next month. Background Growing number of confirmed and deaths cases from the coronavirus worldwide, particularly in Italy, Iran and South Korea, has resulted concerns about the future of these countries and their deterioration. Also the European region is likely to face more casualties due to the delay in the virus reaching most of its regions and, of course, as the trend continues. Methods We conducted a simulation in both current and ideal situation for the next month to predict the death rate and examine the reason for the difference in Italy, Iran and South Korea individually. If we assume the cultural and political factors and age pyramids distribution are similar across regions, the differences are mainly due either to the heavier health-care burden owing to the larger population or to the medical facilities diversities. Results Our results for Italy showed higher death number, but the rate would be more for Iran. South Korea is also expected to have a smaller increase in the number of confirmed cases and deaths compared to Iran and Italy by the next month. Conclusion Given the prevailing conditions around the world and the increasing number of casualties, it is essential that all countries, especially those with fewer days of involvement, shall do their best to avoid major losses and damages.", "qid": 21, "docid": "vonizlpv", "rank": 76, "score": 0.7594718933105469}, {"content": "Title: A comparative epidemiologic analysis of SARS in Hong Kong, Beijing and Taiwan Content: BACKGROUND: The 2002-2003 Severe Acute Respiratory Syndrome (SARS) outbreak infected 8,422 individuals leading to 916 deaths around the world. However, there have been few epidemiological studies of SARS comparing epidemiologic features across regions. The aim of this study is to identify similarities and differences in SARS epidemiology in three populations with similar host and viral genotype. METHODS: We present a comparative epidemiologic analysis of SARS, based on an integrated dataset with 3,336 SARS patients from Hong Kong, Beijing and Taiwan, epidemiological and clinical characteristics such as incubation, onset-to-admission, onset-to-discharge and onset-to-death periods, case fatality ratios (CFRs) and presenting symptoms are described and compared between regions. We further explored the influence of demographic and clinical variables on the apparently large differences in CFRs between the three regions. RESULTS: All three regions showed similar incubation periods and progressive shortening of the onset-to-admission interval through the epidemic. Adjusted for sex, health care worker status and nosocomial setting, older age was associated with a higher fatality, with adjusted odds ratio (AOR): 2.10 (95% confidence interval: 1.45, 3.04) for those aged 51-60; AOR: 4.57 (95% confidence interval: 3.32, 7.30) for those aged above 60 compared to those aged 41-50 years. Presence of pre-existing comorbid conditions was also associated with greater mortality (AOR: 1.74; 95% confidence interval: 1.36, 2.21). CONCLUSION: The large discrepancy in crude fatality ratios across the three regions can only be partly explained by epidemiological and clinical heterogeneities. Our findings underline the importance of a common data collection platform, especially in an emerging epidemic, in order to identify and explain consistencies and differences in the eventual clinical and public health outcomes of infectious disease outbreaks, which is becoming increasingly important in our highly interconnected world.", "qid": 21, "docid": "jknfhd7d", "rank": 77, "score": 0.7593936920166016}, {"content": "Title: The Effective Reproduction Number as a Prelude to Statistical Estimation of Time-Dependent Epidemic Trends Content: Although the basic reproduction number, R (0), is useful for understanding the transmissibility of a disease and designing various intervention strategies, the classic threshold quantity theoretically assumes that the epidemic first occurs in a fully susceptible population, and hence, R (0) is essentially a mathematically defined quantity. In many instances, it is of practical importance to evaluate time-dependent variations in the transmission potential of infectious diseases. Explanation of the time course of an epidemic can be partly achieved by estimating the effective reproduction number, R(t), defined as the actual average number of secondary cases per primary case at calendar time t (for t >0). R(t) shows time-dependent variation due to the decline in susceptible individuals (intrinsic factors) and the implementation of control measures (extrinsic factors). If R(t)<1, it suggests that the epidemic is in decline and may be regarded as being under control at time t (vice versa, if R(t)>1). This chapter describes the primer of mathematics and statistics of R(t) and discusses other similar markers of transmissibility as a function of time.", "qid": 21, "docid": "7oxj4coe", "rank": 78, "score": 0.7593222260475159}, {"content": "Title: Early and massive testing saves lives: COVID-19 related infections and deaths in the United States during March of 2020 Content: To optimize epidemiologic interventions, predictors of mortality should be identified. The US COVID-19 epidemic data, reported up to 31 March 2020, were analyzed using kernel regularized least squares regression. Six potential predictors of mortality were investigated: (i) the number of diagnostic tests performed in testing week I; (ii) the proportion of all tests conducted during week I of testing; (iii) the cumulative number of (test-positive) cases through 3-31-2020, (iv) the number of tests performed/million citizens; (v) the cumulative number of citizens tested; and (vi) the apparent prevalence rate, defined as the number of cases/million citizens. Two metrics estimated mortality: the number of deaths and the number of deaths/million citizens. While both expressions of mortality were predicted by the case count and the apparent prevalence rate, the number of deaths/million citizens was {approx}3.5 times better predicted by the apparent prevalence rate than the number of cases. In eighteen states, early testing/million citizens/population density was inversely associated with the cumulative mortality reported by 31 March, 2020. Findings support the hypothesis that early and massive testing saves lives. Other factors --e.g., population density-- may also influence outcomes. To optimize national and local policies, the creation and dissemination of high resolution geo-referenced, epidemic data is recommended.", "qid": 21, "docid": "z2zwdxrk", "rank": 79, "score": 0.7593147158622742}, {"content": "Title: On Determining the Age Distribution of COVID-19 Pandemic Content: Pandemics tend to have higher occurrence (morbidity) in younger individuals but higher mortality for the elderly. The higher rate of mortality of COVID-19 in elderly individuals has been discussed in many reports. However, this pandemic is a double-edged sword as this comment shows higher morbidity rates in elderly as well. This is shown by comparing the age distribution of cases in China and South Korea to the relative populations. In every case, the relative number of elderly contracting the virus is far higher than the proportion of elderly in the population. This is unlike past pandemics and shows that aging populations are at an even higher risk than the perceived age dependent rates may imply.", "qid": 21, "docid": "ldv9hsv1", "rank": 80, "score": 0.7592475414276123}, {"content": "Title: Scientific comment on\"Tail risk of contagious diseases\" Content: Cirillo and Taleb [Nature Phys. 16, 606-613 (2020)] study the size of major epidemics in human history in terms of the number of fatalities. Using the figures from 72 epidemics, from the plague of Athens (429 BC) to the COVID-19 (2019-2020), they claim that the resulting fatality distribution is ``extremely fat-tailed'', i.e., asymptotically a power law. This has important consequences for risk, as the mean value of the fatality distribution becomes infinite. Reanalyzing the same data, we find that, although the data may be compatible with a power-law tail, these results are not conclusive, and other distributions, not fat-tailed, could explain the data equally well. Simulation of a log-normally distributed random variable provides synthetic data whose statistics are undistinguishable from the statistics of the empirical data.", "qid": 21, "docid": "5f2rzh0n", "rank": 81, "score": 0.7591683864593506}, {"content": "Title: Estimation of the true infection rate and infection fatality rate of COVID-19 in the whole population of each country Content: The true infection rate of COVID-19 and the infection fatality rate in the whole population have been estimated for each country. The estimate well coincided with local surveys. The fact that several tens of times, or more, of identified cases are already infected might require reconsideration of the strategy.", "qid": 21, "docid": "yjny2xcf", "rank": 82, "score": 0.758886456489563}, {"content": "Title: Estimating finite-population reproductive numbers in heterogeneous populations Content: Abstract The basic reproductive number, R 0 , is one of the most important epidemiological quantities. R 0 provides a threshold for elimination and determines when a disease can spread or when a disease will die out. Classically, R 0 is calculated assuming an infinite population of identical hosts. Previous work has shown that heterogeneity in the host mixing rate increases R 0 in an infinite population. However, it has been suggested that in a finite population, heterogeneity in the mixing rate may actually decrease the finite-population reproductive numbers. Here, we outline a framework for discussing different types of heterogeneity in disease parameters, and how these affect disease spread and control. We calculate \u201cfinite-population reproductive numbers\u201d with different types of heterogeneity, and show that in a finite population, heterogeneity has complicated effects on the reproductive number. We find that simple heterogeneity decreases the finite-population reproductive number, whereas heterogeneity in the intrinsic mixing rate (which affects both infectiousness and susceptibility) increases the finite-population reproductive number when R 0 is small relative to the size of the population and decreases the finite-population reproductive number when R 0 is large relative to the size of the population. Although heterogeneity has complicated effects on the finite-population reproductive numbers, its implications for control are straightforward: when R 0 is large relative to the size of the population, heterogeneity decreases the finite-population reproductive numbers, making disease control or elimination easier than predicted by R 0 .", "qid": 21, "docid": "ao2w4v71", "rank": 83, "score": 0.7586034536361694}, {"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": 84, "score": 0.7583882808685303}, {"content": "Title: Estimating the case fatality rate using a constant cure-death hazard ratio. Content: The case fatality rate is an important indicator of the severity of a disease, and unbiased and accurate estimates of it during an outbreak are important in the study of epidemic diseases, including severe acute respiratory syndrome (SARS). In this paper, estimation methods are developed using a constant cure-death hazard ratio. A semiparametric model is presented, in which the cure-death hazard ratio is a parameter of interest, and a profile likelihood-based technique is proposed for estimating the case fatality rate. An extensive simulation was carried out to investigate the performance of this technique for small and medium sample sizes, using both summary and individual data. The results show that the performance depends on the model validity but is not heavily dependent on the sample size. The method was applied to summary SARS data obtained from Hong Kong and Singapore.", "qid": 21, "docid": "awb5lzoz", "rank": 85, "score": 0.7581910490989685}, {"content": "Title: Mortality from COVID-19 in 12 countries and 6 states of the United States Content: Importance: Reliable estimates of COVID-19 mortality are crucial to aid control strategies and to assess the effectiveness of interventions. Objective: Project COVID-19 mortality trends to October 1, 2020, in 12 countries or regions that constitute >90% of the global COVID-19 deaths reported as of April 12, 2020. Design, Setting, and Participants: The Global COVID-19 Assessment of Mortality (GCAM) is an open, transparent, and continuously updated (www.cghr.org/covid) statistical model that combines actual COVID-19 mortality counts with Bayesian inference to forecast COVID-19 deaths, the date of peak deaths, and the duration of excess mortality. The analyses covered a total of 700 million population above age 20 in 12 countries or regions: USA; Italy; Spain; France; UK; Iran; Belgium; a province of China (Hubei, which accounted for 90% of reported Chinese deaths); Germany; the Netherlands; Switzerland; and Canada; and six US states: New York, New Jersey, Michigan, Louisiana, California, and Washington. Results: Forecasted deaths across the 12 current high-burden countries sum 167,000 to 593,000 (median 253,000). The trajectory of US deaths (49,000-249,000 deaths; median 86,000)- over half of which are expected in states beyond the initial six states analysed in this study- will have the greatest impact on the eventual total. Mortality ranges are 25,000-109,000 (median 46,000) in the UK; 23,000-31,000 (median 26,000) in Italy; 21,000-37,000 (median 26,000) in France and 21,000-32,000 (median 25,000) in Spain. Estimates are most precise for Hubei, China, where the epidemic curve is complete, and least precise in California, where it is ongoing. New York has the highest cumulative median mortality rate per million (1135), about 12-fold that of Germany. Mortality trajectories are notably flatter in Germany, California, and Washington State, each of which took physical distancing and testing strategies seriously. Using past country-specific mortality as a guide, GCAM predicts surge capacity needs, reaching more than twice existing capacity in a number of places., In every setting, the results might be sensitive to undercounts of COVID-19 deaths, which are already apparent. Conclusion and Relevance: Mortality from COVID-19 will be substantial across many settings, even in the best case scenario. GCAM will provide continually updated and increasingly precise estimates as the pandemic progresses.", "qid": 21, "docid": "2r4uty9g", "rank": 86, "score": 0.7580276727676392}, {"content": "Title: Will COVID\u201019 be a litmus test for post\u2010Ebola sub\u2010Saharan Africa? Content: In 2014, the worst outbreak of Ebola virus disease (EVD) emerged in sub-Saharan Africa (SSA) causing fear and panic. The outbreak which started in Guinea quickly moved across to Sierra Leone and Liberia. With an average EVD case fatality rate of around 50% (range 25-90%), there were many casualties, and the number of recorded deaths exceeded 11,300 by June 2016.1 This article is protected by copyright. All rights reserved.", "qid": 21, "docid": "sbuyn5bx", "rank": 87, "score": 0.7570639848709106}, {"content": "Title: Differences by country-level income in COVID-19 cases, deaths, case-fatality rates, and rates per million population in the first five months of the pandemic Content: Abstract Objective: To describe differences by country-level income in COVID-19 cases, deaths, case-fatality rates, incidence rates, and death rates per million population. Methods: Publicly available data on COVID-19 cases and deaths from December 31, 2019 to June 3, 2020 were analyzed. Kruskal-Wallis tests were used to examine associations of country-level income with COVID-19 cases, deaths, case-fatality rates, incidence rates, and death rates. Results: A total of 380,803 deaths out of 6,348,204 COVID-19 cases were reported from 210 countries and territories globally in the period under study, and the global case-fatality rate was 6.0%. Of the total globally reported cases and deaths, the percentages of cases and deaths were 59.9% and 75.0% for high-income countries, and 30.9% and 20.7% for upper-middle-income countries. Countries in higher-income categories had higher incidence rates and death rates. Between April and May, the incidence rates in higher-income groups of countries decreased, but in other groups, it increased. Conclusions In the first five months of the COVID-19 pandemic, most cases and deaths were reported from high-income and upper-middle-income countries, and those countries had higher incidence rates and death rates per million population than did lower-middle and low-income countries. Keywords: COVID-19, incidence rate, death rate, case fatality rate, income, and country", "qid": 21, "docid": "ux4gr3tq", "rank": 88, "score": 0.756905734539032}, {"content": "Title: How do environmental, economic and health factors influence regional vulnerability to COVID-19? Content: We have studied the correlations between twelve environmental, economic and health variables, by carrying out a statistical analysis of the fatality rate of COVID-19 in 14 countries. Our statistical analysis indicates that, among the 12 variables, the diabetes percentage of the total population and the extent of the population ages 65 and older in each country are correlated most strongly with the total number of deaths in them. Although the strength of the correlations between the variables and the total ND may change as the ongoing pandemic evolves, the study highlights the importance of integrating regional-specific variables in the modelling efforts aimed at projecting how the spread of the virus may influence different parts of the world.", "qid": 21, "docid": "dhy80rkn", "rank": 89, "score": 0.7569046020507812}, {"content": "Title: Communicating the Risk of Death from Novel Coronavirus Disease (COVID-19) Content: To understand the severity of infection for a given disease, it is common epidemiological practice to estimate the case fatality risk, defined as the risk of death among cases. However, there are three technical obstacles that should be addressed to appropriately measure this risk. First, division of the cumulative number of deaths by that of cases tends to underestimate the actual risk because deaths that will occur have not yet observed, and so the delay in time from illness onset to death must be addressed. Second, the observed dataset of reported cases represents only a proportion of all infected individuals and there can be a substantial number of asymptomatic and mildly infected individuals who are never diagnosed. Third, ascertainment bias and risk of death among all those infected would be smaller when estimated using shorter virus detection windows and less sensitive diagnostic laboratory tests. In the ongoing COVID-19 epidemic, health authorities must cope with the uncertainty in the risk of death from COVID-19, and high-risk individuals should be identified using approaches that can address the abovementioned three problems. Although COVID-19 involves mostly mild infections among the majority of the general population, the risk of death among young adults is higher than that of seasonal influenza, and elderly with underlying comorbidities require additional care.", "qid": 21, "docid": "6zlxqhuq", "rank": 90, "score": 0.7568745613098145}, {"content": "Title: Homicide rates among persons aged 10-24 years - United States, 1981-2010. Content: Homicide disproportionately affects persons aged 10-24 years in the United States and consistently ranks in the top three leading causes of death in this age group, resulting in approximately 4,800 deaths and an estimated $9 billion in lost productivity and medical costs in 2010. To investigate trends in homicide among persons aged 10-24 years for the period 1981-2010, CDC analyzed National Vital Statistics System data on deaths caused by homicide of persons in this age group and examined trends by sex, age, race/ethnicity, and mechanism of injury. This report describes the results of that analysis, which indicated that homicide rates varied substantially during the study period, with a sharp rise from 1985 to 1993 followed by a decline that has slowed since 1999. During the period 2000-2010, rates declined for all groups, although the decline was significantly slower for males compared with females and for blacks compared with Hispanics and persons of other racial/ethnic groups. By mechanism of injury, the decline for firearm homicides from 2000 to 2010 was significantly slower than for nonfirearm homicides. The homicide rate among persons aged 10-24 years in 2010 was 7.5 per 100,000, the lowest in the 30-year study period. Primary prevention strategies remain critical, particularly among groups at increased risk for homicide.", "qid": 21, "docid": "fpz3aikk", "rank": 91, "score": 0.7567723989486694}, {"content": "Title: SARS hits hard Content: Death rates higher than expected, but control measures seem to be working.", "qid": 21, "docid": "oqdzv3v3", "rank": 92, "score": 0.7566391825675964}, {"content": "Title: Epidemiologie Content: Fr\u00fcher wurde der Begriff Epidemiologie f\u00fcr die Lehre von den gro\u00dfen, menschheitsbedrohenden Seuchen benutzt. Heute versteht man darunter die Wissenschaft von allen \u00fcbertragbaren und nicht\u00fcbertragbaren Krankheiten in einer Population, unabh\u00e4ngig davon, ob sie zeitlich oder r\u00e4umlich geh\u00e4uft auftreten. Im Bereich der Mikrobiologie befasst sich die Epidemiologie mit Erkrankungen, die durch \u00fcbertragbare Agenzien wie Bakterien, Viren oder auch Prionen verursacht werden, und zwar insbesondere mit deren Verbreitung und den Infektionsfolgen. Epidemiologische Untersuchungen besitzen somit eine gro\u00dfe Bedeutung f\u00fcr die Gesundheit der Weltbev\u00f6lkerung und sind die Grundlage f\u00fcr allgemein- und seuchenhygienische Ma\u00dfnahmen wie Quarant\u00e4ne oder Impfungen zur Verhinderung oder Eind\u00e4mmung von Pandemien und Epidemien. Sie erm\u00f6glichen au\u00dferdem die Entwicklung von Richtlinien und Vorschriften f\u00fcr Impfungen und andere Ma\u00dfnahmen zur Verh\u00fctung von Infektionen.", "qid": 21, "docid": "wqkjzipn", "rank": 93, "score": 0.7566239833831787}, {"content": "Title: COVID-19, Australia: Epidemiology Report 10 (Reporting week to 23:59 AEST 5 April 2020) Content: Confirmed cases in Australia notified up to 5 April 2020: Notifications = 5,805; Deaths = 33. Notifications in Australia remain predominantly among people with recent overseas travel, with some locally-acquired cases being detected. Most locally-acquired cases are able to be linked back to a confirmed case, with a small portion unable to be epidemiologically link. The distribution of overseas-acquired cases to locally acquired cases varies by jurisdiction. Early indications are that reduction in international travel, domestic movement, social distancing measures and public health action are slowing the spread of the disease. Internationally, cases continue to increase, with high rates of increase observed in the European region and the United States of America. The epidemiology differs from country to country depending not only on the disease, but also on differences in case detection, testing and implemented public health measures.", "qid": 21, "docid": "4b7q0ysw", "rank": 94, "score": 0.756439208984375}, {"content": "Title: COVID-19, Australia: Epidemiology Report 10 (Reporting week to 23:59 AEST 5 April 2020). Content: Confirmed cases in Australia notified up to 5 April 2020: Notifications = 5,805; Deaths = 33. Notifications in Australia remain predominantly among people with recent overseas travel, with some locally-acquired cases being detected. Most locally-acquired cases are able to be linked back to a confirmed case, with a small portion unable to be epidemiologically link. The distribution of overseas-acquired cases to locally acquired cases varies by jurisdiction. Early indications are that reduction in international travel, domestic movement, social distancing measures and public health action are slowing the spread of the disease. Internationally, cases continue to increase, with high rates of increase observed in the European region and the United States of America. The epidemiology differs from country to country depending not only on the disease, but also on differences in case detection, testing and implemented public health measures.", "qid": 21, "docid": "xw41gu7v", "rank": 95, "score": 0.756439208984375}, {"content": "Title: The association between Ostertagia ostertagi antibodies in bulk tank milk samples and parameters linked to cattle reproduction and mortality Content: Abstract In Western Europe, gastrointestinal nematodes are widespread in dairy cattle. This study was carried out to evaluate the relationship between optical density ratio (ODR) measured on bulk tank milk with an indirect Ostertagia ostertagi ELISA and reproduction/mortality parameters. Data were collected between 2008 and 2010 from monitoring carried out on 1643 dairy herds (Normandy, Western France). ODR values of 3 samples from each farm taken from November 2008 to 2010 were averaged and then transformed into a categorical variable. Reproductive and mortality data were obtained from 1444 herds using cow records from government databases. Statistical analysis was carried out using ordinary logistic regression (OLR). The outcome variables were the case\u2013control status of a herd for reproductive factors, age at first calving and inter-calving intervals, and mortality ratios of various age classes. The effect of the categorical ODR variable was studied and several potential confounder herd factors were used to improve the model fit. A significant relationship was found between high Ostertagia ODR levels and a late age at the first calving (>34.5 months) (odds ratio (OR)=1.94, p <0.001). No significant relationship was observed with OLR for inter-calving intervals although bivariate analysis showed that herds with high ODR levels had longer inter-calving intervals than herds with low ODR level (first inter-calving interval in herds with low vs. high ODR levels=412 days vs. 422 days, p <0.001; other inter-calving intervals=408 days vs. 413 days, p <0.01). A high ODR level was also associated with high mortality of calves between 0 and 30 days of life (mortality ratio>6%) (OR=1.43, p <0.05) and between 91 and 365 days (ratio>3%) (OR=1.72, p <0.01). No significant relationship was observed with multivariate approach for mortalities in other classes by age, but bivariate analysis showed that herds with high ODR level had higher mortalities than herds with low ODR levels (mortality between 31 and 90 days in herds with low vs. high ODR levels=1.89% vs. 2.91%, p <0.001; mortality after 365 days=1.67% vs. 2.93%, p <0.001). In conclusion, our results confirm the usefulness of ELISA as an indicator for production losses in dairy herds. This inexpensive tool could be advantageous, used to aid farmers and veterinarians to carry out appropriate control measures.", "qid": 21, "docid": "7krin2jv", "rank": 96, "score": 0.7560862898826599}, {"content": "Title: Apoptosis and Cell Death: Relevance to Lung Content: In multicellular organisms, cell death plays an important role in development, morphogenesis, control of cell numbers, and removal of infected, mutated, or damaged cells. The term apoptosis was first coined in 1972 by Kerr et al.1 to describe the morphologic features of a type of cell death that is distinct from necrosis and is today considered to represent programmed cell death. In fact, the evidence that a genetic program existed for physiologic cell death came from the developmental studies of the nematode Caenorhabditis elegans.2 As time has progressed, however, apoptotic cell death has been shown to occur in many cell types under a variety of physiologic and pathologic conditions. Cells dying by apoptosis exhibit several characteristic morphologic features that include cell shrinkage, nuclear condensation, membrane blebbing, nuclear and cellular fragmentation into membrane-bound apoptotic bodies, and eventual phagocytosis of the fragmented cell (Figure 4.1).", "qid": 21, "docid": "q4ivezyq", "rank": 97, "score": 0.755905270576477}, {"content": "Title: Changing pattern of premature mortality burden over 6 years of rapid growth of the economy in suburban south-west China: 1998\u20132003 Content: Summary Background This study was conducted in Kunming, the capital of Yunnan, a poor province in south-west China experiencing rapid economic growth. The study examined the short-term trend in premature mortality burden from common causes of death in a suburban region between 1998 and 2003. Methods Years of life lost (YLL) per 1000 population and mortality rate per 100,000 population were calculated from medical death certificates, and broken down by cause of death, sex and year without age weighting but with a discounting rate of 3%. Results Non-communicable diseases contributed over 80% of all causes of YLL, with a slightly increasing trend. The combined rate for communicable, maternal, prenatal and nutritional deficiencies declined from 4.7 to 2.4 per 1000 population. Remarkably, declining trends in YLL were also seen for chronic obstructive pulmonary disease, drug use and road traffic accidents, whereas increasing trends were seen for ischaemic heart disease (IHD) and liver cancer (males). The YLL rate for stroke, self-inflicted injuries, lung cancer and stomach cancer fluctuated over time. Conclusions The region should focus on further control of IHD and liver cancer.", "qid": 21, "docid": "lf90j7mm", "rank": 98, "score": 0.7556648254394531}, {"content": "Title: Determinants for autopsy after unexplained deaths possibly resulting from infectious causes, United States. Content: We analyzed US multiple cause-of-death data for 2003-2006 for demographic and clinical determinants for autopsy in unexplained deaths possibly resulting from infectious causes. For 96,242 deaths, the definition for unexplained death was met and autopsy status was recorded. Most decedents were male, 40-49 years of age, and white. To identify factors associated with unexplained death, we used data from Arizona records. Multivariate analysis of Arizona records suggested that decedents of races other than white and black and decedents who had clinicopathologic syndromes in the cardiovascular, sepsis/shock, and multisyndrome categories recorded on the death certificate were least likely to have undergone autopsy; children with unexplained death were the most likely to have undergone autopsy. Improved understanding of unexplained deaths can provide opportunities for further studies, strengthen collaboration between investigators of unexplained deaths, and improve knowledge and awareness of infectious diseases of public health concern.", "qid": 21, "docid": "p2eh77es", "rank": 99, "score": 0.7553650140762329}, {"content": "Title: Health Inequalities, General Trends in Mortality and Morbidity, and Associated Factors Content: All measures of health status are ultimately derived from observations of individuals. At the field level we have such measures as self-assessed health status, report of a specific disease, record of a particular death, or an individual\u2019s test on a biomarker, such as blood pressure or serum cholesterol. The observations for individuals are combined and summarized to represent subnational geographic areas, demographic or socioeconomic groups within countries, or national populations. The summary measures, whether they are percentages, averages, or rates, apply to groups. A problem arises when the measures that are based on groups are assumed to represent individuals. The analysis becomes especially problematic when the units analyzed are geographic areas and inferences are being made about individuals from the analysis for these geographic areas.", "qid": 21, "docid": "cqlt5mq2", "rank": 100, "score": 0.7550356388092041}]}
{"query": "are cardiac complications likely in patients with COVID-19?", "hits": [{"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": 1, "score": 0.9199784398078918}, {"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": 2, "score": 0.9195963740348816}, {"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": 3, "score": 0.9188342690467834}, {"content": "Title: Cardiovascular complications in COVID-19 Content: BACKGROUND: The coronavirus disease of 2019 (COVID-19) is caused by the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). While systemic inflammation and pulmonary complications can result in significant morbidity and mortality, cardiovascular complications may also occur. OBJECTIVE: This brief report evaluates cardiovascular complications in the setting of COVID-19 infection. DISCUSSION: The current COVID-19 pandemic has resulted in over one million infected worldwide and thousands of death. The virus binds and enters through angiotensin-converting enzyme 2 (ACE2). COVID-19 can result in systemic inflammation, multiorgan dysfunction, and critical illness. The cardiovascular system is also affected, with complications including myocardial injury, myocarditis, acute myocardial infarction, heart failure, dysrhythmias, and venous thromboembolic events. Current therapies for COVID-19 may interact with cardiovascular medications. CONCLUSIONS: Emergency clinicians should be aware of these cardiovascular complications when evaluating and managing the patient with COVID-19.", "qid": 22, "docid": "hl225efn", "rank": 4, "score": 0.9119325876235962}, {"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": 5, "score": 0.910688579082489}, {"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": 6, "score": 0.9099192023277283}, {"content": "Title: Cardiovascular complications in COVID-19 Content: Abstract Background The coronavirus disease of 2019 (COVID-19) is caused by the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). While systemic inflammation and pulmonary complications can result in significant morbidity and mortality, cardiovascular complications may also occur. Objective This brief report evaluates cardiovascular complications in the setting of COVID-19 infection. Discussion The current COVID-19 pandemic has resulted in over one million infected worldwide and thousands of death. The virus binds and enters through angiotensin-converting enzyme 2 (ACE2). COVID-19 can result in systemic inflammation, multiorgan dysfunction, and critical illness. The cardiovascular system is also affected, with complications including myocardial injury, myocarditis, acute myocardial infarction, heart failure, dysrhythmias, and venous thromboembolic events. Current therapies for COVID-19 may interact with cardiovascular medications. Conclusions Emergency clinicians should be aware of these cardiovascular complications when evaluating and managing the patient with COVID-19.", "qid": 22, "docid": "mbbnk3la", "rank": 7, "score": 0.9056551456451416}, {"content": "Title: Myocardial injury in patients with COVID-19 Content: In patients with COVID-19, myocardial injury is prevalent and is associated with an adverse prognosis and increased mortality, according to two retrospective cohort studies from China and the USA.", "qid": 22, "docid": "jwu0az6g", "rank": 8, "score": 0.9040799140930176}, {"content": "Title: Prognostic significance of cardiac injury in COVID-19 patients with and without coronary artery disease Content: OBJECTIVE: COVID-19 is a disease with high mortality, and risk factors for worse clinical outcome have not been well-defined yet. The aim of this study is to delineate the prognostic importance of presence of concomitant cardiac injury on admission in patients with COVID-19. METHODS: For this multi-center retrospective study, data of consecutive patients who were treated for COVID-19 between 20 March and 20 April 2020 were collected. Clinical characteristics, laboratory findings and outcomes data were obtained from electronic medical records. In-hospital clinical outcome was compared between patients with and without cardiac injury. RESULTS: A total of 607 hospitalized patients with COVID-19 were included in the study; the median age was 62.5 \u00b1 14.3 years, and 334 (55%) were male. Cardiac injury was detected in 150 (24.7%) of patients included in the study. Mortality rate was higher in patients with cardiac injury (42% vs. 8%; P < 0.01). The frequency of patients who required ICU (72% vs. 19%), who developed acute kidney injury (14% vs. 1%) and acute respiratory distress syndrome (71%vs. 18%) were also higher in patients with cardiac injury. In multivariate analysis, age, coronary artery disease (CAD), elevated CRP levels, and presence of cardiac injury [odds ratio (OR) 10.58, 95% confidence interval (CI) 2.42-46.27; P < 0.001) were found to be independent predictors of mortality. In subgroup analysis, including patients free of history of CAD, presence of cardiac injury on admission also predicted mortality (OR 2.52, 95% CI 1.17-5.45; P = 0.018). CONCLUSION: Cardiac injury on admission is associated with worse clinical outcome and higher mortality risk in COVID-19 patients including patients free of previous CAD diagnosis.", "qid": 22, "docid": "dxfyfhnd", "rank": 9, "score": 0.9029890298843384}, {"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": 10, "score": 0.902718186378479}, {"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": 22, "docid": "io8hm94a", "rank": 11, "score": 0.9011887907981873}, {"content": "Title: Prognostic significance of cardiac injury in COVID-19 patients with and without coronary artery disease. Content: OBJECTIVE COVID-19 is a disease with high mortality, and risk factors for worse clinical outcome have not been well-defined yet. The aim of this study is to delineate the prognostic importance of presence of concomitant cardiac injury on admission in patients with COVID-19. METHODS For this multi-center retrospective study, data of consecutive patients who were treated for COVID-19 between 20 March and 20 April 2020 were collected. Clinical characteristics, laboratory findings and outcomes data were obtained from electronic medical records. In-hospital clinical outcome was compared between patients with and without cardiac injury. RESULTS A total of 607 hospitalized patients with COVID-19 were included in the study; the median age was 62.5 \u00b1 14.3 years, and 334 (55%) were male. Cardiac injury was detected in 150 (24.7%) of patients included in the study. Mortality rate was higher in patients with cardiac injury (42% vs. 8%; P < 0.01). The frequency of patients who required ICU (72% vs. 19%), who developed acute kidney injury (14% vs. 1%) and acute respiratory distress syndrome (71%vs. 18%) were also higher in patients with cardiac injury. In multivariate analysis, age, coronary artery disease (CAD), elevated CRP levels, and presence of cardiac injury [odds ratio (OR) 10.58, 95% confidence interval (CI) 2.42-46.27; P < 0.001) were found to be independent predictors of mortality. In subgroup analysis, including patients free of history of CAD, presence of cardiac injury on admission also predicted mortality (OR 2.52, 95% CI 1.17-5.45; P = 0.018). CONCLUSION Cardiac injury on admission is associated with worse clinical outcome and higher mortality risk in COVID-19 patients including patients free of previous CAD diagnosis.", "qid": 22, "docid": "z8ywyb1t", "rank": 12, "score": 0.9006421566009521}, {"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": 13, "score": 0.9003599286079407}, {"content": "Title: Cardiac injuries in coronavirus disease 2019 (COVID-19) Content: As the coronavirus disease 2019 (COVID-19) epidemic worsens, this global pandemic is impacting more than 200 countries/regions and more than 4,500,000 confirmed cases worldwide. COVID-19 is caused by the Severe Acute Respiratory Syndrome Coronavirus-2 (SARS-CoV-2), which might attack not only the respiratory system, but also the other important organs, including the heart. It was reported that COVID-19 patients with a past history of cardiovascular diseases would have a higher mortality. Meanwhile, elevated troponin levels were frequently observed in COVID-19 cases. Besides the comprehensive treatments for COVID-19, as a cardiologist, we should also remain vigilant about the cardiac injuries, especially those with severe emergent cardiovascular symptoms.", "qid": 22, "docid": "2icq0icx", "rank": 14, "score": 0.8989992141723633}, {"content": "Title: Cardiac injuries in coronavirus disease 2019 (COVID-19). Content: As the coronavirus disease 2019 (COVID-19) epidemic worsens, this global pandemic is impacting more than 200 countries/regions and more than 4,500,000 confirmed cases worldwide. COVID-19 is caused by the Severe Acute Respiratory Syndrome Coronavirus-2 (SARS-CoV-2), which might attack not only the respiratory system, but also the other important organs, including the heart. It was reported that COVID-19 patients with a past history of cardiovascular diseases would have a higher mortality. Meanwhile, elevated troponin levels were frequently observed in COVID-19 cases. Besides the comprehensive treatments for COVID-19, as a cardiologist, we should also remain vigilant about the cardiac injuries, especially those with severe emergent cardiovascular symptoms.", "qid": 22, "docid": "zu4i4d3t", "rank": 15, "score": 0.8989992141723633}, {"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": 16, "score": 0.8984153270721436}, {"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": 17, "score": 0.8976168632507324}, {"content": "Title: Cardiovascular disease and COVID-19 Content: BACKGROUND AND AIMS: Many patients with coronavirus disease 2019 (COVID-19) have underlying cardiovascular (CV) disease or develop acute cardiac injury during the course of the illness. Adequate understanding of the interplay between COVID-19 and CV disease is required for optimum management of these patients. METHODS: A literature search was done using PubMed and Google search engines to prepare a narrative review on this topic. RESULTS: Respiratory illness is the dominant clinical manifestation of COVID-19; CV involvement occurs much less commonly. Acute cardiac injury, defined as significant elevation of cardiac troponins, is the most commonly reported cardiac abnormality in COVID-19. It occurs in approximately 8-12% of all patients. Direct myocardial injury due to viral involvement of cardiomyocytes and the effect of systemic inflammation appear to be the most common mechanisms responsible for cardiac injury. The information about other CV manifestations in COVID-19 is very limited at present. Nonetheless, it has been consistently shown that the presence of pre-existing CV disease and/or development of acute cardiac injury are associated with significantly worse outcome in these patients. CONCLUSIONS: Most of the current reports on COVID-19 have only briefly described CV manifestations in these patients. Given the enormous burden posed by this illness and the significant adverse prognostic impact of cardiac involvement, further research is required to understand the incidence, mechanisms, clinical presentation and outcomes of various CV manifestations in COVID-19 patients.", "qid": 22, "docid": "659lz92w", "rank": 18, "score": 0.8975409269332886}, {"content": "Title: Coronavirus Disease 2019 and Cardiovascular System: A Narrative Review Content: At the end of 2019, a viral pneumonia disease called coronavirus disease 2019 (COVID-19), which is caused by severe acute respiratory syndrome coronavirus-2 (SARS-CoV2), emerged in Wuhan, China. This novel disease rapidly spread at an alarming rate that as a result, it has now been declared pandemic by the World Health Organization. Although this infective disease is mostly characterized by respiratory tract symptoms, increasing numbers of evidence had shown considerable amounts of patients with cardiovascular involvements and these were associated with higher mortality among COVID-19 patients. Cardiac involvement as a possible late phenomenon of the viral respiratory infection is an issue that should be anticipated in patients with COVID-19. Cardiovascular manifestation in COVID-19 patients include myocardial injury (MI), arrhythmias, cardiac arrests, heart failure and coagulation abnormality, ranging from 7.2% up to 33%. The mechanism of cardiac involvement in COVID-19 patients involves direct injury to myocardial cells mediated by angiotensin-converting enzyme 2 (ACE2) receptors as suggested by some studies, while the other studies suggest that systemic inflammation causing indirect myocyte injury may also play a role. Combination of proper triage, close monitoring, and avoidance of some drugs that have cardiovascular toxicity are important in the management of cardiovascular system involvement in COVID-19 patients. The involvement of the cardiovascular system in COVID-19 patients is prevalent, variable, and debilitating. Therefore, it requires our attention and comprehensive management.", "qid": 22, "docid": "kt6t41ff", "rank": 19, "score": 0.8974774479866028}, {"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": 20, "score": 0.8972402811050415}, {"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": 21, "score": 0.8971837759017944}, {"content": "Title: Cardiovascular manifestations and treatment considerations in covid-19 Content: Since its recognition in December 2019, covid-19 has rapidly spread globally causing a pandemic. Pre-existing comorbidities such as hypertension, diabetes, and cardiovascular disease are associated with a greater severity and higher fatality rate of covid-19. Furthermore, covid-19 contributes to cardiovascular complications, including acute myocardial injury as a result of acute coronary syndrome, myocarditis, stress-cardiomyopathy, arrhythmias, cardiogenic shock, and cardiac arrest. The cardiovascular interactions of covid-19 have similarities to that of severe acute respiratory syndrome, Middle East respiratory syndrome and influenza. Specific cardiovascular considerations are also necessary in supportive treatment with anticoagulation, the continued use of renin-angiotensin-aldosterone system inhibitors, arrhythmia monitoring, immunosuppression or modulation, and mechanical circulatory support.", "qid": 22, "docid": "873txs85", "rank": 22, "score": 0.8968417644500732}, {"content": "Title: COVID-19 Cardiac Injury: Implications for Long-Term Surveillance and Outcomes in Survivors Content: Up to 20-30% of patients hospitalized with coronavirus disease (COVID-19) have evidence of myocardial involvement. Acute cardiac injury in patients hospitalized with COVID-19 is associated with higher morbidity and mortality. There are no data on how acute treatment for COVID-19 may affect convalescent phase or long-term cardiac recovery and function. Myocarditis from other viral pathogens can evolve into overt or subclinical myocardial dysfunction, and sudden death has been described in the convalescent phase of viral myocarditis. This raises concerns for patients recovering from COVID-19. Some patients will have subclinical and possibly overt cardiovascular abnormalities. Patients with ostensibly recovered cardiac function may still be at risk for cardiomyopathy and cardiac arrhythmias. Screening for residual cardiac involvement in the convalescent phase for patients recovered from COVID-19 associated cardiac injury is needed. The type of testing, and therapies for post COVID-19 myocardial dysfunction will need to be determined. Therefore, now is the time to plan for appropriate registries and clinical trials to properly assess these issues and prepare for long-term sequelae of \"post-COVID-19 Cardiac Syndrome\".", "qid": 22, "docid": "bsqpkjcj", "rank": 23, "score": 0.896622896194458}, {"content": "Title: Heart injury signs are associated with higher and earlier mortality in coronavirus disease 2019 (COVID-19) Content: Importance: Heart injury can be easily induced by viral infection such as adenovirus and enterovirus. However, whether coronavirus disease 2019 (COVID-19) causes heart injury and hereby impacts mortality has not yet been fully evaluated. Objective: To explore whether heart injury occurs in COVID-19 on admission and hereby aggravates mortality later. Design, Setting, and Participants A single-center retrospective cohort study including 188 COVID-19 patients admitted from December 25, 2019 to January 27, 2020 in Wuhan Jinyintan Hospital, China; follow up was completed on February 11, 2020. Exposures: High levels of heart injury indicators on admission (hs-TNI; CK; CK-MB; LDH; \u03b1-HBDH). Main Outcomes and Measures: Mortality in hospital and days from admission to mortality (survival days). Results: Of 188 patients with COVID-19, the mean age was 51.9 years (standard deviation: 14.26; range: 21~83 years) and 119 (63.3%) were male. Increased hs-TnI levels on admission tended to occur in older patients and patients with comorbidity (especially hypertension). High hs-TnI on admission (\u2265 6.126 pg/mL), even within the clinical normal range (0~28 pg/mL), already can be associated with higher mortality. High hs-TnI was associated with increased inflammatory levels (neutrophils, IL-6, CRP, and PCT) and decreased immune levels (lymphocytes, monocytes, and CD4+ and CD8+ T cells). CK was not associated with mortality. Increased CK-MB levels tended to occur in male patients and patients with current smoking. High CK-MB on admission was associated with higher mortality. High CK-MB was associated with increased inflammatory levels and decreased lymphocytes. Increased LDH and \u03b1-HBDH levels tended to occur in older patients and patients with hypertension. Both high LDH and \u03b1-HBDH on admission were associated with higher mortality. Both high LDH and \u03b1-HBDH were associated with increased inflammatory levels and decreased immune levels. hs-TNI level on admission was negatively correlated with survival days (r= -0.42, 95% CI= -0.64~-0.12, P=0.005). LDH level on admission was negatively correlated with survival days (r= -0.35, 95% CI= -0.59~-0.05, P=0.022). Conclusions and Relevance: Heart injury signs arise in COVID-19, especially in older patients, patients with hypertension and male patients with current smoking. COVID-19 virus might attack heart via inducing inflammatory storm. High levels of heart injury indicators on admission are associated with higher mortality and shorter survival days. COVID-19 patients with signs of heart injury on admission must be early identified and carefully managed by cardiologists, because COVID-19 is never just confined to respiratory injury.", "qid": 22, "docid": "nsp2t0i6", "rank": 24, "score": 0.8963170051574707}, {"content": "Title: Cardiovascular Considerations for Patients, Health Care Workers, and Health Systems During the Coronavirus Disease 2019 (COVID-19) Pandemic Content: Abstract The coronavirus disease-2019 (COVID-19) is an infectious disease caused by severe acute respiratory syndrome coronavirus 2 that has significant implications for the cardiovascular care of patients. First, those with COVID-19 and preexisting cardiovascular disease (CVD) have an increased risk of severe disease and death. Second, infection has been associated with multiple direct and indirect cardiovascular complications including acute myocardial injury, myocarditis, arrhythmias and venous thromboembolism. Third, therapies under investigation for COVID-19 may have cardiovascular side effects. Fourth, the response to COVID-19 can compromise the rapid triage of non-COVID-19 patients with cardiovascular conditions. Finally, the provision of cardiovascular care may place health care workers in a position of vulnerability as they become host or vectors of virus transmission. We hereby review the peer-reviewed and preprint literature pertaining to cardiovascular considerations related to COVID-19 and highlight gaps in knowledge that require further study pertinent to patients, health care workers, and health systems.", "qid": 22, "docid": "w49i0xkz", "rank": 25, "score": 0.8961400985717773}, {"content": "Title: COVID-19 and Cardiovascular diseases. Scoping review study Content: BACKGROUND: Many patients with COVID-19 have pre-existing cardiovascular (CV) co-morbidities or develop acute heart damage during the course of the disease. OBJECTIVES: To study the risk of COVID-19 infection in the presence of preexisting CV diseases and to describe new CV manifestations during COVID-19. METHODS: A \"scoping review\" was carried out via PubMed, to synthesize the results of research currently published on this subject. RESULTS: Patients with cardiovascular disease were at greater risk of developing COVID-19, especially in its severe form. These patients were five to ten times more at risk of death. Cardiac manifestations, de novo, were dominated by acute myocardial damage, defined by a significant elevation of cardiac troponins. These occurred in 7 to 17% of hospitalized patients. The presence of a new heart lesion in patients with COVID-19 was consistently associated with a poor prognosis. CONCLUSION: Given the enormous cardiovascular challenge posed by the COVID-19 pandemic and the prognostic impact of heart damage, additional research at a high level of evidence will be necessary.", "qid": 22, "docid": "20zujaha", "rank": 26, "score": 0.8959987163543701}, {"content": "Title: Acute cardiac injury in patients with COVID-19 Content: Introduction: Cardiac complications of COVID-19 are potentially life-threatening. The occurrence of myocardial injury in the context of COVID-19 is multifactorial and has generated increasing interest. Methods: A systematic review with meta-analysis of the literature was performed. MEDLINE and EMBASE were searched. Two independente reviewers evaluated the selected manuscripts for the outcome myocardial injury, defined by troponin elevation above the 99th percentile. Study heterogeneity and risk of bias were evaluated. Results: Eight studies, with a total of 1229 patients, were included. The frequency of myocardial injury was 16% (95% CI: 9% - 27%). The heterogeneity among studies was high (93%). Conclusions: Myocardial injury may occur in patients with COVID-19, with a frequency of 16% among current studies. Continuous research is needed to update these findings, as the pandemic evolves, and to define the implications of myocardial injury in the context of this infection.", "qid": 22, "docid": "wvxybca4", "rank": 27, "score": 0.8958397507667542}, {"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": 28, "score": 0.8956334590911865}, {"content": "Title: Cardiovascular Considerations for Patients, Health Care Workers, and Health Systems During the COVID-19 Pandemic Content: The coronavirus disease 2019 (COVID-19) is an infectious disease caused by severe acute respiratory syndrome coronavirus 2 that has significant implications for the cardiovascular care of patients. First, those with COVID-19 and pre-existing cardiovascular disease have an increased risk of severe disease and death. Second, infection has been associated with multiple direct and indirect cardiovascular complications including acute myocardial injury, myocarditis, arrhythmias, and venous thromboembolism. Third, therapies under investigation for COVID-19 may have cardiovascular side effects. Fourth, the response to COVID-19 can compromise the rapid triage of non-COVID-19 patients with cardiovascular conditions. Finally, the provision of cardiovascular care may place health care workers in a position of vulnerability as they become hosts or vectors of virus transmission. We hereby review the peer-reviewed and pre-print reports pertaining to cardiovascular considerations related to COVID-19 and highlight gaps in knowledge that require further study pertinent to patients, health care workers, and health systems.", "qid": 22, "docid": "e9k6pnr3", "rank": 29, "score": 0.8955750465393066}, {"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": 30, "score": 0.8954119086265564}, {"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": 31, "score": 0.8950616121292114}, {"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": 22, "docid": "tp2tm0vn", "rank": 32, "score": 0.8947373032569885}, {"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": 22, "docid": "7icw3be3", "rank": 33, "score": 0.8947373032569885}, {"content": "Title: Cardiovascular Implications of the COVID-19 Pandemic: A Global Perspective Content: The coronavirus disease 2019 (COVID-19), caused by severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2), represents the pandemic of the century, with approximately 3.5 million cases and 250,000 deaths worldwide as of May 2020. Although respiratory symptoms usually dominate the clinical presentation, COVID-19 is now known to also have potentially serious cardiovascular consequences, including myocardial injury, myocarditis, acute coronary syndromes, pulmonary embolism, stroke, arrhythmias, heart failure, and cardiogenic shock. The cardiac manifestations of COVID-19 might be related to the adrenergic drive, systemic inflammatory milieu and cytokine-release syndrome caused by SARS-CoV-2, direct viral infection of myocardial and endothelial cells, hypoxia due to respiratory failure, electrolytic imbalances, fluid overload, and side effects of certain COVID-19 medications. COVID-19 has profoundly reshaped usual care of both ambulatory and acute cardiac patients, by leading to the cancellation of elective procedures and by reducing the efficiency of existing pathways of urgent care, respectively. Decreased use of health care services for acute conditions by non-COVID-19 patients has also been reported and attributed to concerns about acquiring in-hospital infection. Innovative approaches that leverage modern technologies to tackle the COVID-19 pandemic have been introduced, which include telemedicine, dissemination of educational material over social media, smartphone apps for case tracking, and artificial intelligence for pandemic modelling, among others. This article provides a comprehensive overview of the pathophysiology and cardiovascular implications of COVID-19, its impact on existing pathways of care, the role of modern technologies to tackle the pandemic, and a proposal of novel management algorithms for the most common acute cardiac conditions.", "qid": 22, "docid": "8h36iwxi", "rank": 34, "score": 0.8944520950317383}, {"content": "Title: Cardiovascular implications of the COVID-19 pandemic: a global perspective Content: The Coronavirus disease 2019 (COVID-19), caused by severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2), represents the pandemic of the century, with approximately 3.5 million cases and 250,000 deaths worldwide as of May 2020. Although respiratory symptoms usually dominate the clinical presentation, COVID-19 is now known to also have potentially serious cardiovascular consequences, including myocardial injury, myocarditis, acute coronary syndromes, pulmonary embolism, stroke, arrhythmias, heart failure, and cardiogenic shock. The cardiac manifestations of COVID-19 might be related to the adrenergic drive, systemic inflammatory milieu and cytokine-release syndrome caused by SARS-CoV-2, direct viral infection of myocardial and endothelial cells, hypoxia due to respiratory failure, electrolytic imbalances, fluid overload, and side effects of certain COVID-19 medications. COVID-19 has profoundly reshaped usual care of both ambulatory and acute cardiac patients, by leading to the cancellation of elective procedures and by reducing the efficiency of existing pathways of urgent care, respectively. Decreased utilization of healthcare services for acute conditions by non-COVID-19 patients has also been reported and attributed to concerns about acquiring in-hospital infection. Innovative approaches that leverage modern technologies to tackle the COVID-19 pandemic have been introduced, which include telemedicine, dissemination of educational material over social media, smartphone apps for case tracking, and artificial intelligence for pandemic modelling, among others. This article provides a comprehensive overview of the pathophysiology and cardiovascular implications of COVID-19, its impact on existing pathways of care, the role of modern technologies to tackle the pandemic, and a proposal of novel management algorithms for the most common acute cardiac conditions.", "qid": 22, "docid": "dthdszdn", "rank": 35, "score": 0.8943501710891724}, {"content": "Title: Current perspectives on Coronavirus 2019 (COVID-19) and cardiovascular disease: A white paper by the JAHA editors. Content: Coronavirus Disease 2019 (COVID-19), caused by the Severe Acute Respiratory Syndrome Coronavirus-2 (SARS-CoV-2), has infected more than 3.0 million people worldwide and killed more than 200,000 as of April 27, 2020, making it the most lethal pandemic since the Spanish flu of 1918.1, 2 COVID-19 may preferentially infect individuals with cardiovascular conditions, is more severe in subjects with cardiovascular comorbidities, may directly or indirectly affect the heart and may interact with cardiovascular medications.3 In addition, the widespread effects of the pandemic on the global healthcare system affects the routine and emergency cardiac care for patients who are, may be, or are not infected with COVID-19.", "qid": 22, "docid": "tr5whji0", "rank": 36, "score": 0.8943268060684204}, {"content": "Title: COVID-19 and Cardiovascular diseases. Scoping review study. Content: BACKGROUND Many patients with COVID-19 have pre-existing cardiovascular (CV) co-morbidities or develop acute heart damage during the course of the disease. OBJECTIVES To study the risk of COVID-19 infection in the presence of preexisting CV diseases and to describe new CV manifestations during COVID-19. METHODS A \"scoping review\" was carried out via PubMed, to synthesize the results of research currently published on this subject. RESULTS Patients with cardiovascular disease were at greater risk of developing COVID-19, especially in its severe form. These patients were five to ten times more at risk of death. Cardiac manifestations, de novo, were dominated by acute myocardial damage, defined by a significant elevation of cardiac troponins. These occurred in 7 to 17% of hospitalized patients. The presence of a new heart lesion in patients with COVID-19 was consistently associated with a poor prognosis. CONCLUSION Given the enormous cardiovascular challenge posed by the COVID-19 pandemic and the prognostic impact of heart damage, additional research at a high level of evidence will be necessary.", "qid": 22, "docid": "x4093iad", "rank": 37, "score": 0.8931602239608765}, {"content": "Title: The Spectrum of Cardiac Manifestations in Coronavirus Disease 2019 (COVID-19) - a Systematic Echocardiographic Study. Content: Background: Information regarding the cardiac manifestations of COVID-19 is scarce. We performed a systematic and comprehensive echocardiographic evaluation of consecutive patients hospitalized with COVID-19 infection. Methods: 100 consecutive patients diagnosed with COVID-19 infection underwent complete echocardiographic evaluation within 24 hours of admission and were compared to reference values. Echocardiographic studies included left ventricular (LV) systolic and diastolic function, valve hemodynamics and right ventricular (RV) assessment, as well as lung ultrasound. A second exam was performed in case of clinical deterioration. Results: Thirty two patients (32%) had a normal echocardiogram at baseline. The most common cardiac pathology was RV dilatation and dysfunction (observed in 39% of patients), followed by LV diastolic dysfunction (16%) and LV systolic dysfunction (10%). Patients with elevated troponin (20%) or worse clinical condition did not demonstrate any significant difference in LV systolic function compared to patients with normal troponin or better clinical condition, but had worse RV function. Clinical deterioration occurred in 20% of patients. In these patients, the most common echocardiographic abnormality at follow-up was RV function deterioration (12 patients), followed by LV systolic and diastolic deterioration (in 5 patients). Femoral vein thrombosis (DVT) was diagnosed in 5 of 12 patients with RV failure. Conclusions:In COVID-19 infection, LV systolic function is preserved in the majority of patients, but LV diastolic and RV function are impaired. Elevated troponin and poorer clinical grade are associated with worse RV function. In patients presenting with clinical deterioration at follow-up, acute RV dysfunction, with or without DVT, is more common, but acute LV systolic dysfunction was noted in \u224820%.", "qid": 22, "docid": "jp7xcl96", "rank": 38, "score": 0.8926196098327637}, {"content": "Title: Mechanisms of Myocardial Injury in Coronavirus Disease 2019 Content: Coronavirus disease 2019 (COVID-19) predominantly presents with symptoms of fever, fatigue, cough and respiratory failure. However, it appears to have a unique interplay with cardiovascular disease (CVD); patients with pre-existing CVD are at highest risk for mortality from COVID-19, along with the elderly. COVID-19 contributes to cardiovascular complications including arrhythmias, myocardial dysfunction and myocardial inflammation. Although the exact mechanism of myocardial inflammation in patients with COVID-19 is not known, several plausible mechanisms have been proposed based on early observational reports. In this article, the authors summarise the available literature on mechanisms of myocardial injury in COVID-19.", "qid": 22, "docid": "h2xmxwd1", "rank": 39, "score": 0.8922907114028931}, {"content": "Title: The Spectrum of Cardiac Manifestations in Coronavirus Disease 2019 (COVID-19) - a Systematic Echocardiographic Study Content: Background: Information regarding the cardiac manifestations of COVID-19 is scarce. We performed a systematic and comprehensive echocardiographic evaluation of consecutive patients hospitalized with COVID-19 infection. Methods: 100 consecutive patients diagnosed with COVID-19 infection underwent complete echocardiographic evaluation within 24 hours of admission and were compared to reference values. Echocardiographic studies included left ventricular (LV) systolic and diastolic function, valve hemodynamics and right ventricular (RV) assessment, as well as lung ultrasound. A second exam was performed in case of clinical deterioration. Results: Thirty two patients (32%) had a normal echocardiogram at baseline. The most common cardiac pathology was RV dilatation and dysfunction (observed in 39% of patients), followed by LV diastolic dysfunction (16%) and LV systolic dysfunction (10%). Patients with elevated troponin (20%) or worse clinical condition did not demonstrate any significant difference in LV systolic function compared to patients with normal troponin or better clinical condition, but had worse RV function. Clinical deterioration occurred in 20% of patients. In these patients, the most common echocardiographic abnormality at follow-up was RV function deterioration (12 patients), followed by LV systolic and diastolic deterioration (in 5 patients). Femoral vein thrombosis (DVT) was diagnosed in 5 of 12 patients with RV failure. Conclusions:In COVID-19 infection, LV systolic function is preserved in the majority of patients, but LV diastolic and RV function are impaired. Elevated troponin and poorer clinical grade are associated with worse RV function. In patients presenting with clinical deterioration at follow-up, acute RV dysfunction, with or without DVT, is more common, but acute LV systolic dysfunction was noted in &#8776;20%.", "qid": 22, "docid": "3o504oza", "rank": 40, "score": 0.8921645283699036}, {"content": "Title: Children's heart and COVID-19: Up-to-date evidence in the form of a systematic review Content: The new coronavirus disease outbreak in 2019 (COVID-19) represents a dramatic challenge for healthcare systems worldwide. As to viral tropism, lungs are not the only COVID-19 target but also the heart may be involved in a not negligible percentage of the infected patients. Myocarditis-related cardiac dysfunction and potentially life-threatening arrhythmias are the main aftermaths. A few studies showed that myocardial injury in adult patients is often linked with a fatal outcome. Conversely, scientific evidence in children is sparse, although several reports were published with the description of a cardiac involvement in COVID-19 paediatric patients. In these young subjects, a background of surgically treated congenital heart disease seems to be a predisposing factor.Conclusion: This systematic review is aimed at summarizing all COVID-19 cases with a cardiac involvement published in paediatric age and trying to explain the underlying mechanisms responsible for COVID-19-related myocardial damage.What is Known:\u00e2\u0080\u00a2 Coronaviruses proved to be able to jump from animals to humans.\u00e2\u0080\u00a2 The outbreak of COVID-19 started from China (Dec 2019) and became pandemic.What is New:\u00e2\u0080\u00a2 Even in childhood, COVID-19 is not without the risk of cardiac involvement.\u00e2\u0080\u00a2 Myocarditis, heart failure, and arrhythmias are among the possible manifestations.", "qid": 22, "docid": "b1roq671", "rank": 41, "score": 0.891952633857727}, {"content": "Title: COVID-19 Cardiovascular Epidemiology, Cellular Pathogenesis, Clinical Manifestations and Management Content: Abstract Coronavirus Disease 2019 (COVID-19) is a rapidly progressing global pandemic that may present with a variety of cardiac manifestations including, but not limited to, myocardial injury, myocardial infarction, arrhythmias, heart failure, cardiomyopathy, shock, thromboembolism, and cardiac arrest. These cardiovascular effects are worse in patients who have pre-existing cardiac conditions such as coronary artery disease, hypertension, diabetes mellitus, and coagulation abnormalities. Other predisposing risk factors include advanced age, immunocompromised state, and underlying systemic inflammatory conditions. Here we review the cellular pathophysiology, clinical manifestations and treatment modalities of the cardiac manifestations seen in patients with COVID-19.", "qid": 22, "docid": "dl8vjwfn", "rank": 42, "score": 0.8917015194892883}, {"content": "Title: Cardiovascular disease and COVID-19 Content: Abstract Background and aims Many patients with coronavirus disease 2019 (COVID-19) have underlying cardiovascular (CV) disease or develop acute cardiac injury during the course of the illness. Adequate understanding of the interplay between COVID-19 and CV disease is required for optimum management of these patients. Methods A literature search was done using PubMed and Google search engines to prepare a narrative review on this topic. Results Respiratory illness is the dominant clinical manifestation of COVID-19; CV involvement occurs much less commonly. Acute cardiac injury, defined as significant elevation of cardiac troponins, is the most commonly reported cardiac abnormality in COVID-19. It occurs in approximately 8\u201312% of all patients. Direct myocardial injury due to viral involvement of cardiomyocytes and the effect of systemic inflammation appear to be the most common mechanisms responsible for cardiac injury. The information about other CV manifestations in COVID-19 is very limited at present. Nonetheless, it has been consistently shown that the presence of pre-existing CV disease and/or development of acute cardiac injury are associated with significantly worse outcome in these patients. Conclusions Most of the current reports on COVID-19 have only briefly described CV manifestations in these patients. Given the enormous burden posed by this illness and the significant adverse prognostic impact of cardiac involvement, further research is required to understand the incidence, mechanisms, clinical presentation and outcomes of various CV manifestations in COVID-19 patients.", "qid": 22, "docid": "wztm0rbx", "rank": 43, "score": 0.8913341164588928}, {"content": "Title: Children\u2019s heart and COVID-19: Up-to-date evidence in the form of a systematic review Content: The new coronavirus disease outbreak in 2019 (COVID-19) represents a dramatic challenge for healthcare systems worldwide. As to viral tropism, lungs are not the only COVID-19 target but also the heart may be involved in a not negligible percentage of the infected patients. Myocarditis-related cardiac dysfunction and potentially life-threatening arrhythmias are the main aftermaths. A few studies showed that myocardial injury in adult patients is often linked with a fatal outcome. Conversely, scientific evidence in children is sparse, although several reports were published with the description of a cardiac involvement in COVID-19 paediatric patients. In these young subjects, a background of surgically treated congenital heart disease seems to be a predisposing factor. Conclusion: This systematic review is aimed at summarizing all COVID-19 cases with a cardiac involvement published in paediatric age and trying to explain the underlying mechanisms responsible for COVID-19-related myocardial damage.", "qid": 22, "docid": "czn8bpz7", "rank": 44, "score": 0.8911550045013428}, {"content": "Title: COVID-19 (SARS-Cov-2) and the heart \u2013 An ominous association Content: Coronavirus disease 2019 (COVID-19) is an infectious disease caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). Cardiovascular manifestations of COVID-19 are diverse and complex and include acute coronary syndrome, myocarditis masquerading as ST-segment elevation myocardial infarction, pericarditis and pericardial effusion. We present 2 cases of COVID-19 infection with myocardial involvement with distinct mechanistic pathways and outcomes. Important decision strategies such as the timing of cardiac catheterization (when indicated) and requirement of early hemodynamic support in critically ill patients are discussed.", "qid": 22, "docid": "rsyiemgn", "rank": 45, "score": 0.8910970687866211}, {"content": "Title: COVID-19 (SARS-Cov-2) and the heart - An ominous association Content: Coronavirus disease 2019 (COVID-19) is an infectious disease caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). Cardiovascular manifestations of COVID-19 are diverse and complex and include acute coronary syndrome, myocarditis masquerading as ST-segment elevation myocardial infarction, pericarditis and pericardial effusion. We present 2 cases of COVID-19 infection with myocardial involvement with distinct mechanistic pathways and outcomes. Important decision strategies such as the timing of cardiac catheterization (when indicated) and requirement of early hemodynamic support in critically ill patients are discussed.", "qid": 22, "docid": "q0qjfoc0", "rank": 46, "score": 0.8910970687866211}, {"content": "Title: A review of cardiac manifestations and predictors of outcome in patients with COVID - 19 Content: Coronavirus disease (COVID-19) pandemic has so far involved 184 countries and more than 2.79 million patients worldwide. Over the past three months, it has attributed to more than 196,000 deaths, with more than 50,000 deaths in the United States alone. Pulmonary manifestations are predominant and have been well identified. Cardiac involvement is also common. Acute cardiac injury, the most common cardiac manifestation of this disease can be seen in patients even without prior cardiac comorbidities. Established cardiovascular risk factors such as diabetes mellitus, hypertension, and coronary artery disease predispose to cardiac injury, the severity of illness and mortality. Non-ischemic myocardial injury secondary to cytokine storm is thought to be the predominant mechanism of acute cardiac injury associated with COVID-19. Multiple mechanisms and processes contribute to cardiac injury resulting in a poor outcome. Some of these are not clearly understood. Clinical and diagnostic details of cardiovascular involvement in these patients are mostly limited to biochemical markers. Multiple therapeutic agents have been tried with questionable efficacy and without clinical evidence. Interactions of comorbidities, cardiovascular drugs, the cardiac effect of therapeutic agents on the illness continue to be under investigation. With an increasing number of patients, newer promising therapies, and ongoing clinical trials, the exact mechanisms and extent to which these risk factors contribute to outcomes will be clearer in the future.", "qid": 22, "docid": "bus1nb6t", "rank": 47, "score": 0.8907795548439026}, {"content": "Title: What should a cardiologist know about coronavirus disease 2019? Content: Severe acute respiratory syndrome coronavirus 2 (SARS\u00adCoV\u00ad2) is the cause of coronavirus disease 2019 (COVID\u00ad19). The most common symptoms of COVID\u00ad19 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\u00ad19 include decreased lymphocyte count (35%-82.1%), thrombocytopenia (17%-36.2%), elevated serum C\u00adreactive protein (60.7%-93%), lactate dehydrogenase (41%-76%), and D\u00addimer concentrations (36%-46.4%). Among comorbidities in patients with COVID\u00ad19, 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\u00ad19 develop cardiac injury. Cardiac injury is more prevalent among patients with COVID\u00ad19 who require ICU care. In a group of critically ill patients, 27.5% had an elevated N\u00adterminal pro-B\u00adtype natriuretic peptide concentration, and increased cardiac troponin level was found in 10% of patients. One of the life\u00adthreatening 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\u00ad19 are limited. Coronavirus disease 2019 impacts patients with cardiovascular comorbidities and affects daily practice of cardiologists. Thus, it is important to know typical COVID\u00ad19 symptoms, possible clinical manifestations, complications, and recommended treatment.", "qid": 22, "docid": "yw3jei78", "rank": 48, "score": 0.8898447751998901}, {"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": 49, "score": 0.8898248672485352}, {"content": "Title: A review of cardiac manifestations and predictors of outcome in patients with COVID \u2013 19 Content: Abstract Coronavirus disease (COVID-19) pandemic has so far involved 184 countries and more than 2.79 million patients worldwide. Over the past three months, it has attributed to more than 196, 000 deaths, with more than 50, 000 deaths in the United States alone. Pulmonary manifestations are predominant and have been well identified. Cardiac involvement is also common. Acute cardiac injury, the most common cardiac manifestation of this disease can be seen in patients even without prior cardiac comorbidities. Established cardiovascular risk factors such as diabetes mellitus, hypertension, and coronary artery disease predispose to cardiac injury, the severity of illness and mortality. Non-ischemic myocardial injury secondary to cytokine storm is thought to be the predominant mechanism of acute cardiac injury associated with COVID-19. Multiple mechanisms and processes contribute to cardiac injury resulting in a poor outcome. Some of these are not clearly understood. Clinical and diagnostic details of cardiovascular involvement in these patients are mostly limited to biochemical markers. Multiple therapeutic agents have been tried with questionable efficacy and without clinical evidence. Interactions of comorbidities, cardiovascular drugs, the cardiac effect of therapeutic agents on the illness continue to be under investigation. With an increasing number of patients, newer promising therapies, and ongoing clinical trials, the exact mechanisms and extent to which these risk factors contribute to outcomes will be clearer in the future.", "qid": 22, "docid": "lbt57ccs", "rank": 50, "score": 0.8891252875328064}, {"content": "Title: Cardiac function in relation to myocardial injury in hospitalised patients with COVID-19 Content: BACKGROUND: Previous studies have reported on myocardial injury in patients with coronavirus infectious disease 19 (COVID-19) defined as elevated cardiac biomarkers. Whether elevated biomarkers truly represent myocardial dysfunction is not known. The aim of this study was to explore the incidence of ventricular dysfunction and assess its relationship with biomarker analyses. METHODS: This cross-sectional study ran from April 1 to May 12, 2020, and consisted of all consecutively admitted patients to the Radboud university medical centre nursing ward for COVID-19. Laboratory assessment included high-sensitivity Troponin T and N\u00adterminal pro-B-type natriuretic peptide (NT-proBNP). Echocardiographic evaluation focused on left and right ventricular systolic function and global longitudinal strain (GLS). RESULTS: In total, 51 patients were included, with a median age of 63 years (range 51-68 years) of whom 80% was male. Troponin T was elevated (>14\u00e2\u0080\u00afng/l) in 47%, and a clinically relevant Troponin T elevation (10\u00e2\u0080\u00af\u00d7 URL) was found in three patients (6%). NT-proBNP was elevated (>300\u00e2\u0080\u00afpg/ml) in 24 patients (47%), and in four (8%) the NT-proBNP concentration was >1,000\u00e2\u0080\u00afpg/ml. Left ventricular dysfunction (ejection fraction <52% and/or GLS >-18%) was observed in 27%, while right ventricular dysfunction (TAPSE <17\u00e2\u0080\u00afmm and/or RV S'\u00e2\u0080\u00af< 10\u00e2\u0080\u00afcm/s) was seen in 10%. There was no association between elevated Troponin T or NT-proBNP and left or right ventricular dysfunction. Patients with confirmed pulmonary embolism had normal right ventricular function. CONCLUSIONS: In hospitalised patients, it seems that COVID-19 predominantly affects the respiratory system, while cardiac dysfunction occurs less often. Based on a single echocardiographic evaluation, we found no relation between elevated Troponin T or NT-proBNP, and ventricular dysfunction. Echocardiography has limited value in screening for ventricular dysfunction.", "qid": 22, "docid": "mmarbtt5", "rank": 51, "score": 0.8887474536895752}, {"content": "Title: Cardiac Injury and COVID-19: A Systematic Review and Meta-Analysis Content: BACKGROUND: During the current coronavirus disease 2019 (COVID-19) pandemic, a link between acute cardiac injury and COVID-19 infection has been observed. There is currently no consensus on the incidence of cardiac injury, its relationship to prognosis, or its possible cause. This article provides a comprehensive review and meta-analysis of the incidence, comorbidities, outcomes and possible mechanisms of acute cardiac injury in COVID-19 patients. METHODS: We searched PubMed and Embase for studies that evaluated cardiac injury in hospitalized COVID-19 patients. Demographic information, co-morbidities, and relevant laboratory values were extracted and a meta-analysis was performed. RESULTS: Sixteen studies from China, Italy and the US with 2224 patients were included in this meta-analysis. The incidence of cardiac injury was 24.4% (542/2224 patients) in hospitalized COVID-19 patients. The all-cause mortality in patients with cardiac injury was 72.6% (OR=17.32, 95% CI 9.21-32.57) compared to those without cardiac injury (14.5%). In subgroup analyses, factors associated with increased risk of developing cardiac injury were older age and history of hypertension (HTN), and chronic obstructive respiratory disease (COPD). CONCLUSION: Cardiac injury is common in hospitalized COVID-19 patients and is significantly associated with mortality. Patients who were older with HTN and COPD were prone to develop cardiac injury. Early screening, triage and cardiac monitoring are recommended for these patients.", "qid": 22, "docid": "zr96k6p1", "rank": 52, "score": 0.8883222341537476}, {"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": 53, "score": 0.8881627321243286}, {"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": 22, "docid": "5svfhlzh", "rank": 54, "score": 0.8881289958953857}, {"content": "Title: Cardiac Structural and Functional Characteristics in Patients with Coronavirus Disease 2019: A Serial Echocardiographic Study Content: BACKGROUND: Increasing attention has been paid to cardiac involvement in patients with coronavirus disease 2019 (COVID-19). Yet, scarce information is available regarding the morphological and functional features of cardiac impairments in these patients. METHODS: We conducted a prospective and serial echocardiographic study to investigate the structural and functional cardiac changes among COVID-19 patients admitted to the intensive care unit (ICU). From January 21 to April 8, 2020, a total of 51 ICU patients (31 critically ill and 20 severely ill) with confirmed COVID-19 were monitored by serial transthoracic echocardiography examinations. Outcomes were followed up until April 8, 2020. RESULTS: Of 51 ICU patients, 33 (64.7%) had cardiovascular comorbidities. Elevations of levels of cardiac biomarkers including high-sensitivity cardiac troponin-I (hs-cTnI) and brain natriuretic peptide were observed in 62.7% and 86.3% of patients, respectively. Forty-two (82.3%) had at least one left-heart and/or right-heart echocardiographic abnormality. The overall median left ventricular ejection fraction (LVEF) was 65.0% (IQR 58.0-69.0%), with most (44,86.3%) having preserved LVEF. Sixteen patients (31.4%) had increased pulmonary artery systolic pressure, and 14 (27.5%) had right-ventricle (RV) enlargement. During the study period, 12 (23.5%) patients died. LVEF was comparable between survivors and non-survivors, while non-survivors had more often pulmonary hypertension (58.3% vs. 23.1%; P=0.028) and RV enlargement (58.3% vs. 17.9%, P=0.011). Kaplan-Meier analysis demonstrated similar survival curves between patients with vs. without echocardiographic left-heart abnormalities (P=0.450 by log-rank test), while right-heart abnormalities had adverse impact on mortality (P=0.012 by log-rank test). CONCLUSIONS: Typical cardiac abnormality in ICU patients with COVID-19 was right-heart dysfunction with preserved LVEF. Echocardiographic right-heart dysfunction was associated with disease severity and increased mortality in patients affected by COVID-19.", "qid": 22, "docid": "846vqdz7", "rank": 55, "score": 0.8880808353424072}, {"content": "Title: COVID-19 Cardiac Injury: Implications for Long-Term Surveillance and Outcomes in Survivors Content: Up to 20-30% of patients hospitalized with coronavirus disease (COVID-19) have evidence of myocardial involvement. Acute cardiac injury in patients hospitalized with COVID-19 is associated with higher morbidity and mortality. There are no data on how acute treatment for COVID-19 may affect convalescent phase or long-term cardiac recovery and function. Myocarditis from other viral pathogens can evolve into overt or subclinical myocardial dysfunction, and sudden death has been described in the convalescent phase of viral myocarditis. This raises concerns for patients recovering from COVID-19. Some patients will have subclinical and possibly overt cardiovascular abnormalities. Patients with ostensibly recovered cardiac function may still be at risk for cardiomyopathy and cardiac arrhythmias. Screening for residual cardiac involvement in the convalescent phase for patients recovered from COVID-19 associated cardiac injury is needed. The type of testing, and therapies for post COVID-19 myocardial dysfunction will need to be determined. Therefore, now is the time to plan for appropriate registries and clinical trials to properly assess these issues and prepare for long-term sequelae of \u201cpost-COVID-19 Cardiac Syndrome\u201d", "qid": 22, "docid": "3tna1y5o", "rank": 56, "score": 0.8879827857017517}, {"content": "Title: Electrical Storm in COVID-19 Content: Abstract COVID-19 is a global pandemic caused by SARS-CoV-2. Infection is associated with significant morbidity and mortality. Individuals with pre-existing cardiovascular disease or evidence of myocardial injury are at risk for severe disease and death. Little is understood about the mechanisms of myocardial injury or life-threatening cardiovascular sequelae.", "qid": 22, "docid": "98xisxg7", "rank": 57, "score": 0.8873507976531982}, {"content": "Title: Cardiovascular manifestations in severe and critical patients with COVID-19 Content: BACKGROUND: Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) could cause virulent infection leading to Corona Virus Disease 2019 (COVID-19)-related pneumonia as well as multiple organ injuries. HYPOTHESIS: COVID-19 infection may result in cardiovascular manifestations leading to worse clinical outcome. METHODS: Fifty four severe and critical patients with confirmed COVID-19 were enrolled. Risk factors predicting the severity of COVID-19 were analyzed. RESULTS: Of the 54 patients (56.1 \u00b1 13.5 years old, 66.7% male) with COVID-19, 39 were diagnosed as severe and 15 as critical cases. The occurrence of diabetes, the level of D-dimer, inflammatory and cardiac markers in critical cases were significantly higher. Troponin I (TnI) elevation occurred in 42.6% of all the severe and critical patients. Three patients experienced hypotension at admission and were all diagnosed as critical cases consequently. Hypotension was found in one severe case and seven critical cases during hospitalization. Sinus tachycardia is the most common type of arrythmia and was observed in 23 severe patients and all the critical patients. Atrioventricular block and ventricular tachycardia were observed in critical patients at end stage while bradycardia and atrial fibrillation were less common. Mild pericardial effusion was observed in one severe case and five critical cases. Three critical cases suffered new onset of heart failure. Hypotension during treatment, severe myocardial injury and pericardial effusion were independent risk factors predicting the critical status of COVID-19 infection. CONCLUSION: This study has systemically observed the impact of COVID-19 on cardiovascular system, including myocardial injury, blood pressure, arrythmia and cardiac function in severe and critical cases. Monitoring of vital signs and cardiac function of COVID-19 patients and applying potential interventions especially for those with hypotension during treatment, severe myocardial injury or pericardial effusion, is of vital importance.", "qid": 22, "docid": "x9qxnybj", "rank": 58, "score": 0.8873164057731628}, {"content": "Title: Global evaluation of echocardiography in patients with COVID-19 Content: AIMS: To describe the cardiac abnormalities in patients with COVID-19 and identify the characteristics of patients who would benefit most from echocardiography. METHODS AND RESULTS: In a prospective international survey, we captured echocardiography findings in patients with presumed or confirmed COVID-19 between 3 and 20 April 2020. Patient characteristics, indications, findings, and impact of echocardiography on management were recorded. Multivariable logistic regression identified predictors of echocardiographic abnormalities. A total of 1216 patients [62 (52-71) years, 70% male] from 69 countries across six continents were included. Overall, 667 (55%) patients had an abnormal echocardiogram. Left and right ventricular abnormalities were reported in 479 (39%) and 397 (33%) patients, respectively, with evidence of new myocardial infarction in 36 (3%), myocarditis in 35 (3%), and takotsubo cardiomyopathy in 19 (2%). Severe cardiac disease (severe ventricular dysfunction or tamponade) was observed in 182 (15%) patients. In those without pre-existing cardiac disease (n = 901), the echocardiogram was abnormal in 46%, and 13% had severe disease. Independent predictors of left and right ventricular abnormalities were distinct, including elevated natriuretic peptides [adjusted odds ratio (OR) 2.96, 95% confidence interval (CI) 1.75-5.05) and cardiac troponin (OR 1.69, 95% CI 1.13-2.53) for the former, and severity of COVID-19 symptoms (OR 3.19, 95% CI 1.73-6.10) for the latter. Echocardiography changed management in 33% of patients. CONCLUSION: In this global survey, cardiac abnormalities were observed in half of all COVID-19 patients undergoing echocardiography. Abnormalities were often unheralded or severe, and imaging changed management in one-third of patients.", "qid": 22, "docid": "3yxepzwv", "rank": 59, "score": 0.8870880603790283}, {"content": "Title: Global evaluation of echocardiography in patients with COVID-19 Content: AIMS: To describe the cardiac abnormalities in patients with COVID-19 and identify the characteristics of patients who would benefit most from echocardiography. METHODS AND RESULTS: In a prospective international survey, we captured echocardiography findings in patients with presumed or confirmed COVID-19 between 3 and 20 April 2020. Patient characteristics, indications, findings, and impact of echocardiography on management were recorded. Multivariable logistic regression identified predictors of echocardiographic abnormalities. A total of 1216 patients [62 (52\u201371) years, 70% male] from 69 countries across six continents were included. Overall, 667 (55%) patients had an abnormal echocardiogram. Left and right ventricular abnormalities were reported in 479 (39%) and 397 (33%) patients, respectively, with evidence of new myocardial infarction in 36 (3%), myocarditis in 35 (3%), and takotsubo cardiomyopathy in 19 (2%). Severe cardiac disease (severe ventricular dysfunction or tamponade) was observed in 182 (15%) patients. In those without pre-existing cardiac disease (n = 901), the echocardiogram was abnormal in 46%, and 13% had severe disease. Independent predictors of left and right ventricular abnormalities were distinct, including elevated natriuretic peptides [adjusted odds ratio (OR) 2.96, 95% confidence interval (CI) 1.75\u20135.05) and cardiac troponin (OR 1.69, 95% CI 1.13\u20132.53) for the former, and severity of COVID-19 symptoms (OR 3.19, 95% CI 1.73\u20136.10) for the latter. Echocardiography changed management in 33% of patients. CONCLUSION: In this global survey, cardiac abnormalities were observed in half of all COVID-19 patients undergoing echocardiography. Abnormalities were often unheralded or severe, and imaging changed management in one-third of patients.", "qid": 22, "docid": "e01ayyqk", "rank": 60, "score": 0.8868744373321533}, {"content": "Title: [COVID-19 andcardiovascular diseases]. Content: COVID-2019 disease mainly affects the respiratory tract and can progress in severe cases to pneumonia, acute respiratory distress syndrome and multi-organ failure. Patients with prior cardiovascular disease are at higher risk of developing an infection and progressing to a severe form of the disease. Also, due to the growing number of infected cases, it is clear that, in addition to the typical respiratory symptoms caused by the infection, some patients suffer from cardiovascular damage. This condition can, in fact, cause significant myocardial damage, which worsens the disease and affects the prognosis. Based on the results of currently published research, it seems important to discuss the manifestations and characteristics of myocardial damage induced by COVID-19 and its impact on patient prognosis.", "qid": 22, "docid": "w996v6od", "rank": 61, "score": 0.8858860731124878}, {"content": "Title: COVID-19 et maladies cardiovasculaires./ [COVID-19 andcardiovascular diseases] Content: COVID-2019 disease mainly affects the respiratory tract and can progress in severe cases to pneumonia, acute respiratory distress syndrome and multi-organ failure. Patients with prior cardiovascular disease are at higher risk of developing an infection and progressing to a severe form of the disease. Also, due to the growing number of infected cases, it is clear that, in addition to the typical respiratory symptoms caused by the infection, some patients suffer from cardiovascular damage. This condition can, in fact, cause significant myocardial damage, which worsens the disease and affects the prognosis. Based on the results of currently published research, it seems important to discuss the manifestations and characteristics of myocardial damage induced by COVID-19 and its impact on patient prognosis.", "qid": 22, "docid": "f7ne994m", "rank": 62, "score": 0.885886013507843}, {"content": "Title: Dilated Cardiomyopathy Risk in Patients with Coronavirus Disease 2019: How to Identify and Characterise it Early? Content: Multiple lines of evidence have shown that elevated blood troponin is strongly associated with poor prognosis in patients with the novel coronavirus disease 2019 (COVID-19). Possible mechanisms of myocardial injury in COVID-19 include ischaemia due to circulatory and respiratory failure, epicardial or intramyocardial small coronary artery thrombotic obstruction due to increased coagulability, and myocarditis caused by systemic inflammation or direct binding of the virus to its receptor, angiotensin-converting enzyme-2 (ACE2), which is abundantly expressed in the heart. It is postulated that persistent immune activation upon viral infection increases the risk of developing dilated cardiomyopathy in COVID-19 patients.", "qid": 22, "docid": "suje0oo8", "rank": 63, "score": 0.8858237266540527}, {"content": "Title: Cardiac function in relation to myocardial injury in hospitalised patients with COVID-19 Content: BACKGROUND: Previous studies have reported on myocardial injury in patients with coronavirus infectious disease 19 (COVID-19) defined as elevated cardiac biomarkers. Whether elevated biomarkers truly represent myocardial dysfunction is not known. The aim of this study was to explore the incidence of ventricular dysfunction and assess its relationship with biomarker analyses. METHODS: This cross-sectional study ran from April 1 to May 12, 2020, and consisted of all consecutively admitted patients to the Radboud university medical centre nursing ward for COVID-19. Laboratory assessment included high-sensitivity Troponin T and N\u2011terminal pro-B-type natriuretic peptide (NT-proBNP). Echocardiographic evaluation focused on left and right ventricular systolic function and global longitudinal strain (GLS). RESULTS: In total, 51 patients were included, with a median age of 63 years (range 51\u201368 years) of whom 80% was male. Troponin T was elevated (>14 ng/l) in 47%, and a clinically relevant Troponin T elevation (10 \u00d7 URL) was found in three patients (6%). NT-proBNP was elevated (>300 pg/ml) in 24 patients (47%), and in four (8%) the NT-proBNP concentration was >1,000 pg/ml. Left ventricular dysfunction (ejection fraction <52% and/or GLS >\u221218%) was observed in 27%, while right ventricular dysfunction (TAPSE <17 mm and/or RV S\u2019 < 10 cm/s) was seen in 10%. There was no association between elevated Troponin T or NT-proBNP and left or right ventricular dysfunction. Patients with confirmed pulmonary embolism had normal right ventricular function. CONCLUSIONS: In hospitalised patients, it seems that COVID-19 predominantly affects the respiratory system, while cardiac dysfunction occurs less often. Based on a single echocardiographic evaluation, we found no relation between elevated Troponin T or NT-proBNP, and ventricular dysfunction. Echocardiography has limited value in screening for ventricular dysfunction. ELECTRONIC SUPPLEMENTARY MATERIAL: The online version of this article (10.1007/s12471-020-01458-2) contains supplementary material, which is available to authorized users.", "qid": 22, "docid": "ipcvepia", "rank": 64, "score": 0.885783314704895}, {"content": "Title: SARS-CoV-2 and Cardiovascular Complications: from Molecular Mechanisms to Pharmaceutical Management Content: The coronavirus disease 2019 (COVID-19), elicited by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection, is a pandemic public health emergency of global concern. Other than the profound severe pulmonary damage, SARS-CoV-2 infection also leads to a series of cardiovascular abnormalities, including myocardial injury, myocarditis and pericarditis, arrhythmia and cardiac arrest, cardiomyopathy, heart failure, cardiogenic shock, and coagulation abnormalities. Meanwhile, COVID-19 patients with preexisting cardiovascular diseases are often at a much higher risk of increased morbidity and mortality. Up\u2013to-date, a number of mechanisms have been postulated for COVID-19-associated cardiovascular damage including SARS-CoV-2 receptor angiotensin-converting enzyme 2 (ACE2) activation, cytokine storm, hypoxemia, stress and cardiotoxicity of antiviral drugs. In this context, special attention should be given towards COVID-19 patients with concurrent cardiovascular diseases, and special cardiovascular attention is warranted for treatment of COVID-19.", "qid": 22, "docid": "5fn1nfpf", "rank": 65, "score": 0.8857021331787109}, {"content": "Title: [Risks factors for death among COVID-19 patients combined with hypertension, coronary heart disease or diabetes] Content: OBJECTIVE: The pathogenesis of myocardial injury upon corona virus disease 2019 (COVID-19) infection remain unknown,evidence of impact on outcome is insufficient, therefore, we aim to investigate the risk factors for death among COVID-19 patients combined with hypertension, coronary heart disease or diabetes in this study. METHODS: This was a single-centered, retrospective, observational study. Patients of Sino-French Eco-City section of Tongji Hospital, Wuhan, China attended by Peking University Supporting Medical Team and admitted from Jan. 29, 2020 to Mar. 20, 2020 were included. The positive nucleic acid of COVID-19 virus and combination with hypertension, coronary heart disease or diabetes were in the standard. We collected the clinical data and laboratory examination results of the eligible patients to evaluate the related factors of death. RESULTS: In the study, 94 COVID-19 patients enrolled were divided into the group of death (13 cases) and the group of survivors (81 cases), the average age was 66.7 years. Compared with the survival group, the death group had faster basal heart rate(103.2 beats/min vs. 88.4 beats /min, P=0.004), shortness of breath(29.0 beats /min vs. 20.0 beats /min, P<0.001), higher neutrophil count(9.2\u00d7109/L vs. 3.8\u00d7109/L, P<0.001), lower lymphocyte count(0.5\u00d7109/L vs. 1.1\u00d7109/L, P<0.001), creatine kinase MB(CK-MB, 3.2 \u00b5g/L vs. 0.8 \u00b5g/L, P<0.001), high sensitivity cardiac troponin \u00e2 (hs-cTn\u00e2 , 217.2 ng/L vs. 4.9 ng/L, P<0.001), N-terminal pro brain natriuretic peptide(NT-proBNP; 945.0 \u00b5g/L vs. 154.0 \u00b5g/L, P<0.001), inflammatory factor ferritin(770.2 \u00b5g/L vs. 622.8 \u00b5g/L , P=0.050), interleukin-2 recepter(IL-2R, 1 586.0 U/mL vs. 694.0 U/mL, P<0.001), interleukin-6(IL-6, 82.3 ng/L vs. 13.0 ng/L, P<0.001), interleukin-10(IL-10, 9.8 ng/L vs. 5.0 ng/L, P<0.001)were higher than those in the survival group. Univariate logistic regression analysis showed that the risk factors for death were old age, low non oxygen saturation, low lymphocyte count, myocardial injury, abnormal increase of IL 2R, IL-6, and IL-10. Multivariate regression showed that old age (OR=1.11, 95%CI=1.03-1.19, P=0.026), low non oxygen saturation(OR=0.85, 95%CI=0.72-0.99, P=0.041), and abnormal increase of IL-10(\u00ef\u00bc\u009e9.1 ng/L, OR=101.93, 95%CI=4.74-2190.71, P=0.003)were independent risk factors for COVID-19 patients combined with hypertension, coronary heart disease or diabetes. CONCLUSION: In COVID-19 patients combined with hypertension, coronary heart disease or diabetes, the risk factors for death were old age, low non oxygen saturation, low lymphocyte count, myocardial injury, and abnormal increase of IL-2R, IL-6, and IL-10. Old age, low non oxygen saturation and abnormal increase of IL-10 were independent risk factors.", "qid": 22, "docid": "ylyzmwcn", "rank": 66, "score": 0.8856105804443359}, {"content": "Title: Impact of Cardiovascular Disease on Clinical Characteristics and Outcomes of Coronavirus Disease 2019 (COVID-19). Content: BACKGROUND To investigate the effect of cardiovascular disease (CVD) on the global pandemic, coronavirus disease 2019 (COVID-19), we analyzed the cases of laboratory-confirmed COVID-19 patients in Wuhan.Methods and Results:Data were extracted from the medical records. SARS-CoV-2 RNA was confirmed by RT-PCR. A total of 33 (53.2%) of 62 cases with CVD, who had higher prevalence of severe COVID-19 compared with non-CVD patients (P=0.027). The median age of all patients was 66.0 (53.3, 73.0) years old. Coronary artery disease (11.3%) and hypertension (38.7%) were the common coexisting CVDs in COVID-19 patients. High-sensitivity cardiac troponin I (hs-cTnI), creatinine, high-density lipoprotein-cholesterol, interleukin-6, C-reactive protein, prothrombin time, and D-dimer levels in the severe COVID-19 with CVD group were higher than in the non-severe COVID-19 with CVD group (P<0.05). For all patients, chest computed tomography (CT) showed ground-glass opacity (66.1%), local (21.0%), bilateral (77.4%), and interstitial abnormalities (4.8%). In COVID-19 patients with CVD, 27 (81.8%) were cured and discharged. 6 (18.2%) remained in hospital, including 2 (3.2%) patients requiring intubation and mechanical ventilation. The hs-cTnI levels in the remaining hospitalized patients were higher than in the discharged patients (P=0.047). CONCLUSIONS CVDs play a vital role in the disease severity of COVID-19. COVID-19 could result in myocardial injury, which affects the prognosis of COVID-19.", "qid": 22, "docid": "4598qcur", "rank": 67, "score": 0.8855623006820679}, {"content": "Title: SARS-CoV-2 and cardiovascular complications: From molecular mechanisms to pharmaceutical management Content: The coronavirus disease 2019 (COVID-19), elicited by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection, is a pandemic public health emergency of global concern. Other than the profound severe pulmonary damage, SARS-CoV-2 infection also leads to a series of cardiovascular abnormalities, including myocardial injury, myocarditis and pericarditis, arrhythmia and cardiac arrest, cardiomyopathy, heart failure, cardiogenic shock, and coagulation abnormalities. Meanwhile, COVID-19 patients with preexisting cardiovascular diseases are often at a much higher risk of increased morbidity and mortality. Up-to-date, a number of mechanisms have been postulated for COVID-19-associated cardiovascular damage including SARS-CoV-2 receptor angiotensin-converting enzyme 2 (ACE2) activation, cytokine storm, hypoxemia, stress and cardiotoxicity of antiviral drugs. In this context, special attention should be given towards COVID-19 patients with concurrent cardiovascular diseases, and special cardiovascular attention is warranted for treatment of COVID-19.", "qid": 22, "docid": "ye7yxtd3", "rank": 68, "score": 0.8855209946632385}, {"content": "Title: Recommendations for the care of patients with heart failure and COVID-19. Content: The COVID-19 pandemic decreed by the World Health Organization (WHO) since March 12, 2020 is wreaking havoc globally and it is a true economic, social and health challenge. Although the clinical manifestations of COVID-19 are respiratory symptoms, some patients also have cardiological symptoms. Among patients with cardiological conditions2 they represent a group of higher risk and, in fact, they are a particularly vulnerable group, due to their higher risk of contagion and greater severity in case of acquiring the disease1 those with heart failure (HF), including heart transplant (CT) and ventricular assists, as well as patients with pulmonary arterial hypertension (PAH). HF is the main chronic cardiovascular disease and patients in this group are the most vulnerable for the development of more serious clinical symptoms after suffering the infection, and to a greater extent cases with advanced HF3. In fact, HF is one of the most frequent complications in patients with COVID-194. Likewise, transplant patients who require immunosuppressants to avoid graft rejection, constitute a population especially susceptible to infection and to develop more serious processes. This situation has made the National Association of Cardiologists of Mexico (ANCAM) and the Mexican Society of Cardiology (SMC) together with their respective chapters, have prepared the following recommendations for medical personnel, who participate in the care of this special group of patients in the different clinical settings, who suffer or not, of COVID-19.", "qid": 22, "docid": "cp23x6lp", "rank": 69, "score": 0.8854332566261292}, {"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": 70, "score": 0.8845924735069275}, {"content": "Title: Conduction abnormalities in hydroxychloroquine add on therapy to lopinavir/ritonavir in COVID\u201019 Content: COVID-19 is a contagious disease caused by Severe Adult Respiratory Syndrome Corona Virus-2 (SARS-CoV-2). Currently the role of HCQ in COVID-19 remains controversial but HCQ continued to be used in the absence of any effective therapy. We showed that cardiac conduction abnormalities were common in patients with HCQ added on to lopinavir/ritonavir. After starting HCQ, there were 5 (45.5%) new events of which four (36.3%) were attributed to HCQ: QTc prolongations in 3 patients with additional development of conduction blocks (fascicular block and right bundle brunch block in one patient respectively) and one patient with bradycardia. All conduction abnormalities settled after discontinuation of HCQ. Therefore monitoring is recommended when considering HCQ in treating patients with COVID-19. This article is protected by copyright. All rights reserved.", "qid": 22, "docid": "y6cau1q6", "rank": 71, "score": 0.8845812082290649}, {"content": "Title: Impact of Cardiovascular Disease on Clinical Characteristics and Outcomes of Coronavirus Disease 2019 (COVID-19) Content: BACKGROUND: To investigate the effect of cardiovascular disease (CVD) on the global pandemic, coronavirus disease 2019 (COVID-19), we analyzed the cases of laboratory-confirmed COVID-19 patients in Wuhan.Methods\u00e2\u0080\u0084and\u00e2\u0080\u0084Results:Data were extracted from the medical records. SARS-CoV-2 RNA was confirmed by RT-PCR. A total of 33 (53.2%) of 62 cases with CVD, who had higher prevalence of severe COVID-19 compared with non-CVD patients (P=0.027). The median age of all patients was 66.0 (53.3, 73.0) years old. Coronary artery disease (11.3%) and hypertension (38.7%) were the common coexisting CVDs in COVID-19 patients. High-sensitivity cardiac troponin I (hs-cTnI), creatinine, high-density lipoprotein-cholesterol, interleukin-6, C-reactive protein, prothrombin time, and D-dimer levels in the severe COVID-19 with CVD group were higher than in the non-severe COVID-19 with CVD group (P<0.05). For all patients, chest computed tomography (CT) showed ground-glass opacity (66.1%), local (21.0%), bilateral (77.4%), and interstitial abnormalities (4.8%). In COVID-19 patients with CVD, 27 (81.8%) were cured and discharged. 6 (18.2%) remained in hospital, including 2 (3.2%) patients requiring intubation and mechanical ventilation. The hs-cTnI levels in the remaining hospitalized patients were higher than in the discharged patients (P=0.047). CONCLUSIONS: CVDs play a vital role in the disease severity of COVID-19. COVID-19 could result in myocardial injury, which affects the prognosis of COVID-19.", "qid": 22, "docid": "w2huxj8q", "rank": 72, "score": 0.8841385841369629}, {"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": 73, "score": 0.8841086626052856}, {"content": "Title: Prevalence and Impact of Myocardial Injury in Patients Hospitalized with COVID-19 Infection Content: BACKGROUND: The degree of myocardial injury, as reflected by troponin elevation, and associated outcomes among US hospitalized patients with Coronavirus Disease 2019 (COVID-19) are unknown. OBJECTIVES: To describe the degree of myocardial injury and associated outcomes in a large hospitalized cohort with laboratory-confirmed COVID-19. METHODS: Patients with COVID-19 admitted to one of five Mount Sinai Health System hospitals in New York City between February 27th and April 12th, 2020 with troponin-I (normal value <0.03ng/mL) measured within 24 hours of admission were included (n=2,736). Demographics, medical history, admission labs, and outcomes were captured from the hospitals' EHR. RESULTS: The median age was 66.4 years, with 59.6% men. Cardiovascular disease (CVD) including coronary artery disease, atrial fibrillation, and heart failure, was more prevalent in patients with higher troponin concentrations, as were hypertension and diabetes. A total of 506 (18.5%) patients died during hospitalization. In all, 985 (36%) patients had elevated troponin concentrations. After adjusting for disease severity and relevant clinical factors, even small amounts of myocardial injury (e.g. troponin I 0.03-0.09ng/mL, n=455, 16.6%) were significantly associated with death (adjusted HR: 1.75, 95% CI 1.37-2.24; P<0.001) while greater amounts (e.g. troponin I>0.09 ng/dL, n=530, 19.4%) were significantly associated with higher risk (adjusted HR 3.03, 95% CI 2.42-3.80; P<0.001). CONCLUSIONS: Myocardial injury is prevalent among patients hospitalized with COVID-19 however troponin concentrations were generally present at low levels. Patients with CVD are more likely to have myocardial injury than patients without CVD. Troponin elevation among patients hospitalized with COVID-19 is associated with higher risk of mortality.", "qid": 22, "docid": "uvkq7m84", "rank": 74, "score": 0.8837787508964539}, {"content": "Title: Cardiac injury is associated with severe outcome and death in patients with Coronavirus disease 2019 (COVID-19) infection: A systematic review and meta-analysis of observational studies Content: Coronavirus disease 2019 (COVID-19) is a global pandemic impacting 213 countries/territories and more than 5,934,936 patients worldwide. Cardiac injury has been reported to occur in severe and death cases. This meta-analysis was done to summarize available findings on the association between cardiac injury and severity of COVID-19 infection. Online databases including Scopus, PubMed, Web of Science, Cochrane Library and Google Scholar were searched to detect relevant publications up to 20 May 2020, using relevant keywords. To pool data, a fixed- or random-effects model was used depending on the heterogeneity between studies. In total, 22 studies with 3684 COVID-19 infected patients (severe cases=1095 and death cases=365) were included in this study. Higher serum levels of lactate dehydrogenase (weighted mean difference (WMD) =108.86 U/L, 95% confidence interval (CI)=75.93-141.79, p<0.001) and creatine kinase-MB (WMD=2.60 U/L, 95% CI=1.32-3.88, p<0.001) were associated with a significant increase in the severity of COVID-19 infection. Furthermore, higher serum levels of lactate dehydrogenase (WMD=213.44 U/L, 95% CI=129.97-296.92, p<0.001), cardiac troponin I (WMD=26.35 pg/mL, 95% CI=14.54-38.15, p<0.001), creatine kinase (WMD=48.10 U/L, 95% CI=0.27-95.94, p = 0.049) and myoglobin (WMD=159.77 ng/mL, 95% CI=99.54-220.01, p<0.001) were associated with a significant increase in the mortality of COVID-19 infection. Cardiac injury, as assessed by serum analysis (lactate dehydrogenase, cardiac troponin I, creatine kinase (-MB) and myoglobin), was associated with severe outcome and death from COVID-19 infection.", "qid": 22, "docid": "cn40g3c9", "rank": 75, "score": 0.88374924659729}, {"content": "Title: Cardiac injury is associated with severe outcome and death in patients with Coronavirus disease 2019 (COVID-19) infection: A systematic review and meta-analysis of observational studies. Content: Coronavirus disease 2019 (COVID-19) is a global pandemic impacting 213 countries/territories and more than 5,934,936 patients worldwide. Cardiac injury has been reported to occur in severe and death cases. This meta-analysis was done to summarize available findings on the association between cardiac injury and severity of COVID-19 infection. Online databases including Scopus, PubMed, Web of Science, Cochrane Library and Google Scholar were searched to detect relevant publications up to 20 May 2020, using relevant keywords. To pool data, a fixed- or random-effects model was used depending on the heterogeneity between studies. In total, 22 studies with 3684 COVID-19 infected patients (severe cases=1095 and death cases=365) were included in this study. Higher serum levels of lactate dehydrogenase (weighted mean difference (WMD) =108.86 U/L, 95% confidence interval (CI)=75.93-141.79, p<0.001) and creatine kinase-MB (WMD=2.60 U/L, 95% CI=1.32-3.88, p<0.001) were associated with a significant increase in the severity of COVID-19 infection. Furthermore, higher serum levels of lactate dehydrogenase (WMD=213.44 U/L, 95% CI=129.97-296.92, p<0.001), cardiac troponin I (WMD=26.35 pg/mL, 95% CI=14.54-38.15, p<0.001), creatine kinase (WMD=48.10 U/L, 95% CI=0.27-95.94, p = 0.049) and myoglobin (WMD=159.77 ng/mL, 95% CI=99.54-220.01, p<0.001) were associated with a significant increase in the mortality of COVID-19 infection. Cardiac injury, as assessed by serum analysis (lactate dehydrogenase, cardiac troponin I, creatine kinase (-MB) and myoglobin), was associated with severe outcome and death from COVID-19 infection.", "qid": 22, "docid": "qtu0f0vz", "rank": 76, "score": 0.88374924659729}, {"content": "Title: Pathologies cardiovasculaires et Covid-19 : particularit\u00e9s chez les personnes \u00e2g\u00e9es./ COVID-19 and cardiovascular diseases: viewpoint for older patients Content: The coronavirus disease-2019 (COVID-19) is an infectious disease caused by severe acute respiratory syndrome coronavirus 2. The link between cardiovascular disease and COVID-19 appears to be twofold. First, some reports of data indicate that certain groups of patients are more at risk of COVID-19. This includes patients with cardiovascular risk factors or pre-existing cardiovascular conditions and older patients. In addition, these patients incur disproportionately worse outcome. Second, SARS-CoV2 infection can be complicated by life-threatening cardiovascular acute diseases. Despite the rapid evolution of data on this pandemic, this review aims to highlight the cardiovascular considerations related to COVID-19 whether as comorbidities including concerns and uncertainty regarding the effect of renin-angiotensin-aldosterone system (RAAS) inhibitors on angiotensin conversion enzyme 2 or related to acute cardiovascular complications.", "qid": 22, "docid": "pjtlk8ni", "rank": 77, "score": 0.8836559653282166}, {"content": "Title: COVID-19 and cardiovascular diseases: viewpoint for older patients. Content: The coronavirus disease-2019 (COVID-19) is an infectious disease caused by severe acute respiratory syndrome coronavirus 2. The link between cardiovascular disease and COVID-19 appears to be twofold. First, some reports of data indicate that certain groups of patients are more at risk of COVID-19. This includes patients with cardiovascular risk factors or pre-existing cardiovascular conditions and older patients. In addition, these patients incur disproportionately worse outcome. Second, SARS-CoV2 infection can be complicated by life-threatening cardiovascular acute diseases. Despite the rapid evolution of data on this pandemic, this review aims to highlight the cardiovascular considerations related to COVID-19 whether as comorbidities including concerns and uncertainty regarding the effect of renin-angiotensin-aldosterone system (RAAS) inhibitors on angiotensin conversion enzyme 2 or related to acute cardiovascular complications.", "qid": 22, "docid": "7rf532b9", "rank": 78, "score": 0.8836559653282166}, {"content": "Title: The cardiovascular burden of coronavirus disease 2019 (COVID-19) with a focus on congenital heart disease Content: Coronavirus disease 2019 (COVID-19), caused by a novel betacoronavirus severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), was first described in a cluster of patients presenting with pneumonia symptoms in Wuhan, China, in December of 2019. Over the past few months, COVID-19 has developed into a worldwide pandemic, with over 400,000 documented cases globally as of March 24, 2020. The SARS-CoV-2 virus is most likely of zoonotic origin, but has been shown to have effective human-to-human transmission. COVID-19 results in mild symptoms in the majority of infected patients, but can cause severe lung injury, cardiac injury, and death. Given the novel nature of COVID-19, no established treatment beyond supportive care exists currently, but extensive public-health measures to reduce person-to-person transmission of COVID-19 have been implemented globally to curb the spread of disease, reduce the burden on healthcare systems, and protect vulnerable populations, including the elderly and those with underlying medical comorbidities. Since this is an emerging infectious disease, there is, as of yet, limited data on the effects of this infection on patients with cardiovascular disease, particularly so for those with congenital heart disease. We summarize herewith the early experience with COVID-19 and consider the potential applicability to and implications for patients with cardiovascular disease in general and congenital heart disease in particular.", "qid": 22, "docid": "7wusbdmm", "rank": 79, "score": 0.8835244178771973}, {"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": 80, "score": 0.8835144639015198}, {"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": 22, "docid": "u42iq0jk", "rank": 81, "score": 0.8830841779708862}, {"content": "Title: Acute myocardial injury in patients hospitalized with COVID-19 infection: A review Content: The Coronavirus Disease 2019 (COVID-19) is now a global pandemic with millions affected and millions more at risk for contracting the infection. The COVID-19 virus, SARS-CoV-2, affects multiple organ systems, especially the lungs and heart. Elevation of cardiac biomarkers, particularly high-sensitivity troponin and/or creatine kinase MB, is common in patients with COVID-19 infection. In our review of clinical analyses, we found that in 26 studies including 11,685 patients, the weighted pooled prevalence of acute myocardial injury was 20% (ranged from 5% to 38% depending on the criteria used). The plausible mechanisms of myocardial injury include, 1) hyperinflammation and cytokine storm mediated through pathologic T-cells and monocytes leading to myocarditis, 2) respiratory failure and hypoxemia resulting in damage to cardiac myocytes, 3) down regulation of ACE2 expression and subsequent protective signaling pathways in cardiac myocytes, 4) hypercoagulability and development of coronary microvascular thrombosis, 5) diffuse endothelial injury and 'endotheliitis' in several organs including the heart, and, 6) inflammation and/or stress causing coronary plaque rupture or supply-demand mismatch leading to myocardial ischemia/infarction. Cardiac biomarkers can be used to aid in diagnosis as well as risk stratification. In patients with elevated hs-troponin, clinical context is important and myocarditis as well as stress induced cardiomyopathy should be considered in the differential, along with type I and type II myocardial infarction. Irrespective of etiology, patients with acute myocardial injury should be prioritized for treatment. Clinical decisions including interventions should be individualized and carefully tailored after thorough review of risks/benefits. Given the complex interplay of SARS-CoV-2 with the cardiovascular system, further investigation into potential mechanisms is needed to guide effective therapies. Randomized trials are urgently needed to investigate treatment modalities to reduce the incidence and mortality associated with COVID-19 related acute myocardial injury.", "qid": 22, "docid": "iik3mpmw", "rank": 82, "score": 0.8830287456512451}, {"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": 22, "docid": "r4e4tg7r", "rank": 83, "score": 0.882972240447998}, {"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": 84, "score": 0.8827255368232727}, {"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": 85, "score": 0.8827255368232727}, {"content": "Title: Recognizing COVID-19-related myocarditis: the possible pathophysiology and proposed guideline for diagnosis and management Content: Abstract Human coronavirus-associated myocarditis is known, and a number of COVID-19-related myocarditis cases have been reported. The pathophysiology of COVID-19-related myocarditis is thought to be a combination of direct viral injury and cardiac damage due to the host\u2019s immune response. COVID-19 myocarditis diagnosis should be guided by insights from previous coronavirus and other myocarditis experience. The clinical findings include changes in ECG, cardiac biomarkers, and impaired cardiac function. When cardiac MRI is infeasible, cardiac CT angiography with delayed myocardial imaging may serve to exclude significant coronary artery disease and identify myocardial inflammatory patterns. Because many COVID-19 patients have cardiovascular comorbidities, myocardial infarction should be considered. Where the diagnosis remains uncertain, an endomyocardial biopsy may help identify active cardiac infection through viral genome amplification and possibly refine the treatment risks of systemic immunosuppression. Arrhythmias are not uncommon in the COVID-19 patients; however, its pathophysiology is still speculative. Nevertheless, clinicians should be vigilant to provide prompt monitoring and treatments. The long-term impact of COVID-19 myocarditis, including in the majority of mild cases remains unknown.", "qid": 22, "docid": "4mjg7jul", "rank": 86, "score": 0.8826035261154175}, {"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": 87, "score": 0.8824366331100464}, {"content": "Title: Venous and arterial thromboembolic complications in COVID-19 patients admitted to an academic hospital in Milan, Italy Content: BACKGROUND: Few data are available on the rate and characteristics of thromboembolic complications in hospitalized patients with COVID-19. METHODS: We studied consecutive symptomatic patients with laboratory-proven COVID-19 admitted to a university hospital in Milan, Italy (13.02.2020-10.04.2020). The primary outcome was any thromboembolic complication, including venous thromboembolism (VTE), ischemic stroke, and acute coronary syndrome (ACS)/myocardial infarction (MI). Secondary outcome was overt disseminated intravascular coagulation (DIC). RESULTS: We included 388 patients (median age 66 years, 68% men, 16% requiring intensive care [ICU]). Thromboprophylaxis was used in 100% of ICU patients and 75% of those on the general ward. Thromboembolic events occurred in 28 (7.7% of closed cases; 95%CI 5.4%-11.0%), corresponding to a cumulative rate of 21% (27.6% ICU, 6.6% general ward). Half of the thromboembolic events were diagnosed within 24 h of hospital admission. Forty-four patients underwent VTE imaging tests and VTE was confirmed in 16 (36%). Computed tomography pulmonary angiography (CTPA) was performed in 30 patients, corresponding to 7.7% of total, and pulmonary embolism was confirmed in 10 (33% of CTPA). The rate of ischemic stroke and ACS/MI was 2.5% and 1.1%, respectively. Overt DIC was present in 8 (2.2%) patients. CONCLUSIONS: The high number of arterial and, in particular, venous thromboembolic events diagnosed within 24 h of admission and the high rate of positive VTE imaging tests among the few COVID-19 patients tested suggest that there is an urgent need to improve specific VTE diagnostic strategies and investigate the efficacy and safety of thromboprophylaxis in ambulatory COVID-19 patients.", "qid": 22, "docid": "wel4ggh3", "rank": 88, "score": 0.88239586353302}, {"content": "Title: [Risks factors for death among COVID-19 patients combined with hypertension, coronary heart disease or diabetes]. Content: OBJECTIVE The pathogenesis of myocardial injury upon corona virus disease 2019 (COVID-19) infection remain unknown,evidence of impact on outcome is insufficient, therefore, we aim to investigate the risk factors for death among COVID-19 patients combined with hypertension, coronary heart disease or diabetes in this study. METHODS This was a single-centered, retrospective, observational study. Patients of Sino-French Eco-City section of Tongji Hospital, Wuhan, China attended by Peking University Supporting Medical Team and admitted from Jan. 29, 2020 to Mar. 20, 2020 were included. The positive nucleic acid of COVID-19 virus and combination with hypertension, coronary heart disease or diabetes were in the standard. We collected the clinical data and laboratory examination results of the eligible patients to evaluate the related factors of death. RESULTS In the study, 94 COVID-19 patients enrolled were divided into the group of death (13 cases) and the group of survivors (81 cases), the average age was 66.7 years. Compared with the survival group, the death group had faster basal heart rate(103.2 beats/min vs. 88.4 beats /min, P=0.004), shortness of breath(29.0 beats /min vs. 20.0 beats /min, P<0.001), higher neutrophil count(9.2\u00d7109/L vs. 3.8\u00d7109/L, P<0.001), lower lymphocyte count(0.5\u00d7109/L vs. 1.1\u00d7109/L, P<0.001), creatine kinase MB(CK-MB, 3.2 \u03bcg/L vs. 0.8 \u03bcg/L, P<0.001), high sensitivity cardiac troponin \u2160(hs-cTn\u2160, 217.2 ng/L vs. 4.9 ng/L, P<0.001), N-terminal pro brain natriuretic peptide(NT-proBNP; 945.0 \u03bcg/L vs. 154.0 \u03bcg/L, P<0.001), inflammatory factor ferritin(770.2 \u03bcg/L vs. 622.8 \u03bcg/L , P=0.050), interleukin-2 recepter(IL-2R, 1 586.0 U/mL vs. 694.0 U/mL, P<0.001), interleukin-6(IL-6, 82.3 ng/L vs. 13.0 ng/L, P<0.001), interleukin-10(IL-10, 9.8 ng/L vs. 5.0 ng/L, P<0.001)were higher than those in the survival group. Univariate logistic regression analysis showed that the risk factors for death were old age, low non oxygen saturation, low lymphocyte count, myocardial injury, abnormal increase of IL 2R, IL-6, and IL-10. Multivariate regression showed that old age (OR=1.11, 95%CI=1.03-1.19, P=0.026), low non oxygen saturation(OR=0.85, 95%CI=0.72-0.99, P=0.041), and abnormal increase of IL-10(\uff1e9.1 ng/L, OR=101.93, 95%CI=4.74-2190.71, P=0.003)were independent risk factors for COVID-19 patients combined with hypertension, coronary heart disease or diabetes. CONCLUSION In COVID-19 patients combined with hypertension, coronary heart disease or diabetes, the risk factors for death were old age, low non oxygen saturation, low lymphocyte count, myocardial injury, and abnormal increase of IL-2R, IL-6, and IL-10. Old age, low non oxygen saturation and abnormal increase of IL-10 were independent risk factors.", "qid": 22, "docid": "f7s8s770", "rank": 89, "score": 0.8821386098861694}, {"content": "Title: Venous and arterial thromboembolic complications in COVID-19 patients admitted to an academic hospital in Milan, Italy Content: Abstract Background Few data are available on the rate and characteristics of thromboembolic complications in hospitalized patients with COVID-19. Methods We studied consecutive symptomatic patients with laboratory-proven COVID-19 admitted to a university hospital in Milan, Italy (13.02.2020\u201310.04.2020). The primary outcome was any thromboembolic complication, including venous thromboembolism (VTE), ischemic stroke, and acute coronary syndrome (ACS)/myocardial infarction (MI). Secondary outcome was overt disseminated intravascular coagulation (DIC). Results We included 388 patients (median age 66 years, 68% men, 16% requiring intensive care [ICU]). Thromboprophylaxis was used in 100% of ICU patients and 75% of those on the general ward. Thromboembolic events occurred in 28 (7.7% of closed cases; 95%CI 5.4%\u201311.0%), corresponding to a cumulative rate of 21% (27.6% ICU, 6.6% general ward). Half of the thromboembolic events were diagnosed within 24 h of hospital admission. Forty-four patients underwent VTE imaging tests and VTE was confirmed in 16 (36%). Computed tomography pulmonary angiography (CTPA) was performed in 30 patients, corresponding to 7.7% of total, and pulmonary embolism was confirmed in 10 (33% of CTPA). The rate of ischemic stroke and ACS/MI was 2.5% and 1.1%, respectively. Overt DIC was present in 8 (2.2%) patients. Conclusions The high number of arterial and, in particular, venous thromboembolic events diagnosed within 24 h of admission and the high rate of positive VTE imaging tests among the few COVID-19 patients tested suggest that there is an urgent need to improve specific VTE diagnostic strategies and investigate the efficacy and safety of thromboprophylaxis in ambulatory COVID-19 patients.", "qid": 22, "docid": "x92bxifa", "rank": 90, "score": 0.8821347951889038}, {"content": "Title: Recognizing COVID-19-related myocarditis: The possible pathophysiology and proposed guideline for diagnosis and management Content: Human coronavirus-associated myocarditis is known, and a number of coronavirus disease 19 (COVID-19)-related myocarditis cases have been reported. The pathophysiology of COVID-19-related myocarditis is thought to be a combination of direct viral injury and cardiac damage due to the host's immune response. COVID-19 myocarditis diagnosis should be guided by insights from previous coronavirus and other myocarditis experience. The clinical findings include changes in electrocardiogram and cardiac biomarkers, and impaired cardiac function. When cardiac magnetic resonance imaging is not feasible, cardiac computed tomographic angiography with delayed myocardial imaging may serve to exclude significant coronary artery disease and identify myocardial inflammatory patterns. Because many COVID-19 patients have cardiovascular comorbidities, myocardial infarction should be considered. If the diagnosis remains uncertain, an endomyocardial biopsy may help identify active cardiac infection through viral genome amplification and possibly refine the treatment risks of systemic immunosuppression. Arrhythmias are not uncommon in COVID-19 patients, but the pathophysiology is still speculative. Nevertheless, clinicians should be vigilant to provide prompt monitoring and treatment. The long-term impact of COVID-19 myocarditis, including the majority of mild cases, remains unknown.", "qid": 22, "docid": "zwy2wym7", "rank": 91, "score": 0.8821132779121399}, {"content": "Title: Characteristics and clinical significance of myocardial injury in patients with severe coronavirus disease 2019 Content: AIMS: To investigate the characteristics and clinical significance of myocardial injury in patients with severe coronavirus disease 2019 (COVID-19). METHODS AND RESULTS: We enrolled 671 eligible hospitalized patients with severe COVID-19 from 1 January to 23 February 2020, with a median age of 63 years. Clinical, laboratory, and treatment data were collected and compared between patients who died and survivors. Risk factors of death and myocardial injury were analysed using multivariable regression models. A total of 62 patients (9.2%) died, who more often had myocardial injury (75.8% vs. 9.7%; P < 0.001) than survivors. The area under the receiver operating characteristic curve of initial cardiac troponin I (cTnI) for predicting in-hospital mortality was 0.92 [95% confidence interval (CI), 0.87-0.96; sensitivity, 0.86; specificity, 0.86; P < 0.001]. The single cut-off point and high level of cTnI predicted risk of in-hospital death, hazard ratio (HR) was 4.56 (95% CI, 1.28-16.28; P = 0.019) and 1.25 (95% CI, 1.07-1.46; P = 0.004), respectively. In multivariable logistic regression, senior age, comorbidities (e.g. hypertension, coronary heart disease, chronic renal failure, and chronic obstructive pulmonary disease), and high level of C-reactive protein were predictors of myocardial injury. CONCLUSION: The risk of in-hospital death among patients with severe COVID-19 can be predicted by markers of myocardial injury, and was significantly associated with senior age, inflammatory response, and cardiovascular comorbidities.", "qid": 22, "docid": "gtno1kib", "rank": 92, "score": 0.8815582394599915}, {"content": "Title: Coronavirus Disease 2019 (COVID-19) Pandemic Implications in Pediatric and Adult Congenital Heart Disease Content: The corona virus disease -2019 (COVID-19) is a recently described infectious disease caused by the severe acute respiratory syndrome corona virus 2 with significant cardiovascular implications. Given the increased risk for severe COVID-19 observed in adults with underlying cardiac involvement, there is concern that patients with pediatric and congenital heart disease (CHD) may likewise be at increased risk for severe infection. The cardiac manifestations of COVID-19 include myocarditis, arrhythmia and myocardial infarction. Importantly, the pandemic has stretched health care systems and many care team members are at risk for contracting and possibly transmitting the disease which may further impact the care of patients with cardiovascular disease. In this review, we describe the effects of COVID-19 in the pediatric and young adult population and review the cardiovascular involvement in COVID-19 focusing on implications for patients with congenital heart disease in particular.", "qid": 22, "docid": "dcf82t8n", "rank": 93, "score": 0.8815128803253174}, {"content": "Title: Coronavirus Disease 2019 (COVID-19) Pandemic Implications in Pediatric and Adult Congenital Heart Disease. Content: The corona virus disease -2019 (COVID-19) is a recently described infectious disease caused by the severe acute respiratory syndrome corona virus 2 with significant cardiovascular implications. Given the increased risk for severe COVID-19 observed in adults with underlying cardiac involvement, there is concern that patients with pediatric and congenital heart disease (CHD) may likewise be at increased risk for severe infection. The cardiac manifestations of COVID-19 include myocarditis, arrhythmia and myocardial infarction. Importantly, the pandemic has stretched health care systems and many care team members are at risk for contracting and possibly transmitting the disease which may further impact the care of patients with cardiovascular disease. In this review, we describe the effects of COVID-19 in the pediatric and young adult population and review the cardiovascular involvement in COVID-19 focusing on implications for patients with congenital heart disease in particular.", "qid": 22, "docid": "5f9ofdsc", "rank": 94, "score": 0.8815128803253174}, {"content": "Title: Cardiovascular disease potentially contributes to the progression and poor prognosis of COVID-19 Content: BACKGROUND AND AIM: A novel coronavirus severe acute respiratory syndrome corona virus 2 (SARS-CoV-2) caused pneumonia, Coronavirus Disease 2019 (COVID-19), broke out in Wuhan, China in December 2019, and spread all over the world. Patients with COVID-19 showed huge differences in the hospital stay, progression, and prognosis. As reported, the comorbidities may play an important role in COVID-19. Here, we aim to address the role of cardiovascular disease (CVD) in the progression and prognosis of COVID-19. METHODS AND RESULTS: Eighty-three confirmed COVID-19 patients were divided into CVD (n = 42) and non-CVD (n = 41) group according to their medical history. Medical records including demographic data, medical history, clinical characteristics, laboratory examinations, chest computed tomography (CT), and treatment measures were collected, analyzed, and compared between the two groups. COVID-19 patients with CVD showed (1) more severe pathological changes in the lungs, (2) elevated injury-related enzymes including &#945;-hydroxybutyrate dehydrogenase (HDBH), lactic dehydrogenase (LDH), \u00ce\u00b3-glutamyltransferase (GGT), creatine kinase (CK), and alanine aminotransferase (ALT), (3) significantly increased uncontrolled inflammation related markers, such as c-reactive protein (CRP), interleukin (IL)-6, serum ferritin, erythrocyte sedimentation rate (ESR), and serum amyloid A (SAA), (4) serious hypercoagulable status reflected by increased D-dimer and serum fibrinogen (FIB), and (5) higher mortality, compared to COVID-19 patients without CVD. CONCLUSIONS: Our data indicated that CVD is a strong risk factor for rapid progression and bad prognosis of COVID-19. More intensive medical care should be applied to patients with CVD to prevent rapid deterioration of the disease.", "qid": 22, "docid": "gf9wripj", "rank": 95, "score": 0.881389319896698}, {"content": "Title: Characteristics and clinical significance of myocardial injury in patients with severe coronavirus disease 2019 Content: AIMS: To investigate the characteristics and clinical significance of myocardial injury in patients with severe coronavirus disease 2019 (COVID-19). METHODS AND RESULTS: We enrolled 671 eligible hospitalized patients with severe COVID-19 from 1 January to 23 February 2020, with a median age of 63 years. Clinical, laboratory, and treatment data were collected and compared between patients who died and survivors. Risk factors of death and myocardial injury were analysed using multivariable regression models. A total of 62 patients (9.2%) died, who more often had myocardial injury (75.8% vs. 9.7%; P < 0.001) than survivors. The area under the receiver operating characteristic curve of initial cardiac troponin I (cTnI) for predicting in-hospital mortality was 0.92 [95% confidence interval (CI), 0.87\u20130.96; sensitivity, 0.86; specificity, 0.86; P < 0.001]. The single cut-off point and high level of cTnI predicted risk of in-hospital death, hazard ratio (HR) was 4.56 (95% CI, 1.28\u201316.28; P = 0.019) and 1.25 (95% CI, 1.07\u20131.46; P = 0.004), respectively. In multivariable logistic regression, senior age, comorbidities (e.g. hypertension, coronary heart disease, chronic renal failure, and chronic obstructive pulmonary disease), and high level of C-reactive protein were predictors of myocardial injury. CONCLUSION: The risk of in-hospital death among patients with severe COVID-19 can be predicted by markers of myocardial injury, and was significantly associated with senior age, inflammatory response, and cardiovascular comorbidities.", "qid": 22, "docid": "lzaxzuwe", "rank": 96, "score": 0.8813647627830505}, {"content": "Title: Prior treatment with immunosuppressants among COVID-19 inpatients at one hospital in Spain Content: Vulnerability to coronavirus disease 2019 (COVID-19) in patients with cardiovascular risk factors is well known. However, the prognostic influence of immunosuppressive drugs or their ability to counteract the cytokine storm involving critically-ill patients are uncertain. The scarce related literature mainly involves transplantation.", "qid": 22, "docid": "fc1x5u63", "rank": 97, "score": 0.881308376789093}, {"content": "Title: Impaired cardiac function is associated with mortality in patients with acute COVID-19 infection Content: BACKGROUND: COVID-19 infection may cause severe respiratory distress and is associated with increased morbidity and mortality. Impaired cardiac function and/or pre-existing cardiovascular disease may be associated with poor prognosis. In the present study, we report a comprehensive cardiovascular characterization in the first consecutive collective of patients that was admitted and treated at the University Hospital of T\u00fcbingen, Germany. METHODS: 123 consecutive patients with COVID-19 were included. Routine blood sampling, transthoracic echocardiography and electrocardiography were performed at hospital admission. RESULTS: We found that impaired left-ventricular and right-ventricular function as well as tricuspid regurgitation > grade 1 were significantly associated with higher mortality. Furthermore, elevated levels of myocardial distress markers (troponin-I and NT pro-BNP) were associated with poor prognosis in this patient collective. CONCLUSION: Impaired cardiac function is associated with poor prognosis in COVID-19 positive patients. Consequently, treatment of these patients should include careful guideline-conform cardiovascular evaluation and treatment. Thus, formation of a competent Cardio-COVID-19 team may represent a major clinical measure to optimize therapy of cardiovascular patients during this pandemic.", "qid": 22, "docid": "07iqhhcl", "rank": 98, "score": 0.8811852931976318}, {"content": "Title: Characteristics and outcomes of patients hospitalized for COVID-19 and cardiac disease in Northern Italy Content: AIMS: To compare demographic characteristics, clinical presentation, and outcomes of patients with and without concomitant cardiac disease, hospitalized for COVID-19 in Brescia, Lombardy, Italy. METHODS AND RESULTS: The study population includes 99 consecutive patients with COVID-19 pneumonia admitted to our hospital between 4 March and 25 March 2020. Fifty-three patients with a history of cardiac disease were compared with 46 without cardiac disease. Among cardiac patients, 40% had a history of heart failure, 36% had atrial fibrillation, and 30% had coronary artery disease. Mean age was 67 \u00b1 12 years, and 80 (81%) patients were males. No differences were found between cardiac and non-cardiac patients except for higher values of serum creatinine, N-terminal probrain natriuretic peptide, and high sensitivity troponin T in cardiac patients. During hospitalization, 26% patients died, 15% developed thrombo-embolic events, 19% had acute respiratory distress syndrome, and 6% had septic shock. Mortality was higher in patients with cardiac disease compared with the others (36% vs. 15%, log-rank P = 0.019; relative risk 2.35; 95% confidence interval 1.08\u20135.09). The rate of thrombo-embolic events and septic shock during the hospitalization was also higher in cardiac patients (23% vs. 6% and 11% vs. 0%, respectively). CONCLUSIONS: Hospitalized patients with concomitant cardiac disease and COVID-19 have an extremely poor prognosis compared with subjects without a history of cardiac disease, with higher mortality, thrombo-embolic events, and septic shock rates.", "qid": 22, "docid": "1xkl3mof", "rank": 99, "score": 0.881170392036438}, {"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": 100, "score": 0.8811622858047485}]}
{"query": "what kinds of complications related to COVID-19 are associated with hypertension?", "hits": [{"content": "Title: The importance of hypertension as a risk factor for severe illness and mortality in COVID\u201019 Content: The virus responsible for COVID-19 binds to the angiotensin converting enzyme-2 (ACE-2) receptor [1]. Several articles have noted that hypertension is a risk factor for COVID-19 [2-7]. It is currently difficult to distinguish between hypertension as an independent risk factor in COVID-19 from one that co-varies with other patient factors such as age and cardiovascular disease. It is difficult from individual reports to determine whether hypertension is a risk factor for development of symptomatic disease or hospitalisation or for more severe disease. Reviewing the literature that reports rates of hypertension amongst included patients indicates a consistent association with more severe disease and increased mortality.", "qid": 23, "docid": "4ko4lwjz", "rank": 1, "score": 0.8926601409912109}, {"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": 2, "score": 0.8915313482284546}, {"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": 3, "score": 0.8809276819229126}, {"content": "Title: Association of hypertension with the severity and fatality of SARS-CoV-2 infection: A meta-analysis Content: Hypertension is a common comorbidity in COVID-19 patients. However, the association of hypertension with the severity and fatality of COVID-19 remain unclear. In the present meta-analysis, relevant studies reported the impacts of hypertension on SARS-CoV-2 infection were identified by searching PubMed, Elsevier Science Direct, Web of Science, Wiley Online Library, Embase and CNKI up to 20 March 2020. As the results shown, 12 publications with 2389 COVID-19 patients (674 severe cases) were included for the analysis of disease severity. The severity rate of COVID-19 in hypertensive patients was much higher than in non-hypertensive cases (37.58% vs 19.73%, pooled OR: 2.27, 95% CI: 1.80-2.86). Moreover, the pooled ORs of COVID-19 severity for hypertension vs. non-hypertension was 2.21 (95% CI: 1.58-3.10) and 2.32 (95% CI: 1.70-3.17) in age <50 years and \u00e2\u00a9\u00be50 years patients, respectively. Additionally, six studies with 151 deaths of 2116 COVID-19 cases were included for the analysis of disease fatality. The results showed that hypertensive patients carried a nearly 3.48-fold higher risk of dying from COVID-19 (95% CI: 1.72-7.08). Meanwhile, the pooled ORs of COVID-19 fatality for hypertension vs. non-hypertension was 6.43 (95% CI: 3.40-12.17) and 2.66 (95% CI: 1.27-5.57) in age <50 years and \u00e2\u00a9\u00be50 years patients, respectively. Neither considerable heterogeneity nor publication bias was observed in the present analysis. Therefore, our present results provided further evidence that hypertension could significantly increase the risks of severity and fatality of SARS-CoV-2 infection.", "qid": 23, "docid": "u7fqjti5", "rank": 4, "score": 0.8807161450386047}, {"content": "Title: Association of hypertension with the severity and fatality of SARS-CoV-2 infection: A meta-analysis Content: Hypertension is a common comorbidity in COVID-19 patients. However, the association of hypertension with the severity and fatality of COVID-19 remain unclear. In the present meta-analysis, relevant studies reported the impacts of hypertension on SARS-CoV-2 infection were identified by searching PubMed, Elsevier Science Direct, Web of Science, Wiley Online Library, Embase and CNKI up to 20 March 2020. As the results shown, 12 publications with 2389 COVID-19 patients (674 severe cases) were included for the analysis of disease severity. The severity rate of COVID-19 in hypertensive patients was much higher than in non-hypertensive cases (37.58% vs 19.73%, pooled OR: 2.27, 95% CI: 1.80\u20132.86). Moreover, the pooled ORs of COVID-19 severity for hypertension vs. non-hypertension was 2.21 (95% CI: 1.58\u20133.10) and 2.32 (95% CI: 1.70\u20133.17) in age <50 years and \u2a7e50 years patients, respectively. Additionally, six studies with 151 deaths of 2116 COVID-19 cases were included for the analysis of disease fatality. The results showed that hypertensive patients carried a nearly 3.48-fold higher risk of dying from COVID-19 (95% CI: 1.72\u20137.08). Meanwhile, the pooled ORs of COVID-19 fatality for hypertension vs. non-hypertension was 6.43 (95% CI: 3.40\u201312.17) and 2.66 (95% CI: 1.27\u20135.57) in age <50 years and \u2a7e50 years patients, respectively. Neither considerable heterogeneity nor publication bias was observed in the present analysis. Therefore, our present results provided further evidence that hypertension could significantly increase the risks of severity and fatality of SARS-CoV-2 infection.", "qid": 23, "docid": "lnjlyaex", "rank": 5, "score": 0.8798409700393677}, {"content": "Title: Cardiovascular manifestations and treatment considerations in covid-19 Content: Since its recognition in December 2019, covid-19 has rapidly spread globally causing a pandemic. Pre-existing comorbidities such as hypertension, diabetes, and cardiovascular disease are associated with a greater severity and higher fatality rate of covid-19. Furthermore, covid-19 contributes to cardiovascular complications, including acute myocardial injury as a result of acute coronary syndrome, myocarditis, stress-cardiomyopathy, arrhythmias, cardiogenic shock, and cardiac arrest. The cardiovascular interactions of covid-19 have similarities to that of severe acute respiratory syndrome, Middle East respiratory syndrome and influenza. Specific cardiovascular considerations are also necessary in supportive treatment with anticoagulation, the continued use of renin-angiotensin-aldosterone system inhibitors, arrhythmia monitoring, immunosuppression or modulation, and mechanical circulatory support.", "qid": 23, "docid": "873txs85", "rank": 6, "score": 0.877025842666626}, {"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": 23, "docid": "jhkc8of3", "rank": 7, "score": 0.8755965232849121}, {"content": "Title: Hypertension in patients with coronavirus disease 2019 (COVID-19): a pooled analysis Content: INTRODUCTION: As the outbreak of coronavirus disease 2019 (COVID\u00ad19) was recognized, the clinical predictors of severe or fatal course of the disease should be identified to enable risk stratification and to allocate limited resources optimally. Hypertension has been widely reported to be associated with increased disease severity; however, some studies reported different findings. OBJECTIVES: The study aimed to evaluate the association between hypertension and severe and fatal COVID\u00ad19. PATIENTS AND METHODS: The Scopus, Medline, and Web of Science databases were searched to identify studies reporting the rate of hypertensive patients in the population diagnosed with severe or nonsevere COVID\u00ad19 or in COVID-19 survivors and nonsurvivors. The obtained data were pooled into a meta\u00adanalysis to calculate odds ratios (ORs) with 95% CIs. RESULTS: Hypertension was associated with a nearly 2.5\u00adfold increased risk of severe COVID\u00ad19 (OR, 2.49; 95% CI, 1.98-3.12; I2 = 24%), as well as with a similarly significant higher mortality risk (OR, 2.42; 95% CI, 1.51-3.90; I2 = 0%). In a meta\u00adregression analysis, a correlation was observed between an increase in the mean age of patients with severe COVID\u00ad19 and an increased log OR of hypertension and COVID-19 severity (P = 0.03). CONCLUSIONS: This pooled analysis of the current literature would suggest that hypertension may be associated with an up to 2.5\u00adfold higher risk of severe or fatal COVID\u00ad19, especially in older individuals.", "qid": 23, "docid": "g484ymy9", "rank": 8, "score": 0.8738316297531128}, {"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": 9, "score": 0.8723813891410828}, {"content": "Title: Cardiovascular complications in COVID-19 Content: BACKGROUND: The coronavirus disease of 2019 (COVID-19) is caused by the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). While systemic inflammation and pulmonary complications can result in significant morbidity and mortality, cardiovascular complications may also occur. OBJECTIVE: This brief report evaluates cardiovascular complications in the setting of COVID-19 infection. DISCUSSION: The current COVID-19 pandemic has resulted in over one million infected worldwide and thousands of death. The virus binds and enters through angiotensin-converting enzyme 2 (ACE2). COVID-19 can result in systemic inflammation, multiorgan dysfunction, and critical illness. The cardiovascular system is also affected, with complications including myocardial injury, myocarditis, acute myocardial infarction, heart failure, dysrhythmias, and venous thromboembolic events. Current therapies for COVID-19 may interact with cardiovascular medications. CONCLUSIONS: Emergency clinicians should be aware of these cardiovascular complications when evaluating and managing the patient with COVID-19.", "qid": 23, "docid": "hl225efn", "rank": 10, "score": 0.8698828220367432}, {"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": 11, "score": 0.8694930672645569}, {"content": "Title: COVID-19, hipertensi\u00f3n y enfermedad cardiovascular./ [COVID-19 and its relationship with hypertension and cardiovascular disease] Content: The association between hypertension, diabetes, cardio and cerebrovascular disease and severe and fatal COVID-19, described in different countries, is remarkable. Myocardial damage and myocardial dysfunction are postulated as a possible causal nexus. Frequent findings of elevated troponin levels and electrocardiographic anomalies support this concept. On the other hand, hypotheses in favour and against a deleterious effect of angiotensin converting enzyme inhibitors and angiotensin receptor blockers, a usual treatment for cardiovascular disease, have been raised. There is currently no solid evidence and thus properly designed studies on this subject are urgently needed. In this context, patients with cardiovascular disease should especially avoid being exposed to the virus, should not self-medicate and rapidly seek medical advice should they show symptoms of infection.", "qid": 23, "docid": "f8v51ouz", "rank": 12, "score": 0.8688486814498901}, {"content": "Title: SARS-CoV-2 (COVID 19) Infection in Hypertensive Patients and in Patients With Cardiac Disease Content: COVID 19, caused by the SARS-CoV-2 virus, a newly discovered coronavirus, has caused the global pandemic of early 2020. The first case was described in December 2019 in Wuhan, China, and by March 2020, most countries around the world have put in place some of the strictest restrictions seen in decades in order to slow down the spread of the disease. Patients with pre-existing hypertension and cardiovascular comorbidities were reported to be at an increased risk of serious infections caused by SARS-CoV-2. Considering that those are among the most common chronic medical conditions in the Western world, the potential impact of it is huge. The proposed mechanism behind those associations is the expression of angiotensin converting enzyme II (ACE II) in those patients. Furthermore, the association between ACE inhibitors/AR blockers, which are among the most frequently prescribed medications, and serious cases of COVID 19 has been studied with the same mechanism in mind. The reports on the association between hypertension and COVID 19 morbidity and mortality are less clear, and the International Society of Hypertension even claims that there is none. The reports on the association between heart failure or coronary disease and COVID 19 are more uniform, and all seem to point to a greater risk from serious infections faced by patients with those comorbidities. A significant effort will need to be invested by the scientific community into finding strategies for protecting those patients from contracting the virus in the first place and then, once infected, into developing management plans aimed at preserving cardiac function as much as possible.", "qid": 23, "docid": "xw817l53", "rank": 13, "score": 0.8652455806732178}, {"content": "Title: COVID-19 patients with hypertension have more severe disease: a multicenter retrospective observational study Content: This study aims to explore the effect of hypertension on disease progression and prognosis in patients with coronavirus disease 2019 (COVID-19). A total of 310 patients diagnosed with COVID-19 were studied. A comparison was made between two groups of patients, those with hypertension and those without hypertension. Their demographic data, clinical manifestations, laboratory indicators, and treatment methods were collected and analyzed. A total of 310 patients, including 113 patients with hypertension and 197 patients without hypertension, were included in the analysis. Compared with patients without hypertension, patients with hypertension were older, were more likely to have diabetes and cerebrovascular disease, and were more likely to be transferred to the intensive care unit. The neutrophil count and lactate dehydrogenase, fibrinogen, and D-dimer levels in hypertensive patients were significantly higher than those in nonhypertensive patients (P < 0.05). However, multivariate analysis (adjusted for age and sex) failed to show that hypertension was an independent risk factor for COVID-19 mortality or severity. COVID-19 patients with hypertension were more likely than patients without hypertension to have severe pneumonia, excessive inflammatory reactions, organ and tissue damage, and deterioration of the disease. Patients with hypertension should be given additional attention to prevent worsening of their condition.", "qid": 23, "docid": "es8ztvq5", "rank": 14, "score": 0.8650520443916321}, {"content": "Title: Endocrine and metabolic link to coronavirus infection Content: Type 2 diabetes mellitus and hypertension are the most common comorbidities in patients with coronavirus infections. Emerging evidence demonstrates an important direct metabolic and endocrine mechanistic link to the viral disease process. Clinicians need to ensure early and thorough metabolic control for all patients affected by COVID-19.", "qid": 23, "docid": "puu8wib8", "rank": 15, "score": 0.8643849492073059}, {"content": "Title: COVID-19-Related Aortic Thrombosis: A Report of Four Cases Content: COVID-19 may predispose patients to an increased risk of thrombotic complications through various pathophysiological mechanisms. Most of the reports on a high incidence of thrombotic complications are in relation to deep vein thrombosis and pulmonary embolism, while the evidence about arterial thrombosis in patients with COVID-19 is limited. We describe 4 cases of aortic thrombosis and associated ischemic complications in patients with severe SARS-CoV-2 infection.", "qid": 23, "docid": "ir6d85fr", "rank": 16, "score": 0.8621466159820557}, {"content": "Title: Cardiovascular complications in COVID-19 Content: Abstract Background The coronavirus disease of 2019 (COVID-19) is caused by the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). While systemic inflammation and pulmonary complications can result in significant morbidity and mortality, cardiovascular complications may also occur. Objective This brief report evaluates cardiovascular complications in the setting of COVID-19 infection. Discussion The current COVID-19 pandemic has resulted in over one million infected worldwide and thousands of death. The virus binds and enters through angiotensin-converting enzyme 2 (ACE2). COVID-19 can result in systemic inflammation, multiorgan dysfunction, and critical illness. The cardiovascular system is also affected, with complications including myocardial injury, myocarditis, acute myocardial infarction, heart failure, dysrhythmias, and venous thromboembolic events. Current therapies for COVID-19 may interact with cardiovascular medications. Conclusions Emergency clinicians should be aware of these cardiovascular complications when evaluating and managing the patient with COVID-19.", "qid": 23, "docid": "mbbnk3la", "rank": 17, "score": 0.8621448278427124}, {"content": "Title: Association of diabetes and hypertension with disease severity in covid-19 patients: a systematic literature review and exploratory meta-analysis Content: AIM: The novel coronavirus infection (COVID-19), now a worldwide public health concern is associated with varied fatality. Patients with chronic underlying conditions like diabetes and hypertension have shown worst outcomes. The understanding of the association might be helpful in early vigilant monitoring and better management of COVID-19 patients at high risk. The aim of the meta-analysis was to assess the association of diabetes and hypertension with severity of disease. METHODS: A literature search was conducted using the databases PubMed and Cochrane until March 31, 2020. Seven studies were included in the meta- analysis, including 2018 CIVID-19 patients. RESULTS: Diabetes was lower in the survivors (OR: 0.56; 95%CI: 0.35-0.90; p=0.017; I2: 0.0%) and non-severe (OR: 1.66; 95%CI: 1.20-2.30; p=0.002; I2: 0.0%) patients. No association of diabetes was found with ICU care. Hypertension was positively associated with death (OR: 0.49; 95%CI: 0.34-0.73; p=0.000; I2: 0.0%), ICU care (OR: 0.42; 95%CI: 0.22-0.81; p=0.009; I2: 0.0%) and severity (OR: 2.69; 95%CI: 1.27-5.73; p=0.01; I2: 52.4%). CONCLUSIONS: Our findings suggest that diabetes and hypertension have a negative effect on health status of COVID-19 patients. However, large prevalence studies demonstrating the consequences of comorbid diabetes and hypertension are urgently needed to understand the magnitude of these vexatious comorbidities.", "qid": 23, "docid": "04s7w017", "rank": 18, "score": 0.8618869781494141}, {"content": "Title: COVID-19-RELATED AORTIC THROMBOSIS: A REPORT OF FOUR CASES Content: COVID-19 may predispose patients to an increased risk of thrombotic complications through various pathophysiological mechanisms. Most of the reports on a high incidence of thrombotic complications are in relation to deep vein thrombosis and pulmonary embolism, while the evidence about arterial thrombosis in patients with COVID-19 is limited. We describe four cases of aortic thrombosis and associated ischemic complications in patients with severe SARS-CoV-2 infection.", "qid": 23, "docid": "q7yavza2", "rank": 19, "score": 0.8615195751190186}, {"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": 20, "score": 0.8613606095314026}, {"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": 23, "docid": "01yzk0au", "rank": 21, "score": 0.861034631729126}, {"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": 22, "score": 0.8606226444244385}, {"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": 23, "score": 0.8597009181976318}, {"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": 24, "score": 0.8593943119049072}, {"content": "Title: SGLT2 inhibition and COVID-19: The road not taken Content: The COVID-19 pandemic, caused by SARS-CoV-2, is an immense challenge for global healthcare. Diabetes mellitus, hypertension and obesity have been shown to portend poor prognosis in COVID-19 despite no greater susceptibility to the infection (1). Chronic hypertension is commonly associated with vasculopathy which can predispose to severe infection. In patients with diabetes, severity is attributable to impaired innate, adaptive immunity, upregulation of ACE2 (entry receptor for SARS-CoV2) by acute hyperglycemia and diabetic vasculopathy. The background of chronic low grade inflammation characterised by increased levels of IL-6 and CRP in diabetes and obesity can also lead to an enhanced 'cytokine storm' in COVID-19 (2). ACE2 expression on endothelial cells has been reported to cause viral mediated endothelitis and precipitate vascular dysfunction manifesting as acute respiratory distress syndrome as well as myocarditis, heart failure, arrhythmias, myocardial infarction and renal failure (3). In patients with pre-existing comorbidities like hypertension, diabetes, obesity and chronic kidney disease, this new-onset organ dysfunction can have deleterious additive effects.", "qid": 23, "docid": "ojoqsdn1", "rank": 25, "score": 0.8588916063308716}, {"content": "Title: SGLT2 inhibition and COVID-19: The road not taken. Content: The COVID-19 pandemic, caused by SARS-CoV-2, is an immense challenge for global healthcare. Diabetes mellitus, hypertension and obesity have been shown to portend poor prognosis in COVID-19 despite no greater susceptibility to the infection (1). Chronic hypertension is commonly associated with vasculopathy which can predispose to severe infection. In patients with diabetes, severity is attributable to impaired innate, adaptive immunity, upregulation of ACE2 (entry receptor for SARS-CoV2) by acute hyperglycemia and diabetic vasculopathy. The background of chronic low grade inflammation characterised by increased levels of IL-6 and CRP in diabetes and obesity can also lead to an enhanced 'cytokine storm' in COVID-19 (2). ACE2 expression on endothelial cells has been reported to cause viral mediated endothelitis and precipitate vascular dysfunction manifesting as acute respiratory distress syndrome as well as myocarditis, heart failure, arrhythmias, myocardial infarction and renal failure (3). In patients with pre-existing comorbidities like hypertension, diabetes, obesity and chronic kidney disease, this new-onset organ dysfunction can have deleterious additive effects.", "qid": 23, "docid": "md9dbxb5", "rank": 26, "score": 0.8588916063308716}, {"content": "Title: Arterial and venous thromboembolic disease in a patient with COVID-19: A case report Content: \u2022 Hypercoagulability is a major contributor to COVID-19 related pulmonary complications; \u2022 Commonly used approaches may be insufficient to ameliorate the risk of thromboembolic events in patients with COVID-19; \u2022 Even when on thromboprophylaxis, it is crucial to remain vigilant for the occurrence of VTE in patients with COVID-19.", "qid": 23, "docid": "lmz56pdm", "rank": 27, "score": 0.8588219881057739}, {"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": 28, "score": 0.8585243821144104}, {"content": "Title: Controversies of renin\u2013angiotensin system inhibition during the COVID-19 pandemic Content: The current COVID-19 pandemic is associated with unprecedented morbidity and mortality. Early reports suggested an association between disease severity and hypertension but did not account for sources of confounding. However, the responsible virus \u2014 SARS-CoV-2 \u2014 gains entry to host cells via angiotensin-converting enzyme 2 (ACE2), highlighting the need to understand the relationship between the virus and the renin\u2013angiotensin system (RAS) and how this might be affected by RAS inhibitors.", "qid": 23, "docid": "va34p27b", "rank": 29, "score": 0.8584966063499451}, {"content": "Title: Hypertension is associated with increased mortality and severity of disease in COVID-19 pneumonia: A systematic review, meta-analysis and meta-regression Content: OBJECTIVE: To investigate the association between hypertension and outcome in patients with Coronavirus Disease 2019 (COVID-19) pneumonia. METHODS: We performed a systematic literature search from several databases on studies that assess hypertension and outcome in COVID-19. Composite of poor outcome, comprising of mortality, severe COVID-19, acute respiratory distress syndrome (ARDS), need for intensive care unit (ICU) care and disease progression were the outcomes of interest. RESULTS: A total of 6560 patients were pooled from 30 studies. Hypertension was associated with increased composite poor outcome (risk ratio (RR) 2.11 (95% confidence interval (CI) 1.85, 2.40), p < 0.001; I2, 44%) and its sub-group, including mortality (RR 2.21 (1.74, 2.81), p < 0.001; I2, 66%), severe COVID-19 (RR 2.04 (1.69, 2.47), p < 0.001; I2 31%), ARDS (RR 1.64 (1.11, 2.43), p = 0.01; I2,0%, p = 0.35), ICU care (RR 2.11 (1.34, 3.33), p = 0.001; I2 18%, p = 0.30), and disease progression (RR 3.01 (1.51, 5.99), p = 0.002; I2 0%, p = 0.55). Meta-regression analysis showed that gender (p = 0.013) was a covariate that affects the association. The association was stronger in studies with a percentage of males < 55% compared to \u00e2\u00a9\u00be 55% (RR 2.32 v. RR 1.79). CONCLUSION: Hypertension was associated with increased composite poor outcome, including mortality, severe COVID-19, ARDS, need for ICU care and disease progression in patients with COVID-19.", "qid": 23, "docid": "z9u229yg", "rank": 30, "score": 0.8574779033660889}, {"content": "Title: Association of diabetes and hypertension with disease severity in covid-19 patients: a systematic literature review and exploratory meta-analysis Content: Abstract Aim The novel coronavirus infection (COVID-19), now a worldwide public health concern is associated with varied fatality. Patients with chronic underlying conditions like diabetes and hypertension have shown worst outcomes. The understanding of the association might be helpful in early vigilant monitoring and better management of COVID-19 patients at high risk. The aim of the meta-analysis was to assess the association of diabetes and hypertension with severity of disease. Methods A literature search was conducted using the databases PubMed and Cochrane until March 31, 2020. Seven studies were included in the meta- analysis, including 2018 CIVID-19 patients. Results Diabetes was lower in the survivors (OR: 0.56; 95%CI: 0.35-0.90; p=0.017; I2 : 0.0%) and non-severe (OR: 1.66; 95%CI: 1.20-2.30; p=0.002; I2 : 0.0%) patients. No association of diabetes was found with ICU care. Hypertension was positively associated with death (OR: 0.49; 95%CI: 0.34-0.73; p=0.000; I2 : 0.0%), ICU care (OR: 0.42; 95%CI: 0.22-0.81; p=0.009; I2 : 0.0%) and severity (OR: 2.69; 95%CI: 1.27-5.73; p=0.01; I2 : 52.4%). Conclusions Our findings suggest that diabetes and hypertension have a negative effect on health status of COVID-19 patients. However, large prevalence studies demonstrating the consequences of comorbid diabetes and hypertension are urgently needed to understand the magnitude of these vexatious comorbidities.", "qid": 23, "docid": "9qq049qb", "rank": 31, "score": 0.8565298914909363}, {"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": 23, "docid": "254z62e4", "rank": 32, "score": 0.8562811613082886}, {"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": 23, "docid": "tu36aisz", "rank": 33, "score": 0.8561751842498779}, {"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": 23, "docid": "qt02t6tf", "rank": 34, "score": 0.8561751842498779}, {"content": "Title: Effect of hypertension on outcomes of adult inpatients with COVID-19 in Wuhan, China: a propensity score\u2013matching analysis Content: BACKGROUND: Previous studies have shown that Coronavirus Disease 2019 (COVID-19) patients with underlying comorbidities can have worse outcomes. However, the effect of hypertension on outcomes of COVID-19 patients remains unclear. RESEARCH QUESTION: The aim of this study was to explore the effect of hypertension on the outcomes of patients with COVID-19 by using propensity score\u2013matching (PSM) analysis. STUDY DESIGN AND METHODS: Participants enrolled in this study were patients with COVID-19 who had been hospitalized at the Central Hospital of Wuhan, China. Chronic comorbidities and laboratory and radiological data were reviewed; patient outcomes and lengths of stay were obtained from discharge records. We used the Cox proportional-hazard model (CPHM) to analyze the effect of hypertension on these patients\u2019 outcomes and PSM analysis to further validate the abovementioned effect. RESULTS: A total of 226 patients with COVID-19 were enrolled in this study, of whom 176 survived and 50 died. The proportion of patients with hypertension among non-survivors was higher than that among survivors (26.70% vs. 74.00%; P < 0.001). Results obtained via CPHM showed that hypertension could increase risk of mortality in COVID-19 patients (hazard ratio 3.317; 95% CI [1.709\u20136.440]; P < 0.001). Increased D-dimer levels and higher ratio of neutrophils to lymphocytes (N/L) were also found to increase these patients\u2019 mortality risk. After matching on propensity score, we still came to similar conclusions. After we applied the same method in critically ill patients, we found that hypertension also increased risk of death in patients with severe COVID-19. CONCLUSION: Hypertension, increased D-dimer and the ratio of neutrophil to lymphocyte increased mortality in patients with COVID-19, with hypertension in particular.", "qid": 23, "docid": "xj50b7zo", "rank": 35, "score": 0.8558974266052246}, {"content": "Title: Posterior reversible encephalopathy syndrome in severe SARS-COV-2 infection Content: \u2022 PRES is potentially a complication of severe SARS-CoV-2 infection. \u2022 Consider PRES in COVID-19 patients with altered mentation. \u2022 Consider tight blood pressure control in ventilated patients with COVID-19. \u2022 Hypertensive encephalopathy may prolong ventilator times in COVID-19 patients.", "qid": 23, "docid": "3j68j67i", "rank": 36, "score": 0.8556196093559265}, {"content": "Title: Coronavirus SARS-Cov-2 and arterial hypertension - facts and myths. Content: Arterial hypertension is the most common comorbid disease in patients who died as a result of SARS-Cov-2 infection. Numerous observational studies indicate a relationship between arterial hypertension and its treatment and SARS-Cov-2 coronavirus infection. It is known from experimental studies that SARS-Cov-2 enters the cells by interacting with the ACE2 enzyme, while it is not known whether ACE2 is the only factor that allows the virus to enter the cell. There is no clear evidence of a link between the use of medications such as ACE and ARB and an increased risk of SARS-Cov-2 infection. It has been shown that the use of recombinant ACE2 can be potentially beneficial in COVID-19 therapy by limiting the entry of the virus into the cell. Blood glucose as well as lipid profile should be monitored during SARS-Cov-2 coronavirus infection. This article attempts to gather key information on arterial hypertension and COVID-19.", "qid": 23, "docid": "r7vx32o2", "rank": 37, "score": 0.8555060625076294}, {"content": "Title: Hypertension is associated with increased mortality and severity of disease in COVID-19 pneumonia: A systematic review, meta-analysis and meta-regression Content: OBJECTIVE: To investigate the association between hypertension and outcome in patients with Coronavirus Disease 2019 (COVID-19) pneumonia. METHODS: We performed a systematic literature search from several databases on studies that assess hypertension and outcome in COVID-19. Composite of poor outcome, comprising of mortality, severe COVID-19, acute respiratory distress syndrome (ARDS), need for intensive care unit (ICU) care and disease progression were the outcomes of interest. RESULTS: A total of 6560 patients were pooled from 30 studies. Hypertension was associated with increased composite poor outcome (risk ratio (RR) 2.11 (95% confidence interval (CI) 1.85, 2.40), p < 0.001; I(2), 44%) and its sub-group, including mortality (RR 2.21 (1.74, 2.81), p < 0.001; I(2), 66%), severe COVID-19 (RR 2.04 (1.69, 2.47), p < 0.001; I(2) 31%), ARDS (RR 1.64 (1.11, 2.43), p = 0.01; I(2),0%, p = 0.35), ICU care (RR 2.11 (1.34, 3.33), p = 0.001; I(2) 18%, p = 0.30), and disease progression (RR 3.01 (1.51, 5.99), p = 0.002; I(2) 0%, p = 0.55). Meta-regression analysis showed that gender (p = 0.013) was a covariate that affects the association. The association was stronger in studies with a percentage of males < 55% compared to \u2a7e 55% (RR 2.32 v. RR 1.79). CONCLUSION: Hypertension was associated with increased composite poor outcome, including mortality, severe COVID-19, ARDS, need for ICU care and disease progression in patients with COVID-19.", "qid": 23, "docid": "ucimsb8d", "rank": 38, "score": 0.8554936647415161}, {"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": 39, "score": 0.8552451133728027}, {"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": 23, "docid": "umhj7nk7", "rank": 40, "score": 0.8547409772872925}, {"content": "Title: Long term complications and rehabilitation of COVID-19 patients Content: With the ongoing pandemic of COVID-19 having caught the world almost unaware millions of people across the globe are presently grappling to deal with its acute effects . Our previous experience with members of the same corona virus family (SARS and MERS) which have caused two major epidemics in the past albeit of much lower magnitude , has taught us that the harmful effect of such outbreaks are not limited to acute complications alone .Long term cardiopulmonary, glucometabolic and neuropsychiatric complications have been documented following these infections .In the given circumstance it is therefore imperative to keep in mind the possible complications that may occur after the acute phase of the disease subsides and to prepare the healthcare system for such challenges.", "qid": 23, "docid": "yudrouue", "rank": 41, "score": 0.8546071648597717}, {"content": "Title: Long term complications and rehabilitation of COVID-19 patients. Content: With the ongoing pandemic of COVID-19 having caught the world almost unaware millions of people across the globe are presently grappling to deal with its acute effects . Our previous experience with members of the same corona virus family (SARS and MERS) which have caused two major epidemics in the past albeit of much lower magnitude , has taught us that the harmful effect of such outbreaks are not limited to acute complications alone .Long term cardiopulmonary, glucometabolic and neuropsychiatric complications have been documented following these infections .In the given circumstance it is therefore imperative to keep in mind the possible complications that may occur after the acute phase of the disease subsides and to prepare the healthcare system for such challenges.", "qid": 23, "docid": "7s04ygm2", "rank": 42, "score": 0.854607105255127}, {"content": "Title: Angiotensin converting enzyme 2 (ACE2) and COVID-19: using antihypertensive medications, pharmacogenetic considerations Content: COVID-19 utilizes the angiotensin-converting enzyme-2 (ACE2) pathway as a means of infection. Early data on COVID-19 suggest heterogeneity in the severity of symptoms during transmission and infection ranging from no symptoms to death. The source of this heterogeneity is likely multifaceted and may have a genetic component. Demographic and clinical comorbidities associated with the severity of infection suggest that possible variants known to influence the renin-angiotensin-aldosterone system pathway (particularly those that influence ACE2) may contribute to the heterogenous infection response. ACE2 and angiotensin(1-7) (the product of ACE2) seem to have a protective effect on the pulmonary and cardiac systems. Hypertension medication modulation, may alter ACE2 and angiotensin(1-7), particularly in variants that have been shown to influence renin-angiotensin-aldosterone system function, which could be clinically useful in patients with COVID-19.", "qid": 23, "docid": "pzkzpd2j", "rank": 43, "score": 0.8545175790786743}, {"content": "Title: Angiotensin converting enzyme 2 (ACE2) and COVID-19: using antihypertensive medications, pharmacogenetic considerations. Content: COVID-19 utilizes the angiotensin-converting enzyme-2 (ACE2) pathway as a means of infection. Early data on COVID-19 suggest heterogeneity in the severity of symptoms during transmission and infection ranging from no symptoms to death. The source of this heterogeneity is likely multifaceted and may have a genetic component. Demographic and clinical comorbidities associated with the severity of infection suggest that possible variants known to influence the renin-angiotensin-aldosterone system pathway (particularly those that influence ACE2) may contribute to the heterogenous infection response. ACE2 and angiotensin(1-7) (the product of ACE2) seem to have a protective effect on the pulmonary and cardiac systems. Hypertension medication modulation, may alter ACE2 and angiotensin(1-7), particularly in variants that have been shown to influence renin-angiotensin-aldosterone system function, which could be clinically useful in patients with COVID-19.", "qid": 23, "docid": "ilufqcsq", "rank": 44, "score": 0.8545175790786743}, {"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": 23, "docid": "q82gkygd", "rank": 45, "score": 0.8539503812789917}, {"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": 23, "docid": "dm9nefdg", "rank": 46, "score": 0.8535738587379456}, {"content": "Title: Pathologies cardiovasculaires et Covid-19 : particularit\u00e9s chez les personnes \u00e2g\u00e9es./ COVID-19 and cardiovascular diseases: viewpoint for older patients Content: The coronavirus disease-2019 (COVID-19) is an infectious disease caused by severe acute respiratory syndrome coronavirus 2. The link between cardiovascular disease and COVID-19 appears to be twofold. First, some reports of data indicate that certain groups of patients are more at risk of COVID-19. This includes patients with cardiovascular risk factors or pre-existing cardiovascular conditions and older patients. In addition, these patients incur disproportionately worse outcome. Second, SARS-CoV2 infection can be complicated by life-threatening cardiovascular acute diseases. Despite the rapid evolution of data on this pandemic, this review aims to highlight the cardiovascular considerations related to COVID-19 whether as comorbidities including concerns and uncertainty regarding the effect of renin-angiotensin-aldosterone system (RAAS) inhibitors on angiotensin conversion enzyme 2 or related to acute cardiovascular complications.", "qid": 23, "docid": "pjtlk8ni", "rank": 47, "score": 0.8530998229980469}, {"content": "Title: COVID-19 and cardiovascular diseases: viewpoint for older patients. Content: The coronavirus disease-2019 (COVID-19) is an infectious disease caused by severe acute respiratory syndrome coronavirus 2. The link between cardiovascular disease and COVID-19 appears to be twofold. First, some reports of data indicate that certain groups of patients are more at risk of COVID-19. This includes patients with cardiovascular risk factors or pre-existing cardiovascular conditions and older patients. In addition, these patients incur disproportionately worse outcome. Second, SARS-CoV2 infection can be complicated by life-threatening cardiovascular acute diseases. Despite the rapid evolution of data on this pandemic, this review aims to highlight the cardiovascular considerations related to COVID-19 whether as comorbidities including concerns and uncertainty regarding the effect of renin-angiotensin-aldosterone system (RAAS) inhibitors on angiotensin conversion enzyme 2 or related to acute cardiovascular complications.", "qid": 23, "docid": "7rf532b9", "rank": 48, "score": 0.8530998229980469}, {"content": "Title: Cardiovascular Considerations for the Internist and Hospitalist in the COVID-19 Era Content: It is clear that existing cardiovascular disease is a major risk factor for COVID-19 and related adverse outcomes. In addition to acute respiratory syndrome, a large cohort also develop myocardial and/or vascular dysfunction, in part from inflammation and renin angiotensin system activation with increased sympathetic outflow, cardiac arrhythmias, ischemia, heart failure, and thromboembolic complications that portend poor COVID-19 outcomes. We summarize here recent information for hospitalists/internists on the front-line of this pandemic regarding its cardiovascular impacts and management and need for cardiovascular consultation.", "qid": 23, "docid": "fitz1vjs", "rank": 49, "score": 0.8525534868240356}, {"content": "Title: COVID-19-Related Stroke Content: The COVID-19 pandemic is associated with neurological symptoms and complications including stroke. There is hypercoagulability associated with COVID-19 that is likely a \"sepsis-induced coagulopathy\" and may predispose to stroke. The SARS-CoV-2 virus binds to angiotensin-converting enzyme 2 (ACE2) present on brain endothelial and smooth muscle cells. ACE2 is a key part of the renin angiotensin system (RAS) and a counterbalance to angiotensin-converting enzyme 1 (ACE1) and angiotensin II. Angiotensin II is proinflammatory, is vasoconstrictive, and promotes organ damage. Depletion of ACE2 by SARS-CoV-2 may tip the balance in favor of the \"harmful\" ACE1/angiotensin II axis and promote tissue injury including stroke. There is a rationale to continue to treat with tissue plasminogen activator for COVID-19-related stroke and low molecular weight heparinoids may reduce thrombosis and mortality in sepsis-induced coagulopathy.", "qid": 23, "docid": "rl4n4a9w", "rank": 50, "score": 0.8523608446121216}, {"content": "Title: A Case Series of Stent Thrombosis During the COVID-19 Pandemic Content: Abstract COVID-19 triggers a hypercoagulable state with a high incidence of thrombotic complications. We have noted a higher than expected incidence of stent thrombosis in these patients.", "qid": 23, "docid": "qslq7sny", "rank": 51, "score": 0.8519304990768433}, {"content": "Title: Cardiovascular Considerations for Patients, Health Care Workers, and Health Systems During the COVID-19 Pandemic Content: The coronavirus disease 2019 (COVID-19) is an infectious disease caused by severe acute respiratory syndrome coronavirus 2 that has significant implications for the cardiovascular care of patients. First, those with COVID-19 and pre-existing cardiovascular disease have an increased risk of severe disease and death. Second, infection has been associated with multiple direct and indirect cardiovascular complications including acute myocardial injury, myocarditis, arrhythmias, and venous thromboembolism. Third, therapies under investigation for COVID-19 may have cardiovascular side effects. Fourth, the response to COVID-19 can compromise the rapid triage of non-COVID-19 patients with cardiovascular conditions. Finally, the provision of cardiovascular care may place health care workers in a position of vulnerability as they become hosts or vectors of virus transmission. We hereby review the peer-reviewed and pre-print reports pertaining to cardiovascular considerations related to COVID-19 and highlight gaps in knowledge that require further study pertinent to patients, health care workers, and health systems.", "qid": 23, "docid": "e9k6pnr3", "rank": 52, "score": 0.8511742353439331}, {"content": "Title: Cardiological society of India position statement on COVID-19 and heart failure Content: The COVID 19 global pandemic has engulfed humanity with a huge impact on health systems across the world. Many patients develop myocardial injury which can lead to significant cardiovascular complications including HF. This will require aggressive management strategies which are evolving. Guideline directed drug therapy including ACEI/ARB/ARNI is to be continued in patients with pre-existing HF. Long-term cardiovascular effects of COVID-19 are yet to be ascertained. Protection of health care personnel from contracting the disease should be given high priority.", "qid": 23, "docid": "49mantab", "rank": 53, "score": 0.8511103391647339}, {"content": "Title: Cardiovascular Considerations for Patients, Health Care Workers, and Health Systems During the Coronavirus Disease 2019 (COVID-19) Pandemic Content: Abstract The coronavirus disease-2019 (COVID-19) is an infectious disease caused by severe acute respiratory syndrome coronavirus 2 that has significant implications for the cardiovascular care of patients. First, those with COVID-19 and preexisting cardiovascular disease (CVD) have an increased risk of severe disease and death. Second, infection has been associated with multiple direct and indirect cardiovascular complications including acute myocardial injury, myocarditis, arrhythmias and venous thromboembolism. Third, therapies under investigation for COVID-19 may have cardiovascular side effects. Fourth, the response to COVID-19 can compromise the rapid triage of non-COVID-19 patients with cardiovascular conditions. Finally, the provision of cardiovascular care may place health care workers in a position of vulnerability as they become host or vectors of virus transmission. We hereby review the peer-reviewed and preprint literature pertaining to cardiovascular considerations related to COVID-19 and highlight gaps in knowledge that require further study pertinent to patients, health care workers, and health systems.", "qid": 23, "docid": "w49i0xkz", "rank": 54, "score": 0.8509852886199951}, {"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": 55, "score": 0.8508658409118652}, {"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": 56, "score": 0.8503700494766235}, {"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": 23, "docid": "tp2tm0vn", "rank": 57, "score": 0.8497352004051208}, {"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": 23, "docid": "7icw3be3", "rank": 58, "score": 0.8497352004051208}, {"content": "Title: Anti-cardiolipin IgG autoantibodies are an independent risk factor of COVID-19 severity Content: A growing body of evidence indicates that patients with cardiovascular complications are at a higher risk for developing severe Coronavirus Disease 2019 (COVID-19) (1). In addition, the high incidence of thromboembolic events suggests an important role of COVID-19-induced coagulopathy (2). Antiphospholipid autoantibodies (aPL), that are essential markers for antiphospholipid syndrome, are considered as a cardiovascular risk factor.", "qid": 23, "docid": "koyvaqgd", "rank": 59, "score": 0.8494628071784973}, {"content": "Title: SARS-CoV-2 and Guillain-Barr\u00e9 syndrome: AIDP variant with favorable outcome Content: The entire world has been experiencing the outbreak of a novel infectious agent known as severe acute respiratory syndrome corona virus 2 (SARS-CoV-2), which is responsible for the coronavirus disease 19 (COVID-19)1 . Life-threatening complications described in SARS-CoV-2 infected patients include acute respiratory distress syndrome, acute kidney failure and cardiac injury2 . Nonetheless, only few neurological complications have been described so far3 .", "qid": 23, "docid": "xui1famo", "rank": 60, "score": 0.8485955595970154}, {"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": 61, "score": 0.8485897183418274}, {"content": "Title: COVID-19 and pulmonary hypertension Content: Pulmonary hypertension (PH) is a pulmonary vascular disease characterized by pulmonary arterial remodeling and vasoconstriction leading to elevated pulmonary artery pressure and, ultimately, right heart failure. So far, few cases of COVID-19 disease in patients with PH have been reported. Caution is warranted in interpreting this observation as data are evolving and several factors may influence the number of reported cases of PH and COVID-19. Social distancing and quarantine could play a role, especially for patients with chronic diseases who might be more vigilant of their potential for respiratory infection. In addition, PH is a rare disease, and because testing is not universal, we could be underestimating the number of cases. Other hypothetical factors to consider are the underlying pathophysiology of PH and the medications used to treat PH and their implications in COVID-19.", "qid": 23, "docid": "duohnpj2", "rank": 62, "score": 0.848474383354187}, {"content": "Title: COVID-19 and pulmonary hypertension. Content: Pulmonary hypertension (PH) is a pulmonary vascular disease characterized by pulmonary arterial remodeling and vasoconstriction leading to elevated pulmonary artery pressure and, ultimately, right heart failure. So far, few cases of COVID-19 disease in patients with PH have been reported. Caution is warranted in interpreting this observation as data are evolving and several factors may influence the number of reported cases of PH and COVID-19. Social distancing and quarantine could play a role, especially for patients with chronic diseases who might be more vigilant of their potential for respiratory infection. In addition, PH is a rare disease, and because testing is not universal, we could be underestimating the number of cases. Other hypothetical factors to consider are the underlying pathophysiology of PH and the medications used to treat PH and their implications in COVID-19.", "qid": 23, "docid": "q571agza", "rank": 63, "score": 0.848474383354187}, {"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": 64, "score": 0.8480962514877319}, {"content": "Title: Covid-19 nephropathy; an emerging condition caused by novel coronavirus infection Content: Implication for health policy/practice/research/medical education: COVID-19, a pandemic caused by a novel coronavirus, has become a major public health problem worldwide. It principally affects the upper and lower respiratory tract in the majority of cases. In severe cases, it may involve multiple organs including the kidneys. Kidney involvement has been reported to be around 3-9% and the most common presentation is with acute kidney injury (AKI); however, the data is still preliminary. Data regarding COVID-19 virus affecting patients with prior kidney diseases are still rudimentary. Further research is needed to understand the full spectrum of COVID-19 infection on kidney health.", "qid": 23, "docid": "jh4g5brk", "rank": 65, "score": 0.847814679145813}, {"content": "Title: The Role of Data Registries in the Time of COVID-19. Content: On April 1, 2020, the confirmed global burden of COVID-19 was more than 900,000 with 46,413 deaths. Despite worldwide calls for social distancing and containment, the incidence of the disease continues to increase. COVID-19 is a respiratory tract infection caused by the novel coronavirus (SARS-CoV2). Preliminary analyses from the Chinese Center for Disease Control and Prevention indicated an overall case fatality rate (CFR) of 2.3%; however the CFR was higher in older adults (14.8% in those 80\u00b1 years) and 49% of all critical cases. Those with preexisting conditions (cardiovascular disease (CVD), diabetes, chronic respiratory disease, hypertension, and cancer) also had higher CRFs. In the United States, 116 million adults have hypertension, 26 million US adults have diabetes mellitus, 9% have preexisting CVD and may therefore be at greater risk of complications or adverse health outcomes from COVID-19 infection.", "qid": 23, "docid": "2tlbeqvb", "rank": 66, "score": 0.8472127914428711}, {"content": "Title: Pand\u00e9mie COVID-19 : impact sur le systeme cardiovasculaire. Donn\u00e9es disponibles au 1er avril 2020./ [COVID-19 pandemia: Impact on the cariovascular system. Data of 1st April 2020] Content: Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infects host cells with angiotensin receptors, leading to pneumonia linked to COVID-19. The virus has a double impact on the cardiovascular system, the infection will be more intense if the host has cardiovascular co-morbidities and the virus can cause life-threatening cardiovascular lesions. Therapies associated with COVID-19 may have adverse cardiovascular effects. Therefore, special attention should be given to cardiovascular protection during COVID-19 infection.", "qid": 23, "docid": "uykao62t", "rank": 67, "score": 0.8462845087051392}, {"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": 23, "docid": "lfjud2aq", "rank": 68, "score": 0.8460301160812378}, {"content": "Title: Electrical Storm in COVID-19 Content: Abstract COVID-19 is a global pandemic caused by SARS-CoV-2. Infection is associated with significant morbidity and mortality. Individuals with pre-existing cardiovascular disease or evidence of myocardial injury are at risk for severe disease and death. Little is understood about the mechanisms of myocardial injury or life-threatening cardiovascular sequelae.", "qid": 23, "docid": "98xisxg7", "rank": 69, "score": 0.8458887934684753}, {"content": "Title: Effects of hypertension, diabetes and coronary heart disease on COVID-19 diseases severity: a systematic review and meta-analysis Content: Background: COVID-19 patients with chronic diseases such as hypertension, diabetes and coronary heart diseases is more likely to worsen, but with mixed results for COVID-19 severity. This meta-analysis is to analyze the correlation between hypertension, diabetes, coronary heart disease and COVID-19 disease severity. Methods: Available data from PubMed, Web of Science, China National Knowledge Infrastructure Database, WanFang Database and VIP Database, were analyzed using a fixed effects model meta-analysis to derive overall odds ratios (OR) with 95% CIs. Funnel plots and Begg's were used to assess publication bias. Findings: Of 182 articles found following our initial search, we assessed 34 full-text articles, of which 9 articles with 1936 COVID-19 patients met all selection criteria for our meta-analysis. No significant heterogeneity between studies. There were significant correlations between COVID-19 severity and hypertension [OR=2.3 [95% CI (1.76, 3.00), P<0.01], diabetes [OR=2.67, 95% CI (1.91, 3.74), P<0.01], coronary heart disease [OR=2.85 [95% CI (1.68, 4.84), P<0.01]. Most of the studies in the funnel plot are on the upper part and few on the base part, and are roughly symmetrical left and right. Begg's test: hypertension (Z=-0.1, P=1.0), diabetes (Z=0.73, P=0.466), coronary heart disease (Z=0.38, P=0.707), all found no publication bias. Interpretation: Hypertension, diabetes, and coronary heart disease can affect the severity of COVID-19. It may be related to the imbalance of angiotensin-converting enzyme 2 (ACE2) and the cytokine storm induced by Glucolipid metabolic disorders (GLMD).", "qid": 23, "docid": "v6frcc5r", "rank": 70, "score": 0.8457148671150208}, {"content": "Title: Coronavirus SARS-Cov-2 and arterial hypertension - facts and myths Content: Arterial hypertension is the most common comorbid disease in patients who died as a result of SARS-Cov-2 infection Numerous observational studies indicate a relationship between arterial hypertension and its treatment and SARS-Cov-2 coronavirus infection It is known from experimental studies that SARS-Cov-2 enters the cells by interacting with the ACE2 enzyme, while it is not known whether ACE2 is the only factor that allows the virus to enter the cell There is no clear evidence of a link between the use of medications such as ACE and ARB and an increased risk of SARS-Cov-2 infection It has been shown that the use of recombinant ACE2 can be potentially beneficial in COVID-19 therapy by limiting the entry of the virus into the cell Blood glucose as well as lipid profile should be monitored during SARS-Cov-2 coronavirus infection This article attempts to gather key information on arterial hypertension and COVID-19", "qid": 23, "docid": "yg1mma87", "rank": 71, "score": 0.845686137676239}, {"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": 72, "score": 0.8453136682510376}, {"content": "Title: Considera\u00e7\u00f5es sobre a rela\u00e7\u00e3o entre a hipertens\u00e3o e o progn\u00f3stico da COVID-19 Content: Objetivo: iinvestigar a potencial associa\u00e7\u00e3o entre a hipertens\u00e3o arterial sist\u00eamica (HAS) e a gravidade da COVID-19 M\u00e9todos: realizou-se uma pesquisa eletr\u00f4nica no Medline, Scopus e Web of Science acerca da rela\u00e7\u00e3o entre HAS e COVID-19 Resultados: as primeiras hip\u00f3teses levantadas revelaram que a associa\u00e7\u00e3o entre as doen\u00e7as estava no tratamento com inibidores da enzima de convers\u00e3o da angiotensina e bloqueadores dos receptores da angiotensina Contudo, em um estudo experimental, observou-se que os pacientes hipertensos tratados com esses medicamentos apresentaram menor taxa de gravidade da doen\u00e7a Conclus\u00e3o: at\u00e9 o momento, a rela\u00e7\u00e3o de HAS e COVID-19 \u00e9 conflitante (AU)Objective: to investigate the potential association between systemic arterial hypertension (SAH) and the severity of COVID-19 Methods: An electronic research on Medline, Scopus and Web of Science was conducted about the relationship between SAH and COVID-19 Results: The first hypotheses raised revealed that the association between the diseases was in the treatment with angiotensin conversion enzyme inhibitors and angiotensin receptor blockers However, in an experimental study it was observed that hypertensive patients treated with these drugs had a lower rate of disease severity Conclusion: So far, the relationship between SAH and COVID-19 is conflicting (AU)", "qid": 23, "docid": "xtmbj408", "rank": 73, "score": 0.8450417518615723}, {"content": "Title: Endothelial dysfunction in Coronavirus disease 2019 (COVID-19): gender and age influences Content: Several risk factors are associated with a worse outcome for COVID-19 patients; the most recognized are demographic characteristics such as older age and male gender, and pre-existing cardiovascular conditions. About the latter, hypertension and coronary heart disease are among the most common comorbidities recorded in infected patients, together with type 2 diabetes mellitus (T2DM). Data from Istituto Superiore di Sanit\u00e0 (ISS, Italy) show that more than 68.3% of patients had hypertension, 28.2% ischemic heart disease, 22.5% atrial fibrillation, while 30.1% T2DM. Several authors suggested that cardiovascular diseases and diabetes mellitus are linked to endothelial dysfunction, and all of them are strictly related to aging. Considering the impact of the gender on the COVID-19 epidemic, even if confirmed cases from each nation are changing every day, epidemiological data clearly evidence that in men the infection causes worse outcomes compared to women. In Italy, up to 21 May, in the age range of 60-89 years, male deaths were 63.9% of total cases. The reason behind this difference between genders appears not clear; however, the diversity in sex-hormones and styles of life are believed to play a role in the patient's susceptibility to severe SARS-CoV-2 outcomes. It is known that the activation of endothelial estrogen receptors increases NO and decreases ROS, protecting the vascular system from angiotensin II-mediated vasoconstriction, inflammation, and ROS production. During the pandemic, joining forces is vital; thus, as people help doctors by limiting their displacements out of their houses avoiding hence the spread of the infection, doctors help patients to overcome severe SARS-CoV-2 infections by using multiple pharmacological approaches. In this context, the preservation of endothelial function and the mitigation of vascular inflammation are prominent targets, essential to reduce severe outcomes also in male older patients.", "qid": 23, "docid": "f5n1xyyt", "rank": 74, "score": 0.8448587656021118}, {"content": "Title: Endothelial dysfunction in Coronavirus disease 2019 (COVID-19): Gender and age influences Content: Several risk factors are associated with a worse outcome for COVID-19 patients; the most recognized are demographic characteristics such as older age and male gender, and pre-existing cardiovascular conditions. About the latter, hypertension and coronary heart disease are among the most common comorbidities recorded in infected patients, together with type 2 diabetes mellitus (T2DM). Data from Istituto Superiore di Sanit\u00e0 (ISS, Italy) show that more than 68.3% of patients had hypertension, 28.2% ischemic heart disease, 22.5% atrial fibrillation, while 30.1% T2DM. Several authors suggested that cardiovascular diseases and diabetes mellitus are linked to endothelial dysfunction, and all of them are strictly related to aging. Considering the impact of the gender on the COVID-19 epidemic, even if confirmed cases from each nation are changing every day, epidemiological data clearly evidence that in men the infection causes worse outcomes compared to women. In Italy, up to 21 May, in the age range of 60-89 years, male deaths were 63.9% of total cases. The reason behind this difference between genders appears not clear; however, the diversity in sex-hormones and styles of life are believed to play a role in the patient's susceptibility to severe SARS-CoV-2 outcomes. It is known that the activation of endothelial estrogen receptors increases NO and decreases ROS, protecting the vascular system from angiotensin II-mediated vasoconstriction, inflammation, and ROS production. During the pandemic, joining forces is vital; thus, as people help doctors by limiting their displacements out of their houses avoiding hence the spread of the infection, doctors help patients to overcome severe SARS-CoV-2 infections by using multiple pharmacological approaches. In this context, the preservation of endothelial function and the mitigation of vascular inflammation are prominent targets, essential to reduce severe outcomes also in male older patients.", "qid": 23, "docid": "8z6qs443", "rank": 75, "score": 0.8448587656021118}, {"content": "Title: Obesity is the comorbidity more strongly associated for Covid-19 in Mexico. A case-control study Content: Some comorbidities are associated with severe coronavirus disease (Covid-19) but it is unclear whether some increase susceptibility to Covid-19. In this case-control Mexican study we found that obesity represents the strongest predictor for Covid-19 followed by diabetes and hypertension in both sexes and chronic renal failure in females only. Active smoking was associated with decreased odds of Covid-19. These findings indicate that these comorbidities are not only associated with severity of disease but also predispose for getting Covid-19. Future research is needed to establish the mechanisms involved in each comorbidity and the apparent \"protective\" effect of cigarette smoking.", "qid": 23, "docid": "d0ddb21n", "rank": 76, "score": 0.8447988629341125}, {"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": 23, "docid": "ejsqsn59", "rank": 77, "score": 0.8445827960968018}, {"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": 78, "score": 0.8444223403930664}, {"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": 79, "score": 0.8443986773490906}, {"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": 23, "docid": "ih8oxr40", "rank": 80, "score": 0.8443657159805298}, {"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": 81, "score": 0.8443197011947632}, {"content": "Title: Prognostic Factors for Adverse Outcomes in COVID-19 Infection Content: Whilst COVID-19 infection generally run a mild course in up to 80% of those affected, a number of pre-existing co-morbidities determine the severity of infection and the outcome in an individual patient. The most important of these co-morbidities that have consistently emerged in studies from across the globe, are the patients age and sex. Other important co-morbidities that adversely affect outcomes include pre-existing diabetes, obesity, hypertension, chronic lung disease and malignancy. This comprehensive review discusses the impact of these co-morbidities and the role of laboratory predictors of poor patient outcomes.", "qid": 23, "docid": "pebhhmz3", "rank": 82, "score": 0.8440320491790771}, {"content": "Title: Prognostic Factors for Adverse Outcomes in COVID-19 Infection. Content: Whilst COVID-19 infection generally run a mild course in up to 80% of those affected, a number of pre-existing co-morbidities determine the severity of infection and the outcome in an individual patient. The most important of these co-morbidities that have consistently emerged in studies from across the globe, are the patients age and sex. Other important co-morbidities that adversely affect outcomes include pre-existing diabetes, obesity, hypertension, chronic lung disease and malignancy. This comprehensive review discusses the impact of these co-morbidities and the role of laboratory predictors of poor patient outcomes.", "qid": 23, "docid": "vcoqptfx", "rank": 83, "score": 0.8440320491790771}, {"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": 84, "score": 0.8438311815261841}, {"content": "Title: Cholesterol: A new game player accelerating endothelial injuries caused by SARS-CoV-2? Content: The pandemic of coronavirus disease 2019 (COVID-19) has become a global threat to public health. Functional impairments in multiple organs have been reported in COVID-19 including lungs, heart, kidney, liver, brain and vascular system. Patients with metabolic-associated preconditions such as hypertension, obesity and diabetes are susceptible to experience severe symptoms. The recent emerging evidence of coagulation disorders in COVID-19 suggests that vasculopathy appears to be an independent risk factor promoting disease severity and mortality of affected patients. We have recently found that the decreased levels of low-density lipoprotein cholesterols (LDL-c) correlate with disease severity in COVID-19 patients, indicating pathological interactions between dyslipidemia and vasculopothy in COVID-19 patients. However, this clinical manifestation has been unintentionally underestimated by physicians and scientific communities. As metabolic-associated morbidities are generally accompanied with endothelial cell (EC) dysfunctions, these pre-existing conditions may make ECs more vulnerable to SARS-CoV-2 attack. In this mini-review, we summarize the metabolic and vascular manifestations of COVID-19 with an emphasis on the association between changes in LDL-c levels and the development of severe symptoms as well as the pathophysiologic mechanisms underlying the synergistic effect of LDL-c and SARS-CoV-2 on EC injuries and vasculopathy.", "qid": 23, "docid": "q3rzhy2i", "rank": 85, "score": 0.8436837196350098}, {"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": 86, "score": 0.8433114290237427}, {"content": "Title: COVID-19 and diabetes: Is there enough evidence? Content: The pandemic of COVID-19, a disease caused by a novel coronavirus SARS-CoV-2, is associated with significant morbidity and mortality. Recent data showed that hypertension, diabetes mellitus, cardiovascular diseases, and chronic obstructive pulmonary disease were the most prevalent comorbidities in COVID-19 patients. Additionally, data indicate that hypertension, diabetes, and cardiovascular diseases are important risk factors for progression and unfavorable outcome in COVID-19 patients. There is only limited amount of data regarding follow-up of these patients, and they provided conflicting results. The main limitation is a small number of participants and particularly those who experienced primary composite outcome (admission in intensive care unit, use of mechanical ventilation, or death). Additionally, the limited number of patients was essential obstacle for performing analysis that would include many confounding factors such as advanced age, smoking status, and obesity and potentially change conclusion. So far, there is no study that demonstrated independent predictive value of diabetes on mortality in COVID-19 patients, but there are many speculations about the association between diabetes and susceptibility to novel coronavirus, as well as its impact on progression and prognosis of COVID-19. The aim of this review article was to summarize the current knowledge about the relationship between diabetes and COVID-19 and its role in outcome in these patients.", "qid": 23, "docid": "f0pwjxfv", "rank": 87, "score": 0.843073844909668}, {"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": 88, "score": 0.8430534601211548}, {"content": "Title: Hypertension in patients hospitalized with COVID-19 in Wuhan, China: A single-center retrospective observational study Content: Objectives: It is unclear whether patients with hypertension are more likely to be infected with SARS-COV-2 than the general population and whether there is a difference in the severity of COVID-19 pneumonia in patients who have taken ACEI/ARB drugs to lower blood pressure compared to those who have not. Methods: This observational study included data from all patients with clinically confirmed COVID-19 who were admitted to the Hankou Hospital, Wuhan, China between January 5 and March 8, 2020. Data were extracted from clinical and laboratory records. Follow-up was cutoff on March 8, 2020. Results: A total of 274 patients, 75 with hypertension and 199 without hypertension, were included in the analysis. Patients with hypertension were older and were more likely to have pre-existing comorbidities, including chronic renal insufficiency, cardiovascular disease, diabetes mellitus, and cerebrovascular disease than patients without hypertension. Moreover, patients with hypertension tended to have higher positive COVID-19 PCR detection rates. Patients with hypertension who had previously taken ACEI/ARB drugs for antihypertensive treatment have an increased tendency to develop severe pneumonia after infection with SARS-COV-2 (P = 0.064). Conclusions: COVID-19 patients with hypertension were significantly older and were more likely to have underlying comorbidities, including chronic renal insufficiency, cardiovascular disease, diabetes mellitus, and cerebrovascular disease. Patients with hypertension who had taken ACEI/ARB drugs for antihypertensive treatment have an increased tendency to develop severe pneumonia after infection with SARS-COV-2. In future studies, a larger sample size and multi-center clinical data will be needed to support our conclusions.", "qid": 23, "docid": "lujxql3a", "rank": 89, "score": 0.8429979085922241}, {"content": "Title: Unraveling the mystery of Covid-19 cytokine storm: From skin to organ systems Content: COVID-19 is a global pandemic that emerged from Wuhan, China. Besides pneumonia and acute respiratory distress syndrome, the disease leads to multisystem involvement in the form of myocarditis, arrhythmias, cardiac arrest, gastrointestinal symptoms, hypoxemic brain injury, acute liver, and renal function impairment. There are also reports of cutaneous lesions in form of urticarial and maculopapular rashes, chilblain like fingers and toes (covid feet), livedoid vasculopathy, and chicken-pox like or varicelliform vesicles. Clinically, many of these skin lesions are likely secondary to occlusion of small to medium blood vessels due to microthrombi formation or due to viral laden antigen-antibody immune complexes; and same explanation may hold true for possible hypoxemic injury simultaneously occurring in other vital organs like lungs, heart, brain, and kidneys. The histopathology, immunoflorescence and RT-PCR analysis of skin biopsies can provide useful insights for ascertaining the pathogenesis of this complex viral syndrome. Apparently, it is interplay of disarmed cellular immunity and over-activated humoral immunity that culminates in end-organ changes. The morbidity and mortality can be significantly reduced by upgrading the cellular immunity and downgrading the humoral response; along with prevention of hypoxemic and reperfusion injuries by using antivirals, immunomodulators, antioxidants, anti-platelets, and anticoagulants in judicious and phased manner.", "qid": 23, "docid": "zbkukpdc", "rank": 90, "score": 0.8426834344863892}, {"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": 91, "score": 0.8423614501953125}, {"content": "Title: Cholesterol: A new game player accelerating vasculopathy caused by SARS-CoV-2? Content: The pandemic of coronavirus disease (COVID-19) has become a global threat to public health. Functional impairments in multiple organs have been reported in COVID-19, including lungs, heart, kidney, liver, brain, and vascular system. Patients with metabolic-associated preconditions, such as hypertension, obesity, and diabetes, are susceptible to experiencing severe symptoms. The recent emerging evidence of coagulation disorders in COVID-19 suggests that vasculopathy appears to be an independent risk factor promoting disease severity and mortality of affected patients. We recently found that the decreased levels of low-density lipoprotein cholesterols (LDL-c) correlate with disease severity in COVID-19 patients, indicating pathological interactions between dyslipidemia and vasculopothy in patients with COVID-19. However, this clinical manifestation has been unintentionally underestimated by physicians and scientific communities. As metabolic-associated morbidities are generally accompanied with endothelial cell (EC) dysfunctions, these pre-existing conditions may make ECs more vulnerable to SARS-CoV-2 attack. In this mini-review, we summarize the metabolic and vascular manifestations of COVID-19 with an emphasis on the association between changes in LDL-c levels and the development of severe symptoms as well as the pathophysiologic mechanisms underlying the synergistic effect of LDL-c and SARS-CoV-2 on EC injuries and vasculopathy.", "qid": 23, "docid": "lpuo4lzt", "rank": 92, "score": 0.8418916463851929}, {"content": "Title: SARS-CoV-2 Infection and COVID-19 During Pregnancy: A Multidisciplinary Review Content: Abstract The global pandemic of SARS-CoV-2, the cause of Coronavirus disease 2019 (COVID-19), has been associated with worse outcomes in several patient populations, including the elderly and those with chronic comorbidities. Data from previous pandemics and seasonal influenza suggest that pregnant women may be at increased risk for infection-associated morbidity and mortality. Physiological changes in normal pregnancy and metabolic and vascular changes of high-risk pregnancies may affect pathogenesis or exacerbate the clinical presentation of COVID-19. Specifically, SARS-CoV-2 enters the cell via the angiotensin converting enzyme 2 (ACE2) receptor, which is upregulated in normal pregnancy. Upregulation of ACE2 mediates conversion of Angiotensin II (vasoconstrictor) to Angiotensin 1-7 (vasodilator) and contributes to relatively low blood pressures, despite upregulation of other components of the renin angiotensin aldosterone system. As a result of higher ACE2 expression, pregnant women may be at an elevated risk of complications from SARS-CoV-2 infection. Upon binding to ACE2, SARS-CoV-2 causes its downregulation, thus lowering Angiotensin 1-7 levels, which can mimic/worsen vasoconstriction, inflammation, and pro-coagulopathic effects that occur in preeclampsia. Indeed, early reports suggest that, among other adverse outcomes, preeclampsia may be more common in pregnant women with COVID-19. Medical therapy, during both pregnancy and breast feeding, relies on medications with proven safety, but safety data are often missing for medications in the early stages of clinical trials. We summarize guidelines for medical/obstetric care and outline future directions for optimization of treatment and preventive strategies for pregnant patients with COVID-19 with the understanding that relevant data are limited and rapidly changing.", "qid": 23, "docid": "2fcon39t", "rank": 93, "score": 0.8417824506759644}, {"content": "Title: Coronavirus disease\u20102019 in pregnancy with neurological manifestations versus pregnancy with eclampsia: Need for liberal testing to rule out the masquerades Content: We read with interest, the article by Gidl\u00f6f et al on the management of a twin pregnancy with severe preeclampsia and Coronavirus disease-2019 (Covid-19) and their call for more liberal testing guidelines in women with high-risk pregnancies, and agree with their suggestion. A severe complication of preeclampsia is eclampsia. Presentations include neurological manifestations such as headache, seizures, loss of consciousness, along with raised blood pressure.", "qid": 23, "docid": "i7w7d62m", "rank": 94, "score": 0.8417516350746155}, {"content": "Title: COVID-19 and intracerebral haemorrhage: causative or coincidental? Content: Pneumonia appears to be the most common manifestation of coronavirus disease 2019 (COVID-19), but some extrapulmonary involvement, such as gastrointestinal, cardiac and renal, has been reported. The limited clinical data about the virus's behavior to date, especially extrapulmonary symptoms, suggest that we should be aware of the possibility of initial cerebrovascular manifestations of COVID-19.", "qid": 23, "docid": "ylr2b8ck", "rank": 95, "score": 0.8417403101921082}, {"content": "Title: Building a COVID-19 Vulnerability Index Content: COVID-19 is an acute respiratory disease that has been classified as a pandemic by the World Health Organization. Information regarding this particular disease is limited, however, it is known to have high mortality rates, particularly among individuals with preexisting medical conditions. Creating models to identify individuals who are at the greatest risk for severe complications due to COVID-19 will be useful to help for outreach campaigns in mitigating the diseases worst effects. While information specific to COVID-19 is limited, a model using complications due to other upper respiratory infections can be used as a proxy to help identify those individuals who are at the greatest risk. We present the results for three models predicting such complications, with each model having varying levels of predictive effectiveness at the expense of ease of implementation.", "qid": 23, "docid": "37dadupn", "rank": 96, "score": 0.8414797782897949}, {"content": "Title: Cardiovascular Implications of the COVID-19 Pandemic: A Global Perspective Content: The coronavirus disease 2019 (COVID-19), caused by severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2), represents the pandemic of the century, with approximately 3.5 million cases and 250,000 deaths worldwide as of May 2020. Although respiratory symptoms usually dominate the clinical presentation, COVID-19 is now known to also have potentially serious cardiovascular consequences, including myocardial injury, myocarditis, acute coronary syndromes, pulmonary embolism, stroke, arrhythmias, heart failure, and cardiogenic shock. The cardiac manifestations of COVID-19 might be related to the adrenergic drive, systemic inflammatory milieu and cytokine-release syndrome caused by SARS-CoV-2, direct viral infection of myocardial and endothelial cells, hypoxia due to respiratory failure, electrolytic imbalances, fluid overload, and side effects of certain COVID-19 medications. COVID-19 has profoundly reshaped usual care of both ambulatory and acute cardiac patients, by leading to the cancellation of elective procedures and by reducing the efficiency of existing pathways of urgent care, respectively. Decreased use of health care services for acute conditions by non-COVID-19 patients has also been reported and attributed to concerns about acquiring in-hospital infection. Innovative approaches that leverage modern technologies to tackle the COVID-19 pandemic have been introduced, which include telemedicine, dissemination of educational material over social media, smartphone apps for case tracking, and artificial intelligence for pandemic modelling, among others. This article provides a comprehensive overview of the pathophysiology and cardiovascular implications of COVID-19, its impact on existing pathways of care, the role of modern technologies to tackle the pandemic, and a proposal of novel management algorithms for the most common acute cardiac conditions.", "qid": 23, "docid": "8h36iwxi", "rank": 97, "score": 0.841468095779419}, {"content": "Title: COVID-19 and Cardiovascular diseases. Scoping review study Content: BACKGROUND: Many patients with COVID-19 have pre-existing cardiovascular (CV) co-morbidities or develop acute heart damage during the course of the disease. OBJECTIVES: To study the risk of COVID-19 infection in the presence of preexisting CV diseases and to describe new CV manifestations during COVID-19. METHODS: A \"scoping review\" was carried out via PubMed, to synthesize the results of research currently published on this subject. RESULTS: Patients with cardiovascular disease were at greater risk of developing COVID-19, especially in its severe form. These patients were five to ten times more at risk of death. Cardiac manifestations, de novo, were dominated by acute myocardial damage, defined by a significant elevation of cardiac troponins. These occurred in 7 to 17% of hospitalized patients. The presence of a new heart lesion in patients with COVID-19 was consistently associated with a poor prognosis. CONCLUSION: Given the enormous cardiovascular challenge posed by the COVID-19 pandemic and the prognostic impact of heart damage, additional research at a high level of evidence will be necessary.", "qid": 23, "docid": "20zujaha", "rank": 98, "score": 0.8414480686187744}, {"content": "Title: Cardiovascular implications of the COVID-19 pandemic: a global perspective Content: The Coronavirus disease 2019 (COVID-19), caused by severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2), represents the pandemic of the century, with approximately 3.5 million cases and 250,000 deaths worldwide as of May 2020. Although respiratory symptoms usually dominate the clinical presentation, COVID-19 is now known to also have potentially serious cardiovascular consequences, including myocardial injury, myocarditis, acute coronary syndromes, pulmonary embolism, stroke, arrhythmias, heart failure, and cardiogenic shock. The cardiac manifestations of COVID-19 might be related to the adrenergic drive, systemic inflammatory milieu and cytokine-release syndrome caused by SARS-CoV-2, direct viral infection of myocardial and endothelial cells, hypoxia due to respiratory failure, electrolytic imbalances, fluid overload, and side effects of certain COVID-19 medications. COVID-19 has profoundly reshaped usual care of both ambulatory and acute cardiac patients, by leading to the cancellation of elective procedures and by reducing the efficiency of existing pathways of urgent care, respectively. Decreased utilization of healthcare services for acute conditions by non-COVID-19 patients has also been reported and attributed to concerns about acquiring in-hospital infection. Innovative approaches that leverage modern technologies to tackle the COVID-19 pandemic have been introduced, which include telemedicine, dissemination of educational material over social media, smartphone apps for case tracking, and artificial intelligence for pandemic modelling, among others. This article provides a comprehensive overview of the pathophysiology and cardiovascular implications of COVID-19, its impact on existing pathways of care, the role of modern technologies to tackle the pandemic, and a proposal of novel management algorithms for the most common acute cardiac conditions.", "qid": 23, "docid": "dthdszdn", "rank": 99, "score": 0.8413938283920288}, {"content": "Title: Why obesity, hypertension, diabetes, and ethnicities are common risk factors for COVID\u201019 and H1N1 influenza infections Content: Obesity, hypertension, diabetes, and specific ethnicities (Black and Hispanic) have been reported to be common comorbidities and possible risk factors for the severity of both COVID-19 and H1N1 influenza infections. Thus, it is important to understand why these four risk factors are common to both COVID-19 and H1N1 influenza infections, and whether a common mechanism exists. Respiratory failure is the most important pathology that contributes to the severity of both COVID-19 and H1N1 influenza infections. Additionally, obesity has been reported to be a risk factor for the development of acute respiratory distress syndrome (ARDS), which is a serious clinical manifestation of both COVID-19 and H1N1 infections. Obesity is a risk factor for hypertension. Most of the previous studies showing hypertension as a risk factor for the severity of COVID-19 and H1N1 infections were either not based on multiple logistic regression analyses or did not include obesity or BMI as an explanatory variable in their multiple logistic regression models. Moreover, similar attention is needed when specifying patients with diabetes or of specific ethnicities (Black and Hispanic) as potentially more vulnerable to either infection, because obesity also correlates with diabetes, and is more prevalent in these ethnicities. Notably, a retrospective cohort study has shown that obesity or high BMI are predictive risk factors for severe COVID-19 outcomes, independent of age, diabetes, and hypertension. Associations between hypertension, diabetes, ethnicities and severity of COVID-19 and H1N1 infections may be confounded by obesity to a considerable extent. This article is protected by copyright. All rights reserved.", "qid": 23, "docid": "nlqz2nnh", "rank": 100, "score": 0.8412353992462158}]}
{"query": "what kinds of complications related to COVID-19 are associated with diabetes", "hits": [{"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": 1, "score": 0.9031411409378052}, {"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": 2, "score": 0.9016148447990417}, {"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": 3, "score": 0.9011200666427612}, {"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": 4, "score": 0.9004346132278442}, {"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": 5, "score": 0.90021812915802}, {"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": 6, "score": 0.9001775979995728}, {"content": "Title: Patients with diabetes are at higher risk for severe illness from COVID-19 Content: \u2022 It is currently uncertain whether people with diabetes are at higher risk of severe illness from coronavirus disease 2019 (COVID-19). \u2022 We found that diabetes was associated with an approximately 4-fold increased risk of having severe/critical COVID-19 illness. \u2022 This association was independent of age, sex, obesity, hypertension and smoking. \u2022 These findings highlight the urgent need for a multidisciplinary team-based approach to management of this patient population.", "qid": 24, "docid": "z0t43pmx", "rank": 7, "score": 0.8993345499038696}, {"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": 0.8991215229034424}, {"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": 9, "score": 0.8987255096435547}, {"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": 10, "score": 0.8986132144927979}, {"content": "Title: COVID-19 and diabetes mellitus: An unholy interaction of two pandemics Content: BACKGROUND AND AIMS: Diabetes mellitus is associated with poor prognosis in patients with COVID-19. On the other hand, COVID-19 contributes to worsening of dysglycemia in people with diabetes mellitus over and above that contributed by stress hyperglycemia. Herein, we have reviewed the two-way interactions between COVID-19 and diabetes mellitus. METHODS: We have performed an extensive literature search for articles in PubMed, EMBASE and Google Scholar databases till April 25, 2020, with the following keywords: \"COVID-19\", \"SARS-CoV-2\", \"diabetes\", \"diabetes mellitus\", \"SARS\", \"infection\" and \"management of diabetes mellitus\" with interposition of the Boolean operator \"AND\". RESULTS: Compromised innate immunity, pro-inflammatory cytokine milieu, reduced expression of ACE2 and use of renin-angiotensin-aldosterone system antagonists in people with diabetes mellitus contribute to poor prognosis in COVID-19. On the contrary, direct \u00df-cell damage, cytokine-induced insulin resistance, hypokalemia and drugs used in the treatment of COVID-19 (like corticosteroids, lopinavir/ritonavir) can contribute to worsening of glucose control in people with diabetes mellitus. CONCLUSIONS: The two-way interaction between COVID-19 and diabetes mellitus sets up a vicious cycle wherein COVID-19 leads to worsening of dysglycemia and diabetes mellitus, in turn, exacerbates the severity of COVID-19. Thus, it is imperative that people with diabetes mellitus take all necessary precautions and ensure good glycemic control amid the ongoing pandemic.", "qid": 24, "docid": "dgl7qapx", "rank": 11, "score": 0.8980588912963867}, {"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": 12, "score": 0.8960427045822144}, {"content": "Title: The Relationship between Diabetes Mellitus and COVID-19 Prognosis: A Retrospective Cohort Study in Wuhan, China Content: BACKGROUND: Coronavirus disease 2019 (COVID-19) is an emerging infectious disease, first appeared in Wuhan, China, and quickly spread throughout the world. We aimed to understand the relationship between diabetes mellitus and the prognosis of COVID-19. METHODS: Demographic, clinical, laboratory, radiologic, treatments, complications, and clinical outcomes data were extracted from electronic medical records and compared between diabetes (n=84) and non-diabetes (n=500) groups. Kaplan-Meier method and multivariate Cox analysis were applied to determine the risk factors for the prognosis of COVID-19. RESULTS: Compared to non-diabetic patients, diabetic patients had higher levels of neutrophils (p = 0.014), c-reactive protein (p = 0.008), procalcitonin (p < 0.01), and D-dimer (p = 0.033), and lower levels of lymphocytes (p = 0.032) and albumin (p = 0.035). Furthermore, diabetic patients had a significant higher incidence of bilateral pneumonia (86.9%, p = 0.020). In terms of complications and clinical outcomes, the incidence of respiratory failure (36.9% vs. 24.2%, p = 0.022), acute cardiac injury (47.4% vs. 21.2%, p < 0.01) and death (20.2% vs. 8.0%, p = 0.001) in the diabetes group was significantly higher than that in non-diabetes group. Kaplan-Meier survival curve showed that COVID-19 patients with diabetes had a shorter overall survival time. Multivariate Cox analysis indicated that diabetes (HR 2.180, p = 0.031) was an independent risk factor for COVID-19 prognosis. In subgroup analysis, we divided diabetic patients into insulin required and non-insulin required groups according to whether they needed insulin, and found that diabetic patients requiring insulin may have a higher risk of disease progression and worse prognosis after the infection of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). CONCLUSIONS: Diabetes is an independent risk factor for the prognosis of COVID-19. More attention should be paid to the prevention and treatment for diabetic patients, especially those who require insulin therapy.", "qid": 24, "docid": "zcdkohu6", "rank": 13, "score": 0.8957409858703613}, {"content": "Title: COVID-19 and diabetes mellitus: An unholy interaction of two pandemics Content: Abstract Background and aims Diabetes mellitus is associated with poor prognosis in patients with COVID-19. On the other hand, COVID-19 contributes to worsening of dysglycemia in people with diabetes mellitus over and above that contributed by stress hyperglycemia. Herein, we have reviewed the two-way interactions between COVID-19 and diabetes mellitus. Methods We have performed an extensive literature search for articles in PubMed, EMBASE and Google Scholar databases till April 25, 2020, with the following keywords: \u201cCOVID-19\u201d, \u201cSARS-CoV-2\u201d, \u201cdiabetes\u201d, \u201cdiabetes mellitus\u201d, \u201cSARS\u201d, \u201cinfection\u201d and \u201cmanagement of diabetes mellitus\u201d with interposition of the Boolean operator \u201cAND\u201d. Results Compromised innate immunity, pro-inflammatory cytokine milieu, reduced expression of ACE2 and use of renin-angiotensin-aldosterone system antagonists in people with DM contribute to poor prognosis in COVID-19. On the contrary, direct \u03b2-cell damage, cytokine-induced insulin resistance, hypokalemia and drugs used in the treatment of COVID-19 (like corticosteroids, lopinavir/ritonavir) can contribute to worsening of glucose control in people with diabetes mellitus. Conclusions The two-way interaction between COVID-19 and diabetes mellitus sets up a vicious cycle wherein COVID-19 leads to worsening of dysglycemia and diabetes mellitus, in turn, exacerbates the severity of COVID-19. Thus, it is imperative that people with DM take all necessary precautions and ensure good glycemic control amid the ongoing pandemic.", "qid": 24, "docid": "fe8f7tk1", "rank": 14, "score": 0.8954593539237976}, {"content": "Title: Coronavirus Disease 2019 and Diabetes: The Epidemic and the Korean Diabetes Association Perspective Content: Diabetes has been associated with more severe outcomes and higher mortality in coronavirus disease 2019 (COVID-19) patients compare to morbidity and mortality in patients without diabetes. Several mechanisms may play a role in this greater morbidity and mortality, especially uncontrolled hyperglycemia, an impaired immune system, pre-existing proinflammatory states, multiple comorbidities, and dysregulated angiotensin-converting enzyme 2 signaling. Thus, the diabetes medical community emergently needs to know about COVID-19 and its effects on patients with diabetes, as they must take precautions to carefully manage these patients during the COVID-19 pandemic. The Korean Diabetes Association provides some guidance and practical recommendations for the management of diabetes during the pandemic. This report provides insight into the association between diabetes and COVID-19, proper management of diabetes in patients with COVID-19 and an official suggestion by the Korean Diabetes Association for managing the COVID-19 outbreak.", "qid": 24, "docid": "u1c9pusk", "rank": 15, "score": 0.895404577255249}, {"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": 24, "docid": "i4t1jq29", "rank": 16, "score": 0.8946675062179565}, {"content": "Title: Clinical analysis of risk factors for severe COVID-19 patients with type 2 diabetes Content: AIMS: To describe characteristics of COVID-19 patients with type 2 diabetes and to analyze risk factors for severity. METHODS: Demographics, comorbidities, symptoms, laboratory findings, treatments and outcomes of COVID-19 patients with diabetes were collected and analyzed. RESULTS: Seventy-fourCOVID-19 patients with diabetes were included. Twenty-seven patients (36.5%) were severe and 10 patients (13.5%) died. Higher levels of blood glucose, serum amyloid A (SAA), C reactive protein and interleukin 6 were associated with severe patients compared to non-severe ones (P<0.05). Levels of albumin, cholesterol, high density lipoprotein, small and dense low density lipoprotein and CD4+T lymphocyte counts in severe patients were lower than those in non-severe patients (P<0.05). Logistic regression analysis identified decreased CD4+T lymphocyte counts (odds ratio [OR]=0.988, 95%Confidence interval [95%CI] 0.979-0.997) and increased SAA levels (OR=1.029, 95%CI 1.002-1.058) as risk factors for severity of COVID-19 with diabetes (P<0.05). CONCLUSIONS: Type 2 diabetic patients were more susceptible to COVID-19 than overall population, which might be associated with hyperglycemia and dyslipidemia. Aggressive treatment should be suggested, especially when these patients had low CD4+T lymphocyte counts and high SAA levels.", "qid": 24, "docid": "rf6651nd", "rank": 17, "score": 0.8945212364196777}, {"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": 18, "score": 0.8941704034805298}, {"content": "Title: Clinical analysis of risk factors for severe COVID-19 patients with type 2 diabetes() Content: AIMS: To describe characteristics of COVID-19 patients with type 2 diabetes and to analyze risk factors for severity. METHODS: Demographics, comorbidities, symptoms, laboratory findings, treatments and outcomes of COVID-19 patients with diabetes were collected and analyzed. RESULTS: Seventy-four COVID-19 patients with diabetes were included. Twenty-seven patients (36.5%) were severe and 10 patients (13.5%) died. Higher levels of blood glucose, serum amyloid A (SAA), C reactive protein and interleukin 6 were associated with severe patients compared to non-severe ones (P < 0.05). Levels of albumin, cholesterol, high density lipoprotein, small and dense low density lipoprotein and CD4(+) T lymphocyte counts in severe patients were lower than those in non-severe patients (P < 0.05). Logistic regression analysis identified decreased CD4(+) T lymphocyte counts (odds ratio [OR] = 0.988, 95%Confidence interval [95%CI] 0.979\u20130.997) and increased SAA levels (OR = 1.029, 95%CI 1.002\u20131.058) as risk factors for severity of COVID-19 with diabetes (P < 0.05). CONCLUSIONS: Type 2 diabetic patients were more susceptible to COVID-19 than overall population, which might be associated with hyperglycemia and dyslipidemia. Aggressive treatment should be suggested, especially when these patients had low CD4(+) T lymphocyte counts and high SAA levels.", "qid": 24, "docid": "ulmm28d5", "rank": 19, "score": 0.8940659165382385}, {"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": 24, "docid": "qzev2reb", "rank": 20, "score": 0.894055962562561}, {"content": "Title: Diabetes and COVID-19: Global and Regional Perspectives Content: The coronavirus disease-2019 (COVID-19) has been designated as a highly contagious infectious disease caused by the severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2) since December 2019, when an outbreak of pneumonia cases emerged in Wuhan, China. The COVID-19 pandemic has led to a global health crisis, devastating the social, economic and political aspects of life. Many clinicians, health professionals, scientists, organizations, and governments have actively defeated COVID-19 and shared their experiences of the SARS-CoV2. Diabetes is one of the major risk factors for fatal outcomes from COVID-19. Patients with diabetes are vulnerable to infection because of hyperglycemia; impaired immune function; vascular complications; and comorbidities such as hypertension, dyslipidemia, and cardiovascular disease. In addition, angiotensin-converting enzyme 2 (ACE2) is a receptor for SARS-CoV-2 in the human body. Hence, the use of angiotensin-directed medications in patients with diabetes requires attention. The severity and mortality from COVID-19 was significantly higher in patients with diabetes than in those without. Thus, the patients with diabetes should take precautions during the COVID-19 pandemic. Therefore, we review the current knowledge of COVID-19 including the global and regional epidemiology, virology, impact of diabetes on COVID-19, treatment of COVID-19, and standard of care in the management of diabetes during this critical period.", "qid": 24, "docid": "t8wg07ew", "rank": 21, "score": 0.8937599658966064}, {"content": "Title: The Relationship between Diabetes Mellitus and COVID-19 Prognosis: A Retrospective Cohort Study in Wuhan, China Content: BACKGROUND: Coronavirus disease 2019 (COVID-19) is an emerging infectious disease, first appeared in Wuhan, China, and quickly spread throughout the world. We aimed to understand the relationship between diabetes mellitus and the prognosis of COVID-19. METHODS: Demographic, clinical, laboratory, radiologic, treatments, complications, and clinical outcomes data were extracted from electronic medical records and compared between diabetes (n=84) and non-diabetes (n=500) groups. Kaplan-Meier method and multivariate Cox analysis were applied to determine the risk factors for the prognosis of COVID-19. RESULTS: Compared to non-diabetic patients, diabetic patients had higher levels of neutrophils (p\u00e2\u0080\u00af=\u00e2\u0080\u00af0.014), c-reactive protein (p\u00e2\u0080\u00af=\u00e2\u0080\u00af0.008), procalcitonin (p < 0.01), and D-dimer (p\u00e2\u0080\u00af=\u00e2\u0080\u00af0.033), and lower levels of lymphocytes (p\u00e2\u0080\u00af=\u00e2\u0080\u00af0.032) and albumin (p\u00e2\u0080\u00af=\u00e2\u0080\u00af0.035). Furthermore, diabetic patients had a significant higher incidence of bilateral pneumonia (86.9%, p\u00e2\u0080\u00af=\u00e2\u0080\u00af0.020). In terms of complications and clinical outcomes, the incidence of respiratory failure (36.9% vs. 24.2%, p\u00e2\u0080\u00af=\u00e2\u0080\u00af0.022), acute cardiac injury (47.4% vs. 21.2%, p < 0.01) and death (20.2% vs. 8.0%, p\u00e2\u0080\u00af=\u00e2\u0080\u00af0.001) in the diabetes group was significantly higher than that in non-diabetes group. Kaplan-Meier survival curve showed that COVID-19 patients with diabetes had a shorter overall survival time. Multivariate Cox analysis indicated that diabetes (HR 2.180, p\u00e2\u0080\u00af=\u00e2\u0080\u00af0.031) was an independent risk factor for COVID-19 prognosis. In subgroup analysis, we divided diabetic patients into insulin required and non-insulin required groups according to whether they needed insulin, and found that diabetic patients requiring insulin may have a higher risk of disease progression and worse prognosis after the infection of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). CONCLUSIONS: Diabetes is an independent risk factor for the prognosis of COVID-19. More attention should be paid to the prevention and treatment for diabetic patients, especially those who require insulin therapy.", "qid": 24, "docid": "f4qljghz", "rank": 22, "score": 0.8932638168334961}, {"content": "Title: COVID-19 and diabetes: Is there enough evidence? Content: The pandemic of COVID-19, a disease caused by a novel coronavirus SARS-CoV-2, is associated with significant morbidity and mortality. Recent data showed that hypertension, diabetes mellitus, cardiovascular diseases, and chronic obstructive pulmonary disease were the most prevalent comorbidities in COVID-19 patients. Additionally, data indicate that hypertension, diabetes, and cardiovascular diseases are important risk factors for progression and unfavorable outcome in COVID-19 patients. There is only limited amount of data regarding follow-up of these patients, and they provided conflicting results. The main limitation is a small number of participants and particularly those who experienced primary composite outcome (admission in intensive care unit, use of mechanical ventilation, or death). Additionally, the limited number of patients was essential obstacle for performing analysis that would include many confounding factors such as advanced age, smoking status, and obesity and potentially change conclusion. So far, there is no study that demonstrated independent predictive value of diabetes on mortality in COVID-19 patients, but there are many speculations about the association between diabetes and susceptibility to novel coronavirus, as well as its impact on progression and prognosis of COVID-19. The aim of this review article was to summarize the current knowledge about the relationship between diabetes and COVID-19 and its role in outcome in these patients.", "qid": 24, "docid": "f0pwjxfv", "rank": 23, "score": 0.8931100964546204}, {"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": 24, "score": 0.8930315971374512}, {"content": "Title: Practical recommendations for the management of diabetes in patients with COVID-19 Content: Diabetes is one of the most important comorbidities linked to the severity of all three known human pathogenic coronavirus infections, including severe acute respiratory syndrome coronavirus 2. Patients with diabetes have an increased risk of severe complications including Adult Respiratory Distress Syndrome and multi-organ failure. Depending on the global region, 20-50% of patients in the coronavirus disease 2019 (COVID-19) pandemic had diabetes. Given the importance of the link between COVID-19 and diabetes, we have formed an international panel of experts in the field of diabetes and endocrinology to provide some guidance and practical recommendations for the management of diabetes during the pandemic. We aim to briefly provide insight into potential mechanistic links between the novel coronavirus infection and diabetes, present practical management recommendations, and elaborate on the differential needs of several patient groups.", "qid": 24, "docid": "grz8hhal", "rank": 25, "score": 0.8928349018096924}, {"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": 26, "score": 0.8927722573280334}, {"content": "Title: Diabetes and COVID-19: Global and Regional Perspectives Content: Abstract The coronavirus disease-2019 (COVID-19) has been designated as a highly contagious infectious disease caused by the severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2) since December 2019, when an outbreak of pneumonia cases emerged in Wuhan, China. The COVID-19 pandemic has led to a global health crisis, devastating the social, economic and political aspects of life. Many clinicians, health professionals, scientists, organizations, and governments have actively defeated COVID-19 and shared their experiences of the SARS-CoV2. Diabetes is one of the major risk factors for fatal outcomes from COVID-19. Patients with diabetes are vulnerable to infection because of hyperglycemia; impaired immune function; vascular complications; and comorbidities such as hypertension, dyslipidemia, and cardiovascular disease. In addition, angiotensin-converting enzyme 2 (ACE2) is a receptor for SARS-CoV-2 in the human body. Hence, the use of angiotensin-directed medications in patients with diabetes requires attention. The severity and mortality from COVID-19 was significantly higher in patients with diabetes than in those without. Thus, the patients with diabetes should take precautions during the COVID-19 pandemic. Therefore, we review the current knowledge of COVID-19 including the global and regional epidemiology, virology, impact of diabetes on COVID-19, treatment of COVID-19, and standard of care in the management of diabetes during this critical period.", "qid": 24, "docid": "cvltwjbz", "rank": 27, "score": 0.8920753002166748}, {"content": "Title: Diabetes, Infection Risk And Covid-19 Content: Abstract Background Individuals with diabetes are at a greater risk of hospitalization and mortality resulting from viral, bacterial and fungal infections. The Coronavirus Disease-2019 (COVID-19), caused by severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2), has spread quickly to more than 213 countries across the world and has claimed 395,779 lives as of June 7, 2020. Notably, in several studies, diabetes is one of the most reported comorbidities in patients with severe COVID-19. Scope of Review In this review, I will summarize the clinical data on the risk for infectious diseases in individuals with diabetes, highlighting the mechanisms for altered immune regulation. A special focus will be given to coronaviruses. In the light of the new clinical data obtained from COVID-19 patients, mechanisms such as cytokine storm, pulmonary and endothelial dysfunction, hypercoagulation that may render individuals with diabetes more vulnerable to COVID-19 will be discussed in the end. Major Conclusions Epidemiological studies show that poorly controlled diabetes is a risk factor for various infectious diseases. Given the global burden of diabetes and pandemic nature of coronaviruses, understanding how diabetes affects COVID-19 severity is critical to design tailored treatments and clinical management of individuals affected by diabetes.", "qid": 24, "docid": "12q9jjbb", "rank": 28, "score": 0.8919897675514221}, {"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": 29, "score": 0.8918821811676025}, {"content": "Title: Diabetes in COVID-19: Prevalence, pathophysiology, prognosis and practical considerations Content: Abstract Background and aims High prevalence of diabetes makes it an important comorbidity in patients with COVID-19. We sought to review and analyze the data regarding the association between diabetes and COVID-19, pathophysiology of the disease in diabetes and management of patients with diabetes who develop COVID-19 infection. Methods PubMed database and Google Scholar were searched using the key terms \u2018COVID-19\u2019, \u2018SARS-CoV-2\u2019, \u2018diabetes\u2019, \u2018antidiabetic therapy\u2019 up to April 2, 2020. Full texts of the retrieved articles were accessed. Results There is evidence of increased incidence and severity of COVID-19 in patients with diabetes. COVID-19 could have effect on the pathophysiology of diabetes. Blood glucose control is important not only for patients who are infected with COVID-19, but also for those without the disease. Innovations like telemedicine are useful to treat patients with diabetes in today\u2019s times.", "qid": 24, "docid": "bqxyb61p", "rank": 30, "score": 0.8918397426605225}, {"content": "Title: Practical recommendations for the management of diabetes in patients with COVID-19 Content: Summary Diabetes is one of the most important comorbidities linked to the severity of all three known human pathogenic coronavirus infections, including severe acute respiratory syndrome coronavirus 2. Patients with diabetes have an increased risk of severe complications including Adult Respiratory Distress Syndrome and multi-organ failure. Depending on the global region, 20\u201350% of patients in the coronavirus disease 2019 (COVID-19) pandemic had diabetes. Given the importance of the link between COVID-19 and diabetes, we have formed an international panel of experts in the field of diabetes and endocrinology to provide some guidance and practical recommendations for the management of diabetes during the pandemic. We aim to briefly provide insight into potential mechanistic links between the novel coronavirus infection and diabetes, present practical management recommendations, and elaborate on the differential needs of several patient groups.", "qid": 24, "docid": "118x15od", "rank": 31, "score": 0.8918226361274719}, {"content": "Title: Diabetes, infection risk and COVID-19 Content: BACKGROUND: Individuals with diabetes are at a greater risk of hospitalization and mortality resulting from viral, bacterial, and fungal infections. The coronavirus disease-2019 (COVID-19), caused by severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2), has spread quickly to more than 213 countries and claimed 395,779 lives as of June 7, 2020. Notably, in several studies, diabetes is one of the most reported comorbidities in patients with severe COVID-19. SCOPE OF REVIEW: In this review, I summarize the clinical data on the risk for infectious diseases in individuals with diabetes while highlighting the mechanisms for altered immune regulation. The focus is on coronaviruses. Based on the new clinical data obtained from COVID-19 patients, a discussion of mechanisms, such as cytokine storm, pulmonary and endothelial dysfunction, and hypercoagulation, that may render individuals with diabetes more vulnerable to COVID-19 is provided. MAJOR CONCLUSIONS: Epidemiological studies show that poorly controlled diabetes is a risk factor for various infectious diseases. Given the global burden of diabetes and the pandemic nature of coronaviruses, understanding how diabetes affects COVID-19 severity is critical to designing tailored treatments and clinical management of individuals affected by diabetes.", "qid": 24, "docid": "x9h81ij0", "rank": 32, "score": 0.8905481100082397}, {"content": "Title: Diabetes and COVID-19: Risks, Management, and Learnings From Other National Disasters Content: Evidence relating to the impact of COVID-19 in people with diabetes (PWD) is limited but continuing to emerge. PWD appear to be at increased risk of more severe COVID-19 infection, though evidence quantifying the risk is highly uncertain. The extent to which clinical and demographic factors moderate this relationship is unclear, though signals are emerging that link higher BMI and higher HbA1c to worse outcomes in PWD with COVID-19. As well as posing direct immediate risks to PWD, COVID-19 also risks contributing to worse diabetes outcomes due to disruptions caused by the pandemic, including stress and changes to routine care, diet, and physical activity. Countries have used various strategies to support PWD during this pandemic. There is a high potential for COVID-19 to exacerbate existing health disparities, and research and practice guidelines need to take this into account. Evidence on the management of long-term conditions during national emergencies suggests various ways to mitigate the risks presented by these events.", "qid": 24, "docid": "a7npp99p", "rank": 33, "score": 0.890117883682251}, {"content": "Title: Diabetes and COVID-19: Risks, Management, and Learnings From Other National Disasters. Content: Evidence relating to the impact of COVID-19 in people with diabetes (PWD) is limited but continuing to emerge. PWD appear to be at increased risk of more severe COVID-19 infection, though evidence quantifying the risk is highly uncertain. The extent to which clinical and demographic factors moderate this relationship is unclear, though signals are emerging that link higher BMI and higher HbA1c to worse outcomes in PWD with COVID-19. As well as posing direct immediate risks to PWD, COVID-19 also risks contributing to worse diabetes outcomes due to disruptions caused by the pandemic, including stress and changes to routine care, diet, and physical activity. Countries have used various strategies to support PWD during this pandemic. There is a high potential for COVID-19 to exacerbate existing health disparities, and research and practice guidelines need to take this into account. Evidence on the management of long-term conditions during national emergencies suggests various ways to mitigate the risks presented by these events.", "qid": 24, "docid": "8qao0tmx", "rank": 34, "score": 0.890117883682251}, {"content": "Title: COVID-19 and diabetes: Knowledge in progress Content: AIMS: We aimed to briefly review the general characteristics of the novel coronavirus (SARS-CoV-2) and provide a better understanding of the coronavirus disease (COVID-19) in people with diabetes, and its management. METHODS: We searched for articles in PubMed and Google Scholar databases till 02 April 2020, with the following keywords: \"SARS-CoV-2\", \"COVID-19\", \"infection\", \"pathogenesis\", \"incubation period\", \"transmission\", \"clinical features\", \"diagnosis\", \"treatment\", \"diabetes\", with interposition of the Boolean operator \"AND\". RESULTS: The clinical spectrum of COVID-19 is heterogeneous, ranging from mild flu-like symptoms to acute respiratory distress syndrome, multiple organ failure and death. Older age, diabetes and other comorbidities are reported as significant predictors of morbidity and mortality. Chronic inflammation, increased coagulation activity, immune response impairment, and potential direct pancreatic damage by SARS-CoV-2 might be among the underlying mechanisms of the association between diabetes and COVID-19. No conclusive evidence exists to support the discontinuation of angiotensin-converting enzyme inhibitors (ACEI), angiotensin receptor blockers or thiazolidinediones because of COVID-19 in people with diabetes. Caution should be taken to potential hypoglycemic events with the use of chloroquine in these subjects. Patient tailored therapeutic strategies, rigorous glucose monitoring and careful consideration of drug interactions might reduce adverse outcomes. CONCLUSIONS: Suggestions are made on the possible pathophysiological mechanisms of the relationship between diabetes and COVID-19, and its management. No definite conclusions can be made based on current limited evidence. Further research regarding this relationship and its clinical management is warranted.", "qid": 24, "docid": "0tdt0wej", "rank": 35, "score": 0.889987051486969}, {"content": "Title: COVID 19: Diabetes and Obesity API-ICP Recommendations Content: Diabetes and Obesity are major risk factors which confer vulnerability to Covid 19 . Diabetes has immune defects which makes the individual susceptible to infections and covid 19 is no exception . Also covid 19 can cause pancreatic damage as well as stress hyperglycaemia in hospitals which may need Insulin . Among diabetes male gender,elderly,hypertension ,heart disease and chronic renal disease are more vulbwdvale to covid 19 and need strict supervision . Diabetes management in hospitalised situation merits early diabetes specific nutrition with Insulin. Adherence to lifestyle with self monitoring of blood glucose and adequate supply of Insulin and Oral antidiabetic agents is encouraged.", "qid": 24, "docid": "e582ueut", "rank": 36, "score": 0.8898863792419434}, {"content": "Title: COVID 19: Diabetes and Obesity API-ICP Recommendations. Content: Diabetes and Obesity are major risk factors which confer vulnerability to Covid 19 . Diabetes has immune defects which makes the individual susceptible to infections and covid 19 is no exception . Also covid 19 can cause pancreatic damage as well as stress hyperglycaemia in hospitals which may need Insulin . Among diabetes male gender,elderly,hypertension ,heart disease and chronic renal disease are more vulbwdvale to covid 19 and need strict supervision . Diabetes management in hospitalised situation merits early diabetes specific nutrition with Insulin. Adherence to lifestyle with self monitoring of blood glucose and adequate supply of Insulin and Oral antidiabetic agents is encouraged.", "qid": 24, "docid": "25v7qies", "rank": 37, "score": 0.8898863792419434}, {"content": "Title: COVID-19 Pandemic, Corona Viruses, and Diabetes Mellitus. Content: The pandemic of COVID-19, a disease caused by a novel coronavirus (CoV), SARS-CoV-2, is causing substantial morbidity and mortality. Older age and presence of diabetes mellitus, hypertension, and obesity significantly increases the risk for hospitalization and death in COVID-19 patients. In this Perspective, informed by the studies on severe acute respiratory syndrome, SARS-CoV, and Middle East respiratory syndrome, MERS-CoV, and the current literature on SARS-CoV-2, we discuss potential mechanisms by which diabetes modulates the host-viral interactions and host-immune responses. We hope to highlight gaps in knowledge that require further studies pertinent to COVID-19 in patients with diabetes.", "qid": 24, "docid": "22vz79nz", "rank": 38, "score": 0.8898122310638428}, {"content": "Title: COVID-19 pandemic, coronaviruses, and diabetes mellitus Content: The pandemic of coronavirus disease (COVID-19), a disease caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), is causing substantial morbidity and mortality. Older age and presence of diabetes mellitus, hypertension, and obesity significantly increases the risk for hospitalization and death in COVID-19 patients. In this Perspective, informed by the studies on SARS-CoV-2, Middle East respiratory syndrome (MERS-CoV), and the current literature on SARS-CoV-2, we discuss potential mechanisms by which diabetes modulates the host-viral interactions and host-immune responses. We hope to highlight gaps in knowledge that require further studies pertinent to COVID-19 in patients with diabetes.", "qid": 24, "docid": "lntg6yb8", "rank": 39, "score": 0.8893570899963379}, {"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": 40, "score": 0.8891885280609131}, {"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": 41, "score": 0.8879991173744202}, {"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": 24, "docid": "ntv2g7ne", "rank": 42, "score": 0.8874524235725403}, {"content": "Title: Can We Reduce Mortality of COVID-19 if We do Better in Glucose Control? Content: The SARS-CoV-2 has infected more than 3 million people and caused more than 240,000 death globally. Among the COVID-19 patients, the prevalence of people with other chronic diseases, such as diabetes, high blood pressure, and coronary heart disease is much higher than others. More strikingly, the survival rate of diabetic patients is also much lower than in non-diabetic patients. In addition to the general damage of high glucose to cells and tissues, a recent discovery that high glucose activates interferon regulatory factor 15 promotes influenza virus -induced cytokine storm. This discovery may shed light on the high incidence of diabetes in COVID-19. Several diabetes prevention strategies together with recent significant data-driven diabetes prediction approaches, which may help COVID-19 treatments, have been proposed.", "qid": 24, "docid": "kbj72qye", "rank": 43, "score": 0.886146068572998}, {"content": "Title: Solving one of the pieces of the puzzle: COVID-19 and type 2 diabetes() Content: The emergence of the COVID-19 pandemic represents an enormous challenge. Given the considerable presence of type 2 diabetes mellitus in the current population, the pandemic is a health issue that requires an effort to provide better responses to our patients who are more vulnerable to the onset of infection and who are candidates for presenting more severe symptoms. This document attempts to address the relationship between COVID-19 infection and type 2 diabetes mellitus. To this end, we will briefly analyse whether the epidemiological data support this association and, subsequently, go in depth on the pathophysiological mechanisms that might connect the 2 diseases.", "qid": 24, "docid": "sdpa0372", "rank": 44, "score": 0.8860576152801514}, {"content": "Title: Resolviendo Una De Las Piezas Del Puzle: Covid-19 Y Diabetes Tipo 2./ [solving One of the Pieces of the Puzzle: Covid-19 and Type 2 Diabetes] Content: The emergence of the COVID-19 pandemic represents an enormous challenge. Given the considerable presence of type 2 diabetes mellitus in the current population, the pandemic is a health issue that requires an effort to provide better responses to our patients who are more vulnerable to the onset of infection and who are candidates for presenting more severe symptoms. This document attempts to address the relationship between COVID-19 infection and type 2 diabetes mellitus. To this end, we will briefly analyse whether the epidemiological data support this association and, subsequently, go in depth on the pathophysiological mechanisms that might connect the two diseases.", "qid": 24, "docid": "luz9q2rd", "rank": 45, "score": 0.8852493762969971}, {"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": 46, "score": 0.8847867250442505}, {"content": "Title: Association of diabetes and hypertension with disease severity in covid-19 patients: a systematic literature review and exploratory meta-analysis Content: AIM: The novel coronavirus infection (COVID-19), now a worldwide public health concern is associated with varied fatality. Patients with chronic underlying conditions like diabetes and hypertension have shown worst outcomes. The understanding of the association might be helpful in early vigilant monitoring and better management of COVID-19 patients at high risk. The aim of the meta-analysis was to assess the association of diabetes and hypertension with severity of disease. METHODS: A literature search was conducted using the databases PubMed and Cochrane until March 31, 2020. Seven studies were included in the meta- analysis, including 2018 CIVID-19 patients. RESULTS: Diabetes was lower in the survivors (OR: 0.56; 95%CI: 0.35-0.90; p=0.017; I2: 0.0%) and non-severe (OR: 1.66; 95%CI: 1.20-2.30; p=0.002; I2: 0.0%) patients. No association of diabetes was found with ICU care. Hypertension was positively associated with death (OR: 0.49; 95%CI: 0.34-0.73; p=0.000; I2: 0.0%), ICU care (OR: 0.42; 95%CI: 0.22-0.81; p=0.009; I2: 0.0%) and severity (OR: 2.69; 95%CI: 1.27-5.73; p=0.01; I2: 52.4%). CONCLUSIONS: Our findings suggest that diabetes and hypertension have a negative effect on health status of COVID-19 patients. However, large prevalence studies demonstrating the consequences of comorbid diabetes and hypertension are urgently needed to understand the magnitude of these vexatious comorbidities.", "qid": 24, "docid": "04s7w017", "rank": 47, "score": 0.8847730159759521}, {"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": 48, "score": 0.8846443295478821}, {"content": "Title: Is diabetes mellitus associated with mortality and severity of COVID-19? A meta-analysis Content: BACKGROUND: Many studies on COVID-19 have reported diabetes to be associated with severe disease and mortality, however, the data is conflicting. The objectives of this meta-analysis were to explore the relationship between diabetes and COVID-19 mortality and severity, and to determine the prevalence of diabetes in patients with COVID-19. METHODS: We searched the PubMed for case-control studies in English, published between Jan 1 and Apr 22, 2020, that had data on diabetes in patients with COVID-19. The frequency of diabetes was compared between patients with and without the composite endpoint of mortality or severity. Random effects model was used with odds ratio as the effect size. We also determined the pooled prevalence of diabetes in patients with COVID-19. Heterogeneity and publication bias were taken care by meta-regression, sub-group analyses, and trim and fill methods. RESULTS: We included 33 studies (16,003 patients) and found diabetes to be significantly associated with mortality of COVID-19 with a pooled odds ratio of 1.90 (95% CI: 1.37-2.64; p < 0.01). Diabetes was also associated with severe COVID-19 with a pooled odds ratio of 2.75 (95% CI: 2.09-3.62; p < 0.01). The combined corrected pooled odds ratio of mortality or severity was 2.16 (95% CI: 1.74-2.68; p < 0.01). The pooled prevalence of diabetes in patients with COVID-19 was 9.8% (95% CI: 8.7%-10.9%) (after adjusting for heterogeneity). CONCLUSIONS: Diabetes in patients with COVID-19 is associated with a two-fold increase in mortality as well as severity of COVID-19, as compared to non-diabetics. Further studies on the pathogenic mechanisms and therapeutic implications need to be done.", "qid": 24, "docid": "ufasdi1b", "rank": 49, "score": 0.8844861388206482}, {"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": 24, "docid": "4ti8l2ea", "rank": 50, "score": 0.8842302560806274}, {"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": 24, "docid": "sjcadz5j", "rank": 51, "score": 0.8842301368713379}, {"content": "Title: Diabetes and COVID-19 : Disease-Management-People Content: The current pandemic of SARS-CoV\u00ad2 coronavirus disease 2019 (COVID-19) is a particular challenge for diabetes patients. Diabetes mellitus predisposes to a particularly severe course of the disease and doubles the COVID-19 mortality risk due to pulmonary and cardiac involvement. In addition, diabetes patients often suffer from comorbidities which further worsen clinical outcomes. Glycemic control during infectious diseases is often suboptimal, and antidiabetic drugs and insulin therapy have to be adapted accordingly. On the other hand, access of diabetes patients to outpatient clinics are limited during the ongoing season urging alternative treatment options, particularly the implementation of novel telemedicine strategies. Hence, the opportunity of the COVID 19 crisis should be taken to make a significant step forward in the care for diabetes patients.", "qid": 24, "docid": "7ptxz652", "rank": 52, "score": 0.8839603662490845}, {"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": 53, "score": 0.8837019801139832}, {"content": "Title: Diabetes and COVID-19: Disease\u2014Management\u2014People Content: The current pandemic of SARS-CoV\u20112 coronavirus disease 2019 (COVID-19) is a particular challenge for diabetes patients. Diabetes mellitus predisposes to a particularly severe course of the disease and doubles the COVID-19 mortality risk due to pulmonary and cardiac involvement. In addition, diabetes patients often suffer from comorbidities which further worsen clinical outcomes. Glycemic control during infectious diseases is often suboptimal, and antidiabetic drugs and insulin therapy have to be adapted accordingly. On the other hand, access of diabetes patients to outpatient clinics are limited during the ongoing season urging alternative treatment options, particularly the implementation of novel telemedicine strategies. Hence, the opportunity of the COVID 19 crisis should be taken to make a significant step forward in the care for diabetes patients.", "qid": 24, "docid": "mx9nyd2q", "rank": 54, "score": 0.8832876086235046}, {"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": 55, "score": 0.8829673528671265}, {"content": "Title: Issues of Cardiovascular Risk Management in People With Diabetes in the COVID-19 Era Content: People with diabetes compared with people without exhibit worse prognosis if affected by coronavirus disease 2019 (COVID-19) induced by the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), particularly when compromising metabolic control and concomitant cardiovascular disorders are present. This Perspective seeks to explore newly occurring cardio-renal-pulmonary organ damage induced or aggravated by the disease process of COVID-19 and its implications for the cardiovascular risk management of people with diabetes, especially taking into account potential interactions with mechanisms of cellular intrusion of SARS-CoV-2. Severe infection with SARS-CoV-2 can precipitate myocardial infarction, myocarditis, heart failure, and arrhythmias as well as an acute respiratory distress syndrome and renal failure. They may evolve along with multiorgan failure directly due to SARS-CoV-2-infected endothelial cells and resulting endotheliitis. This complex pathology may bear challenges for the use of most diabetes medications in terms of emerging contraindications that need close monitoring of all people with diabetes diagnosed with SARS-CoV-2 infection. Whenever possible, continuous glucose monitoring should be implemented to ensure stable metabolic compensation. Patients in the intensive care unit requiring therapy for glycemic control should be handled solely by intravenous insulin using exact dosing with a perfusion device. Although not only ACE inhibitors and angiotensin 2 receptor blockers but also SGLT2 inhibitors, GLP-1 receptor agonists, pioglitazone, and probably insulin seem to increase the number of ACE2 receptors on the cells utilized by SARS-CoV-2 for penetration, no evidence presently exists that shows this might be harmful in terms of acquiring or worsening COVID-19. In conclusion, COVID-19 and related cardio-renal-pulmonary damage can profoundly affect cardiovascular risk management of people with diabetes.", "qid": 24, "docid": "34qqxkby", "rank": 56, "score": 0.8823832273483276}, {"content": "Title: Issues of Cardiovascular Risk Management in People With Diabetes in the COVID-19 Era. Content: People with diabetes compared with people without exhibit worse prognosis if affected by coronavirus disease 2019 (COVID-19) induced by the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), particularly when compromising metabolic control and concomitant cardiovascular disorders are present. This Perspective seeks to explore newly occurring cardio-renal-pulmonary organ damage induced or aggravated by the disease process of COVID-19 and its implications for the cardiovascular risk management of people with diabetes, especially taking into account potential interactions with mechanisms of cellular intrusion of SARS-CoV-2. Severe infection with SARS-CoV-2 can precipitate myocardial infarction, myocarditis, heart failure, and arrhythmias as well as an acute respiratory distress syndrome and renal failure. They may evolve along with multiorgan failure directly due to SARS-CoV-2-infected endothelial cells and resulting endotheliitis. This complex pathology may bear challenges for the use of most diabetes medications in terms of emerging contraindications that need close monitoring of all people with diabetes diagnosed with SARS-CoV-2 infection. Whenever possible, continuous glucose monitoring should be implemented to ensure stable metabolic compensation. Patients in the intensive care unit requiring therapy for glycemic control should be handled solely by intravenous insulin using exact dosing with a perfusion device. Although not only ACE inhibitors and angiotensin 2 receptor blockers but also SGLT2 inhibitors, GLP-1 receptor agonists, pioglitazone, and probably insulin seem to increase the number of ACE2 receptors on the cells utilized by SARS-CoV-2 for penetration, no evidence presently exists that shows this might be harmful in terms of acquiring or worsening COVID-19. In conclusion, COVID-19 and related cardio-renal-pulmonary damage can profoundly affect cardiovascular risk management of people with diabetes.", "qid": 24, "docid": "tpkl3x02", "rank": 57, "score": 0.8823832273483276}, {"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": 58, "score": 0.8823668956756592}, {"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": 59, "score": 0.8821674585342407}, {"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": 60, "score": 0.8821210861206055}, {"content": "Title: Influence of diabetes mellitus on the severity and fatality of SARS-CoV-2 (COVID-19) infection Content: AIM: To evaluate the influence of diabetes on the severity and fatality of severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2) infection. MATERIALS AND METHODS: The medical records of 66 hospitalized coronavirus disease 2019 (COVID-19) patients were collected and classified into non-severe (mild/moderate cases) and severe (severe/critical cases) groups. Logistic regression analysis was used to estimate the risk of severe COVID-19 (severe/critical infection). In addition, a meta-analysis including published studies reported the impact of diabetes on the severity and fatality of COVID-19. The current study was conducted using fixed effects models. RESULTS: There were 22 diabetes and 44 non-diabetes cases among the 66 hospitalized COVID-19 patients. Seven patients with diabetes (31.82%) were diagnosed as severe COVID-19 cases, which was significantly higher than that in the non-diabetes group (4/44, 9.09%, P = .033). After adjustment for age and gender, diabetes was significantly associated with COVID-19 severity (OR: 5.29, 95% CI: 1.07-26.02). A meta-analysis further confirmed the positive association between diabetes and COVID-19 severity (pooled OR = 2.58, 95% CI: 1.93-3.45). Moreover, the patients with diabetes infected with SARS-CoV-2 had a 2.95-fold higher risk of fatality compared with those patients without diabetes (95% CI: 1.93-4.53). CONCLUSIONS: Our findings provide new evidence that diabetes is associated with a higher risk of severity and fatality of COVID-19. Therefore, intensive monitoring and antidiabetic therapy should be considered in patients with diabetes with SARS-CoV-2 infection.", "qid": 24, "docid": "i8uwia3a", "rank": 61, "score": 0.8817360401153564}, {"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": 62, "score": 0.8813561201095581}, {"content": "Title: Is diabetes mellitus associated with mortality and severity of COVID-19? A meta-analysis Content: Abstract Background Many studies on COVID-19 have reported diabetes to be associated with severe disease and mortality, however, the data is conflicting. The objectives of this meta-analysis were to explore the relationship between diabetes and COVID-19 mortality and severity, and to determine the prevalence of diabetes in patients with COVID-19. Methods We searched the PubMed for case-control studies in English, published between Jan 1 and Apr 22, 2020, that had data on diabetes in patients with COVID-19. The frequency of diabetes was compared between patients with and without the composite endpoint of mortality or severity. Random effects model was used with odds ratio as the effect size. We also determined the pooled prevalence of diabetes in patients with COVID-19. Heterogeneity and publication bias were taken care by meta-regression, sub-group analyses, and trim and fill methods. Results We included 33 studies (16,003 patients) and found diabetes to be significantly associated with mortality of COVID-19 with a pooled odds ratio of 1.90 (95% CI: 1.37\u20132.64; p < 0.01). Diabetes was also associated with severe COVID-19 with a pooled odds ratio of 2.75 (95% CI: 2.09\u20133.62; p < 0.01). The combined corrected pooled odds ratio of mortality or severity was 2.16 (95% CI: 1.74\u20132.68; p < 0.01). The pooled prevalence of diabetes in patients with COVID-19 was 9.8% (95% CI: 8.7%\u201310.9%) (after adjusting for heterogeneity). Conclusions Diabetes in patients with COVID-19 is associated with a two-fold increase in mortality as well as severity of COVID-19, as compared to non-diabetics. Further studies on the pathogenic mechanisms and therapeutic implications need to be done.", "qid": 24, "docid": "ja9qu3p8", "rank": 63, "score": 0.8812500834465027}, {"content": "Title: CLINICAL CHARACTERISTICS OF 28 PATIENTS WITH DIABETES AND COVID-19 IN WUHAN, CHINA. Content: Objective: Previous studies on coronavirus disease 2019 (COVID-19) were based on information from the general population. We aimed to further clarify the clinical characteristics of diabetes with COVID-19. Methods: Twenty-eight patients with diabetes and COVID-19 were enrolled from January 29, 2020, to February 10, 2020, with a final follow-up on February 22, 2020. Epidemiologic, demographic, clinical, laboratory, treatment, and outcome data were analyzed. Results: The average age of the 28 patients was 68.6 \u00b1 9.0 years. Most (75%) patients were male. Only 39.3% of the patients had a clear exposure of COVID-19. Fever (92.9%), dry cough (82.1%), and fatigue (64.3%) were the most common symptoms, followed by dyspnea (57.1%), anorexia (57.1%), diarrhea (42.9%), expectoration (25.0%), and nausea (21.4%). Fourteen patients were admitted to the intensive care unit (ICU). The hemoglobin A1c level was similar between ICU and non-ICU patients. ICU patients had a higher respiratory rate, higher levels of random blood glucose, aspartate transaminase, bilirubin, creatine, N-terminal prohormone of brain natriuretic peptide, troponin I, D-dimers, procalcitonin, C-reactive protein, ferritin, interleukin (IL)-2R, IL-6, and IL-8 than non-ICU patients. Eleven of 14 ICU patients received noninvasive ventilation and 7 patients received invasive mechanical ventilation. Twelve patients died in the ICU group and no patients died in the nonICU group. Conclusion: ICU cases showed higher rates of organ failure and mortality than non-ICU cases. The poor outcomes of patients with diabetes and COVID-19 indicated that more supervision is required in these patients. (Endocr Pract. 2020;26:xxx-xxx).", "qid": 24, "docid": "flqtiz52", "rank": 64, "score": 0.8812294602394104}, {"content": "Title: Clinical Characteristics of 28 Patients with Diabetes and Covid-19 in Wuhan, China Content: Objective: Previous studies on coronavirus disease 2019 (COVID-19) were based on information from the general population. We aimed to further clarify the clinical characteristics of diabetes with COVID-19. Methods: Twenty-eight patients with diabetes and COVID-19 were enrolled from January 29, 2020, to February 10, 2020, with a final follow-up on February 22, 2020. Epidemiologic, demographic, clinical, laboratory, treatment, and outcome data were analyzed. Results: The average age of the 28 patients was 68.6 \u00b1 9.0 years. Most (75%) patients were male. Only 39.3% of the patients had a clear exposure of COVID-19. Fever (92.9%), dry cough (82.1%), and fatigue (64.3%) were the most common symptoms, followed by dyspnea (57.1%), anorexia (57.1%), diarrhea (42.9%), expectoration (25.0%), and nausea (21.4%). Fourteen patients were admitted to the intensive care unit (ICU). The hemoglobin A1c level was similar between ICU and non-ICU patients. ICU patients had a higher respiratory rate, higher levels of random blood glucose, aspartate transaminase, bilirubin, creatine, N-terminal prohormone of brain natriuretic peptide, troponin I, D-dimers, procalcitonin, C-reactive protein, ferritin, interleukin (IL)-2R, IL-6, and IL-8 than non-ICU patients. Eleven of 14 ICU patients received noninvasive ventilation and 7 patients received invasive mechanical ventilation. Twelve patients died in the ICU group and no patients died in the non-ICU group. Conclusion: ICU cases showed higher rates of organ failure and mortality than non-ICU cases. The poor outcomes of patients with diabetes and COVID-19 indicated that more supervision is required in these patients. Abbreviations: COVID-19 = coronavirus disease 2019; ICU = intensive care unit; MERS-CoV = middle East respiratory syndrome-related coronavirus; 2019- nCoV = 2019 novel coronavirus; NT-proBNP = N-terminal prohormone of brain natriuretic peptide; SARS-CoV = severe acute respiratory syndrome-related coronavirus.", "qid": 24, "docid": "hpsk5kn8", "rank": 65, "score": 0.8811647891998291}, {"content": "Title: Clinical Characteristics and Risk Factors for Mortality of COVID-19 Patients With Diabetes in Wuhan, China: A Two-Center, Retrospective Study Content: OBJECTIVE: Diabetes is common in COVID-19 patients and associated with unfavorable outcomes. We aimed to describe the characteristics and outcomes and to analyze the risk factors for in-hospital mortality of COVID-19 patients with diabetes. RESEARCH DESIGN AND METHODS: This two-center retrospective study was performed at two tertiary hospitals in Wuhan, China. Confirmed COVID-19 patients with diabetes (N = 153) who were discharged or died from 1 January 2020 to 8 March 2020 were identified. One sex- and age-matched COVID-19 patient without diabetes was randomly selected for each patient with diabetes. Demographic, clinical, and laboratory data were abstracted. Cox proportional hazards regression analyses were performed to identify the risk factors associated with the mortality in these patients. RESULTS: Of 1,561 COVID-19 patients, 153 (9.8%) had diabetes, with a median age of 64.0 (interquartile range 56.0-72.0) years. A higher proportion of intensive care unit admission (17.6% vs. 7.8%, P = 0.01) and more fatal cases (20.3% vs. 10.5%, P = 0.017) were identified in COVID-19 patients with diabetes than in the matched patients. Multivariable Cox regression analyses of these 306 patients showed that hypertension (hazard ratio [HR] 2.50, 95% CI 1.30-4.78), cardiovascular disease (HR 2.24, 95% CI 1.19-4.23), and chronic pulmonary disease (HR 2.51, 95% CI 1.07-5.90) were independently associated with in-hospital death. Diabetes (HR 1.58, 95% CI 0.84-2.99) was not statistically significantly associated with in-hospital death after adjustment. Among patients with diabetes, nonsurvivors were older (76.0 vs. 63.0 years), most were male (71.0% vs. 29.0%), and they were more likely to have underlying hypertension (83.9% vs. 50.0%) and cardiovascular disease (45.2% vs. 14.8%) (all P values <0.05). Age &#8805;70 years (HR 2.39, 95% CI 1.03-5.56) and hypertension (HR 3.10, 95% CI 1.14-8.44) were independent risk factors for in-hospital death of patients with diabetes. CONCLUSIONS: COVID-19 patients with diabetes had worse outcomes compared with the sex- and age-matched patients without diabetes. Older age and comorbid hypertension independently contributed to in-hospital death of patients with diabetes.", "qid": 24, "docid": "1pwlctxb", "rank": 66, "score": 0.8807768821716309}, {"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": 67, "score": 0.8807001113891602}, {"content": "Title: The COVID-19 Pandemic during the Time of the Diabetes Pandemic: Likely Fraternal Twins? Content: An altered immune response to pathogens has been suggested to explain increased susceptibility to infectious diseases in patients with diabetes. Recent evidence has documented several immunometabolic pathways in patients with diabetes directly related to the COVID-19 infection. This also seems to be the case for prediabetic subjects with proinflammatory insulin resistance syndrome accompanied with prothrombotic hyperinsulinemic and dysglycemic states. Patients with frank hyperglycemia, dysglycemia and/or hyperinsulinemia develop systemic immunometabolic inflammation with higher levels of circulating cytokines. This deleterious scenario has been proposed as the underlying mechanism enhancing a cytokine storm-like hyperinflammatory state in diabetics infected with severe COVID-19 triggering multi-organ failure. Compared with moderately affected COVID-19 patients, diabetes was found to be highly prevalent among severely affected patients suggesting that this non-communicable disease should be considered as a risk factor for adverse outcomes. The COVID-19 pandemic mirrors with the diabetes pandemic in many pathobiological aspects. Our interest is to emphasize the ties between the immunoinflammatory mechanisms that underlie the morbidity and lethality when COVID-19 meets diabetes. This review brings attention to two pathologies of highly complex, multifactorial, developmental and environmentally dependent manifestations of critical importance to human survival. Extreme caution should be taken with diabetics with suspected symptoms of COVID-19 infection.", "qid": 24, "docid": "pruvl2l4", "rank": 68, "score": 0.8806067705154419}, {"content": "Title: SGLT2 inhibition and COVID-19: The road not taken Content: The COVID-19 pandemic, caused by SARS-CoV-2, is an immense challenge for global healthcare. Diabetes mellitus, hypertension and obesity have been shown to portend poor prognosis in COVID-19 despite no greater susceptibility to the infection (1). Chronic hypertension is commonly associated with vasculopathy which can predispose to severe infection. In patients with diabetes, severity is attributable to impaired innate, adaptive immunity, upregulation of ACE2 (entry receptor for SARS-CoV2) by acute hyperglycemia and diabetic vasculopathy. The background of chronic low grade inflammation characterised by increased levels of IL-6 and CRP in diabetes and obesity can also lead to an enhanced 'cytokine storm' in COVID-19 (2). ACE2 expression on endothelial cells has been reported to cause viral mediated endothelitis and precipitate vascular dysfunction manifesting as acute respiratory distress syndrome as well as myocarditis, heart failure, arrhythmias, myocardial infarction and renal failure (3). In patients with pre-existing comorbidities like hypertension, diabetes, obesity and chronic kidney disease, this new-onset organ dysfunction can have deleterious additive effects.", "qid": 24, "docid": "ojoqsdn1", "rank": 69, "score": 0.8805322647094727}, {"content": "Title: SGLT2 inhibition and COVID-19: The road not taken. Content: The COVID-19 pandemic, caused by SARS-CoV-2, is an immense challenge for global healthcare. Diabetes mellitus, hypertension and obesity have been shown to portend poor prognosis in COVID-19 despite no greater susceptibility to the infection (1). Chronic hypertension is commonly associated with vasculopathy which can predispose to severe infection. In patients with diabetes, severity is attributable to impaired innate, adaptive immunity, upregulation of ACE2 (entry receptor for SARS-CoV2) by acute hyperglycemia and diabetic vasculopathy. The background of chronic low grade inflammation characterised by increased levels of IL-6 and CRP in diabetes and obesity can also lead to an enhanced 'cytokine storm' in COVID-19 (2). ACE2 expression on endothelial cells has been reported to cause viral mediated endothelitis and precipitate vascular dysfunction manifesting as acute respiratory distress syndrome as well as myocarditis, heart failure, arrhythmias, myocardial infarction and renal failure (3). In patients with pre-existing comorbidities like hypertension, diabetes, obesity and chronic kidney disease, this new-onset organ dysfunction can have deleterious additive effects.", "qid": 24, "docid": "md9dbxb5", "rank": 70, "score": 0.8805322647094727}, {"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": 71, "score": 0.8803544044494629}, {"content": "Title: COVID-19 and Diabetes: Knowledge in Progress Content: Abstract Aims We aimed to briefly review the general characteristics of the novel coronavirus (SARS-CoV-2) and provide a better understanding of the coronavirus disease (COVID-19) in people with diabetes, and its management. Methods We searched for articles in PubMed and Google Scholar databases till 02 April 2020, with the following keywords: \u201cSARS-CoV-2\u201d, \u201cCOVID-19\u201d, \u201cinfection\u201d, \u201cpathogenesis\u201d, \u201cincubation period\u201d, \u201ctransmission\u201d, \u201cclinical features\u201d, \u201cdiagnosis\u201d, \u201ctreatment\u201d, \u201cdiabetes\u201d, with interposition of the Boolean operator \u201cAND\u201d. Results The clinical spectrum of COVID-19 is heterogeneous, ranging from mild flu-like symptoms to acute respiratory distress syndrome, multiple organ failure and death. Older age, diabetes and other comorbidities are reported as significant predictors of morbidity and mortality. Chronic inflammation, increased coagulation activity, immune response impairment, and potential direct pancreatic damage by SARS-CoV-2 might be among the underlying mechanisms of the association between diabetes and COVID-19. No conclusive evidence exists to support the discontinuation of angiotensin-converting enzyme inhibitors (ACEI) or angiotensin receptor blockers because of COVID-19 in people with diabetes. Caution should be taken to potential hypoglycemic events with the use of chloroquine in these subjects. Patient tailored therapeutic strategies, rigorous glucose monitoring and careful consideration of drug interactions might reduce adverse outcomes. Conclusions Suggestions are made on the possible pathological mechanisms of the relationship between diabetes and COVID-19, and its management. No definite conclusions can be made based on current limited evidence. Further research regarding this relationship and its clinical management is warranted.", "qid": 24, "docid": "4cx6fe5v", "rank": 72, "score": 0.8802635073661804}, {"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": 73, "score": 0.8793836832046509}, {"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": 74, "score": 0.8793133497238159}, {"content": "Title: Association of diabetes and hypertension with disease severity in covid-19 patients: a systematic literature review and exploratory meta-analysis Content: Abstract Aim The novel coronavirus infection (COVID-19), now a worldwide public health concern is associated with varied fatality. Patients with chronic underlying conditions like diabetes and hypertension have shown worst outcomes. The understanding of the association might be helpful in early vigilant monitoring and better management of COVID-19 patients at high risk. The aim of the meta-analysis was to assess the association of diabetes and hypertension with severity of disease. Methods A literature search was conducted using the databases PubMed and Cochrane until March 31, 2020. Seven studies were included in the meta- analysis, including 2018 CIVID-19 patients. Results Diabetes was lower in the survivors (OR: 0.56; 95%CI: 0.35-0.90; p=0.017; I2 : 0.0%) and non-severe (OR: 1.66; 95%CI: 1.20-2.30; p=0.002; I2 : 0.0%) patients. No association of diabetes was found with ICU care. Hypertension was positively associated with death (OR: 0.49; 95%CI: 0.34-0.73; p=0.000; I2 : 0.0%), ICU care (OR: 0.42; 95%CI: 0.22-0.81; p=0.009; I2 : 0.0%) and severity (OR: 2.69; 95%CI: 1.27-5.73; p=0.01; I2 : 52.4%). Conclusions Our findings suggest that diabetes and hypertension have a negative effect on health status of COVID-19 patients. However, large prevalence studies demonstrating the consequences of comorbid diabetes and hypertension are urgently needed to understand the magnitude of these vexatious comorbidities.", "qid": 24, "docid": "9qq049qb", "rank": 75, "score": 0.8792819976806641}, {"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": 76, "score": 0.8792336583137512}, {"content": "Title: Clinical Characteristics and Risk Factors for Mortality of COVID-19 Patients With Diabetes in Wuhan, China: A Two-Center, Retrospective Study. Content: OBJECTIVE Diabetes is common in COVID-19 patients and associated with unfavorable outcomes. We aimed to describe the characteristics and outcomes and to analyze the risk factors for in-hospital mortality of COVID-19 patients with diabetes. RESEARCH DESIGN AND METHODS This two-center retrospective study was performed at two tertiary hospitals in Wuhan, China. Confirmed COVID-19 patients with diabetes (N = 153) who were discharged or died from 1 January 2020 to 8 March 2020 were identified. One sex- and age-matched COVID-19 patient without diabetes was randomly selected for each patient with diabetes. Demographic, clinical, and laboratory data were abstracted. Cox proportional hazards regression analyses were performed to identify the risk factors associated with the mortality in these patients. RESULTS Of 1,561 COVID-19 patients, 153 (9.8%) had diabetes, with a median age of 64.0 (interquartile range 56.0-72.0) years. A higher proportion of intensive care unit admission (17.6% vs. 7.8%, P = 0.01) and more fatal cases (20.3% vs. 10.5%, P = 0.017) were identified in COVID-19 patients with diabetes than in the matched patients. Multivariable Cox regression analyses of these 306 patients showed that hypertension (hazard ratio [HR] 2.50, 95% CI 1.30-4.78), cardiovascular disease (HR 2.24, 95% CI 1.19-4.23), and chronic pulmonary disease (HR 2.51, 95% CI 1.07-5.90) were independently associated with in-hospital death. Diabetes (HR 1.58, 95% CI 0.84-2.99) was not statistically significantly associated with in-hospital death after adjustment. Among patients with diabetes, nonsurvivors were older (76.0 vs. 63.0 years), most were male (71.0% vs. 29.0%), and were more likely to have underlying hypertension (83.9% vs. 50.0%) and cardiovascular disease (45.2% vs. 14.8%) (all P values <0.05). Age \u226570 years (HR 2.39, 95% CI 1.03-5.56) and hypertension (HR 3.10, 95% CI 1.14-8.44) were independent risk factors for in-hospital death of patients with diabetes. CONCLUSIONS COVID-19 patients with diabetes had worse outcomes compared with the sex- and age-matched patients without diabetes. Older age and comorbid hypertension independently contributed to in-hospital death of patients with diabetes.", "qid": 24, "docid": "4fqsx5y5", "rank": 77, "score": 0.8786782622337341}, {"content": "Title: Diabetes as a risk factor for greater COVID-19 severity and in-hospital death: A meta-analysis of observational studies Content: AIMS: To estimate the prevalence of established diabetes and its association with the clinical severity and in-hospital mortality associated with COVID-19. DATA SYNTHESIS: We systematically searched PubMed, Scopus and Web of Science, from 1st January 2020 to 15th May 2020, for observational studies of patients admitted to hospital with COVID-19. Meta-analysis was performed using random-effects modeling. A total of 83 eligible studies with 78,874 hospitalized patients with laboratory-confirmed COVID-19 were included. The pooled prevalence of established diabetes was 14.34% (95% CI 12.62-16.06%). However, the prevalence of diabetes was higher in non-Asian vs. Asian countries (23.34% [95% CI 16.40-30.28] vs. 11.06% [95% CI 9.73-12.39]), and in patients aged &#8805;60 years vs. those aged <60 years (23.30% [95% CI 19.65-26.94] vs. 8.79% [95% CI 7.56-10.02]). Pre-existing diabetes was associated with an approximate twofold higher risk of having severe/critical COVID-19 illness (n = 22 studies; random-effects odds ratio 2.10, 95% CI 1.71-2.57; I2 = 41.5%) and ~threefold increased risk of in-hospital mortality (n = 15 studies; random-effects odds ratio 2.68, 95% CI 2.09-3.44; I2 = 46.7%). Funnel plots and Egger's tests did not reveal any significant publication bias. CONCLUSIONS: Pre-existing diabetes is significantly associated with greater risk of severe/critical illness and in-hospital mortality in patients admitted to hospital with COVID-19.", "qid": 24, "docid": "x22nems9", "rank": 78, "score": 0.8756679892539978}, {"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": 79, "score": 0.8756192922592163}, {"content": "Title: Diabetes Epidemiology in the COVID-19 Pandemic Content: Diabetes has been identified as an important risk factor for mortality and rates of progression to acute respiratory distress syndrome (ARDS) in hospitalized patients with coronavirus disease 2019 (COVID-19). However, many recent reports on this topic reflect hurried approaches and have lacked careful epidemiologic design, conduct, and analysis. Features of prior studies have posed problems for our understanding of the true contribution of diabetes and other underlying comorbidities to prognosis in COVID-19. In this Perspective, we discuss some of the challenges of interpreting the current literature on diabetes and COVID-19 and discuss opportunities for future epidemiologic studies. We contend that the COVID-19 pandemic is a defining moment for the field of epidemiology and that diabetes epidemiology should play a significant role.", "qid": 24, "docid": "vhmga8rh", "rank": 80, "score": 0.8746999502182007}, {"content": "Title: Diabetes Epidemiology in the COVID-19 Pandemic. Content: Diabetes has been identified as an important risk factor for mortality and rates of progression to acute respiratory distress syndrome (ARDS) in hospitalized patients with coronavirus disease 2019 (COVID-19). However, many recent reports on this topic reflect hurried approaches and have lacked careful epidemiologic design, conduct, and analysis. Features of prior studies have posed problems for our understanding of the true contribution of diabetes and other underlying comorbidities to prognosis in COVID-19. In this Perspective, we discuss some of the challenges of interpreting the current literature on diabetes and COVID-19 and discuss opportunities for future epidemiologic studies. We contend that the COVID-19 pandemic is a defining moment for the field of epidemiology and that diabetes epidemiology should play a significant role.", "qid": 24, "docid": "ina400b0", "rank": 81, "score": 0.8746999502182007}, {"content": "Title: Dissecting the Interaction between Coronavirus Disease 2019 and Diabetes Mellitus Content: Coronavirus disease 2019 (COVID-19) is a global pandemic that is caused by a novel coronavirus, severe acute respiratory syndrome-coronavirus-2 (SARS-CoV-2). Data from several countries have demonstrated higher morbidity and mortality among individuals with chronic metabolic diseases such as diabetes mellitus (DM). In this review, we explore the contributing factors for poorer prognosis in these individuals. As a significant proportion of patients with COVID-19 also have DM, this adds another layer of complexity to their management. We explore potential interactions between anti-diabetic medications and renin-angiotensin-aldosterone-system inhibitors with COVID-19. Suggested recommendations for the use of anti-diabetic medications in COVID-19 patients with DM are provided. We also review pertinent clinical considerations in the management of diabetic ketoacidosis in the COVID-19 patient. In addition, we aim to increase the awareness of clinicians to the metabolic effects of promising drug therapies for COVID-19. Finally, we highlight the importance of timely vaccinations for patients with DM.", "qid": 24, "docid": "09qp0sts", "rank": 82, "score": 0.8735590577125549}, {"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": 83, "score": 0.8733668923377991}, {"content": "Title: Diabetes and covid-19: more than the sum of two morbidities Content: The coronavirus disease 2019 (covid-19) pandemic has caused a public health emergency worldwide. Risk, severity and mortality of the disease have been associated with non-communicable chronic diseases, such as diabetes mellitus. Accumulated evidence has caused great concern in countries with high prevalence of this morbidity, such as Brazil. This text shows the picture of diabetes in Brazil, followed by epidemiological data and explanatory hypothesis for the association between diabetes and covid-19. We emphasized how the burden of these two morbidities in a middle-income country has aggravated this pandemic scenario. The comprehension of this association and biological plausibility may help face this pandemic and future challenges.", "qid": 24, "docid": "lxjgysp9", "rank": 84, "score": 0.8733057975769043}, {"content": "Title: Endocrine and metabolic link to coronavirus infection Content: Type 2 diabetes mellitus and hypertension are the most common comorbidities in patients with coronavirus infections. Emerging evidence demonstrates an important direct metabolic and endocrine mechanistic link to the viral disease process. Clinicians need to ensure early and thorough metabolic control for all patients affected by COVID-19.", "qid": 24, "docid": "puu8wib8", "rank": 85, "score": 0.8732958436012268}, {"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": 86, "score": 0.8727774024009705}, {"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": 87, "score": 0.8722161054611206}, {"content": "Title: COVID\u201019 and diabetes: Is there enough evidence? Content: The pandemic of COVID\u201019, a disease caused by a novel coronavirus SARS\u2010CoV\u20102, is associated with significant morbidity and mortality. Recent data showed that hypertension, diabetes mellitus, cardiovascular diseases, and chronic obstructive pulmonary disease were the most prevalent comorbidities in COVID\u201019 patients. Additionally, data indicate that hypertension, diabetes, and cardiovascular diseases are important risk factors for progression and unfavorable outcome in COVID\u201019 patients. There is only limited amount of data regarding follow\u2010up of these patients, and they provided conflicting results. The main limitation is a small number of participants and particularly those who experienced primary composite outcome (admission in intensive care unit, use of mechanical ventilation, or death). Additionally, the limited number of patients was essential obstacle for performing analysis that would include many confounding factors such as advanced age, smoking status, and obesity and potentially change conclusion. So far, there is no study that demonstrated independent predictive value of diabetes on mortality in COVID\u201019 patients, but there are many speculations about the association between diabetes and susceptibility to novel coronavirus, as well as its impact on progression and prognosis of COVID\u201019. The aim of this review article was to summarize the current knowledge about the relationship between diabetes and COVID\u201019 and its role in outcome in these patients.", "qid": 24, "docid": "sntawlnf", "rank": 88, "score": 0.8720687627792358}, {"content": "Title: Diabetes and Novel Coronavirus Infection: Implications for Treatment Content: The novel coronavirus (severe acute respiratory syndrome coronavirus 2 [SARS-CoV-2]) outbreak originating in December 2019 has resulted in a worldwide pandemic affecting millions across almost 200 countries. People with diabetes appear to develop more severe forms of the disease and to require intensive care unit support and/or mechanical ventilation more frequently than those with other underlying medical conditions. The mortality rate among people with diabetes is also significantly higher than that among people without diabetes. A diagnosis of diabetes is often an indicator of poor underlying metabolic health, and frequently people with diabetes have multiple risk factors for severe coronavirus disease 2019 (COVID-19), including cardiovascular and renal disease. In this review, we discuss the potential biological mechanisms by which SARS-CoV-2 may interact with disease processes implicated in diabetes and discuss how treatments commonly used for people with diabetes may affect COVID-19 severity and progression. There is currently a lack of evidence from human studies, and further trials in this area will prove useful to further expand our understanding of this rapidly developing disease process to improve outcomes for this high-risk group of patients. ELECTRONIC SUPPLEMENTARY MATERIAL: The online version of this article (10.1007/s13300-020-00858-2) contains supplementary material, which is available to authorized users.", "qid": 24, "docid": "8t7rrgmp", "rank": 89, "score": 0.8707709908485413}, {"content": "Title: Risk and predictors of in-hospital mortality from COVID-19 in patients with diabetes and cardiovascular disease Content: BACKGROUND: Diabetes mellitus (DM) and cardiovascular disease (CVD) are present in a large number of patients with novel Coronavirus disease 2019 (COVID-19). We aimed to determine the risk and predictors of in-hospital mortality from COVID-19 in patients with DM and CVD. METHODS: This retrospective cohort study included hospitalized patients aged \u2265 18 years with confirmed COVID-19 in Alborz province, Iran, from 20 February 2020 to 25 March 2020. Data on demographic, clinical and outcome (in-hospital mortality) data were obtained from electronic medical records. Self-reported comorbidities were classified into the following groups: \u201cDM\u201d (having DM with or without other comorbidities), \u201conly DM\u201d (having DM without other comorbidities), \u201cCVD\u201d (having CVD with or without other comorbidities), \u201conly CVD\u201d (having CVD without other comorbidities), and \u201chaving any comorbidity\u201d. Multivariate logistic regression models were fitted to quantify the risk and predictors of in-hospital mortality from COVID-19 in patients with these comorbidities. RESULTS: Among 2957 patients with COVID-19, 2656 were discharged as cured, and 301 died. In multivariate model, DM (OR: 1.62 (95% CI 1.14\u20132.30)) and only DM (1.69 (1.05\u20132.74)) increased the risk of death from COVID-19; but, both CVD and only CVD showed non-significant associations (p > 0.05). Moreover, \u201chaving any comorbidities\u201d increased the risk of in-hospital mortality from COVID-19 (OR: 2.66 (95% CI 2.09\u20133.40)). Significant predictors of mortality from COVID-19 in patients with DM were lymphocyte count, creatinine and C-reactive protein (CRP) level (all P-values < 0.05). CONCLUSIONS: Our findings suggest that diabetic patients have an increased risk of in-hospital mortality following COVID-19; also, lymphocyte count, creatinine and CRP concentrations could be considered as significant predictors for the death of COVID-19 in these patients.", "qid": 24, "docid": "5o1jzwjq", "rank": 90, "score": 0.8700419664382935}, {"content": "Title: Clinical characteristics and outcomes of patients with severe covid-19 with diabetes Content: OBJECTIVE: This study explores the clinical characteristics of patients with diabetes with severe covid-19, and the association of diabetes with survival duration in patients with severe covid-19. RESEARCH DESIGN AND METHODS: In this single-center, retrospective, observational study, the clinical and laboratory characteristics of 193 patients with severe covid-19 were collected. 48 patients with severe covid-19 had diabetes, and 145 patients (ie, the controls) did not have diabetes. A severe case was defined as including at least one of the following criteria: (1) Respiratory rate >30/min. (2) Oxygen saturation \u226493%. (3) PaO(2)/FiO(2)\u2264300 mm Hg. (4) Patients, either with shock or respiratory failure, requiring mechanical ventilation, or combined with other organ failure, requiring admission to intensive care unit (ICU). RESULTS: Of 193 patients with severe covid-19, 48 (24.9%) had diabetes. Compared with patients with severe covid-19 without diabetes, patients with diabetes were older, susceptible to receiving mechanical ventilation and admission to ICU, and had higher mortality. In addition, patients with severe covid-19 with diabetes had higher levels of leukocyte count, neutrophil count, high-sensitivity C reaction protein, procalcitonin, ferritin, interleukin (IL) 2 receptor, IL-6, IL-8, tumor necrosis factor \u03b1, D-dimer, fibrinogen, lactic dehydrogenase and N-terminal pro-brain natriuretic peptide. Among patients with severe covid-19 with diabetes, more non-survivors were men (30 (76.9%) vs 9 (23.1%)). Non-survivors had severe inflammatory response, and cardiac, hepatic, renal and coagulation impairment. Finally, the Kaplan-Meier survival curve showed a trend towards poorer survival in patients with severe covid-19 with diabetes than patients without diabetes. The HR was 1.53 (95% CI 1.02 to 2.30; p=0.041) after adjustment for age, sex, hypertension, cardiovascular disease and cerebrovascular disease by Cox regression. The median survival durations from hospital admission in patients with severe covid-19 with and without diabetes were 10 days and 18 days, respectively. CONCLUSION: The mortality rate in patients with severe covid-19 with diabetes is considerable. Diabetes may lead to an increase in the risk of death.", "qid": 24, "docid": "wtov0a4f", "rank": 91, "score": 0.8699840307235718}, {"content": "Title: The clinical characteristics and outcomes of patients with diabetes and secondary hyperglycaemia with coronavirus disease 2019: A single-centre, retrospective, observational study in Wuhan Content: AIM: To explore whether coronavirus disease 2019 (COVID-19) patients with diabetes and secondary hyperglycaemia have different clinical characteristics and prognoses than those without significantly abnormal glucose metabolism. MATERIALS AND METHODS: We retrospectively analysed 166 COVID-19 patients at Tongji Hospital (Wuhan) from 8 February to 21 March 2020. Clinical characteristics and outcomes (as of 4 April 2020) were compared among control (group 1), secondary hyperglycaemia (group 2: no diabetes history, fasting plasma glucose levels of &#8805;7.0 mmol/L once and HbA1c values <6.5%) and patients with diabetes (group 3). RESULTS: Compared with group 1, groups 2 and 3 had higher rates of leukocytosis, neutrophilia, lymphocytopenia, eosinopenia and levels of hypersensitive C-reactive protein, ferritin and d-dimer (P < .05 for all). Group 2 patients had higher levels of lactate dehydrogenase, prevalence of liver dysfunction and increased interleukin-8 (IL-8) than those in group 1, and a higher prevalence of increased IL-8 was found in group 2 than in group 3 (P < .05 for all). The proportions of critical patients in groups 2 and 3 were significantly higher compared with group 1 (38.1%, 32.8% vs. 9.5%, P < .05 for both). Groups 2 and 3 had significantly longer hospital stays than group 1, which was nearly 1 week longer. The composite outcomes risks were 5.47 (1.56-19.82) and 2.61 (0.86-7.88) times greater in groups 2 and 3 than in group 1. CONCLUSIONS: Hyperglycaemia in both diabetes and secondary hyperglycaemia patients with COVID-19 may indicate poor prognoses. There were differences between patients with secondary hyperglycaemia and those with diabetes. We recommend that clinicians pay more attention to the blood glucose status of COVID-19 patients, even those not diagnosed with diabetes before admission.", "qid": 24, "docid": "269kzfd7", "rank": 92, "score": 0.8693020343780518}, {"content": "Title: Influence of diabetes mellitus on the severity and fatality of SARS\u2010CoV\u20102 infection Content: AIMS: Diabetes mellitus is one of the most common comorbidities in Coronavirus disease 2019 (COVID\u201019) patients. The objective of this study was to evaluate the influences of diabetes mellitus on the severity and fatality of SARS\u2010CoV\u20102 infection. MATERIALS AND METHODS: Medical records of 66 hospitalized COVID\u201019 patients were collected and classified into non\u2010severe (mild/moderate cases) and severe (severe/critical cases) groups, respectively. Logistic regression analysis was used to estimate the risk of severe COVID\u201019 (severe/critical infection). In addition, a meta\u2010analysis including published studies reported the impacts of diabetes mellitus on severity and fatality of COVID\u201019, and our current study was conducted using fixed\u2010effects models. RESULTS: There were 22 diabetic and 44 non\u2010diabetic cases among the 66 hospitalized COVID\u201019 patients. As the results shown, seven cases (31.82%) were diagnosed as severe COVID\u201019 in diabetic patients, which was significantly higher than that in non\u2010diabetic group (4/44, 9.09%, P = 0.033). After adjustment for age and gender, the results showed that diabetes mellitus was significantly associated with COVID\u201019 severity (OR: 5.29, 95% CI: 1.07\u201326.02). A meta\u2010analysis further confirmed the positive association between diabetes mellitus and COVID\u201019 severity (pooled OR = 2.58, 95% CI: 1.93\u20133.45). Moreover, the diabetic patients infected with SARS\u2010CoV\u20102 showed to have 2.95\u2010fold higher risk of fatality compared to those patients without diabetes mellitus (95% CI: 1.93\u20134.53). CONCLUSIONS: Our findings provide new evidences that diabetes mellitus is associated with a higher risk of severity and fatality of COVID\u201019. Therefore, intensive monitoring and antidiabetic therapy should be considered in diabetic patients with SARS\u2010CoV\u20102 infection. This article is protected by copyright. All rights reserved.", "qid": 24, "docid": "bq7460ca", "rank": 93, "score": 0.8692213296890259}, {"content": "Title: SARS-CoV-2 and DPP4 inhibition: Is it time to pray for Janus Bifrons? Content: Diabetes could be a risk factor for severity and mortality in patients with coronavirus disease 2019 COVID-19. It has been hypothesized that DPP4 inhibition, a therapy currently available for type 2 diabetes, might represent a target for decreasing the risk of the acute respiratory complications of the COVID-19 infection but (1) lack of demonstration of SARS-CoV2 binding to DPP4 (2) possible protective role of sDPP4 in Middle East respiratory Syndrome (MERS-CoV) (3) demonstrated inhibition and downregulation of DPP4 by HIV1 and MERS-CoV and (4) not exclusive role of the receptor binding in tropism of the Coronavirus family, support that DPP4 inhibition at present doesn't represent a plausible approach to mitigate COVID-19.", "qid": 24, "docid": "5k61tlva", "rank": 94, "score": 0.8688828945159912}, {"content": "Title: Cardiovascular complications in COVID-19 Content: BACKGROUND: The coronavirus disease of 2019 (COVID-19) is caused by the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). While systemic inflammation and pulmonary complications can result in significant morbidity and mortality, cardiovascular complications may also occur. OBJECTIVE: This brief report evaluates cardiovascular complications in the setting of COVID-19 infection. DISCUSSION: The current COVID-19 pandemic has resulted in over one million infected worldwide and thousands of death. The virus binds and enters through angiotensin-converting enzyme 2 (ACE2). COVID-19 can result in systemic inflammation, multiorgan dysfunction, and critical illness. The cardiovascular system is also affected, with complications including myocardial injury, myocarditis, acute myocardial infarction, heart failure, dysrhythmias, and venous thromboembolic events. Current therapies for COVID-19 may interact with cardiovascular medications. CONCLUSIONS: Emergency clinicians should be aware of these cardiovascular complications when evaluating and managing the patient with COVID-19.", "qid": 24, "docid": "hl225efn", "rank": 95, "score": 0.8685717582702637}, {"content": "Title: Cardiovascular manifestations and treatment considerations in covid-19 Content: Since its recognition in December 2019, covid-19 has rapidly spread globally causing a pandemic. Pre-existing comorbidities such as hypertension, diabetes, and cardiovascular disease are associated with a greater severity and higher fatality rate of covid-19. Furthermore, covid-19 contributes to cardiovascular complications, including acute myocardial injury as a result of acute coronary syndrome, myocarditis, stress-cardiomyopathy, arrhythmias, cardiogenic shock, and cardiac arrest. The cardiovascular interactions of covid-19 have similarities to that of severe acute respiratory syndrome, Middle East respiratory syndrome and influenza. Specific cardiovascular considerations are also necessary in supportive treatment with anticoagulation, the continued use of renin-angiotensin-aldosterone system inhibitors, arrhythmia monitoring, immunosuppression or modulation, and mechanical circulatory support.", "qid": 24, "docid": "873txs85", "rank": 96, "score": 0.8685077428817749}, {"content": "Title: Clinical characteristics and outcomes of patients with severe covid-19 with diabetes Content: OBJECTIVE: This study explores the clinical characteristics of patients with diabetes with severe covid-19, and the association of diabetes with survival duration in patients with severe covid-19. RESEARCH DESIGN AND METHODS: In this single-center, retrospective, observational study, the clinical and laboratory characteristics of 193 patients with severe covid-19 were collected. 48 patients with severe covid-19 had diabetes, and 145 patients (ie, the controls) did not have diabetes. A severe case was defined as including at least one of the following criteria: (1) Respiratory rate >30/min. (2) Oxygen saturation &#8804;93%. (3) PaO2/FiO2&#8804;300 mm Hg. (4) Patients, either with shock or respiratory failure, requiring mechanical ventilation, or combined with other organ failure, requiring admission to intensive care unit (ICU). RESULTS: Of 193 patients with severe covid-19, 48 (24.9%) had diabetes. Compared with patients with severe covid-19 without diabetes, patients with diabetes were older, susceptible to receiving mechanical ventilation and admission to ICU, and had higher mortality. In addition, patients with severe covid-19 with diabetes had higher levels of leukocyte count, neutrophil count, high-sensitivity C reaction protein, procalcitonin, ferritin, interleukin (IL) 2 receptor, IL-6, IL-8, tumor necrosis factor &#945;, D-dimer, fibrinogen, lactic dehydrogenase and N-terminal pro-brain natriuretic peptide. Among patients with severe covid-19 with diabetes, more non-survivors were men (30 (76.9%) vs 9 (23.1%)). Non-survivors had severe inflammatory response, and cardiac, hepatic, renal and coagulation impairment. Finally, the Kaplan-Meier survival curve showed a trend towards poorer survival in patients with severe covid-19 with diabetes than patients without diabetes. The HR was 1.53 (95% CI 1.02 to 2.30; p=0.041) after adjustment for age, sex, hypertension, cardiovascular disease and cerebrovascular disease by Cox regression. The median survival durations from hospital admission in patients with severe covid-19 with and without diabetes were 10 days and 18 days, respectively. CONCLUSION: The mortality rate in patients with severe covid-19 with diabetes is considerable. Diabetes may lead to an increase in the risk of death.", "qid": 24, "docid": "lf88bwh2", "rank": 97, "score": 0.8679479360580444}, {"content": "Title: Diabetes as a risk factor for greater COVID-19 severity and in-hospital death: a meta-analysis of observational studies Content: Abstract Aims To estimate the prevalence of established diabetes and its association with the clinical severity and in-hospital mortality associated with COVID-19. Data synthesis We systematically searched PubMed, Scopus and Web of Science, from 1st January 2020 to 15th May 2020, for observational studies of patients admitted to hospital with COVID-19. Meta-analysis was performed using random-effects modeling. A total of 83 eligible studies with 78,874 hospitalized patients with laboratory-confirmed COVID-19 were included. The pooled prevalence of established diabetes was 14.34% (95% CI 12.62-16.06%). However, the prevalence of diabetes was higher in non-Asian vs. Asian countries (23.34% [95% CI 16.40-30.28] vs. 11.06% [95% CI 9.73-12.39]), and in patients aged \u226560 years vs. those aged <60 years (23.30% [95% CI 19.65-26.94] vs. 8.79% [95% CI 7.56-10.02]). Pre-existing diabetes was associated with an approximate twofold higher risk of having severe/critical COVID-19 illness (n=22 studies; random-effects odds ratio 2.10, 95% CI 1.71-2.57; I 2 =41.5%) and \u223cthreefold increased risk of in-hospital mortality (n=15 studies; random-effects odds ratio 2.68, 95% CI 2.09-3.44; I 2 =46.7%). Funnel plots and Egger\u2019s tests did not reveal any significant publication bias. Conclusions Pre-existing diabetes is significantly associated with greater risk of severe/critical illness and in-hospital mortality in patients admitted to hospital with COVID-19.", "qid": 24, "docid": "rhojc8hx", "rank": 98, "score": 0.8678797483444214}, {"content": "Title: Does glycemic control rescue type 2 diabetes patients from COVID-19-related deaths? Content: COVID-19 patients with diabetes are reported to have higher mortality compared with non-diabetic COVID-19 patients. However, recent investigations showed the importance of better glycemic control among diabetes patients to avoid death from COVID-19.", "qid": 24, "docid": "wu1izy9r", "rank": 99, "score": 0.8678553700447083}, {"content": "Title: How do we recover from COVID-19? Helping diabetes teams foresee and prepare for the psychological harms Content: The scale of the COVID-19 pandemic is entirely unprecedented. However, as depicted in Fig. 1, evidence from previous large-scale disasters indicates that following a first wave of admissions and deaths from COVID-19, there are likely to be subsequent waves of people with acute care needs worsened by delayed hospital treatment, and people with long-term conditions whose routine care has been disrupted [1]. People with diabetes are likely to constitute a large proportion of those with acute second- and third-wave care needs, and in many cases, management of their condition may also have been negatively affected by lockdown.", "qid": 24, "docid": "q79r4dbl", "rank": 100, "score": 0.867311954498291}]}
{"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. 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": 1, "score": 0.8794523477554321}, {"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": 2, "score": 0.8785663843154907}, {"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": 3, "score": 0.8621311187744141}, {"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": 4, "score": 0.8620628118515015}, {"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": 5, "score": 0.8620628118515015}, {"content": "Title: [Clinical analysis of 150 cases of 2019 novel coronavirus infection in Nanyang City, Henan Province] Content: Objective: To analyze the epidemiological characteristics and clinical features of the patients with 2019-nCoV infection in Nanyang City, so as to provide evidence for clinical diagnosis and treatment. Methods: The epidemiology, clinical symptoms, atory and radiologic data of 150 patients with 2019-nCoV infection admitted to the designated hospitals in Nanyang City from January 24,2020 to February 16, 2020 were retrospectively analyzed. Results: The 150 patients with 2019 nCov infection consisted of 67 men and 83 women, and the median age was (45\u00b116) years; 69 of them were the first generation case,60 of them were the second generation case, 6 of them were the third generation case,the median incubation period of the first generation case was (5.4\u00b12.2) days, and the second generation case was (6.7\u00b13.1) days, and the first-generation cases are the majority in severe patients (69%) . The most common basic disease was hypertension (13 cases, 9%), diabetes (9 cases, 6%), and the most common symptom is fever(142 cases, 95%, 63% showed moderate fever) , cough and sputum(108 cases,72%), fatigue(23 cases,15%), anorexia(20 cases, 13%), headache, diarrhea, muscle soreness, sore throat as the first symptoms. The average time from onset of symptoms to consultation was (4.2\u00b12.2) days for all patients. The changes in peripheral blood cells were mainly lymphonpenia (83 cases, 55%) and eosinophilia (95 cases, 63%), The lymphocyte count of the severe and critically ill patients was more significantly reduced, and some patients had increased myocardial enzymes, mainly LDH (47 cases, 31%), and a few patients had liver function damage, mainly manifested in ALT and AST. High, very few patients have renal impairment. Among the inflammation-related indicators, the main manifestations are increased CRP (66 cases, 43%) and ESR (86 cases, 57%), elevated D-Dimer in 29% of patients. 144 cases have different degrees of infective lesions in chest CT examination, with 30 cases (21%) on one side and 144 cases (79%) on both sides. Morphologically, most of the lesions were patchy ground glass lesions, which could be accompanied by air bronchus signs and some consolidation and paving stone signs. Of the cases showing \"white lung\", 87% were sever ill or critically ill. After active treatment, 45% of patients were discharged according to discharge standards. 33% of sever and critically ill patients were discharged, 49% of them were degraded hospitalization.The average length of hospitalization was (12\u00b14) days. Conclusion: A history of epidemiological exposure, fever, chest CT with signs of pneumonia, normal or decreased WBC, and lymphocytopenia, eosinophilia are the clinical basis for the diagnosis of this disease, and most of the sever patients were the first generation cases. The degree of lymphocytopenia is related to the severity of the disease.", "qid": 25, "docid": "r8gyi3dn", "rank": 6, "score": 0.8516941666603088}, {"content": "Title: [Clinical analysis of 150 cases of 2019 novel coronavirus infection in Nanyang City, Henan Province]. Content: Objective: To analyze the epidemiological characteristics and clinical features of the patients with 2019-nCoV infection in Nanyang City, so as to provide evidence for clinical diagnosis and treatment. Methods: The epidemiology, clinical symptoms, atory and radiologic data of 150 patients with 2019-nCoV infection admitted to the designated hospitals in Nanyang City from January 24,2020 to February 16, 2020 were retrospectively analyzed. Results: The 150 patients with 2019 nCov infection consisted of 67 men and 83 women, and the median age was 45\u00b116 years; 69 of them were the first generation case,60 of them were the second generation case, 6 of them were the third generation case,the median incubation period of the first generation case was 5.4\u00b12.2 days, and the second generation case was 6.7\u00b13.1 days, and the first-generation cases are the majority in severe patients (69%) . The most common basic disease was hypertension (13 cases, 9%), diabetes (9 cases, 6%), and the most common symptom is fever(142 cases, 95%, 63% showed moderate fever) , cough and sputum(108 cases,72%), fatigue(23 cases,15%), anorexia(20 cases, 13%), headache, diarrhea, muscle soreness, sore throat as the first symptoms. The average time from onset of symptoms to consultation was 4.2\u00b12.2 days for all patients. The changes in peripheral blood cells were mainly lymphonpenia (83 cases, 55%) and eosinophilia (95 cases, 63%), The lymphocyte count of the severe and critically ill patients was more significantly reduced, and some patients had increased myocardial enzymes, mainly LDH (47 cases, 31%), and a few patients had liver function damage, mainly manifested in ALT and AST. High, very few patients have renal impairment. Among the inflammation-related indicators, the main manifestations are increased CRP (66 cases, 43%) and ESR (86 cases, 57%), elevated D-Dimer in 29% of patients. 144 cases have different degrees of infective lesions in chest CT examination, with 30 cases (21%) on one side and 144 cases (79%) on both sides. Morphologically, most of the lesions were patchy ground glass lesions, which could be accompanied by air bronchus signs and some consolidation and paving stone signs. Of the cases showing \"white lung\", 87% were sever ill or critically ill. After active treatment, 45% of patients were discharged according to discharge standards. 33% of sever and critically ill patients were discharged, 49% of them were degraded hospitalization.The average length of hospitalization was 12\u00b14 days. Conclusion: A history of epidemiological exposure, fever, chest CT with signs of pneumonia, normal or decreased WBC, and lymphocytopenia, eosinophilia are the clinical basis for the diagnosis of this disease, and most of the sever patients were the first generation cases. The degree of lymphocytopenia is related to the severity of the disease.", "qid": 25, "docid": "h5rewhil", "rank": 7, "score": 0.8509786128997803}, {"content": "Title: Clinical analysis of 23 cases of 2019 novel coronavirus infection in Xinyang City, Henan Province/ \u4e2d\u534e\u5371\u91cd\u75c5\u6025\u6551\u533b\u5b66 Content: Objective@#To analyze the epidemiological characteristics and clinical features of the patients with 2019-nCoV infection, so as to provide basis for clinical diagnosis.@*Methods@#The epidemiology, clinical symptoms, laboratory and radiologic data of 23 patients with 2019-nCoV infection admitted to the Fifth People&apos;s Hospital of Xinyang City from January 22,2020 to January 29, 2020 were retrospectively analyzed.@*Results@#The 23 patients with 2019 nCov infection consisted of 15 men and 8 women, and the median age was 46.0 (40.5, 52.0) years (27-80 years); 9 of them had basic disease (39%), including hypertension (17%), cardiovascular diseases (17%), diabetes (9%), hypothyroidism (4%) and old tuberculosis (4%). All the 23 patients had contact history in Wuhan area or with confirmed infections. Clinical symptoms included: fever (100%), cough (70%), expectoration (43%), myalgia (26%), headache (17%) and dyspnea (17%), and the less common symptoms were diarrhea (4.3%). Blood routine test: white blood cells (WBC) &lt; 4\u00d7109/L in 11 cases (48%), (4-10)\u00d7109/L in 10 cases (43%), &gt;10 \u00d7 109/L in 2 cases (9%); lymphocytopenia in 13 cases (56%). All 23 patients had different degrees of infective lesions in chest CT examination, with 9 cases (39%) on one side and 14 cases (61%) on both sides. Classification: 19 mild cases, 4 severe cases, no critical or death case. Complications included acute respiratory distress syndrome [4 (17%)]. No case was reported with the damage of liver or kidney function and with secondary infection.@*Conclusions@#Epidemic history of contact, fever, pneumonia signs of chest CT, normal or decreased count of WBC and lymphocytopenia are the clinical basis for diagnosis of the disease. However, at present, the treatment of patients has not been completed, the effective treatment strategy and final prognosis are not clear.", "qid": 25, "docid": "vuc9loqi", "rank": 8, "score": 0.850730299949646}, {"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": 9, "score": 0.8505364656448364}, {"content": "Title: Potential biochemical markers to identify severe cases among COVID-19 patients Content: There is a high mortality and long hospitalization period for severe cases with 2019 novel coronavirus disease (COVID-19) pneumonia. Therefore, it makes sense to search for a potential biomarker that could rapidly and effectively identify severe cases early. Clinical samples from 28 cases of COVID-19 (8 severe cases, 20 mild cases) in Zunyi District from January 29, 2020 to February 21, 2020 were collected and otherwise statistically analysed for biochemical markers. Serum urea, creatinine (CREA) and cystatin C (CysC) concentrations in severe COVID-19 patients were significantly higher than those in mild COVID-19 patients (P<0.001), and there were also significant differences in serum direct bilirubin (DBIL), cholinesterase (CHE) and lactate dehydrogenase (LDH) concentrations between severe and mild COVID-19 patients (P<0.05). Serum urea, CREA, CysC, DBIL, CHE and LDH could be used to distinguish severe COVID-19 cases from mild COVID-19 cases. In particular, serum biomarkers, including urea, CREA, CysC, which reflect glomerular filtration function, may have some significance as potential indicators for the early diagnosis of severe COVID-19 and to distinguish it from mild COVID-19. Glomerular filtration function injury in severe COVID-19 patients should also be considered by clinicians.", "qid": 25, "docid": "6rs86u5v", "rank": 10, "score": 0.8487308025360107}, {"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": 11, "score": 0.847480058670044}, {"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": 12, "score": 0.847480058670044}, {"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": 13, "score": 0.846738338470459}, {"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": 14, "score": 0.8459256887435913}, {"content": "Title: Strategies for the development of drugs targeting novel coronavirus 2019-nCoV/ \u836f\u5b66\u5b66\u62a5 Content: @# There is no specific drug that has been approved for 2019-nCoV. There are a number of factors that pose major challenges in their development. Approaches to the development of anti-2019-nCoV include screening existing broad-spectrum antiviral drugs, repositioning of readily available clinical compounds, and &lt;italic&gt;de novo&lt;/italic&gt; development of novel and specific agents for 2019-nCoV. Candidate compounds can be developed either to inhibit virus-based targets, such as RNA proteases, polymerase, spike glycoproteins, and viral envelop and membrane proteins, or to inhibit host-based targets, such as receptors and proteases that are utilized by virus for viral entry and endocytosis. Recently, the RNA polymerase remdesivir had demonstrated clinical efficacy in one patient with severe novel coronavirus pneumonia (NCP). The broad-spectrum viral protease inhibitor Kaletra&lt;sup&gt;&reg;&lt;/sup&gt; is also recommended in the current NCP clinical practice. Both drugs had lately been proceeded into multiple controlled phase III clinical trials to test their safety and efficacy in NCP. Combinational therapies consisting of multiple drugs provide other viable options against 2019-nCoV, based on scientific and clinical rationales. Using bioinformatics and database analysis, we have identified 75 clinically compounds, including 20 marketed compounds, that are efficacious in inhibiting key targets in virus- and host-based approaches, which may facilitate the development of new therapeutic options for 2019-nCoV.", "qid": 25, "docid": "31y378jx", "rank": 15, "score": 0.8435048460960388}, {"content": "Title: Risk factors associated with disease progression in a cohort of patients infected with the 2019 novel coronavirus Content: BACKGROUND: The emerging infection of the 2019 novel coronavirus (2019-nCoV) in late December, 2019 in Wuhan, China, has caused an extreme health concern, with many patients having progressed to acute respiratory disease or other complications in a short period. Meanwhile, the risk factors associated with the disease progression still remain elusive. METHODS: A cohort of 17 patients with laboratory-confirmed 2019-nCoV infections who were admitted to the Ninth Hospital of Nanchang between January 28 and February 6, 2020, were enrolled in this study. All the patients received standardized treatment. The disease progression was evaluated every 7 days after admission. The clinical, radiologic, and laboratory characteristics were retrospectively analyzed, and the factors associated with the disease progression were screened by binary logistic regression analysis. RESULTS: The cohort comprised 11 women (64.7%) and 6 men (35.3%) between the ages of 18 to 70 years old. All patients had a reported history of contact with infection-confirmed patients. Fever (11/64.7%) and cough (8/47.1%) were the most common symptoms, whereas dyspnea (2/11.8%) and fatigue (3/17.6%) were rare, and there was no patient with diarrhea symptoms. There were 5 patients with aggravated disease at the first disease progression evaluation, and no patient received mechanical ventilation, transferred to the intensive care unit (ICU), or progressed to acute respiratory distress syndrome, septic shock, refractory metabolic acidosis, coagulation dysfunction, or death. Based on the disease progression, patients were divided into the non-aggravation group (12 cases) and the aggravation group (5 cases). There were no significant differences between the 2 groups with respect to their clinical characteristics. Chest computed tomography (CT) on admission revealed there were 8 patients (47.1%) with invasive lesions found bilaterally on the lungs on multiple lobes, 4 patients (23.5%) with invasive lesions on 1 lobe, and 5 patients (29.4%) with normal chest CT. The aggravation group had1 patient (20.0%) with invasive lesions on one lobe, 3 (60.0%) with invasive lesions on multiple lobes, bilaterally, and 1 (20.0%) with normal chest CT; meanwhile, the nonaggravation group had 3 patients (25.0%) with invasive lesions on one lobe, 5 (41.7%) with invasive lesions on multiple lobes, bilaterally, and 4 (33.3%) with normal chest CT. No significant difference was found between the 2 groups. In the aggravation group, the total lymphocyte counts significantly decreased in comparison to that in the non-aggravation group. Further analysis showed that the CD4+ T cell count but not the CD8+ T cell count of the aggravation group was significantly lower than that of the non-aggravation group. Correlation analysis indicated total lymphocyte count was positively correlated with CD4+ T cell count, and no significant differences were found between the 2 groups in other laboratory measurements, including those of white blood cell (WBC) count, C-reactive protein (CRP), albumin, lactate dehydrogenase (LDH), and D-dimer. Finally, a binary logistic regression model was used to identify the factors associated with the disease progression. It was found that total lymphocyte count was a risk factor associated with disease progression in patients infected with 2019-nCoV. CONCLUSIONS: A higher cell count of total lymphocytes may indicate a better outcome of the disease, and immune response may be a vital factor for directing disease progression in the early stage of 2019-nCoV infection.", "qid": 25, "docid": "ijtz50ut", "rank": 16, "score": 0.843415379524231}, {"content": "Title: NLR: A Cost-effective Nomogram to Guide Therapeutic Interventions in COVID-19 Content: COVID-19 exhibits a non-yet elucidated heterogeneity dominated by mild form of the illness. Nevertheless, mortality is frequent among patients with a delayed innate immune response that suddenly exacerbates during the second week after admission leading to a lethal over inflammation. Therefore, this rapid and unpredictable deterioration requires timely prediction of COVID-19 refractoriness and critical illness. The two biomarkers readily available in routine laboratories, blood lymphocytes and neutrophil counts, are expected to provide an accurate clinical tool to incline reasonable medication and care because lymphopenia marks immune exhaustion while neutrophilia demonstrates the immunological exuberation. Meanwhile, combining the two parameters as a Neutrophil-to-lymphocyte ratio (NLR) helps to constitute a powerful predictive and prognostic nomogram. This scoring tool allows clinicians to stratify COVID-19 severities on admission and guide early interventions to accelerate recovery and shorten the course of disease in order to alleviate the shortage of medical resources and reduce mortality.", "qid": 25, "docid": "z48686qf", "rank": 17, "score": 0.8414942026138306}, {"content": "Title: NLR: A Cost-effective Nomogram to Guide Therapeutic Interventions in COVID-19. Content: COVID-19 exhibits a non-yet elucidated heterogeneity dominated by mild form of the illness. Nevertheless, mortality is frequent among patients with a delayed innate immune response that suddenly exacerbates during the second week after admission leading to a lethal over inflammation. Therefore, this rapid and unpredictable deterioration requires timely prediction of COVID-19 refractoriness and critical illness. The two biomarkers readily available in routine laboratories, blood lymphocytes and neutrophil counts, are expected to provide an accurate clinical tool to incline reasonable medication and care because lymphopenia marks immune exhaustion while neutrophilia demonstrates the immunological exuberation. Meanwhile, combining the two parameters as a Neutrophil-to-lymphocyte ratio (NLR) helps to constitute a powerful predictive and prognostic nomogram. This scoring tool allows clinicians to stratify COVID-19 severities on admission and guide early interventions to accelerate recovery and shorten the course of disease in order to alleviate the shortage of medical resources and reduce mortality.", "qid": 25, "docid": "g1gpv9i7", "rank": 18, "score": 0.8414942026138306}, {"content": "Title: Blood parameters measured on admission as predictors of outcome for COVID-19; a prospective UK cohort study Content: Abstract: Introduction: COVID-19 has an unpredictable clinical course so prognostic biomarkers would be invaluable when triaging patients on admission to hospital. Many biomarkers have been suggested using large observational datasets but sample timing is crucial to ensure prognostic relevance. The DISCOVER study prospectively recruited patients with COVID-19 admitted to a UK hospital and analysed a panel of putative prognostic biomarkers on the admission blood sample to identify markers of poor outcome. Methods: Consecutive patients admitted to hospital with proven or clinicoradiological suspected COVID-19 were recruited. Admission bloods were extracted from the clinical laboratory. A panel of biomarkers (IL-6, suPAR, KL-6, Troponin, Ferritin, LDH, BNP, Procalcitonin) were performed in addition to routinely performed markers (CRP, neutrophils, lymphocytes, neutrophil:lymphocyte ratio). Age, NEWS score and CURB-65 were included as comparators. All biomarkers were tested in logistic regression against a composite outcome of non-invasive ventilation, intensive care admission, or death, with Area Under the Curve (AUC) figures calculated. Results: 155 patients had 28-day outcomes at the time of analysis. CRP (AUC 0.51 ,CI:0.40-0.62), lymphocyte count (AUC 0.62 ,CI:0.51-0.72), and other routine markers did not predict the primary outcome. IL-6 (AUC: 0.78,0.65-0.89) and suPAR (AUC 0.77 ,CI: 0.66-0.85) showed some promise, but simple clinical features alone such as NEWS score (AUC: 0.74 ,0.64-0.83) or age (AUC: 0.70 ,0.61-0.78) performed nearly as well. Discussion: Admission blood biomarkers have only moderate predictive value for predicting COVID-19 outcomes, while simple clinical features such as age and NEWS score outperform many biomarkers. IL-6 and suPAR had the best performance, and further studies should validate these biomarkers in a prospective fashion.", "qid": 25, "docid": "50ovfwvo", "rank": 19, "score": 0.8406016826629639}, {"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": 20, "score": 0.8398141860961914}, {"content": "Title: [Study on treatment of \"cytokine storm\" by anti-2019-nCoV prescriptions based on arachidonic acid metabolic pathway] Content: Since the outbreak of 2019-nCoV, the epidemic has developed rapidly and the situation is grim. LANCET figured out that the 2019-nCoV is closely related to &quot;cytokine storm&quot;. &quot;Cytokine storm&quot; is an excessive immune response of the body to external stimuli such as viruses and bacteria. As the virus attacking the body, it stimulates the secretion of a large number of inflammatory factors: interleukin(IL), interferon(IFN), C-X-C motif chemokine(CXCL) and so on, which lead to cytokine cascade reaction. With the exudation of inflammatory factors, cytokines increase abnormally in tissues and organs, interfering with the immune system, causing excessive immune response of the body, resulting in diffuse damage of lung cells, pulmonary fibrosis, and multiple organ damage, even death. Arachidonic acid(AA) metabolic pathway is principally used to synthesize inflammatory cytokines, such as monocyte chemotactic protein 1(MCP-1), tumor necrosis factor(TNF), IL, IFN, etc., which is closely related to the occurrence, development and regression of inflammation. Therefore, the inhibition of AA metabolism pathway is benefit for inhibiting the release of inflammatory factors in the body and alleviating the &quot;cytokine storm&quot;. Based on the pharmacophore models of the targets on AA metabolic pathway, the traditional Chinese medicine database 2009(TCMD 2009) was screened. The potential herbs were ranked by the number of hit molecules, which were scored by pharmacophore fit value. In the end, we obtained the potential active prescriptions on &quot;cytokine storm&quot; according to the potential herbs in the &quot;National novel coronavirus pneumonia diagnosis and treatment plan(trial version sixth)&quot;. The results showed that the hit components with the inhibitory effect on AA were magnolignan \u00e2 , lonicerin and physcion-8-O-\u00df-D-glucopy-ranoside, which mostly extracted from Magnoliae Officinalis Cortex, Zingiberis Rhizoma Recens, Lonicerae Japonicae Flos, Rhei Radix et Rhizoma, Salviae Miltiorrhizae Radix et Rhizoma, Scutellariae Radix, Gardeniae Fructus, Ginseng Radix et Rhizoma, Arctii Fructus, Dryopteridis Crassirhizomatis Rhizoma, Paeoniaeradix Rubra, Dioscoreae Rhizoma. Finally the anti-2019-nCoV prescriptions were analyzed to obtain the potential active prescriptions on AA metabolic pathway, Huoxiang Zhengqi Capsules, Jinhua Qinggan Granules, Lianhua Qingwen Capsules, Qingfei Paidu Decoction, Xuebijing Injection, Reduning Injection and Tanreqing Injection were found that may prevent 2019-nCoV via regulate cytokines. This study intends to provide reference for clinical use of traditional Chinese medicine to resist new coronavirus.", "qid": 25, "docid": "r5xyuweg", "rank": 21, "score": 0.8388400077819824}, {"content": "Title: A comprehensive appraisal of laboratory biochemistry tests as major predictors of COVID-19 severity. Content: Context: A relevant portion of COVID-19 patients develop severe disease with negative outcomes. Several biomarkers have been proposed to predict COVID-19 severity, but no definite interpretative criteria have been established to date for stratifying risk. Objective: To evaluate six serum biomarkers (C-reactive protein, lactate dehydrogenase, D-dimer, albumin, ferritin and cardiac troponin T) for predicting COVID-19 severity and to define related cut-offs able to aid clinicians in risk stratification of hospitalized patients. Design: A retrospective study of 427 COVID-19 patients was performed. Patients were divided into groups based on their clinical outcome: non-survivors vs. survivors and patients admitted to intensive care unit vs. others. ROC curves and likelihood ratios were employed to define predictive cut-offs for evaluated markers. Results: Marker concentrations at peak were significantly different between groups for both selected outcomes. At univariate logistic regression analysis, all parameters were significantly associated with higher odds of death and intensive care. At the multivariate analysis, high concentrations of lactate dehydrogenase and low concentrations of albumin in serum remained significantly associated with higher odds of death, while only low lactate dehydrogenase activities remained associated with lower odds of intensive care admission. The best cut-offs for death prediction were >731 U/L for lactate dehydrogenase and \u226418 g/L for albumin, while a lactate dehydrogenase activity <425 U/L was associated with a negative likelihood ratio of 0.10 for intensive treatment. Conclusions: Our study identifies which biochemistry tests represent major predictors of COVID-19 severity and defines the best cut-offs for their use.", "qid": 25, "docid": "dakuwflh", "rank": 22, "score": 0.8385165929794312}, {"content": "Title: [An increased neutrophil/lymphocyte ratio is an early warning signal of severe COVID-19] Content: OBJECTIVE: To identify the biomarkers as early warning signals for severe COVID-19. METHODS: We retrospectively analyzed the clinical data of 63 patients with COVID- 19 from Hubei Provincial Hospital of Integrated Chinese and Western Medicine, including 32 moderate cases and 31 severe cases. The demographic data, underlying diseases, clinical manifestations and laboratory test results were compared between the two groups. Logistic regression analysis was performed to identify the factors that predicted the severity of COVID-19. The receiver- operating characteristic curve (ROC) of neutrophil/lymphocyte ratio (NLR) was calculated, and the area under the curve (AUC) was determined to estimate the optimal threshold of NLR for predicting severe cases of COVID-19. RESULTS: The patients with moderate and server COVID-19 showed significant differences in the rate of diabetes, NLR, serum amyloid A (SSA), C-reactive protein (CRP) and serum albumin (ALB) levels (P < 0.05). The co- morbidity of diabetes, NLR, SSA and CRP were found to positively correlate and ALB to inversely correlate with the severity of COVID-19 (P < 0.05). Multivariate logistic regression analysis showed that NLR was an independent risk factor for severe COVID-19 (OR=1.264, 95% CI: 1.046-1.526, P=0.015) with an AUC of 0.831 (95% CI: 0.730-0.932), an optimal diagnostic threshold of 4.795, a sensitivity of 0.839, and a specificity of 0.750. CONCLUSIONS: An increased NLR can serve as an early warning signal of severe COVID-19.", "qid": 25, "docid": "u1v2p9wp", "rank": 23, "score": 0.838292121887207}, {"content": "Title: A comprehensive appraisal of laboratory biochemistry tests as major predictors of COVID-19 severity Content: Context: A relevant portion of COVID-19 patients develop severe disease with negative outcomes. Several biomarkers have been proposed to predict COVID-19 severity, but no definite interpretative criteria have been established to date for stratifying risk. Objective: To evaluate six serum biomarkers (C-reactive protein, lactate dehydrogenase, D-dimer, albumin, ferritin and cardiac troponin T) for predicting COVID-19 severity and to define related cut-offs able to aid clinicians in risk stratification of hospitalized patients. Design: A retrospective study of 427 COVID-19 patients was performed. Patients were divided into groups based on their clinical outcome: non-survivors vs. survivors and patients admitted to intensive care unit vs. others. ROC curves and likelihood ratios were employed to define predictive cut-offs for evaluated markers. Results: Marker concentrations at peak were significantly different between groups for both selected outcomes. At univariate logistic regression analysis, all parameters were significantly associated with higher odds of death and intensive care. At the multivariate analysis, high concentrations of lactate dehydrogenase and low concentrations of albumin in serum remained significantly associated with higher odds of death, while only low lactate dehydrogenase activities remained associated with lower odds of intensive care admission. The best cut-offs for death prediction were >731 U/L for lactate dehydrogenase and &#8804;18 g/L for albumin, while a lactate dehydrogenase activity <425 U/L was associated with a negative likelihood ratio of 0.10 for intensive treatment. Conclusions: Our study identifies which biochemistry tests represent major predictors of COVID-19 severity and defines the best cut-offs for their use.", "qid": 25, "docid": "ss6nskfk", "rank": 24, "score": 0.8382441997528076}, {"content": "Title: Elevations of serum cancer biomarkers correlate with severity of COVID-19 Content: In this retrospective study, we evaluated the levels of a series of serum biomarkers in coronavirus disease 2019 (COVID-19) patients (mild: 131; severe: 98; critical: 23). We found that there were significant increases in levels of human epididymis protein 4 (HE4) (73.6 \u00b1 38.3 vs 46.5 \u00b1 14.7 pmol/L; P < .001), cytokeratin-19 fragment (CYFRA21-1) (2.2 \u00b1 0.9 vs 1.9 \u00b1 0.8 \u00b5g/L; P < .001), carcinoembryonic antigen (CEA) (3.4 \u00b1 2.2 vs 2.1 \u00b1 1.2 \u00b5g/L; P < .001), carbohydrate antigens (CA) 125 (18.1 \u00b1 13.5 vs 10.5 \u00b1 4.6 \u00b5g/L; P < .001), and 153 (14.4 \u00b1 8.9 vs 10.1 \u00b1 4.4 \u00b5g/L; P < .001) in COVID-19 mild cases as compared to normal control subjects; their levels showed continuous and significant increases in severe and critical cases (HE4, CYFRA21-1, and CA125: P < .001; CEA and CA153: P < .01). Squamous cell carcinoma antigen (SCC) and CA199 increased significantly only in critical cases of COVID-19 as compared with mild and severe cases and normal controls (P < .01). There were positive associations between levels of C-reactive protein and levels of HE4 (R = .631; P < .001), CYFRA21-1 (R = .431; P < .001), CEA (R = .316; P < .001), SCC (R = .351; P < .001), CA153 (R = .359; P < .001) and CA125 (R = .223; P = .031). We concluded that elevations of serum cancer biomarkers positively correlated with the pathological progressions of COVID-19, demonstrating diffuse and acute pathophysiological injuries in COVID-19.", "qid": 25, "docid": "y5ut2w8r", "rank": 25, "score": 0.8382415175437927}, {"content": "Title: Clinical analysis and early differential diagnosis of suspected pediatric patients with 2019 novel coronavirus infection Content: Abstract Background: Early differential diagnosis of suspected pediatric patients is difficult during the 2019-nCoV epidemic. Objective: To identify clinical characteristics and key points of early differential diagnosis. Methods: A retrospective analysis was performed on suspected pediatric cases. Results:A total of 77 suspected cases were admitted from Jan 22nd to Mar 1st. Compared with non-2019-nCoV group (n=33),2019-nCoV confirmed group (n=35) had fewer fever (OR[95% CI] 0.39[0.242 to 0.628];P<.001) and symptoms of ARI (0.454[0.287 to 0.719];P<.001),more asymptomatic (15.086[2.117 to 107.475];P<.001), and more family cluster infections (5.469[2.405 to 12.433]; P<.001),while chest CT had more positive findings of viral pneumonia (1.813[1.131 to 2.908];P=.014).There were significant statistical differences between the two groups in age (7.2[3.9 to 11.4] vs 5[2.1 to 7.8];P=.031),body temperature (36.7[36.2 to 36.9] vs 37[36.7 to 37.9];P=.001), heart rate ([97.1 and 16.8] vs [109.7 and 15.6];P=.002),percentage ([39.4 and 14.9] vs [52.5 and 17.5]; P=.001) and count (2.25[1.43 to 3.53] vs 3.33[2.8 to 5.18];P=.007) of neutrophil, percentage (45.3[39.2 to 56.6] vs 33.2[22.7 to 42.5];P=.001) of lymphocyte,hs-CRP (5.52[1.1 to 9.04] vs 9.04[7.35 to 9.54];P=.002) and PCT (0.05[0.03 to 0.08] vs 0.1[0.05 to 0.21];P<.001),while gender (42.9% vs 57.6%;P=.332),respiratory rate (22[20 to 22] vs 22[20 to 24];P=.092),WBC (5.37[4.67 to 8.08] vs 6.94[5.72 to 8.87];P=.198), lymphocyte count (2.68[1.99 to 4.01] vs 2.26[1.66 to 2.92];P=.096),Hb (128[124 to 142] vs 130[119 to 137];P=.572) and PLT ([279.1 and 77.5] vs [263.4 and 65.1];P=.37) were statistically insignificant. Conclusions: Asymptoms or mild symptoms,positive CT findings and family cluster infection are the main clinical characteristics of infected pediatric patients. The CBC, hs-CRP and PCT can provide an important basis for early differential diagnosis. Compared with other non-bacterial infections,hs-CRP and PCT in 2019-nCoV infection are reduced,but further evidence is needed to support whether their reduction is specific. Keywords: 2019 novel coronavirus;acute respiratory infection; pediatric;differential diagnosis;suspected infection. Abbreviations:2019-nCoV,2019 novel coronavirus;CT,computed tomography; RT-PCR,real-time reverse transcriptase polymerase chain reaction;IQR,interquartile range;OR,odds ratio;CI,confidence interval;SD,standard deviation;ARI,acute respiratory infection; CAP,community-acquired pneumonia;RSV, respiratory syncytial virus; MP, mycoplasma pneumoniae; INF A,B,influenza A,B;CBC,complete blood count;WBC,white blood cell;N%, percentage of neutrophil; L%, percentage of lymphocyte; Hb, Hemoglobin;PLT, platelet; hs-CRP,high sensitivity C-reactive protein; PCT, procalcitonin.", "qid": 25, "docid": "mdt9p6v0", "rank": 26, "score": 0.8380424380302429}, {"content": "Title: Risk factors associated with disease progression in a cohort of patients infected with the 2019 novel coronavirus. Content: BACKGROUND The emerging infection of the 2019 novel coronavirus (2019-nCoV) in late December, 2019 in Wuhan, China, has caused an extreme health concern, with many patients having progressed to acute respiratory disease or other complications in a short period. Meanwhile, the risk factors associated with the disease progression still remain elusive. METHODS A cohort of 17 patients with laboratory-confirmed 2019-nCoV infections who were admitted to the Ninth Hospital of Nanchang between January 28 and February 6, 2020, were enrolled in this study. All the patients received standardized treatment. The disease progression was evaluated every 7 days after admission. The clinical, radiologic, and laboratory characteristics were retrospectively analyzed, and the factors associated with the disease progression were screened by binary logistic regression analysis. RESULTS The cohort comprised 11 women (64.7%) and 6 men (35.3%) between the ages of 18 to 70 years old. All patients had a reported history of contact with infection-confirmed patients. Fever (11/64.7%) and cough (8/47.1%) were the most common symptoms, whereas dyspnea (2/11.8%) and fatigue (3/17.6%) were rare, and there was no patient with diarrhea symptoms. There were 5 patients with aggravated disease at the first disease progression evaluation, and no patient received mechanical ventilation, transferred to the intensive care unit (ICU), or progressed to acute respiratory distress syndrome, septic shock, refractory metabolic acidosis, coagulation dysfunction, or death. Based on the disease progression, patients were divided into the non-aggravation group (12 cases) and the aggravation group (5 cases). There were no significant differences between the 2 groups with respect to their clinical characteristics. Chest computed tomography (CT) on admission revealed there were 8 patients (47.1%) with invasive lesions found bilaterally on the lungs on multiple lobes, 4 patients (23.5%) with invasive lesions on 1 lobe, and 5 patients (29.4%) with normal chest CT. The aggravation group had1 patient (20.0%) with invasive lesions on one lobe, 3 (60.0%) with invasive lesions on multiple lobes, bilaterally, and 1 (20.0%) with normal chest CT; meanwhile, the nonaggravation group had 3 patients (25.0%) with invasive lesions on one lobe, 5 (41.7%) with invasive lesions on multiple lobes, bilaterally, and 4 (33.3%) with normal chest CT. No significant difference was found between the 2 groups. In the aggravation group, the total lymphocyte counts significantly decreased in comparison to that in the non-aggravation group. Further analysis showed that the CD4+ T cell count but not the CD8+ T cell count of the aggravation group was significantly lower than that of the non-aggravation group. Correlation analysis indicated total lymphocyte count was positively correlated with CD4+ T cell count, and no significant differences were found between the 2 groups in other laboratory measurements, including those of white blood cell (WBC) count, C-reactive protein (CRP), albumin, lactate dehydrogenase (LDH), and D-dimer. Finally, a binary logistic regression model was used to identify the factors associated with the disease progression. It was found that total lymphocyte count was a risk factor associated with disease progression in patients infected with 2019-nCoV. CONCLUSIONS A higher cell count of total lymphocytes may indicate a better outcome of the disease, and immune response may be a vital factor for directing disease progression in the early stage of 2019-nCoV infection.", "qid": 25, "docid": "z3rpoqao", "rank": 27, "score": 0.8372374773025513}, {"content": "Title: Diagnostic and prognostic value of hematological and immunological markers in COVID-19 infection: A meta-analysis of 6320 patients Content: Objective Evidence-based characterization of the diagnostic and prognostic value of the hematological and immunological markers related to the epidemic of Coronavirus Disease 2019 (COVID-19) is critical to understand the clinical course of the infection and to assess in development and validation of biomarkers. Methods Based on systematic search in Web of Science, PubMed, Scopus, and Science Direct up to April 22, 2020, a total of 52 eligible articles with 6,320 laboratory-confirmed COVID-19 cohorts were included. Pairwise comparison between severe versus mild disease, Intensive Care Unit (ICU) versus general ward admission, and expired versus survivors were performed for 36 laboratory parameters. The pooled standardized mean difference (SMD) and 95% confidence intervals (CI) were calculated using the DerSimonian Laird method/random effects model and converted to Odds ratio (OR). The decision tree algorithm was employed to identify the key risk factor(s) attributed to severe COVID-19 disease. Results Cohorts with elevated levels of white blood cells (WBCs) (OR=1.75), neutrophil count (OR=2.62), D-dimer (OR=3.97), prolonged prothrombin time (PT) (OR=1.82), fibrinogen (OR=3.14), erythrocyte sedimentation rate (OR=1.60), procalcitonin (OR=4.76), IL-6 (OR=2.10), and IL-10 (OR=4.93) had higher odds of progression to severe phenotype. Decision tree model (sensitivity=100%, specificity=81%) showed the high performance of neutrophil count at a cut-off value of more than 3.74 x109/L for identifying patients at high risk of severe COVID-19. Likewise, ICU admission was associated with higher levels of WBCs (OR=5.21), neutrophils (OR=6.25), D-dimer (OR=4.19), and prolonged PT (OR=2.18). Patients with high IL-6 (OR=13.87), CRP (OR=7.09), D-dimer (OR=6.36), and neutrophils (OR=6.25) had the highest likelihood of mortality. Conclusions Several hematological and immunological markers, in particular neutrophilic count, could be helpful to be included within the routine panel for COVID-19 infection evaluation to ensure risk stratification and effective management.", "qid": 25, "docid": "8nz2lcsa", "rank": 28, "score": 0.8369625210762024}, {"content": "Title: Biomarkers associated with COVID-19 disease progression Content: The coronavirus disease 2019 (COVID-19) pandemic is a scientific, medical, and social challenge. The complexity of the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) is centered on the unpredictable clinical course of the disease that can rapidly develop, causing severe and deadly complications. The identification of effective laboratory biomarkers able to classify patients based on their risk is imperative in being able to guarantee prompt treatment. The analysis of recently published studies highlights the role of systemic vasculitis and cytokine mediated coagulation disorders as the principal actors of multi organ failure in patients with severe COVID-19 complications. The following biomarkers have been identified: hematological (lymphocyte count, neutrophil count, neutrophil\u2013lymphocyte ratio (NLR)), inflammatory (C-reactive protein (CRP), erythrocyte sedimentation rate (ESR), procalcitonin (PCT)), immunological (interleukin (IL)-6 and biochemical (D-dimer, troponin, creatine kinase (CK), aspartate aminotransferase (AST)), especially those related to coagulation cascades in disseminated intravascular coagulation (DIC) and acute respiratory distress syndrome (ARDS). New laboratory biomarkers could be identified through the accurate analysis of multicentric case series; in particular, homocysteine and angiotensin II could play a significant role.", "qid": 25, "docid": "3l2t9w9l", "rank": 29, "score": 0.8350616693496704}, {"content": "Title: Elevations of serum cancer biomarkers correlate with severity of COVID\u201019 Content: In this retrospective study, we evaluated the levels of a series of serum biomarkers in coronavirus disease 2019 (COVID\u201019) patients (mild: 131; severe: 98; critical: 23). We found that there were significant increases in levels of human epididymis protein 4 (HE4) (73.6 \u00b1 38.3 versus 46.5 \u00b1 14.7, p<0.001), cytokeratin\u201019 fragment (CYFRA21\u20101) (2.2 \u00b1 0.9 versus 1.9 \u00b1 0.8, p<0.001), carcinoembryonic antigen (CEA) (3.4 \u00b1 2.2 versus 2.1 \u00b1 1.2, p<0.001), carbohydrate antigens (CA) 125 (18.1 \u00b1 13.5 versus 10.5 \u00b1 4.6, p<0.001) and 153 (14.4 \u00b1 8.9 versus 10.1 \u00b1 4.4, p<0.001) in COVID\u201019 mild cases as compared to normal control subjects; their levels showed continuous and significant increases in severe and critical cases (HE4, CYFRA21\u20101 and CA125: p<0.001; CEA and CA153: p<0.01). Squamous cell carcinoma antigen (SCC) and CA199 increased significantly only in critical cases of COVID\u201019 as compared with mild and severe cases and normal controls (p<0.01). There were positive associations between levels of C\u2010reactive protein and levels of HE4 (R= 0.631, p<0.001), CYFRA21\u20101(R= 0.431, p<0.001), CEA (R= 0.316, p<0.001), SCC (R= 0.351, p<0.001), CA153 (R= 0.359, p<0.001) and CA125 (R= 0.223, p=0.031). We concluded that elevations of serum cancer biomarkers positively correlated with the pathological progressions of COVID\u201019, demonstrating diffuse and acute lung injuries. This article is protected by copyright. All rights reserved.", "qid": 25, "docid": "i1nehm61", "rank": 30, "score": 0.8345097303390503}, {"content": "Title: Biomarkers associated with COVID-19 disease progression Content: The coronavirus disease 2019 (COVID-19) pandemic is a scientific, medical, and social challenge. The complexity of the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) is centered on the unpredictable clinical course of the disease that can rapidly develop, causing severe and deadly complications. The identification of effective laboratory biomarkers able to classify patients based on their risk is imperative in being able to guarantee prompt treatment. The analysis of recently published studies highlights the role of systemic vasculitis and cytokine mediated coagulation disorders as the principal actors of multi organ failure in patients with severe COVID-19 complications. The following biomarkers have been identified: hematological (lymphocyte count, neutrophil count, neutrophil-lymphocyte ratio (NLR)), inflammatory (C-reactive protein (CRP), erythrocyte sedimentation rate (ESR), procalcitonin (PCT)), immunological (interleukin (IL)-6 and biochemical (D-dimer, troponin, creatine kinase (CK), aspartate aminotransferase (AST)), especially those related to coagulation cascades in disseminated intravascular coagulation (DIC) and acute respiratory distress syndrome (ARDS). New laboratory biomarkers could be identified through the accurate analysis of multicentric case series; in particular, homocysteine and angiotensin II could play a significant role.", "qid": 25, "docid": "vcpo3qob", "rank": 31, "score": 0.8342024087905884}, {"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": 32, "score": 0.8335278034210205}, {"content": "Title: Comparative analysis of laboratory indexes of severe and non-severe patients infected with COVID-19 Content: BACKGROUND: The pandemic coronavirus disease 2019 (COVID-19) has threaten the global health. The characteristics of laboratory findings of coronavirus are of great significance for clinical diagnosis and treatment. We found indicators that may most effectively predict a non-severe COVID-19 patient develop into a severe patient. METHODS: We conducted a meta-analysis to compare the laboratory findings of severe patients with non-severe patients with COVID-19 from searched articles. RESULTS: Through the analysis of laboratory examination information of patients with COVID-19 from 35 articles (5912 patients), we demonstrated that severe cases possessed higher levels of leukocyte (1.20-fold), neutrophil (1.33-fold), CRP (3.04-fold), PCT (2.00-fold), ESR (1.44-fold), AST (1.40-fold), ALT (1.34-fold), LDH (1.54-fold), CK (1.44-fold), CK-MB (1.39-fold), total bilirubin (1.14-fold), urea (1.28-fold), creatine (1.09-fold), PT (1.03-fold) and D-dimer (2.74-fold), as well as lower levels of lymphocytes (1.44-fold), eosinophil (2.00-fold), monocyte (1.08-fold), Hemoglobin (1.53-fold), PLT (1.15-fold), albumin (1.15-fold), and APTT (1.02-fold). Lymphocyte subsets and series of inflammatory cytokines were also different in severe cases with the non-severe ones, including lower levels of CD4 T cells (2.10-fold) and CD8 T cells (2.00-fold), higher levels of IL-1\u00df (1.02-fold), IL-6 (1.93-fold) and IL-10 (1.55-fold). CONCLUSIONS: Some certain laboratory inspections could predict the progress of the COVID-19 changes, especially lymphocytes, CRP, PCT, ALT, AST, LDH, D-dimer, CD4 T cells and IL6, which provide valuable signals for preventing the deterioration of the disease.", "qid": 25, "docid": "o2fgobi1", "rank": 33, "score": 0.8332805633544922}, {"content": "Title: Comparative analysis of laboratory indexes of severe and non-severe patients infected with COVID-19 Content: BACKGROUND: The pandemic coronavirus disease 2019 (COVID-19) has threaten the global health. The characteristics of laboratory findings of coronavirus are of great significance for clinical diagnosis and treatment. We found indicators that may most effectively predict a non-severe COVID-19 patient develop into a severe patient. METHODS: We conducted a meta-analysis to compare the laboratory findings of severe patients with non-severe patients with COVID-19 from searched articles. RESULTS: Through the analysis of laboratory examination information of patients with COVID-19 from 35 articles (5912 patients), we demonstrated that severe cases possessed higher levels of leukocyte (1.20-fold), neutrophil (1.33-fold), CRP (3.04-fold), PCT (2.00-fold), ESR (1.44-fold), AST (1.40-fold), ALT (1.34-fold), LDH (1.54-fold), CK (1.44-fold), CK-MB (1.39-fold), total bilirubin(1.14-fold), urea (1.28-fold), creatine (1.09-fold), PT (1.03-fold) and D-dimer (2.74-fold), as well as lower levels of lymphocytes (1.44-fold), eosinophil (2.00-fold), monocyte (1.08-fold), Hemoglobin (1.53-fold), PLT (1.15-fold), albumin (1.15-fold), and APTT (1.02-fold). Lymphocyte subsets and series of inflammatory cytokines were also different in severe cases with the non-severe ones, including lower levels of CD4 T cells (2.10-fold) and CD8 T cells (2.00-fold), higher levels of IL-1\u03b2 (1.02-fold), IL-6 (1.93-fold) and IL-10 (1.55-fold). CONCLUSIONS: Some certain laboratory inspections could predict the progress of the COVID-19 changes, especially lymphocytes, CRP, PCT, ALT, AST, LDH, D-dimer, CD4 T cells and IL6, which provide valuable signals for preventing the deterioration of the disease.", "qid": 25, "docid": "vrsdi2p3", "rank": 34, "score": 0.8330099582672119}, {"content": "Title: Prediction of the severity of Corona Virus Disease 2019 and its adverse clinical outcomes Content: This study aims to investigate blood and biochemical laboratory findings in patients with severe Corona Virus Disease 2019 (COVID-19) and to develop a joint predictor for predicting the likelihood of severe COVID-19 and its adverse clinical outcomes, to provide more information for treatment. We collected the data of 88 patients with laboratory-confirmed COVID-19. Then patients were divided into a non-severe group and a critical group (including critically ill cases). Univariate analysis showed that the absolute lymphocyte count, albumin level, albumin/globulin (A/G) ratio, lactate dehydrogenase (LDH) level, interleukin-6 (IL-6) level, erythrocyte count, globulin level, blood glucose level, and age were significantly correlated with the severity of COVID-19. The multivariate binary logistic regression model revealed that Age, absolute lymphocyte count, and IL-6 level were independent risk factors in patients with COVID-19. The receiver operating characteristic (ROC) curve revealed that the combination of IL-6 level, absolute lymphocyte count and age is superior to a single factor as predictors for predicting severe COVID-19, regardless of whether it is the area under curve (AUC) or the prediction sensitivity and specificity. Early application is beneficial to early identification of critically ill patients and timing individual treatments to reduce mortality.", "qid": 25, "docid": "2bjn0fmr", "rank": 35, "score": 0.8325589895248413}, {"content": "Title: Prediction of the severity of Corona Virus Disease 2019 and its adverse clinical outcomes. Content: This study aims to investigate blood and biochemical laboratory findings in patients with severe Corona Virus Disease 2019 (COVID-19) and to develop a joint predictor for predicting the likelihood of severe COVID-19 and its adverse clinical outcomes, to provide more information for treatment. We collected the data of 88 patients with laboratory-confirmed COVID-19. Then patients were divided into a non-severe group and a critical group (including critically ill cases). Univariate analysis showed that the absolute lymphocyte count, albumin level, albumin/globulin (A/G) ratio, lactate dehydrogenase (LDH) level, interleukin-6 (IL-6) level, erythrocyte count, globulin level, blood glucose level, and age were significantly correlated with the severity of COVID-19. The multivariate binary logistic regression model revealed that Age, absolute lymphocyte count, and IL-6 level were independent risk factors in patients with COVID-19. The receiver operating characteristic (ROC) curve revealed that the combination of IL-6 level, absolute lymphocyte count and age is superior to a single factor as predictors for predicting severe COVID-19, regardless of whether it is the area under curve (AUC) or the prediction sensitivity and specificity. Early application is beneficial to early identification of critically ill patients and timing individual treatments to reduce mortality.", "qid": 25, "docid": "dmbc8kb4", "rank": 36, "score": 0.8325589895248413}, {"content": "Title: Detectable 2019-nCoV viral RNA in blood is a strong indicator for the further clinical severity Content: The novel coronavirus (2019-nCoV) infection caused pneumonia. we retrospectively analyzed the virus presence in the pharyngeal swab, blood, and the anal swab detected by real-time PCR in the clinical lab. Unexpectedly, the 2109-nCoV RNA was readily detected in the blood (6 of 57 patients) and the anal swabs (11 of 28 patients). Importantly, all of the 6 patients with detectable viral RNA in the blood cohort progressed to severe symptom stage, indicating a strong correlation of serum viral RNA with the disease severity (p-value = 0.0001). Meanwhile, 8 of the 11 patients with annal swab virus-positive was in severe clinical stage. However, the concentration of viral RNA in the anal swab (Ct value = 24 + 39) was higher than in the blood (Ct value = 34 + 39) from patient 2, suggesting that the virus might replicate in the digestive tract. Altogether, our results confirmed the presence of virus RNA in extra-pulmonary sites.", "qid": 25, "docid": "eiofivki", "rank": 37, "score": 0.8324028253555298}, {"content": "Title: Clinical value of immune-inflammatory parameters to assess the severity of coronavirus disease 2019 Content: OBJECTIVE: To explore the clinical value of immune-inflammatory markers to assess the severity of coronavirus disease 2019 (COVID-19). METHODS: 127 consecutive hospitalized patients with confirmed COVID-19 were enrolled in this study, and classified into non-severe and severe groups. Demographics, symptoms, underlying diseases and laboratory data were collected and assessed for predictive value. RESULTS: Of 127 COVID-19 patients, 16 cases (12.60%) were classified into the severe group. High level of interleukin-6 (IL-6), C-reaction protein (CRP) and hypertension were independent risk factors for the severity of COVID-19. The risk model based on IL-6, CRP and hypertension had the highest area under the receiver operator characteristic curve (AUROC). Additionally, the baseline IL-6 was positively correlated with other immune-inflammatory parameters and the dynamic change of IL-6 in the severe cases were parallel to the amelioration of the disease. CONCLUSION: Our study showed that high level of IL-6, CRP and hypertension were independent risk factors for assessing the severity of COVID-19. The risk model established upon IL-6, CRP and hypertension had the highest predictability in this study. Besides, IL-6 played a pivotal role in the severity of COVID-19 and had a potential value for monitoring the process of severe cases.", "qid": 25, "docid": "n75u9qk2", "rank": 38, "score": 0.8322054147720337}, {"content": "Title: Integrative Bioinformatics Analysis Provides Insight into the Molecular Mechanisms of 2019-nCoV Content: The 2019-nCoV is reported to share the same entry (ACE2) as SARS-CoV according to the updated findings. Analyzing the distribution and expression level of the route of coronavirus may help reveal underlying mechanisms of viral susceptibility and post-infection modulation. In this study, we found that the expression of ACE2 in healthy populations and patients with underlying diseases was not significantly different, suggesting relatively similar susceptibility, which was consistent with current clinical observations. Moreover, based on the expression of ACE2 in smoking individuals, we inferred that long-term smoking might be a risk factor for 2019-nCoV. Analyzing the ACE2 in SARS-CoV infected cells suggested that ACE2 was more than just a receptor but also participated in post-infection regulation, including immune response, cytokine secretion, and viral genome replication. We also constructed Protein-protein interaction (PPI) networks and identified hub genes in viral activity and cytokine secretion. Our findings could explain the clinical symptoms so far and help clinicians and researchers understand the pathogenesis and design therapeutic strategies for 2019-nCoV.", "qid": 25, "docid": "mjhez5im", "rank": 39, "score": 0.8318160772323608}, {"content": "Title: A comparative study on the clinical features of COVID-19 pneumonia to other pneumonias Content: BACKGROUND: A novel coronavirus (2019-nCoV) has raised world concern since it emerged in Wuhan Hubei China in December, 2019. The infection may result into severe pneumonia with clusters illness onsets. Its impacts on public health make it paramount to clarify the clinical features with other pneumonias. METHODS: Nineteen 2019-nCoV pneumonia (NCOVID-19) and fifteen other pneumonia patients (NON-NCOVID-19) in out of Hubei places were involved in this study. Both NCOVID-19 and NON-NCOVID-19 patients were confirmed to be infected in throat swabs or/and sputa with or without 2019-nCoV by real-time RT-PCR. We analyzed the demographic, epidemiological, clinical, and radiological features from those patients, and compared the difference between NCOVID-19 and NON-NCOVID-19. RESULTS: All patients had a history of exposure to confirmed case of 2019-nCoV or travel to Hubei before illness. The median duration, respectively, was 8 (IQR:6~11) and 5 (IQR:4~11) days from exposure to onset in NCOVID-19 and NON-NCOVID-19. The clinical symptoms were similar between NCOVID-19 and NON-NCOVID-19. The most common symptoms were fever and cough. Fifteen (78.95%) NCOVID-19 but 4 (26.67%) NON-NCOVID-19 patients had bilateral involvement while 17 (89.47%) NCOVID-19 but 1 (6.67%) NON-NCOVID-19 patients had multiple mottling and ground-glass opacity of chest CT images. Compared to NON-NCOVID-19, NCOVID-19 present remarkably more abnormal laboratory tests including AST, ALT, \u03b3-GT, LDH and \u03b1-HBDH. CONCLUSION: The 2019-nCoV infection caused similar onsets to other pneumonias. CT scan may be a reliable test for screening NCOVID-19 cases. Liver function damage is more frequent in NCOVID-19 than NON-NCOVID-19 patients. LDH and \u03b1-HBDH may be considerable markers for evaluation of NCOVID-19.", "qid": 25, "docid": "6lngz7y1", "rank": 40, "score": 0.8317379951477051}, {"content": "Title: Can we predict the severity of coronavirus disease 2019 with a routine blood test? Content: INTRODUCTION: The ongoing worldwide pandemic of coronavirus disease 2019 (COVID\u00ad19) has posed a huge threat to global public health. However, the issue as to whether routine blood tests could be used to monitor and predict the severity and prognosis of COVID\u00ad19 has not been comprehensively investigated so far. OBJECTIVES: This study aimed to provide an overview of the association of markers in the routine blood test with the severity of COVID\u00ad19. METHODS: PubMed, Embase, Cochrane Library, Wanfang, and China National Knowledge Infrastructure (CNKI) databases were searched to identify studies reporting data on markers in the routine blood test and the severity of COVID\u00ad19, published until March 20, 2020. The STATA software was used for meta\u00adanalysis. RESULTS: A total of 15 studies with 3090 patients with COVID\u00ad19 were included in this analysis. Patients in the nonsevere group, compared with those in the severe group, had lower counts of white blood cells (weighted mean difference [WMD], -0.85 [\u00d7109/l]; 95% CI, -1.54 to -0.16; P = 0.02) and neutrophils (WMD, -1.57 [\u00d7109/l]; 95% CI, -2.6 to -0.54; P = 0.003), greater counts of lymphocytes (WMD, 0.29 [\u00d7109/l]; 95% CI, 0.22-0.36; P <0.001) and platelets (WMD, 19.05 [\u00d7109/l]; 95% CI, 3.04-35.06; P = 0.02), and a lower neutrophil\u00adto\u00adlymphocyte (NLR) ratio (WMD, -2.48; 95% CI, -3.81 to -1.15; P <0.001). There was no difference in the monocyte count (WMD, 0.01 [\u00d7109/l]; 95% CI, -0.01 to 0.03; P = 0.029) between these 2 groups. Sensitivity analysis and meta\u00adanalysis based on standard mean difference did not change the conclusions regarding neutrophils, lymphocytes, and NLR, but yielded inconsistent results for white blood cells and platelets. CONCLUSIONS: Severe patients had more neutrophils, higher NLR level, and fewer lymphocytes than non-severe patients with COVID-19. Measurement of these markers might assist clinicians to monitor and predict the severity and prognosis of COVID-19.", "qid": 25, "docid": "o2un26ug", "rank": 41, "score": 0.8317240476608276}, {"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": 42, "score": 0.8317190408706665}, {"content": "Title: C-reactive protein correlates with computed tomographic findings and predicts severe COVID-19 early Content: COVID-19 has developed into a worldwide pandemic; early identification of severe illness is critical for controlling it and improving the prognosis of patients with limited medical resources. The present study aimed to analyze the characteristics of severe COVID-19 and identify biomarkers for differential diagnosis and prognosis prediction. In total, 27 consecutive patients with COVID-19 and 75 patients with flu were retrospectively enrolled. Clinical parameters were collected from electronic medical records. The disease course was divided into four stages: initial, progression, peak, and recovery stages, according to computed tomography (CT) progress. to mild COVID-19, the lymphocytes in the severe COVID-19 progressively decreased at the progression and the peak stages, but rebound in the recovery stage. The levels of C-reactive protein (CRP) in the severe group at the initial and progression stages were higher than those in the mild group. Correlation analysis showed that CRP (R = .62; P < .01), erythrocyte sedimentation rate (R = .55; P < .01) and granulocyte/lymphocyte ratio (R = .49; P < .01) were positively associated with the CT severity scores. In contrast, the number of lymphocytes (R = -.37; P < .01) was negatively correlated with the CT severity scores. The receiver-operating characteristic analysis demonstrated that area under the curve of CRP on the first visit for predicting severe COVID-19 was 0.87 (95% CI 0.10-1.00) at 20.42 mg/L cut-off, with sensitivity and specificity 83% and 91%, respectively. CRP in severe COVID-19 patients increased significantly at the initial stage, before CT findings. Importantly, CRP, which was associated with disease development, predicted early severe COVID-19.", "qid": 25, "docid": "q37fwcgt", "rank": 43, "score": 0.8314869999885559}, {"content": "Title: Prognosis of COVID-19: Changes in laboratory parameters Content: INTRODUCTION: Since December 2019, an outbreak of coronavirus disease 2019 (COVID-19) caused by Severe Acute Respiratory Syndrome - Coronavirus 2 (SARS-CoV-2) emerged in China and has become a global threat Comparison of hematological parameters between mild and severe cases of SARS-CoV 2 is so far limited, but significant differences in parameters such as interleukin-6, d-dimers, glucose, fibrinogen and C-reactive protein have been already reported PURPOSE: In this study we analyzed the changes observed in easily measured blood biomarkers in the patients and provided evidence of how these markers can be used as prognostic factors of the disease METHODS: Demographic characteristics, detailed medical history, and laboratory findings of all enrolled SARS-CoV 2 infection positive patients who were referred to Patras University Hospital from the period of March 4th 2020 (when first confirmed case in Greece appeared in our hospital) until April 4th 2020 were extracted from electronic medical records and analyzed RESULTS: We provided evidence that some very common laboratory values can be used as independent predictive factors in SARS-CoV 2 infection Despite the retrospective nature of this study and the small number of subjects analyzed, we showed that NLR, LDH, d-dimers, CRP, fibrinogen and ferritin can be used early at the patient's first visit for SARS-CoV 2 infection symptoms and can predict the severity of infection CONCLUSION: More studies are warranted to further objectively confirm the clinical value of prognostic factors related to SARS-CoV 2 and establish an easy-to-get panel of laboratory findings for evaluating the disease severity", "qid": 25, "docid": "n4rqz9ho", "rank": 44, "score": 0.8312421441078186}, {"content": "Title: [An increased neutrophil/lymphocyte ratio is an early warning signal of severe COVID-19]. Content: OBJECTIVE To identify the biomarkers as early warning signals for severe COVID-19. METHODS We retrospectively analyzed the clinical data of 63 patients with COVID- 19 from Hubei Provincial Hospital of Integrated Chinese and Western Medicine, including 32 moderate cases and 31 severe cases. The demographic data, underlying diseases, clinical manifestations and laboratory test results were compared between the two groups. Logistic regression analysis was performed to identify the factors that predicted the severity of COVID-19. The receiver- operating characteristic curve (ROC) of neutrophil/lymphocyte ratio (NLR) was calculated, and the area under the curve (AUC) was determined to estimate the optimal threshold of NLR for predicting severe cases of COVID-19. RESULTS The patients with moderate and server COVID-19 showed significant differences in the rate of diabetes, NLR, serum amyloid A (SSA), C-reactive protein (CRP) and serum albumin (ALB) levels (P < 0.05). The co- morbidity of diabetes, NLR, SSA and CRP were found to positively correlate and ALB to inversely correlate with the severity of COVID-19 (P < 0.05). Multivariate logistic regression analysis showed that NLR was an independent risk factor for severe COVID-19 (OR=1.264, 95% CI: 1.046-1.526, P=0.015) with an AUC of 0.831 (95% CI: 0.730-0.932), an optimal diagnostic threshold of 4.795, a sensitivity of 0.839, and a specificity of 0.750. CONCLUSIONS An increased NLR can serve as an early warning signal of severe COVID-19.", "qid": 25, "docid": "japmze1b", "rank": 45, "score": 0.8306716680526733}, {"content": "Title: A comparative study on the clinical features of COVID-19 pneumonia to other pneumonias Content: BACKGROUND: A novel coronavirus (2019-nCoV) has raised world concern since it emerged in Wuhan Hubei China in December, 2019. The infection may result into severe pneumonia with clusters illness onsets. Its impacts on public health make it paramount to clarify the clinical features with other pneumonias. METHODS: Nineteen 2019-nCoV pneumonia (NCOVID-19) and fifteen other pneumonia patients (NON-NCOVID-19) in out of Hubei places were involved in this study. Both NCOVID-19 and NON-NCOVID-19 patients were confirmed to be infected in throat swabs or/and sputa with or without 2019-nCoV by real-time RT-PCR. We analyzed the demographic, epidemiological, clinical, and radiological features from those patients, and compared the difference between NCOVID-19 and NON-NCOVID-19. RESULTS: All patients had a history of exposure to confirmed case of 2019-nCoV or travel to Hubei before illness. The median duration, respectively, was 8 (IQR:6~11) and 5 (IQR:4~11) days from exposure to onset in NCOVID-19 and NON-NCOVID-19. The clinical symptoms were similar between NCOVID-19 and NON-NCOVID-19. The most common symptoms were fever and cough. Fifteen (78.95%) NCOVID-19 but 4 (26.67%) NON-NCOVID-19 patients had bilateral involvement while 17 (89.47%) NCOVID-19 but 1 (6.67%) NON-NCOVID-19 patients had multiple mottling and ground-glass opacity of chest CT images. Compared to NON-NCOVID-19, NCOVID-19 present remarkably more abnormal laboratory tests including AST, ALT, \u00ce\u00b3-GT, LDH and &#945;-HBDH. CONCLUSION: The 2019-nCoV infection caused similar onsets to other pneumonias. CT scan may be a reliable test for screening NCOVID-19 cases. Liver function damage is more frequent in NCOVID-19 than NON-NCOVID-19 patients. LDH and &#945;-HBDH may be considerable markers for evaluation of NCOVID-19.", "qid": 25, "docid": "bveq7kpp", "rank": 46, "score": 0.8305709362030029}, {"content": "Title: C\u2010reactive protein correlates with computed tomographic findings and predicts severe COVID\u201019 early Content: COVID\u201019 has developed into a worldwide pandemic; early identification of severe illness is critical for controlling it and improving the prognosis of patients with limited medical resources. The present study aimed to analyze the characteristics of severe COVID\u201019 and identify biomarkers for differential diagnosis and prognosis prediction. In total, 27 consecutive patients with COVID\u201019 and 75 patients with flu were retrospectively enrolled. Clinical parameters were collected from electronic medical records. The disease course was divided into four stages: initial, progression, peak, and recovery stages, according to computed tomography (CT) progress. to mild COVID\u201019, the lymphocytes in the severe COVID\u201019 progressively decreased at the progression and the peak stages, but rebound in the recovery stage. The levels of C\u2010reactive protein (CRP) in the severe group at the initial and progression stages were higher than those in the mild group. Correlation analysis showed that CRP (R = .62; P < .01), erythrocyte sedimentation rate (R = .55; P < .01) and granulocyte/lymphocyte ratio (R = .49; P < .01) were positively associated with the CT severity scores. In contrast, the number of lymphocytes (R = \u2212.37; P < .01) was negatively correlated with the CT severity scores. The receiver\u2010operating characteristic analysis demonstrated that area under the curve of CRP on the first visit for predicting severe COVID\u201019 was 0.87 (95% CI 0.10\u20131.00) at 20.42 mg/L cut\u2010off, with sensitivity and specificity 83% and 91%, respectively. CRP in severe COVID\u201019 patients increased significantly at the initial stage, before CT findings. Importantly, CRP, which was associated with disease development, predicted early severe COVID\u201019.", "qid": 25, "docid": "xfptlkuc", "rank": 47, "score": 0.8305169343948364}, {"content": "Title: Does infection of 2019 novel coronavirus cause acute and/or chronic sialadenitis? Content: 2019 novel coronavirus (2019-nCoV) is widespread in China and other countries. The target of 2019-nCoV and severe acute respiratory syndrome coronavirus (SARS-CoV) is angiotensin-converting enzyme 2 (ACE2) positive cells. ACE2 is present in the salivary gland duct epithelium, and thus it could be the target of 2019-nCoV and SARS-CoV. SARS-CoV-related animal model experiments show that it can infect the epithelial cells on the salivary gland duct in Chinese rhesus macaques by targeting ACE2. Clinical studies confirmed that 2019-nCoV and SARS-CoV could be detected in saliva of human patients. We hypothesize that the infection of 2019-nCoV and SARS-CoV will lead to inflammatory pathological lesions in patients' target organs, and possibly inflammatory lesions in salivary glands. 2019-nCoV may cause acute sialoadenitis in the acute phase of infection. After the acute phase, chronic sialoadenitis may be caused by fibrosis repairment. Although there was no direct evidence to prove this, the available indirect evidence indicates a high probability of our hypothesis.", "qid": 25, "docid": "q7e8xa4u", "rank": 48, "score": 0.8305137157440186}, {"content": "Title: Clinical diagnosis of 8274 samples with 2019-novel coronavirus in Wuhan Content: Background: 2019-Novel coronavirus (2019-nCoV) outbreaks create challenges for hospital laboratories because thousands of samples must be evaluated each day. Sample types, interpretation methods, and corresponding laboratory standards must be established. The possibility of other infections should be assessed to provide a basis for clinical classification, isolation, and treatment. Accordingly, in the present study, we evaluated the testing methods for 2019-nCoV and co-infections. Methods: We used a fluorescence-based quantitative PCR kit urgently distributed by the Chinese CDC to detect 8274 close contacts in the Wuhan region against two loci on the 2019-nCoV genome. We also analyzed 613 patients with fever who underwent multiple tests for 13 respiratory pathogens; 316 subjects were also tested for 2019-nCoV. Findings: Among the 8274 subjects, 2745 (33.2%) had 2019-nCoV infection; 5277 (63.8%) subjects showed negative results in the 2019-nCoV nucleic acid test (non-019-nCoV); and 252 cases (3.0%) because only one target was positive, the diagnosis was not definitive. Sixteen patients who originally had only one positive target were re-examined a few days later; 14 patients (87.5%) were finally defined as 2019-nCoV-positive, and 2 (12.5%) were finally defined as negative. The positive rates of nCoV-NP and nCovORF1ab were 34.7% and 34.7%, respectively. nCoV-NP-positive only and nCovORF1ab-positive cases accounted for 1.5% and 1.5%, respectively. In the 316 patients with multiple respiratory pathogens, 104 were positive for 2019-nCov and 6/104 had co-infection with coronavirus (3/104), influenza A virus (2/104), rhinovirus (2/104), and influenza A H3N2 (1/104); the remaining 212 patients had influenza A virus (11/202), influenza A H3N2 (11/202), rhinovirus (10/202), respiratory syncytial virus (7/202), influenza B virus (6/202), metapneumovirus (4/202), and coronavirus (2/202). Interpretation: Clinical testing methods for 2019-nCoV require improvement. Importantly, 5.8% of 2019-nCoV infected and 18.4% of non-2019-nCoV-infected patients had other pathogen infections. It is important to treat combined infections and perform rapid screening to avoid cross-contamination of patients. A test that quickly and simultaneously screens as many pathogens as possible is needed.", "qid": 25, "docid": "78qyuk5x", "rank": 49, "score": 0.8304510116577148}, {"content": "Title: A host-protein signature is superior to other biomarkers for differentiating between bacterial and viral disease in patients with respiratory infection and fever without source: a prospective observational study Content: Bacterial and viral infections often present with similar symptoms. Etiologic misdiagnosis can alter the trajectory of patient care, including antibiotic overuse. A host-protein signature comprising tumor necrosis factor-related apoptosis-inducing ligand (TRAIL), interferon gamma-induced protein-10 (IP-10), and C-reactive protein (CRP) was validated recently for differentiating bacterial from viral disease. However, a focused head-to-head comparison of its diagnostic performance against other biomarker candidates for this indication was lacking in patients with respiratory infection and fever without source. We compared the signature to other biomarkers and prediction rules using specimens collected prospectively at two secondary medical centers from children and adults. Inclusion criteria included fever > 37.5 \u00b0C, symptom duration \u2264 12 days, and presentation with respiratory infection or fever without source. Comparator method was based on expert panel adjudication. Signature and biomarker cutoffs and prediction rules were predefined. Of 493 potentially eligible patients, 314 were assigned unanimous expert panel diagnosis and also had sufficient specimen volume. The resulting cohort comprised 175 (56%) viral and 139 (44%) bacterial infections. Signature sensitivity 93.5% (95% CI 89.1\u201397.9%), specificity 94.3% (95% CI 90.7\u201398.0%), or both were significantly higher (all p values < 0.01) than for CRP, procalcitonin, interleukin-6, human neutrophil lipocalin, white blood cell count, absolute neutrophil count, and prediction rules. Signature identified as viral 50/57 viral patients prescribed antibiotics, suggesting potential to reduce antibiotic overuse by 88%. The host-protein signature demonstrated superior diagnostic performance in differentiating viral from bacterial respiratory infections and fever without source. Future utility studies are warranted to validate potential to reduce antibiotic overuse. ELECTRONIC SUPPLEMENTARY MATERIAL: The online version of this article (10.1007/s10096-018-3261-3) contains supplementary material, which is available to authorized users.", "qid": 25, "docid": "v08kag9w", "rank": 50, "score": 0.8300617933273315}, {"content": "Title: [Potential biomarkers predictors of mortality in COVID-19 patients in the Emergency Department]. Content: OBJECTIVE Identify which biomarkers performed in the first emergency analysis help to stratify COVID-19 patients according to mortality risk. METHODS Observational, descriptive and cross-sectional study performed with data collected from patients with suspected COVID-19 in the Emergency Department from February 24 to March 16, 2020. The univariate and multivariate study was performed to find independent mortality markers and calculate risk by building a severity score. RESULTS A total of 163 patients were included, of whom 33 died and 29 of them were positive for the COVID-19 PCR test. We obtained as possible factors to conform the Mortality Risk Score age> 75 years ((adjusted OR = 12,347, 95% CI: 4,138-36,845 p = 0.001), total leukocytes> 11,000 cells / mm3 (adjusted OR = 2,649, 95% CI: 0.879-7.981 p = 0.083), glucose> 126 mg / dL (adjusted OR = 3.716, 95% CI: 1.247-11.074 p = 0.018) and creatinine> 1.1 mg / dL (adjusted OR = 2.566, 95% CI: 0.889- 7.403, p = 0.081) This score was called COVEB (COVID, Age, Basic analytical profile) with an AUC 0.874 (95% CI: 0.816-0.933, p <0.001; Cut-off point = 1 (sensitivity = 89.66 % (95% CI: 72.6% -97.8%), specificity = 75.59% (95% CI: 67.2% -82.8%). A score <1 has a negative predictive value = 100% (95% CI: 93.51% -100%) and a positive predictive value = 18.59% (95% CI: 12.82% -25.59%). CONCLUSIONS Clinical severity scales, kidney function biomarkers, white blood cell count parameters, the total neutrophils / total lymphocytes ratio and procalcitonin are early risk factors for mortality. The variables age, glucose, creatinine and total leukocytes stand out as the best predictors of mortality. A COVEB score <1 indicates with a 100% probability that the patient with suspected COVID-19 will not die in the next 30 days.", "qid": 25, "docid": "goh51sya", "rank": 51, "score": 0.829908013343811}, {"content": "Title: Identification and validation of a novel clinical signature to predict the prognosis in confirmed COVID-19 patients Content: BACKGROUND: This study aims to identify a prognostic biomarker to predict the disease prognosis and reduce the mortality rate of COVID-19, which has caused a worldwide pandemic. METHODS: COVID-19 patients were randomly divided into training and test groups. Univariate and multivariate Cox regression analyses were performed to identify the disease prognosis signature, which was selected to establish a risk model in the training group. Furthermore, the disease prognosis signature of COVID-19 was validated in the test group. RESULTS: The signature of COVID-19 was combined with five indicators, namely neutrophil count, lymphocyte count, procalcitonin, older age, and C-reactive protein. The signature stratified patients into high- and low-risk groups with significantly relevant disease prognosis (log-rank test, P<0.001) in the training group. The survival analysis indicated that the high-risk group displayed substantially lower survival probability than the low-risk group (log-rank test P<0.001). The area under ROC curve (AUC) showed that the signature of COVID-19 displayed the highest predictive accuracy regarding disease prognosis, which was 0.955 in the training group and 0.945 in the test group. The ROC analysis of both groups demonstrated that the predictive ability of the signature surpassed the use of each of the five indicators alone. CONCLUSION: The signature of COVID-19 presents a novel predictor and prognostic biomarker for closely monitoring patients and providing timely treatment for those who are severely or critically ill.", "qid": 25, "docid": "0tte9rf6", "rank": 52, "score": 0.8298261761665344}, {"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": 53, "score": 0.8282238245010376}, {"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": 54, "score": 0.8280469179153442}, {"content": "Title: Laboratory characteristics of patients infected with the novel SARS-CoV-2 virus Content: A subgroup of COVID-19 patients develop very severe disease with requirement for ICU treatment, ventilation, and ECMO therapy. Laboratory tests indicate that the immune and clotting system show marked alterations with hyper-activation, hyper-inflammation, cytokine storm development. Furthermore, organ-specific biomarkers demonstrate the involvement of cardiac muscle, kidney, and liver dysfunction in many patients. In this article the use of laboratory biomarkers is discussed with regard to their use for diagnosis, disease progression, and risk assessment.", "qid": 25, "docid": "j79dfjfh", "rank": 55, "score": 0.8277629613876343}, {"content": "Title: Prompt Predicting of Early Clinical Deterioration of Moderate-to-Severe COVID-19 Patients: Usefulness of a Combined Score Using IL-6 in a Preliminary Study Content: BACKGROUND: The early identification of patients at risk of clinical deterioration is of interest considering the timeline of COVID-19 after the onset of symptoms. OBJECTIVE: The aim of our study was to evaluate the usefulness of testing serum IL-6 and other serological and clinical biomarkers, to predict a short-term negative clinical course of patients with noncritical COVID-19. METHODS: A total of 208 patients with noncritical COVID-19 pneumonia at admission were consecutively enrolled. Clinical and laboratory findings obtained on admission were analyzed by using survival analysis and stepwise logistic regression for variable selection. Three-day worsening as outcome in a logistic model to generate a prognostic score was used. RESULTS: Clinical worsening occurred in 63 patients (16 = died; 39 = transferred to intensive care unit; 8 worsening of respiratory failure). Forty-five of them worsened within 3 days after admission. The risk of clinical worsening was progressively enhanced along with increasing quartiles of IL-6 levels. Multivariate analysis showed that IL-6 (P = .005), C-reactive protein (CRP) (P = .003), and SaO2/FiO2 (P = .014) were the best predictors for clinical deterioration in the first 3 days after admission. The combined score yielded an area under the curve = 0.88 (95% confidence interval: 0.83-0.93). A nomogram predicting the probability of 3-day worsening was generated. The score also showed good performance for 7-day and 14- or 21-day worsening and in predicting death occurring during all the follow-up. CONCLUSIONS: Combining IL-6, CRP, and SaO2/FiO2 in a score may help clinicians to identify on admission those patients with COVID-19 who are at high risk for a further 3-day clinical deterioration.", "qid": 25, "docid": "hf9q39m7", "rank": 56, "score": 0.8266561031341553}, {"content": "Title: Validation of reported risk factors for disease classification and prognosis in COVID-19: a descriptive and retrospective study Content: Risk indicators viral load (ORF1ab Ct), lymphocyte percentage (LYM%), C-reactive protein (CRP), interleukin-6 (IL-6), procalcitonin (PCT) and lactic acid (LA) in COVID-19 patients have been proposed in recent studies. However, the predictive effects of those indicators on disease classification and prognosis remains largely unknown. We dynamically measured those reported indicators in 132 cases of COVID-19 patients including the moderate-cured (moderated and cured), severe-cured (severe and cured) and critically ill (died). Our data showed that CRP, PCT, IL-6, LYM%, lactic acid and viral load could predict prognosis and guide classification of COVID-19 patients in different degrees. CRP, IL-6 and LYM% were more effective than other three factors in predicting prognosis. For disease classification, CRP and LYM% were sensitive in identifying the types between critically ill and severe (or moderate). Notably, among the investigated factors, LYM% was the only one that could distinguish between the severe and moderate types. Collectively, we concluded that LYM% was the most sensitive and reliable predictor for disease typing and prognosis. During the COVID-19 pandemic, the precise classification and prognosis prediction are critical for saving the insufficient medical resources, stratified treatment and improving the survival rate of critically ill patients. We recommend that LYM% be used independently or in combination with other indicators in the management of COVID-19.", "qid": 25, "docid": "j90jc0rj", "rank": 57, "score": 0.8266250491142273}, {"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": 58, "score": 0.8264064788818359}, {"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": 59, "score": 0.8264064788818359}, {"content": "Title: Clinical Laboratory Parameters Associated with Severe or Critical Novel Coronavirus Disease 2019 (COVID-19): A Systematic Review and Meta-analysis Content: Background: To date, several clinical laboratory parameters associated with COVID-19 severity have been reported. However, these parameters have not been observed consistently across studies. The aim of this review was to assess clinical laboratory parameters which may serve as markers or predictors of severe or critical COVID-19 disease Methods: We conducted a systematic search of MEDLINE, Embase, Web of Science, CINAHL and Google Scholar databases from 2019 through April 18, 2020, and reviewed bibliographies of eligible studies, relevant systematic reviews, and the medRxiv pre-print server. We included hospital-based observational studies reporting clinical laboratory parameters of confirmed cases of COVID-19 and excluded studies having large proportions (>10%) of children and pregnant women. Two authors independently carried out screening of articles, data extraction and quality assessment. Meta-analyses were done using random effects model. Meta-median difference (MMD) and 95% confidence interval (CI) was calculated for each laboratory parameter. Results: Forty-five studies in 6 countries were included. Compared to non-severe COVID-19 cases, severe or critical COVID-19 disease was characterised by higher neutrophil count (MMD: 1.23 [95% CI: 0.58 to 1.88] x109 cells/L), and lower lymphocyte and CD4 counts with MMD (95% CI) of -0.39 (-0.47, -0.31) x109 cells/L and -204.9 (-302.6, -107.1) cells/l, respectively. Other notable results were observed for C-reactive protein (MMD: 36.97 [95% CI: 27.58, 46.35] mg/L), interleukin-6 (MMD: 17.37 [95% CI: 4.74, 30.00] pg/ml,), Troponin I (MMD: 0.01 [0.00, 0.02] ng/ml), and D-dimer (MMD: 0.65 [0.45, 0.85] mg/ml). Conclusions and Relevance: Relative to non-severe COVID-19, severe or critical COVID-19 is characterised by increased markers of innate immune response, decreased markers of adaptive immune response, and increased markers of tissue damage and major organ failure. These markers could be used to recognise severe or critical disease and to monitor clinical course of COVID-19.", "qid": 25, "docid": "50usynmq", "rank": 60, "score": 0.8263695240020752}, {"content": "Title: Clinical characteristics of novel coronavirus cases in tertiary hospitals in Hubei Province Content: BACKGROUND: The 2019 novel coronavirus (2019-nCoV) causing an outbreak of pneumonia in Wuhan, Hubei province of China was isolated in January 2020. This study aims to investigate its epidemiologic history, and analyze the clinical characteristics, treatment regimens, and prognosis of patients infected with 2019-nCoV during this outbreak. METHODS: Clinical data from 137 2019-nCoV-infected patients admitted to the respiratory departments of nine tertiary hospitals in Hubei province from December 30, 2019 to January 24, 2020 were retrospectively collected, including general status, clinical manifestations, laboratory test results, imaging characteristics, and treatment regimens. RESULTS: None of the 137 patients (61 males, 76 females, aged 20-83 years, median age 57 years) had a definite history of exposure to Huanan Seafood Wholesale Market. Major initial symptoms included fever (112/137, 81.8%), coughing (66/137, 48.2%), and muscle pain or fatigue (44/137, 32.1%), with other, less typical initial symptoms observed at low frequency, including heart palpitations, diarrhea, and headache. Nearly 80% of the patients had normal or decreased white blood cell counts, and 72.3% (99/137) had lymphocytopenia. Lung involvement was present in all cases, with most chest computed tomography scans showing lesions in multiple lung lobes, some of which were dense; ground-glass opacity co-existed with consolidation shadows or cord-like shadows. Given the lack of effective drugs, treatment focused on symptomatic and respiratory support. Immunoglobulin G was delivered to some critically ill patients according to their conditions. Systemic corticosteroid treatment did not show significant benefits. Notably, early respiratory support facilitated disease recovery and improved prognosis. The risk of death was primarily associated with age, underlying chronic diseases, and median interval from the appearance of initial symptoms to dyspnea. CONCLUSIONS: The majority of patients with 2019-nCoV pneumonia present with fever as the first symptom, and most of them still showed typical manifestations of viral pneumonia on chest imaging. Middle-aged and elderly patients with underlying comorbidities are susceptible to respiratory failure and may have a poorer prognosis.", "qid": 25, "docid": "f02tg7h3", "rank": 61, "score": 0.8260129690170288}, {"content": "Title: Can routine laboratory tests discriminate 2019 novel coronavirus infected pneumonia from other community-acquired pneumonia? Content: Background. The clinical presentation of 2019 Novel Coronavirus (2019-nCov) infected pneumonia (NCIP) resembles that of other etiologies of community-acquired pneumonia (CAP). We aimed to identify clinical laboratory features to distinguish NCIP from CAP. Methods. We compared the ability of the hematological and biochemical features of 84 patients with NCIP at hospital admission and 316 patients with CAP. Parameters independently predictive of NCIP were calculated by multivariate logistic regression. The receiver operating characteristic (ROC) curves were generated and the area under the ROC curve (AUC) was measured to evaluate the discriminative ability. Results. Most hematological and biochemical indexes of patients with NCIP were significantly different from patients with CAP. Nine laboratory parameters were identified to be highly predictive of a diagnosis of NCIP by multivariate analysis. The AUCs demonstrated good discriminatory ability for red cell distribution width (RDW) with an AUC of 0.88 and Hemoglobin (HGB) with an AUC of 0.82. Red blood cell (RBC), albumin (ALB), eosinophil (EO), hematocrit (HCT), alkaline phosphatase (ALP), and white blood cell (WBC) had fair discriminatory ability. Combinations of any two parameters performed better than did the RDW alone. Conclusions. Routine laboratory examinations may be helpful for the diagnosis of NCIP. Application of laboratory tests may help to optimize the use of isolation rooms for patients when they present with unexplained febrile respiratory illnesses.", "qid": 25, "docid": "dy28eo89", "rank": 62, "score": 0.8258895874023438}, {"content": "Title: Novel coronavirus and central nervous system. Content: An outbreak of a novel coronavirus (2019-nCoV) that emerged in Wuhan has rapidly spread throughout China and has now become a global public health concern. As of the early March, a total of 100,000 cases have been confirmed in multiple countries. Clinical characteristics of 2019-nCoV that respiratory symptoms, such as cough, are the most common.[1] This is consistent with the finding that the majority of patients are virus-positive in nasopharyngeal and oropharyngeal swabs suggesting it mainly invades and infects the respiratory system, a hypothesis supported by pathological data.[2] In addition, it has been reported that patients' stool has tested positive for 2019-nCoV, indicating that the virus could spread from the respiratory tract to the digestive tract, or that individuals could be infected via the faecal-oral route. However, the neuroinvasive potential of 2019-nCoV remains poorly understood.", "qid": 25, "docid": "o4rvq84o", "rank": 63, "score": 0.8255739212036133}, {"content": "Title: C-reactive protein, procalcitonin, D-dimer, and ferritin in severe coronavirus disease-2019: a meta-analysis Content: BACKGROUND: Patients critically ill with coronavirus disease-2019 (COVID-19) feature hyperinflammation, and the associated biomarkers may be beneficial for risk stratification. We aimed to investigate the association between several biomarkers, including serum C-reactive protein (CRP), procalcitonin (PCT), D-dimer, and serum ferritin, and COVID-19 severity. METHODS: We performed a comprehensive systematic literature search through electronic databases. The outcome of interest for this study was the composite poor outcome, which comprises mortality, acute respiratory distress syndrome, need for care in an intensive care unit, and severe COVID-19. RESULTS: A total of 5350 patients were pooled from 25 studies. Elevated CRP was associated with an increased composite poor outcome [risk ratio (RR) 1.84 (1.45, 2.33), p < 0.001; I2: 96%] and its severe COVID-19 (RR 1.41; I2: 93%) subgroup. A CRP \u00e2\u00a9\u00be10 mg/L has a 51% sensitivity, 88% specificity, likelihood ratio (LR) + of 4.1, LR- of 0.5, and an area under curve (AUC) of 0.84. An elevated PCT was associated with an increased composite poor outcome [RR 3.92 (2.42, 6.35), p < 0.001; I2: 85%] and its mortality (RR 6.26; I2: 96%) and severe COVID-19 (RR 3.93; I2: 63%) subgroups. A PCT \u00e2\u00a9\u00be0.5 ng/ml has an 88% sensitivity, 68% specificity, LR+ of 2.7, LR- of 0.2, and an AUC of 0.88. An elevated D-dimer was associated with an increased composite poor outcome [RR 2.93 (2.14, 4.01), p < 0.001; I2: 77%], including its mortality (RR 4.15; I2: 83%) and severe COVID-19 (RR 2.42; I2: 58%) subgroups. A D-dimer >0.5 mg/L has a 58% sensitivity, 69% specificity, LR+ of 1.8, LR- of 0.6, and an AUC of 0.69. Patients with a composite poor outcome had a higher serum ferritin with a standardized mean difference of 0.90 (0.64, 1.15), p < 0.0001; I2: 76%. CONCLUSION: This meta-analysis showed that an elevated serum CRP, PCT, D-dimer, and ferritin were associated with a poor outcome in COVID-19. The reviews of this paper are available via the supplemental material section.", "qid": 25, "docid": "s92chxzv", "rank": 64, "score": 0.8253219127655029}, {"content": "Title: Clinical and epidemiological characteristics of 34 children with 2019 novel coronavirus infection in Shenzhen/ \u4e2d\u534e\u513f\u79d1\u6742\u5fd7 Content: Objective@#To describe the characteristics of clinical manifestations and epidemiology of children with 2019 novel coronavirus (2019-nCoV) infection.@*Methods@#All 34 children with laboratory-confirmed 2019-nCoV infection by quantitative real-time reverse transcription-PCR through nasopharyngeal swab specimens were admitted to the Third People\u2019s Hospital of Shenzhen from January 19 to Febuary 7, 2020. Clinical data and epidemiological history of these patients were retrospectively collected and analyzed.@*Results@#Among the 34 cases, 14 were males, and 20 were females. The median age was 8 years and 11 months. No patients had underlying diseases. There were 28 children (82%) related with a family cluster outbreak. There were 26 children (76%) with a travel or residence history in Hubei Province. These patients could be categorized into different clinical types, including 22 (65%) common cases, 9 (26%) mild cases and 3 (8.8%) asymptomatic cases. No severe or critical cases were identified. The most common symptoms were fever (17 cases, 50%) and cough (13 cases, 38% ). In the 34 cases, the white blood cell counts of 28 cases (82%) were normal. Five cases had white blood cell counts more than 10\u00d7109/L. One case had white blood cell counts less than 4\u00d7109/L. Neutropenia and lymphopenia was found in one case, respectively. C-reactive protein levels and erythrocyte sedimentation rates were elevated in 1 and 5 case, respectively. Elevated procalcitonin was found in 1 case and D-Dimer in 3 cases. The levels of lactic dehydrogenase (LDH) were more than 400 U/L in 10 cases. The CT images of these patients showed bilateral multiple patchy or nodular ground-glass opacities and/or infiltrating shadows in middle and outer zone of the lung or under the pleura. Twenty patients were treated with lopinavir and ritonavir. Glucocorticoids and immunoglobulin were not used in any cases. All the cases improved and were discharged from hospital. Further following up was need.@*Conclusions@#The clinical manifestations in children with 2019-nCoV infection are non-specific and are milder than that in adults. Chest CT scanning is heplful for early diagnosis. Children&apos;s infection is mainly caused by family cluster outbreak and imported cases. Family daily prevention is the main way to prevent 2019-nCoV infection.", "qid": 25, "docid": "75qd8h9m", "rank": 65, "score": 0.825275182723999}, {"content": "Title: Potential inhibitors for 2019-nCoV coronavirus M protease from clinically approved medicines Content: Starting from December 2019, a novel coronavirus, named 2019-nCoV, was found to cause Severe Acute Respiratory (SARI) symptoms and rapid pandemic in China. With the hope to identify candidate drugs for 2019-nCoV, we adopted a computational approach to screen for available commercial medicines which may function as inhibitors for the Mpro of 2019-nCoV. Up to 10 commercial medicines that may form hydrogen bounds to key residues within the binding pocket of 2019-nCoV Mpro were identified, which may have higher mutation tolerance than lopinavir/ritonavir and may also function as inhibitors for other coronaviruses with similar Mpro binding sites and pocket structures.", "qid": 25, "docid": "yd7tu7u4", "rank": 66, "score": 0.8252503275871277}, {"content": "Title: Clinical features and outcomes of 2019 novel coronavirus-infected patients with cardiac injury Content: Aims To explore the epidemiological and clinical features of 2019 novel coronavirus(2019-nCoV)-infected patients with cardiac injury . Methods and results Data were collected from patients medical records, and we defined cardiac injury according to cardiac biomarker troponin I level > 0.03>ug/L. Among the 291 patients, 15 (5.2%) showed evidence of cardiac injury. Of 16 hospitalized patients with cardiac injury, the median age was 62 years, and 11/15 (73.3%) were men. Underlying cardiovascular diseases in some patients were hypertension (n=7, 46.6%), coronary heart disease (n=3, 20%) and diabetes (n=3, 20%). The most common symptoms at illness onset in patients with cardiac injury were fever (n=11, 73.3%), cough (n=7, 46.7%), headache or fatigue (n=5, 33.3%) and dyspnoea (n=4, 26.6%). These patients had higher systolic pressures, and lower lymphocyte counts and platelet counts, compared with patients without cardiac injury, respectively. Bilateral infiltrates on chest X-ray and elevated C-reactive protein occurred in all patients with cardiac injury. Compared with patients without cardiac injury, patients with cardiac injury were more likely to develop acute respiratory distress syndrome (73.3%), and receive mechanical ventilation (53.4%), continuous renal replacement therapy (33.3%), extracorporeal membrane oxygenation (26.7%) and vasopressor therapy (26.7%) and be admitted to the intensive care unit (73.3%). One patient died during the study. Conclusion Cardiac injury is a common condition among patients infected with 2019-nCoV.Compared with patients without cardiac injury, the clinical outcomes of patients with cardiac injury are relatively worse. Keywords: 2019-nCoV, Cardiac injury, Clinical features", "qid": 25, "docid": "qbxx6yae", "rank": 67, "score": 0.8252188563346863}, {"content": "Title: [Retracted: Clinical and epidemiological characteristics of 34 children with 2019 novel coronavirus infection in Shenzhen] Content: Objective: To describe the characteristics of clinical manifestations and epidemiology of children with 2019 novel coronavirus (2019-nCoV) infection. Methods: All 34 children with laboratory-confirmed 2019-nCoV infection by quantitative real-time reverse transcription-PCR through nasopharyngeal swab specimens were admitted to the Third People's Hospital of Shenzhen from January 19 to Febuary 7, 2020. Clinical data and epidemiological history of these patients were retrospectively collected and analyzed. Results: Among the 34 cases, 14 were males, and 20 were females. The median age was 8 years and 11 months. No patients had underlying diseases. There were 28 children (82%) related with a family cluster outbreak. There were 26 children (76%) with a travel or residence history in Hubei Province. These patients could be categorized into different clinical types, including 22 (65%) common cases, 9 (26%) mild cases and 3 (8.8%) asymptomatic cases. No severe or critical cases were identified. The most common symptoms were fever (17 cases, 50%) and cough (13 cases, 38% ). In the 34 cases, the white blood cell counts of 28 cases (82%) were normal. Five cases had white blood cell counts more than 10\u00d710(9)/L. One case had white blood cell counts less than 4\u00d710(9)/L. Neutropenia and lymphopenia was found in one case, respectively. C-reactive protein levels and erythrocyte sedimentation rates were elevated in 1 and 5 case, respectively. Elevated procalcitonin was found in 1 case and D-Dimer in 3 cases. The levels of lactic dehydrogenase (LDH) were more than 400 U/L in 10 cases. The CT images of these patients showed bilateral multiple patchy or nodular ground-glass opacities and/or infiltrating shadows in middle and outer zone of the lung or under the pleura. Twenty patients were treated with lopinavir and ritonavir. Glucocorticoids and immunoglobulin were not used in any cases. All the cases improved and were discharged from hospital. Further following up was need. Conclusions: The clinical manifestations in children with 2019-nCoV infection are non-specific and are milder than that in adults. Chest CT scanning is heplful for early diagnosis. Children's infection is mainly caused by family cluster outbreak and imported cases. Family daily prevention is the main way to prevent 2019-nCoV infection.", "qid": 25, "docid": "a0dpwsuf", "rank": 68, "score": 0.825210452079773}, {"content": "Title: [Clinical and epidemiological characteristics of 34 children with 2019 novel coronavirus infection in Shenzhen]. Content: Objective: To describe the characteristics of clinical manifestations and epidemiology of children with 2019 novel coronavirus (2019-nCoV) infection. Methods: All 34 children with laboratory-confirmed 2019-nCoV infection by quantitative real-time reverse transcription-PCR through nasopharyngeal swab specimens were admitted to the Third People's Hospital of Shenzhen from January 19 to Febuary 7, 2020. Clinical data and epidemiological history of these patients were retrospectively collected and analyzed. Results: Among the 34 cases, 14 were males, and 20 were females. The median age was 8 years and 11 months. No patients had underlying diseases. There were 28 children (82%) related with a family cluster outbreak. There were 26 children (76%) with a travel or residence history in Hubei Province. These patients could be categorized into different clinical types, including 22 (65%) common cases, 9 (26%) mild cases and 3 (8.8%) asymptomatic cases. No severe or critical cases were identified. The most common symptoms were fever (17 cases, 50%) and cough (13 cases, 38% ). In the 34 cases, the white blood cell counts of 28 cases (82%) were normal. Five cases had white blood cell counts more than 10\u00d710(9)/L. One case had white blood cell counts less than 4\u00d710(9)/L. Neutropenia and lymphopenia was found in one case, respectively. C-reactive protein levels and erythrocyte sedimentation rates were elevated in 1 and 5 case, respectively. Elevated procalcitonin was found in 1 case and D-Dimer in 3 cases. The levels of lactic dehydrogenase (LDH) were more than 400 U/L in 10 cases. The CT images of these patients showed bilateral multiple patchy or nodular ground-glass opacities and/or infiltrating shadows in middle and outer zone of the lung or under the pleura. Twenty patients were treated with lopinavir and ritonavir. Glucocorticoids and immunoglobulin were not used in any cases. All the cases improved and were discharged from hospital. Further following up was need. Conclusions: The clinical manifestations in children with 2019-nCoV infection are non-specific and are milder than that in adults. Chest CT scanning is heplful for early diagnosis. Children's infection is mainly caused by family cluster outbreak and imported cases. Family daily prevention is the main way to prevent 2019-nCoV infection.", "qid": 25, "docid": "t1n4fbsi", "rank": 69, "score": 0.825210452079773}, {"content": "Title: C-reactive protein, procalcitonin, D-dimer, and ferritin in severe coronavirus disease-2019: a meta-analysis Content: BACKGROUND: Patients critically ill with coronavirus disease-2019 (COVID-19) feature hyperinflammation, and the associated biomarkers may be beneficial for risk stratification. We aimed to investigate the association between several biomarkers, including serum C-reactive protein (CRP), procalcitonin (PCT), D-dimer, and serum ferritin, and COVID-19 severity. METHODS: We performed a comprehensive systematic literature search through electronic databases. The outcome of interest for this study was the composite poor outcome, which comprises mortality, acute respiratory distress syndrome, need for care in an intensive care unit, and severe COVID-19. RESULTS: A total of 5350 patients were pooled from 25 studies. Elevated CRP was associated with an increased composite poor outcome [risk ratio (RR) 1.84 (1.45, 2.33), p < 0.001; I(2): 96%] and its severe COVID-19 (RR 1.41; I(2): 93%) subgroup. A CRP \u2a7e10 mg/L has a 51% sensitivity, 88% specificity, likelihood ratio (LR) + of 4.1, LR- of 0.5, and an area under curve (AUC) of 0.84. An elevated PCT was associated with an increased composite poor outcome [RR 3.92 (2.42, 6.35), p < 0.001; I(2): 85%] and its mortality (RR 6.26; I(2): 96%) and severe COVID-19 (RR 3.93; I(2): 63%) subgroups. A PCT \u2a7e0.5 ng/ml has an 88% sensitivity, 68% specificity, LR+ of 2.7, LR- of 0.2, and an AUC of 0.88. An elevated D-dimer was associated with an increased composite poor outcome [RR 2.93 (2.14, 4.01), p < 0.001; I(2): 77%], including its mortality (RR 4.15; I(2): 83%) and severe COVID-19 (RR 2.42; I(2): 58%) subgroups. A D-dimer >0.5 mg/L has a 58% sensitivity, 69% specificity, LR+ of 1.8, LR- of 0.6, and an AUC of 0.69. Patients with a composite poor outcome had a higher serum ferritin with a standardized mean difference of 0.90 (0.64, 1.15), p < 0.0001; I(2): 76%. CONCLUSION: This meta-analysis showed that an elevated serum CRP, PCT, D-dimer, and ferritin were associated with a poor outcome in COVID-19. The reviews of this paper are available via the supplemental material section.", "qid": 25, "docid": "izzavogm", "rank": 70, "score": 0.8250738382339478}, {"content": "Title: Plasma albumin levels predict risk for nonsurvivors in critically ill patients with COVID-19 Content: Aim: We aimed to explore the biomarkers for disease progression or the risk of nonsurvivors. Materials & methods: This study included 134 hospitalized patients with confirmed COVID-19 infection. The outcome of moderate versus severe versus critically ill patients and survivors versus nonsurvivors were compared. Results: An increase in the severity of COVID-19 pneumonia was positively associated with lower levels of platelets and albumin (all p < 0.05). In the critical group, the plasma levels of albumin continued to have a significant association for the risk of nonsurvivors (p < 0.05), even after adjusting for confounding factors. Conclusion: Albumin levels could be used as an independent predictor of the risk of nonsurvivors in critically ill patients with COVID-19.", "qid": 25, "docid": "kbp47abd", "rank": 71, "score": 0.824936032295227}, {"content": "Title: [Study on treatment of \"cytokine storm\" by anti-2019-nCoV prescriptions based on arachidonic acid metabolic pathway]. Content: Since the outbreak of 2019-nCoV, the epidemic has developed rapidly and the situation is grim. LANCET figured out that the 2019-nCoV is closely related to \"cytokine storm\". \"Cytokine storm\" is an excessive immune response of the body to external stimuli such as viruses and bacteria. As the virus attacking the body, it stimulates the secretion of a large number of inflammatory factors: interleukin(IL), interferon(IFN), C-X-C motif chemokine(CXCL) and so on, which lead to cytokine cascade reaction. With the exudation of inflammatory factors, cytokines increase abnormally in tissues and organs, interfering with the immune system, causing excessive immune response of the body, resulting in diffuse damage of lung cells, pulmonary fibrosis, and multiple organ damage, even death. Arachidonic acid(AA) metabolic pathway is principally used to synthesize inflammatory cytokines, such as monocyte chemotactic protein 1(MCP-1), tumor necrosis factor(TNF), IL, IFN, etc., which is closely related to the occurrence, development and regression of inflammation. Therefore, the inhibition of AA metabolism pathway is benefit for inhibiting the release of inflammatory factors in the body and alleviating the \"cytokine storm\". Based on the pharmacophore models of the targets on AA metabolic pathway, the traditional Chinese medicine database 2009(TCMD 2009) was screened. The potential herbs were ranked by the number of hit molecules, which were scored by pharmacophore fit value. In the end, we obtained the potential active prescriptions on \"cytokine storm\" according to the potential herbs in the \"National novel coronavirus pneumonia diagnosis and treatment plan(trial version sixth)\". The results showed that the hit components with the inhibitory effect on AA were magnolignan \u2160, lonicerin and physcion-8-O-\u03b2-D-glucopy-ranoside, which mostly extracted from Magnoliae Officinalis Cortex, Zingiberis Rhizoma Recens, Lonicerae Japonicae Flos, Rhei Radix et Rhizoma, Salviae Miltiorrhizae Radix et Rhizoma, Scutellariae Radix, Gardeniae Fructus, Ginseng Radix et Rhizoma, Arctii Fructus, Dryopteridis Crassirhizomatis Rhizoma, Paeoniaeradix Rubra, Dioscoreae Rhizoma. Finally the anti-2019-nCoV prescriptions were analyzed to obtain the potential active prescriptions on AA metabolic pathway, Huoxiang Zhengqi Capsules, Jinhua Qinggan Granules, Lianhua Qingwen Capsules, Qingfei Paidu Decoction, Xuebijing Injection, Reduning Injection and Tanreqing Injection were found that may prevent 2019-nCoV via regulate cytokines. This study intends to provide reference for clinical use of traditional Chinese medicine to resist new coronavirus.", "qid": 25, "docid": "2plg8f0u", "rank": 72, "score": 0.8248908519744873}, {"content": "Title: Prognosis of COVID-19: Changes in laboratory parameters. Content: INTRODUCTION Since December 2019, an outbreak of coronavirus disease 2019 (COVID-19) caused by Severe Acute Respiratory Syndrome - Coronavirus 2 (SARS-CoV-2) emerged in China and has become a global threat. Comparison of hematological parameters between mild and severe cases of SARS-CoV 2 is so far limited, but significant differences in parameters such as interleukin-6, d-dimers, glucose, fibrinogen and C-reactive protein have been already reported. PURPOSE In this study we analyzed the changes observed in easily measured blood biomarkers in the patients and provided evidence of how these markers can be used as prognostic factors of the disease. METHODS Demographic characteristics, detailed medical history, and laboratory findings of all enrolled SARS-CoV 2 infection positive patients who were referred to Patras University Hospital from the period of March 4th 2020 (when first confirmed case in Greece appeared in our hospital) until April 4th 2020 were extracted from electronic medical records and analyzed. RESULTS We provided evidence that some very common laboratory values can be used as independent predictive factors in SARS-CoV 2 infection. Despite the retrospective nature of this study and the small number of subjects analyzed, we showed that NLR, LDH, d-dimers, CRP, fibrinogen and ferritin can be used early at the patient's first visit for SARS-CoV 2 infection symptoms and can predict the severity of infection. CONCLUSION More studies are warranted to further objectively confirm the clinical value of prognostic factors related to SARS-CoV 2 and establish an easy-to-get panel of laboratory findings for evaluating the disease severity.", "qid": 25, "docid": "ljc7ojzt", "rank": 73, "score": 0.8248754739761353}, {"content": "Title: Current status of treatment for 2019 novel coronavirus pneumonia/ 2019\u65b0\u578b\u51a0\u72b6\u75c5\u6bd2\u80ba\u708e\u6cbb\u7597\u7814\u7a76\u73b0\u72b6 Content: 2019 novel coronavirus (2019-nCoV) is a new member of coronavirus family that can cause serious respiratory diseases after the emergence of severe acute respiratory syndrome-coronavirus (SARS-CoV) and middle east respiratory syndrome-coronavirus (MERS-CoV). At present, there is no specific antiviral drug targeting 2019-nCoV. In facing of the increasingly serious epidemic of 2019-nCoV pneumonia and the urgent needs in drug treatment strategies, this paper reviewed the current research situation and progress in antiviral treatment for the newly identified disease.", "qid": 25, "docid": "ohj61ee5", "rank": 74, "score": 0.8248231410980225}, {"content": "Title: Does infection of 2019 novel coronavirus cause acute and/or chronic sialadenitis? Content: Abstract 2019 novel coronavirus (2019-nCoV) is widespread in China and other countries. The target of 2019-nCoV and severe acute respiratory syndrome coronavirus (SARS-CoV) is angiotensin-converting enzyme 2 (ACE2) positive cells. ACE2 is present in the salivary gland duct epithelium, and thus it could be the target of 2019-nCoV and SARS-CoV. SARS-CoV-related animal model experiments show that it can infect the epithelial cells on the salivary gland duct in Chinese rhesus macaques by targeting ACE2. Clinical studies confirmed that 2019-nCoV and SARS-CoV could be detected in saliva of human patients. We hypothesize that the infection of 2019-nCoV and SARS-CoV will lead to inflammatory pathological lesions in patients\u2019 target organs, and possibly inflammatory lesions in salivary glands. 2019-nCoV may cause acute sialoadenitis in the acute phase of infection. After the acute phase, chronic sialoadenitis may be caused by fibrosis repairment. Although there was no direct evidence to prove this, the available indirect evidence indicates a high probability of our hypothesis.", "qid": 25, "docid": "sof70xa1", "rank": 75, "score": 0.8247373700141907}, {"content": "Title: Lipocalin-2 is a Sensitive and Specific Marker of Bacterial Infection in Children Content: Bacterial infection is the leading cause of death in children globally. Clinical algorithms to identify children who are likely to benefit from antimicrobial treatment remain suboptimal. Biomarkers that accurately identify serious bacterial infection (SBI) could improve diagnosis and clinical management. Lipocalin 2 (LCN2) and neutrophil collagenase (MMP-8) are neutrophil-derived biomarkers associated with bacterial infection. We evaluated LCN2 and MMP-8 as candidate biomarkers in 40 healthy controls and 151 febrile children categorised confirmed SBI, probable SBI, or viral infection. The diagnostic performance of LCN2 and MMP-8 to predict SBI was estimated by the area under the receiver operating characteristic curve (AUROC) and compared to the performance of C-reactive protein (CRP). Plasma LCN2 and MMP-8 concentration were predictive of SBI. The AUROC (95% CI) for LCN2, MMP8 and CRP to predict SBI was 0.88 (0.82-0.94); 0.80 (0.72-0.87) and 0.89 (0.84-0.94), respectively. The diagnostic performance of LCN2 in combination with CRP was significantly superior to either marker alone: AUROC 0.92 (95% CI: 0.88-0.96). LCN2 is a sensitive and specific predictor of SBI in children which could be used to improve clinical management and antimicrobial stewardship. LCN2 should be further evaluated in prospective clinical studies.", "qid": 25, "docid": "7ybz0rlp", "rank": 76, "score": 0.8246534466743469}, {"content": "Title: Longitudinal hematologic and immunologic variations associated with the progression of COVID-19 patients in China Content: BACKGROUND: Crucial roles of hematologic and immunologic responses in progression of coronavirus disease 2019 (COVID-19) remain largely unclear. OBJECTIVE: We sought to address the dynamic changes in hematologic and immunologic biomarkers and their associations with severity and outcomes of COVID-19. METHODS: A retrospective study including 548 patients with COVID-19 with clarified outcome (discharged or deceased) from a national cohort in China was performed. Cross-sectional and longitudinal variations were compared and the associations with different severity and outcomes were analyzed. RESULTS: On admission, the counts of lymphocytes, T-cell subsets, eosinophils, and platelets decreased markedly, especially in severe/critical and fatal patients. Increased neutrophil count and neutrophils-to-lymphocytes ratio were predominant in severe/critical cases or nonsurvivors. During hospitalization, eosinophils, lymphocytes, and platelets showed an increasing trend in survivors, but maintained lower levels or dropped significantly afterwards in nonsurvivors. Nonsurvivors kept a high level or showed an upward trend for neutrophils, IL-6, procalcitonin, D-dimer, amyloid A protein, and C-reactive protein, which were kept stable or showed a downward trend in survivors. Positive correlation between CD8+ T-cell and lymphocytes count was found in survivors but not in nonsurvivors. A multivariate Cox regression model suggested that restored levels of lymphocytes, eosinophils, and platelets could serve as predictors for recovery, whereas progressive increases in neutrophils, basophils, and IL-6 were associated with fatal outcome. CONCLUSIONS: Hematologic and immunologic impairment showed a significantly different profile between survivors and nonsurvivors in patients with COVID-19 with different severity. The longitudinal variations in these biomarkers could serve to predict recovery or fatal outcome.", "qid": 25, "docid": "u0j1atdh", "rank": 77, "score": 0.8241592645645142}, {"content": "Title: Advance in human coronaviruses research of host interactions/ \u4e2d\u534e\u5b9e\u7528\u513f\u79d1\u4e34\u5e8a\u6742\u5fd7 Content: 2019-novel coronavirus (2019-nCoV) is a highly pathogenic human CoV that first emerged in Wuhan in 2019.2019-nCoV 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 2019-nCoV.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.Human coronaviruses (HCoVs) are known respiratory pathogens associated with a range of respiratory infection.In the past 17 years, the onset of 2019-nCoV, severe acute respiratory syndrome coronavirus (SARS-CoV) and Middle East respiratory syndrome coronavirus (MERS-CoV) have thrust HCoVs into spotlight of the research community due to their high pathogenicity in humans.The recent study of HCoVs-host interactions has contributed extensively to our understanding of infection pathogenesis of 2019-nCoV.This review discuss various host physiopathologic mechanism, such as apoptosis, innate immunity, endoplasmic reticulum (ER) stress response, mitogen-activated protein kinase (MAPK) pathway and nuclear factor kappa B (NF-&#x03BA;B) pathway that may be modulated by HCoVs and provides evidence for the intensive investigate of 2019-nCoV infection.", "qid": 25, "docid": "l6xgrxp5", "rank": 78, "score": 0.824059784412384}, {"content": "Title: Clinical characteristics and outcomes of 112 cardiovascular disease patients infected by 2019-nCoV/ \u4e2d\u534e\u5fc3\u8840\u7ba1\u75c5\u6742\u5fd7 Content: Objective@#To explore the clinical characteristics and prognosis of the new coronavirus 2019-nCoV patients combined with cardiovascular disease (CVD).@*Methods@#A retrospective analysis was performed on 112 COVID-19 patients with CVD admitted to the western district of Union Hospital in Wuhan, from January 20, 2020 to February 15, 2020. They were divided into critical group (ICU, n=16) and general group (n=96) according to the severity of the disease and patients were followed up to the clinical endpoint. The observation indicators included total blood count, C-reactive protein (CRP), arterial blood gas analysis, myocardial injury markers, coagulation function, liver and kidney function, electrolyte, procalcitonin (PCT), B-type natriuretic peptide (BNP), blood lipid, pulmonary CT and pathogen detection.@*Results@#Compared with the general group, the lymphocyte count (0.74\u00d7109 (0.34\u00d7109, 0.94\u00d7109)/L vs. 0.99\u00d7109 (0.71\u00d7109, 1.29\u00d7109)/L, P=0.03) was extremely lower in the critical group, CRP (106.98 (81.57, 135.76) mg/L vs. 34.34 (9.55,76.54) mg/L, P&lt;0.001) and PCT (0.20 (0.15,0.48) &#x03BC;g/L vs. 0.11 (0.06,0.20)&#x03BC;g/L, P&lt;0.001) were significantly higher in the critical group. The BMI of the critical group was significantly higher than that of the general group (25.5 (23.0, 27.5) kg/m2 vs. 22.0 (20.0, 24.0) kg/m2, P=0.003). Patients were further divided into non-survivor group (17, 15.18%) group and survivor group (95, 84.82%). Among the non-survivors, there were 88.24% (15/17) patients with BMI&gt; 25 kg/m2, which was significantly higher than that of survivors (18.95% (18/95), P&lt;0.001). Compared with the survived patients, oxygenation index (130 (102, 415) vs. 434 (410, 444), P&lt;0.001) was significantly lower and lactic acid (1.70 (1.30, 3.00) mmol/L vs. 1.20 (1.10, 1.60) mmol/L, P&lt;0.001) was significantly higher in the non-survivors. There was no significant difference in the proportion of ACEI/ARB medication between the critical group and the general group or between non-survivors and survivors (all P&gt;0.05).@*Conclusion@#COVID-19 patients combined with CVD are associated with a higher risk of mortality. Critical patients are characterized with lower lymphocyte counts. Higher BMI are more often seen in critical patients and non-survivor. ACEI/ARB use does not affect the morbidity and mortality of COVID-19 combined with CVD. Aggravating causes of death include fulminant inflammation, lactic acid accumulation and thrombotic events.", "qid": 25, "docid": "zcjsvwso", "rank": 79, "score": 0.8236507773399353}, {"content": "Title: Can we predict the severity of COVID-19 with a routine blood test? Content: INTRODUCTION The ongoing worldwide pandemic of Coronavirus Disease 2019 (COVID-19) has posed a huge threat to global public health. However, whether routine blood test could be used to monitor and predict the severity and prognosis of COVID-19 has never been comprehensively investigated. OBJECTIVES To provide an overview of the association of markers in routine blood test with the severity of COVID-19. METHODS PubMed, Embase, Cochrane Library, Wanfang and CNKI database were searched to identify studies reporting the markers in the routine blood test with the severity of COVID-19 until March 20, 2020. STATA software was used for the meta- analysis. RESULTS A total of 15 studies with 3090 COVID-19 patients were included in this analysis. Patients in non-severe group had fewer white blood cells (WBC) (WMD = -0.85 [109/L], 95% CI = [-1.54, -0.16], P = 0.02) and neutrophils (WMD = -1.57 [109/L], 95% CI = [-2.60, -0.54], P = 0.003), more lymphocytes (WMD = 0.29 [109/L], 95% CI = [0.22, 0.36], P < 0.001) and platelets (WMD = 19.05 [109/L], 95% CI = [3.04, 35.06], P = 0.02), and lower neutrophil-to-lymphocyte ratio (NLR) level (WMD = -2.48, 95% CI = [-3.81, -1.15], P < 0.001), compared with those in severe group. There was no statistical difference in monocytes (WMD = 0.01 [109/L], 95% CI = [-0.01, 0.03], P = 0.029) between these two groups. Sensitivity analysis and meta-analysis based on standard mean difference (SMD) did not change the conclusions about neutrophils, lymphocytes and NLR while the results were inconsistent in WBC and platelets. CONCLUSIONS Severe patients had more neutrophils, higher NLR level, and fewer lymphocytes than non-severe patients with COVID-19. Measurement of these markers might assist clinicians to monitor and predict the severity and prognosis of COVID-19.", "qid": 25, "docid": "z3pknjbl", "rank": 80, "score": 0.8235867023468018}, {"content": "Title: Factors associated with death outcome in patients with severe coronavirus disease-19 (COVID-19): a case-control study Content: Rationale: Up to date, the exploration of clinical features in severe COVID-19 patients were mostly from the same center in Wuhan, China. The clinical data in other centers is limited. This study aims to explore the feasible parameters which could be used in clinical practice to predict the prognosis in hospitalized patients with severe coronavirus disease-19 (COVID-19). Methods: In this case-control study, patients with severe COVID-19 in this newly established isolation center on admission between 27 January 2020 to 19 March 2020 were divided to discharge group and death event group. Clinical information was collected and analyzed for the following objectives: 1. Comparisons of basic characteristics between two groups; 2. Risk factors for death on admission using logistic regression; 3. Dynamic changes of radiographic and laboratory parameters between two groups in the course. Results: 124 patients with severe COVID-19 on admission were included and divided into discharge group (n=35) and death event group (n=89). Sex, SpO2, breath rate, diastolic pressure, neutrophil, lymphocyte, C-reactive protein (CRP), procalcitonin (PCT), lactate dehydrogenase (LDH), and D-dimer were significantly correlated with death events identified using bivariate logistic regression. Further multivariate logistic regression demonstrated a significant model fitting with C-index of 0.845 (p<0.001), in which SpO2\u226489%, lymphocyte\u22640.64\u00d710(9)/L, CRP>77.35mg/L, PCT>0.20\u03bcg/L, and LDH>481U/L were the independent risk factors with the ORs of 2.959, 4.015, 2.852, 3.554, and 3.185, respectively (p<0.04). In the course, persistently lower lymphocyte with higher levels of CRP, PCT, IL-6, neutrophil, LDH, D-dimer, cardiac troponin I (cTnI), brain natriuretic peptide (BNP), and increased CD4+/CD8+ T-lymphocyte ratio and were observed in death events group, while these parameters stayed stable or improved in discharge group. Conclusions: On admission, the levels of SpO2, lymphocyte, CRP, PCT, and LDH could predict the prognosis of severe COVID-19 patients. Systematic inflammation with induced cardiac dysfunction was likely a primary reason for death events in severe COVID-19 except for acute respiratory distress syndrome.", "qid": 25, "docid": "6i5zbmm1", "rank": 81, "score": 0.8234859108924866}, {"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": 82, "score": 0.8234415054321289}, {"content": "Title: The timeline and risk factors of clinical progression of COVID-19 in Shenzhen, China Content: BACKGROUND: The novel coronavirus disease 2019 (COVID-19) broke out globally. Early prediction of the clinical progression was essential but still unclear. We aimed to evaluate the timeline of COVID-19 development and analyze risk factors of disease progression. METHODS: In this retrospective study, we included 333 patients with laboratory-confirmed COVID-19 infection hospitalized in the Third People\u2019s Hospital of Shenzhen from 10 January to 10 February 2020. Epidemiological feature, clinical records, laboratory and radiology manifestations were collected and analyzed. 323 patients with mild-moderate symptoms on admission were observed to determine whether they exacerbated to severe-critically ill conditions (progressive group) or not (stable group). We used logistic regression to identify the risk factors associated with clinical progression. RESULTS: Of all the 333 patients, 70 (21.0%) patients progressed into severe-critically ill conditions during hospitalization and assigned to the progressive group, 253 (76.0%) patients belonged to the stable group, another 10 patients were severe before admission. we found that the clinical features of aged over 40 (3.80 [1.72, 8.52]), males (2.21 [1.20, 4.07]), with comorbidities (1.78 [1.13, 2.81]) certain exposure history (0.38 [0.20, 0.71]), abnormal radiology manifestations (3.56 [1.13, 11.40]), low level of T lymphocytes (0.99 [0.997, 0.999]), high level of NLR (0.99 [0.97, 1.01]), IL-6 (1.05 [1.03, 1.07]) and CRP (1.67 [1.12, 2.47]) were the risk factors of disease progression by logistic regression. CONCLUSIONS: The potential risk factors of males, older age, with comorbidities, low T lymphocyte level and high level of NLR, CRP, IL-6 can help to predict clinical progression of COVID-19 at an early stage.", "qid": 25, "docid": "87t1yz2z", "rank": 83, "score": 0.8230583071708679}, {"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": 84, "score": 0.8229290843009949}, {"content": "Title: Epidemiological research priorities for public health control of the ongoing global novel coronavirus (2019-nCoV) outbreak Content: Infections with 2019-nCoV can spread from person to person, and in the earliest phase of the outbreak the basic reproductive number was estimated to be around 2 2, assuming a mean serial interval of 7 5 days [2] The serial interval was not precisely estimated, and a potentially shorter mean serial interval would have corresponded to a slightly lower basic reproductive number Control measures and changes in population behaviour later in January should have reduced the effective reproductive number However, it is too early to estimate whether the effective reproductive number has been reduced to below the critical threshold of 1 because cases currently being detected and reported would have mostly been infected in mid- to late-January Average delays between infection and illness onset have been estimated at around 5\u20136 days, with an upper limit of around 11-14 days [2,5], and delays from illness onset to laboratory confirmation added a further 10 days on average [2]", "qid": 25, "docid": "zb37yqjd", "rank": 85, "score": 0.8226442933082581}, {"content": "Title: Clinical features of 30 cases with novel coronavirus pneumonia/ \u4e2d\u534e\u4f20\u67d3\u75c5\u6742\u5fd7 Content: Objective@#To analyze the epidemiological and clinical characteristics of patients with 2019 novel coronavirus (2019-nCoV) infection in Shenyang.@*Methods@#The epidemiological and clinical characteristics of 30 patients diagnosed with 2019-nCoV infection admitted to Shenyang sixth people&apos;s hospital on January 22, 2020 and February 8, 2020 were retrospectively analyzed.@*Results@#Among the 30 cases, 21 were imported, including 17 from Hubei Province and four from other provinces. Nine cases were local infections. There were 18 men and 12 women, aging from 21 to 72 years with the median of 43 years. Eight cases had underlying diseases including hypertension, diabetes, coronary heart disease and bronchitis. On admission, two (7%) cases were mild, 19 (63%) cases were ordinary, eight (27%) cases were severe, and one (3%) case was critical. Clinical manifestations mainly include fever, with or without upper respiratory tract symptoms, normal, decreased or slightly increased white blood cell counts, mainly decreased lymphocyte counts, normal or increased c-reactive protein, and normal procalcitonin. The computed tomography (CT) of the early stage of the lungs showed that multiple patchy ground glass shadows were mainly accompanied by consolidation, which often involved both lungs or multiple lobes of one lung. At the moment, the clinical treatment mainly included respiratory support, symptomatic treatment, antiviral treatment adn anti-bacterial treatment. By February 15, a total of nine cases were cured and discharged, including one mild case, six ordinary cases, and two severe cases. In the comparisons between mild/ordinary patients and severe/critical patients, the fever duration in the severe/critical group (median 11.5 d) was significantly longer than that in the light/normal group (median 2 d) (Z=-2.292, P=0.022), and the laboratory tests indicated elevated d-dimer levels (Z=-2.669, P=0.008) and more cases with neutrophilic/lymphocyte ratio &gt; 3 (Z=-4.071, P&lt;0.01).@*Conclusions@#In Shenyang, the early cases with 2019-nCoV infection are mainly imported cases, and expanding local infections gradually develop. Clinical manifestations are mainly characterized by fever and cough. Lung CT performance shows multiple ground glass shadows, mainly accompanied by consolidation. CT changes in the lungs should be closely monitored during the treatment, and CT findings in the lungs may change earlier than the clinical manifestations. Prolonged fever duration, elevated d-dimer level and neutrophil/lymphocyte ratio &gt;3 could be used as early warning indicators for severe cases.", "qid": 25, "docid": "09vuwtzr", "rank": 86, "score": 0.8226300477981567}, {"content": "Title: Lactate dehydrogenase and C-reactive protein as predictors of respiratory failure in CoVID-19 patients Content: OBJECTIVE: The dramatic worldwide CoVID-19 infection requires the identification of a reliable and inexpensive tool to quickly discriminate patients with a more unfavorable outcome. METHODS: We performed routine laboratory tests suitable to identify tissue damage and inflammatory status in 123 consecutive CoVID-19 patients admitted to the Emergency Department of the hospital of Piacenza (Emilia-Romagna, Northern Italy). The results were correlated with patients\u2019 respiratory function evaluated by the partial pressure of arterial oxygen to fraction of inspired oxygen ratio (PaO2/FiO2). Results: The most common laboratory abnormalities were lymphocytopenia and elevated values of C-reactive protein (CRP) and lactate dehydrogenase (LDH). Aspartate aminotransferase (AST), alanine aminotransferase (ALT) and creatine kinase (CK) were also increased. The respiratory performance (PaO2/FiO2) showed a strong inverse correlation with LDH (r= 0.62, r(2) 0.38, p value< 0.0001) and CRP (r= 0.55, r(2) 0.31, p value< 0.0001). PaO2/FiO2 values also showed a significant inverse correlation with age (r= -0.37, p< 0.0001), AST (r= -0.31, p<0.01), WBC (r= -0.49, p<0.0001), neutrophils count (r= -0.5, p<0.001). ROC curves showed a sensitivity of 75% and specificity of 70% for the LDH cut-off value of 450 U/L and a sensitivity of 72% and specificity of 71% for the CRP cut-off value of 11 mg/dl in identifying CoVID-19 with moderate-severe ARDS. CONCLUSIONS: LDH and CRP may be related to respiratory function (PaO2/FiO2) and be a predictor of respiratory failure in CoVID-19 patients. LDH and CRP should be considered a useful test for the early identification of patients who require closer respiratory monitoring and more aggressive supportive therapies to avoid poor prognosis.", "qid": 25, "docid": "111ymbdy", "rank": 87, "score": 0.82254558801651}, {"content": "Title: Factors associated with death outcome in patients with severe coronavirus disease-19 (COVID-19): a case-control study Content: Rationale: Up to date, the exploration of clinical features in severe COVID-19 patients were mostly from the same center in Wuhan, China. The clinical data in other centers is limited. This study aims to explore the feasible parameters which could be used in clinical practice to predict the prognosis in hospitalized patients with severe coronavirus disease-19 (COVID-19). Methods: In this case-control study, patients with severe COVID-19 in this newly established isolation center on admission between 27 January 2020 to 19 March 2020 were divided to discharge group and death event group. Clinical information was collected and analyzed for the following objectives: 1. Comparisons of basic characteristics between two groups; 2. Risk factors for death on admission using logistic regression; 3. Dynamic changes of radiographic and laboratory parameters between two groups in the course. Results: 124 patients with severe COVID-19 on admission were included and divided into discharge group (n=35) and death event group (n=89). Sex, SpO2, breath rate, diastolic pressure, neutrophil, lymphocyte, C-reactive protein (CRP), procalcitonin (PCT), lactate dehydrogenase (LDH), and D-dimer were significantly correlated with death events identified using bivariate logistic regression. Further multivariate logistic regression demonstrated a significant model fitting with C-index of 0.845 (p<0.001), in which SpO2&#8804;89%, lymphocyte&#8804;0.64\u00d7109/L, CRP>77.35mg/L, PCT>0.20\u00b5g/L, and LDH>481U/L were the independent risk factors with the ORs of 2.959, 4.015, 2.852, 3.554, and 3.185, respectively (p<0.04). In the course, persistently lower lymphocyte with higher levels of CRP, PCT, IL-6, neutrophil, LDH, D-dimer, cardiac troponin I (cTnI), brain natriuretic peptide (BNP), and increased CD4+/CD8+ T-lymphocyte ratio and were observed in death events group, while these parameters stayed stable or improved in discharge group. Conclusions: On admission, the levels of SpO2, lymphocyte, CRP, PCT, and LDH could predict the prognosis of severe COVID-19 patients. Systematic inflammation with induced cardiac dysfunction was likely a primary reason for death events in severe COVID-19 except for acute respiratory distress syndrome.", "qid": 25, "docid": "fa63dmwr", "rank": 88, "score": 0.8225373029708862}, {"content": "Title: Lactate dehydrogenase and C-reactive protein as predictors of respiratory failure in CoVID-19 patients Content: OBJECTIVE: The dramatic worldwide CoVID-19 infection requires the identification of a reliable and inexpensive tool to quickly discriminate patients with a more unfavorable outcome. METHODS: We performed routine laboratory tests suitable to identify tissue damage and inflammatory status in 123 consecutive CoVID-19 patients admitted to the Emergency Department of the hospital of Piacenza (Emilia-Romagna, Northern Italy). The results were correlated with patients' respiratory function evaluated by the partial pressure of arterial oxygen to fraction of inspired oxygen ratio (PaO2/FiO2). RESULTS: The most common laboratory abnormalities were lymphocytopenia and elevated values of C-reactive protein (CRP) and lactate dehydrogenase (LDH). Aspartate aminotransferase (AST), alanine aminotransferase (ALT) and creatine kinase (CK) were also increased. The respiratory performance (PaO2/FiO2) showed a strong inverse correlation with LDH (r = 0.62, r2 0.38, p value < 0.0001) and CRP (r = 0.55, r2 0.31, p value < 0.0001). PaO2/FiO2 values also showed a significant inverse correlation with age (r = -0.37, p < 0.0001), AST (r = -0.31, p < 0.01), WBC (r = -0.49, p < 0.0001), neutrophils count (r = -0.5, p < 0.001). ROC curves showed a sensitivity of 75% and specificity of 70% for the LDH cut-off value of 450 U/L and a sensitivity of 72% and specificity of 71% for the CRP cut-off value of 11 mg/dl in identifying CoVID-19 with moderate-severe ARDS. CONCLUSIONS: LDH and CRP may be related to respiratory function (PaO2/FiO2) and be a predictor of respiratory failure in CoVID-19 patients. LDH and CRP should be considered a useful test for the early identification of patients who require closer respiratory monitoring and more aggressive supportive therapies to avoid poor prognosis.", "qid": 25, "docid": "m4asdesd", "rank": 89, "score": 0.8224978446960449}, {"content": "Title: [Potential antiviral therapeutics for 2019 Novel Coronavirus] Content: The recent outbreak of respiratory illness in Wuhan, China is caused by a novel coronavirus, named 2019-nCoV, which is genetically close to a bat-derived coronavirus. 2019-nCoV is categorized as beta genus coronavirus, same as the two other strains - severe acute respiratory syndrome coronavirus (SARS-CoV) and Middle East respiratory syndrome coronavirus (MERS-CoV). Antiviral drugs commonly used in clinical practice, including neuraminidase inhibitors (oseltamivir, paramivir, zanamivir, etc.), ganciclovir, acyclovir and ribavirin, are invalid for 2019-nCoV and not recommended. Drugs are possibly effective for 2019-nCoV include: remdesivir, lopinavir / ritonavir, lopinavir / ritonavir combined with interferon-\u00df, convalescent plasma, and monoclonal antibodies. But the efficacy and safety of these drugs for 2019-nCoV pneumonia patients need to be assessed by further clinical trials.", "qid": 25, "docid": "aqxeyek2", "rank": 90, "score": 0.8224659562110901}, {"content": "Title: Prospective observational study in two Dutch hospitals to assess the performance of inflammatory plasma markers to determine disease severity of viral respiratory tract infections in children Content: INTRODUCTION: Respiratory viruses causing lower respiratory tract infections (LRTIs) are a major cause of hospital admissions in children. Since the course of these infections is unpredictable with potential fast deterioration into respiratory failure, infants are easily admitted to the hospital for observation. The aim of this study was to examine whether systemic inflammatory markers can be used to predict severity of disease in children with respiratory viral infections. METHODS: Blood and nasopharyngeal washings from children <3 years of age with viral LRTI attending a hospital were collected within 24 hours (acute) and after 4\u20136 weeks (recovery). Patients were assigned to a mild (observation only), moderate (supplemental oxygen and/or nasogastric feeding) or severe (mechanical ventilation) group. Linear regression analysis was used to design a prediction rule using plasma levels of C reactive protein (CRP), serum amyloid A (SAA), pentraxin 3 (PTX3), serum amyloid P component and properdin. This rule was tested in a validation cohort. RESULTS: One hundred and four children (52% male) were included. A combination of CRP, SAA, PTX3 and properdin was a better indicator of severe disease compared with any of the individual makers and age (69% sensitivity (95% CI 50 to 83), 90% specificity (95% CI 80 to 96)). Validation in 141 patients resulted in 71% sensitivity (95% CI 53 to 85), 87% specificity (95% CI 79 to 92), negative predictive value of 64% (95% CI 47 to 78) and positive predictive value of 90% (95% CI 82 to 95). The prediction rule was not able to identify patients with a mild course of disease. CONCLUSION: A combination of CRP, SAA, PTX3 and properdin was able to identify children with a severe course of viral LRTI disease, even in children under 2 months of age. To assess the true impact on clinical management, these results should be validated in a prospective randomised control study.", "qid": 25, "docid": "nph50ms1", "rank": 91, "score": 0.8222411870956421}, {"content": "Title: [Potential antiviral therapeutics for 2019 Novel Coronavirus]. Content: The recent outbreak of respiratory illness in Wuhan, China is caused by a novel coronavirus, named 2019-nCoV, which is genetically close to a bat-derived coronavirus. 2019-nCoV is categorized as beta genus coronavirus, same as the two other strains-severe acute respiratory syndrome coronavirus (SARS-CoV) and Middle East respiratory syndrome coronavirus (MERS-CoV). Antiviral drugs commonly used in clinical practice, including neuraminidase inhibitors (oseltamivir, paramivir, zanamivir, etc.), ganciclovir, acyclovir and ribavirin, are invalid for 2019-nCoV and not recommended. Drugs are possibly effective for 2019-nCoV include: remdesivir, lopinavir/ritonavir, lopinavir/ritonavir combined with interferon-\u03b2, convalescent plasma, and monoclonal antibodies. But the efficacy and safety of these drugs for 2019-nCoV pneumonia patients need to be assessed by further clinical trials.", "qid": 25, "docid": "fxbiadlv", "rank": 92, "score": 0.8221623301506042}, {"content": "Title: [Potential antiviral therapeutics for 2019 Novel Coronavirus]. Content: The recent outbreak of respiratory illness in Wuhan, China is caused by a novel coronavirus, named 2019-nCoV, which is genetically close to a bat-derived coronavirus. 2019-nCoV is categorized as beta genus coronavirus, same as the two other strains - severe acute respiratory syndrome coronavirus (SARS-CoV) and Middle East respiratory syndrome coronavirus (MERS-CoV). Antiviral drugs commonly used in clinical practice, including neuraminidase inhibitors (oseltamivir, paramivir, zanamivir, etc.), ganciclovir, acyclovir and ribavirin, are invalid for 2019-nCoV and not recommended. Drugs are possibly effective for 2019-nCoV include: remdesivir, lopinavir / ritonavir, lopinavir / ritonavir combined with interferon-\u03b2, convalescent plasma, and monoclonal antibodies. But the efficacy and safety of these drugs for 2019-nCoV pneumonia patients need to be assessed by further clinical trials.", "qid": 25, "docid": "fuljgago", "rank": 93, "score": 0.8221623301506042}, {"content": "Title: Development of Genetic Diagnostic Methods for Novel Coronavirus 2019 (nCoV-2019) in Japan Content: At the end of 2019, pneumonia caused by novel coronavirus 2019 (nCoV) emerged in Wuhan city, China. Many airline travelers moved between Wuhan and Japan at that time, suggesting that Japan is at high risk of invasion by the virus. Diagnostic systems for 2019-nCoV were developed with urgency. Two nested RT-PCR assays and two real-time RT-PCR assays were adapted to local Japanese conditions. As of 8 February 2020, the assays developed have successfully detected 25 positive cases of infection in Japan.", "qid": 25, "docid": "wbdgwxoi", "rank": 94, "score": 0.822115421295166}, {"content": "Title: Development of Genetic Diagnostic Methods for Novel Coronavirus 2019 (nCoV-2019) in Japan. Content: At the end of 2019, pneumonia caused by novel coronavirus 2019 (nCoV) emerged in Wuhan city, China. Many airline travelers moved between Wuhan and Japan at that time, suggesting that Japan is at high risk of invasion by the virus. Diagnostic systems for 2019-nCoV were developed with urgency. Two nested RT-PCR assays and two real-time RT-PCR assays were adapted to local Japanese conditions. As of 8 February 2020, the assays developed have successfully detected 25 positive cases of infection in Japan.", "qid": 25, "docid": "5vqf6e93", "rank": 95, "score": 0.822115421295166}, {"content": "Title: Nelfinavir was predicted to be a potential inhibitor of 2019-nCov main protease by an integrative approach combining homology modelling, molecular docking and binding free energy calculation Content: 2019-nCov has caused more than 80 deaths as of 27 January 2020 in China, and infection cases have been reported in more than 10 countries. However, there is no approved drug to treat the disease. 2019-nCov Mpro is a potential drug target to combat the virus. We built homology models based on SARS Mpro structures, and docked 1903 small molecule drugs to the models. Based on the docking score and the 3D similarity of the binding mode to the known Mpro ligands, 4 drugs were selected for binding free energy calculations. Both MM/GBSA and SIE methods voted for nelfinavir, with the binding free energy of \u221224.69\u00b10.52 kcal/mol and \u22129.42\u00b10.04 kcal/mol, respectively. Therefore, we suggested that nelfinavir might be a potential inhibitor against 2019-nCov Mpro.", "qid": 25, "docid": "zgdbvfi4", "rank": 96, "score": 0.8220293521881104}, {"content": "Title: The timeline and risk factors of clinical progression of COVID-19 in Shenzhen, China Content: BACKGROUND: The novel coronavirus disease 2019 (COVID-19) broke out globally. Early prediction of the clinical progression was essential but still unclear. We aimed to evaluate the timeline of COVID-19 development and analyze risk factors of disease progression. METHODS: In this retrospective study, we included 333 patients with laboratory-confirmed COVID-19 infection hospitalized in the Third People's Hospital of Shenzhen from 10 January to 10 February 2020. Epidemiological feature, clinical records, laboratory and radiology manifestations were collected and analyzed. 323 patients with mild-moderate symptoms on admission were observed to determine whether they exacerbated to severe-critically ill conditions (progressive group) or not (stable group). We used logistic regression to identify the risk factors associated with clinical progression. RESULTS: Of all the 333 patients, 70 (21.0%) patients progressed into severe-critically ill conditions during hospitalization and assigned to the progressive group, 253 (76.0%) patients belonged to the stable group, another 10 patients were severe before admission. we found that the clinical features of aged over 40 (3.80 [1.72, 8.52]), males (2.21 [1.20, 4.07]), with comorbidities (1.78 [1.13, 2.81]) certain exposure history (0.38 [0.20, 0.71]), abnormal radiology manifestations (3.56 [1.13, 11.40]), low level of T lymphocytes (0.99 [0.997, 0.999]), high level of NLR (0.99 [0.97, 1.01]), IL-6 (1.05 [1.03, 1.07]) and CRP (1.67 [1.12, 2.47]) were the risk factors of disease progression by logistic regression. CONCLUSIONS: The potential risk factors of males, older age, with comorbidities, low T lymphocyte level and high level of NLR, CRP, IL-6 can help to predict clinical progression of COVID-19 at an early stage.", "qid": 25, "docid": "5iebo61m", "rank": 97, "score": 0.8219278454780579}, {"content": "Title: A machine learning-based model for survival prediction in patients with severe COVID-19 infection Content: The sudden increase of COVID-19 cases is putting a high pressure on healthcare services worldwide. At the current stage, fast, accurate and early clinical assessment of the disease severity is vital. To support decision making and logistical planning in healthcare systems, this study leverages a database of blood samples from 404 infected patients in the region of Wuhan, China to identify crucial predictive biomarkers of disease severity. For this purpose, machine learning tools selected three biomarkers that predict the survival of individual patients with more than 90% accuracy: lactic dehydrogenase (LDH), lymphocyte and high-sensitivity C-reactive protein (hs-CRP). In particular, relatively high levels of LDH alone seem to play a crucial role in distinguishing the vast majority of cases that require immediate medical attention. This finding is consistent with current medical knowledge that high LDH levels are associated with tissue breakdown occurring in various diseases, including pulmonary disorders such as pneumonia. Overall, this paper suggests a simple and operable formula to quickly predict patients at the highest risk, allowing them to be prioritised and potentially reducing the mortality rate.", "qid": 25, "docid": "s9j21zsy", "rank": 98, "score": 0.8210748434066772}, {"content": "Title: [A pathological report of three COVID-19 cases by minimal invasive autopsies] Content: Objective: To investigate the pathological characteristics and the clinical significance of novel coronavirus (2019-nCoV)-infected pneumonia (termed by WHO as coronavirus disease 2019, COVID-19). Methods: Minimally invasive autopsies from lung, heart, kidney, spleen, bone marrow, liver, pancreas, stomach, intestine, thyroid and skin were performed on three patients died of novel coronavirus pneumonia in Chongqing, China. Hematoxylin and eosin staining (HE), transmission electron microcopy, and histochemical staining were performed to investigate the pathological changes of indicated organs or tissues. Immunohistochemical staining was conducted to evaluate the infiltration of immune cells as well as the expression of 2019-nCoV proteins. Real time PCR was carried out to detect the RNA of 2019-nCoV. Results: Various damages were observed in the alveolar structure, with minor serous exudation and fibrin exudation. Hyaline membrane formation was observed in some alveoli. The infiltrated immune cells in alveoli were majorly macrophages and monocytes. Moderate multinucleated giant cells, minimal lymphocytes, eosinophils and neutrophils were also observed. Most of infiltrated lymphocytes were CD4-positive T cells. Significant proliferation of type \u00e2 \u00a1 alveolar epithelia and focal desquamation of alveolar epithelia were also indicated. The blood vessels of alveolar septum were congested, edematous and widened, with modest infiltration of monocytes and lymphocytes. Hyaline thrombi were found in a minority of microvessels. Focal hemorrhage in lung tissue, organization of exudates in some alveolar cavities, and pulmonary interstitial fibrosis were observed. Part of the bronchial epithelia were exfoliated. Coronavirus particles in bronchial mucosal epithelia and type \u00e2 \u00a1 alveolar epithelia were observed under electron microscope. Immunohistochemical staining showed that part of the alveolar epithelia and macrophages were positive for 2019-nCoV antigen. Real time PCR analyses identified positive signals for 2019-nCoV nucleic acid. Decreased numbers of lymphocyte, cell degeneration and necrosis were observed in spleen. Furthermore, degeneration and necrosis of parenchymal cells, formation of hyaline thrombus in small vessels, and pathological changes of chronic diseases were observed in other organs and tissues, while no evidence of coronavirus infection was observed in these organs. Conclusions: The lungs from novel coronavirus pneumonia patients manifest significant pathological lesions, including the alveolar exudative inflammation and interstitial inflammation, alveolar epithelium proliferation and hyaline membrane formation. While the 2019-nCoV is mainly distributed in lung, the infection also involves in the damages of heart, vessels, liver, kidney and other organs. Further studies are warranted to investigate the mechanism underlying pathological changes of this disease.", "qid": 25, "docid": "dawlrbbc", "rank": 99, "score": 0.8209813833236694}, {"content": "Title: Current status of treatment for 2019 novel coronavirus pneumonia/ \u4e2d\u534e\u5fae\u751f\u7269\u5b66\u548c\u514d\u75ab\u5b66\u6742\u5fd7 Content: 2019 novel coronavirus (2019-nCoV) is a new member of coronavirus family that can cause serious respiratory diseases after the emergence of severe acute respiratory syndrome-coronavirus (SARS-CoV) and middle east respiratory syndrome-coronavirus (MERS-CoV). At present, there is no specific antiviral drug targeting 2019-nCoV. In facing of the increasingly serious epidemic of 2019 novel coronavirus pneumonia and the urgent needs in drug treatment strategies, this paper reviewed the current research situation and progress in antiviral treatment for the newly identified disease.", "qid": 25, "docid": "stnjl8f8", "rank": 100, "score": 0.8209277391433716}]}
{"query": "what are the initial symptoms of Covid-19?", "hits": [{"content": "Title: Vascular skin symptoms in COVID-19: a french observational study Content: Coronavirus 19 (COVID-19) was declared as a pandemic viral infection by the World Health organization on March 11th 2020. Usual clinical manifestations of COVID-19 infection include fever, fatigue, myalgia, headache, diarrhea, dry cough, dyspnea that may lead to acute respiratory distress syndrome and death (1). Skin symptoms of COVID-19 have been poorly described but may include erythematous rash, urticaria and chicken pox like lesions (2-7). Angiotensin-converting enzyme 2 (ACE2) is a cellular receptor for COVID-19.", "qid": 26, "docid": "vp5xj8m5", "rank": 1, "score": 0.8678373098373413}, {"content": "Title: The need for neurologists in the care of COVID\u201019 patients Content: Coronavirus disease 2019 (COVID-19) is an infectious disease caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) resulting in severe acute respiratory syndrome in a substantial number of patients. Approximately 5% to 10% of patients need intensive care unit (ICU) admission and mechanical ventilation [1]. The primary symptoms of COVID-19 include fever, dry cough and fatigue [2]. However, a recent report from Shandong, China, disclosed that a subset of patients did not suffer from respiratory symptoms but had neurologic signs and symptoms [3]. Moreover, in a retrospective study from Wuhan, China, neurologic symptoms were observed in 36.4% of the hospitalized patients with COVID-19 infection and pertained to both the central and peripheral nervous system [4].", "qid": 26, "docid": "l21fin9q", "rank": 2, "score": 0.8651716709136963}, {"content": "Title: Comment on \"Cutaneous manifestations in COVID-19: a first perspective \" by Recalcati S Content: Since the coronavirus disease 2019 (COVID 19) outbreak was first reported in the Chinese city of Wuhan on December 31, 2019, it has stricken more than 1,000,000 persons worldwide, of whom over 50,000 have died (1). Having been infected by severe acute respiratory syndrome coronavirus 2 (SARS-COV-2), patients with COVID-19 mainly present with fever and respiratory symptoms (2). Isolated sudden onset anosmia has also frequently been reported (3). Less frequently, rhinorrhea, diarrhoea and dysgeusia may be associated. While only a few reports have evoked cutaneous manifestations (4), we read with interest an initial study on the topic entitled \"Cutaneous manifestations in COVID-19: a first perspective \" by Recalcati S. (5).", "qid": 26, "docid": "5c3t4znm", "rank": 3, "score": 0.8555043935775757}, {"content": "Title: Maternal mortality from COVID-19 in Mexico. Content: COVID-19, the illness caused by the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), is the deadliest pandemic to occur in this century. Common symptoms of COVID-19 include cough, myalgia, fever, chest pain, and headache. However, its clinical presentation ranges from completely asymptomatic to acute respiratory distress syndrome.[1] Pregnant women are susceptible to community spread of COVID-19 because they cannot postpone interactions with healthcare professionals and other women receiving obstetric care.", "qid": 26, "docid": "8noxjjuh", "rank": 4, "score": 0.8551676273345947}, {"content": "Title: Vascular skin symptoms in COVID\u201019: a french observational study Content: Coronavirus 19 (COVID\u201019) was declared as a pandemic viral infection by the World Health organization on March 11(th) 2020. Usual clinical manifestations of COVID\u201019 infection include fever, fatigue, myalgia, headache, diarrhea, dry cough, dyspnea that may lead to acute respiratory distress syndrome and death (1). Skin symptoms of COVID\u201019 have been poorly described but may include erythematous rash, urticaria and chicken pox like lesions (2\u20107). Angiotensin\u2010converting enzyme 2 (ACE2) is a cellular receptor for COVID\u201019.", "qid": 26, "docid": "qreg4emx", "rank": 5, "score": 0.8537298440933228}, {"content": "Title: Endothelial cell dysfunction: a major player in SARS-CoV-2 infection (COVID-19)? Content: Coronavirus disease 2019 (COVID-19) represents a public health crisis of pandemic proportions. Caused by SARS-CoV-2, which stands for severe acute respiratory syndrome (SARS) coronavirus 2, the symptoms most commonly reported include cough, fever, and shortness of breath, but also extra-pulmonary symptoms, such as neurological and gastroenterological manifestations.", "qid": 26, "docid": "xzgfbvqk", "rank": 6, "score": 0.8506685495376587}, {"content": "Title: COVID-19: A New Virus as a Potential Rapidly Spreading in the Worldwide Content: Covid-19 is a novel virus with high affinity to spread in the community In December 2019, it was first identified in Wuhan, China The symptoms are non-specific, so fever, cough, dyspnea, are prominent features Respiratory failure and mortality have also been reported The most common lung CT scan findings are bilateral ground glass opacities", "qid": 26, "docid": "0em5sf3g", "rank": 7, "score": 0.8493985533714294}, {"content": "Title: Fecal-Oral Transmission of COVID-19: Could Hypochlorhydria Play a Role? Content: Coronavirus disease 2019 (COVID-19) is caused by severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2) which emerged in Wuhan, China in 2019 (1). Respiratory symptoms remain the most common clinical manifestations of COVID-19. However, non-respiratory symptoms are increasingly being recognized. Gastrointestinal (GI) symptoms such as anorexia, nausea, vomiting, diarrhea, and abdominal pain are noted in COVID-19 patients either alone or in association with respiratory manifestations (2). Stool viral RNA can be detected by up to 50% in patients with diarrhea (3). This article is protected by copyright. All rights reserved.", "qid": 26, "docid": "y77ui3d9", "rank": 8, "score": 0.8492922782897949}, {"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": 9, "score": 0.8484677076339722}, {"content": "Title: Cutaneous manifestations in COVID\u201019: Family cluster of Urticarial Rash Content: Coronavirus disease (COVID\u201019) is rapidly spread across the world. Many clinical manifestations of the virus are described, and new symptoms are emerging, only few cases of patients with skin manifestation were described since the pandemic was announced by the WHO on March. Common clinical features of COVID\u201019 reported include fever, cough, myalgia, fatigue, headache, shortness of breath and diarrhea.", "qid": 26, "docid": "khsvoyhp", "rank": 10, "score": 0.8478025197982788}, {"content": "Title: Characteristics and Clinical Course and Outcome of COVID-19 in Hispanic/Latino Patients in a Community Setting: A Retrospective Cohort Study Content: Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), the virus which causes coronavirus disease 2019 (COVID-19), has caused significant morbidity and mortality worldwide. The Centers for Disease Control and Prevention (CDC) suggest several possible symptoms associated with coronavirus disease 2019 (COVID-19), including cough, shortness of breath or difficulty breathing, fever, chills, muscle pain, sore throat, new loss of taste or smell, and less commonly nausea/vomiting/diarrhea.1 This article is protected by copyright. All rights reserved.", "qid": 26, "docid": "jt5co0n8", "rank": 11, "score": 0.8477739691734314}, {"content": "Title: Differences in Clinical Characteristics of Covid-19 in Hispanic/Latino Population. Content: The Centers for Disease Control and Prevention (CDC) suggest several possible symptoms associated with coronavirus disease 2019 (COVID-19), including cough, shortness of breath (SOB), fever, chills, muscle pain, sore throats, new loss of taste or smell, nausea, vomiting, or diarrhea. (\"Centers for Disease Control and Prevention. Symptoms of Coronavirus.,\") The clinical characteristics from the study by Yu et al. published in Transboundary and Emerging Diseases and other Chinese studies were different from those we observe in the United States.", "qid": 26, "docid": "03z3wk6i", "rank": 12, "score": 0.8471615314483643}, {"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": 26, "docid": "828ubhzi", "rank": 13, "score": 0.8449780941009521}, {"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": 14, "score": 0.8446894884109497}, {"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": 15, "score": 0.8446894884109497}, {"content": "Title: Clinical Progression of COVID-19 Patient with Extended Incubation Period, Delayed RT-PCR Time-to-positivity, and Potential Role of Chest CT-scan Content: Coronavirus Disease 2019 (COVID-19), previously called 2019-nCoV, is a novel disease caused by SARS- CoV-2 which was first identified as outbreak of unknown respiratory illness in Wuhan, China. COVID- 19 was declared as global health emergency by WHO on March 11, 2020 and quickly elevated to global pandemic on 11 March 2020. COVID-19 symptom is highly various in each patient, with fever, fatigue, shortness of breath, and cough as the main presenting symptoms. Patient with COVID-19 may shows severe symptom with severe pneumonia and ARDS, mild symptom resembling simple upper respiration tract infection, or even completely asymptomatic. Approximately 80% of cases is mild. However the number may changes as more people are getting tested. Some experts are estimating that up to 50% of all cases may be asymptomatic carrier.", "qid": 26, "docid": "3njzz1yi", "rank": 16, "score": 0.8446205258369446}, {"content": "Title: Clinical Progression of COVID-19 Patient with Extended Incubation Period, Delayed RT-PCR Time-to-positivity, and Potential Role of Chest CT-scan. Content: Coronavirus Disease 2019 (COVID-19), previously called 2019-nCoV, is a novel disease caused by SARS- CoV-2 which was first identified as outbreak of unknown respiratory illness in Wuhan, China. COVID- 19 was declared as global health emergency by WHO on March 11, 2020 and quickly elevated to global pandemic on 11 March 2020. COVID-19 symptom is highly various in each patient, with fever, fatigue, shortness of breath, and cough as the main presenting symptoms. Patient with COVID-19 may shows severe symptom with severe pneumonia and ARDS, mild symptom resembling simple upper respiration tract infection, or even completely asymptomatic. Approximately 80% of cases is mild. However the number may changes as more people are getting tested. Some experts are estimating that up to 50% of all cases may be asymptomatic carrier.", "qid": 26, "docid": "e4uzvmmh", "rank": 17, "score": 0.8446205258369446}, {"content": "Title: Altered Mental Status as a Novel Initial Clinical Presentation for COVID-19 Infection in the Elderly Content: The coronavirus disease of 2019 or COVID-19 was first identified in Hubei Province in China in November of 2019 and quickly spread to become a global pandemic. The virus, SARS-Coronavirus-2 (2-SARS-CoV-2), is particularly virulent in the elderly who can develop symptoms and become mortally ill within days of contracting the virus. The virus is easily transmitted by droplets (e.g., sneezing, coughing) and communal living settings such as personal care homes can be vulnerable to the spread of the virus. Identifying patients early in the disease process is important to providing appropriate medical interventions. To date, most of the medical literature, including Center for Disease Control guidelines, has relied on three necessary symptoms in making the diagnosis of COVID-19: fever, cough and shortness of breath. We present four cases of elderly patients who developed altered mental status as their presenting symptom without associated fever or respiratory symptoms.", "qid": 26, "docid": "78rv366w", "rank": 18, "score": 0.8430095911026001}, {"content": "Title: COVID-19: Specific and non-specific clinical manifestations and symptoms: The current state of knowledge Content: Coronavirus disease 2019 (COVID-19), due to the severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2), has become an epidemiological threat and a worldwide concern. SARS-CoV-2 has spread to 210 countries worldwide and more than 6,500,000 confirmed cases and 384,643 deaths have been reported, while the number of both confirmed and fatal cases is continually increasing. COVID-19 is a viral disease that can affect every age group\u2014from infants to the elderly\u2014resulting in a wide spectrum of various clinical manifestations. COVID-19 might present different degrees of severity\u2014from mild or even asymptomatic carriers, even to fatal cases. The most common complications include pneumonia and acute respiratory distress syndrome. Fever, dry cough, muscle weakness, and chest pain are the most prevalent and typical symptoms of COVID-19. However, patients might also present atypical symptoms that can occur alone, which might indicate the possible SARS-CoV-2 infection. The aim of this paper is to review and summarize all of the findings regarding clinical manifestations of COVID-19 patients, which include respiratory, neurological, olfactory and gustatory, gastrointestinal, ophthalmic, dermatological, cardiac, and rheumatologic manifestations, as well as specific symptoms in pediatric patients.", "qid": 26, "docid": "s7b3sw74", "rank": 19, "score": 0.8426281213760376}, {"content": "Title: COVID-19 in der zentralen Notaufnahme: \u00dcbersicht \u00fcber die klinische Pr\u00e4sentation der ersten 35 Patienten in der Fr\u00fchphase der Pandemie Content: BACKGROUND: The corona pandemic is currently the greatest challenge for health systems of all countries worldwide. The timely detection of the disease and the immediate separation and isolation of suspected cases make a significant contribution to breaking the chain of infection. METHODS: Based on the first 35 patients admitted to the hospital with COVID-19, we evaluated the various symptoms with which patients presented. RESULTS: The majority of patients have respiratory symptoms (e.g., cough and reduced peripheral oxygen saturation) and fever. In individual patients, however, there may only be other symptoms, e.g., gastrointestinal, neurological, or nonspecific symptoms.", "qid": 26, "docid": "pe7as1qp", "rank": 20, "score": 0.8417015671730042}, {"content": "Title: Angiotensin-converting enzyme 2, a SARS-CoV-2 receptor, is upregulated by interleukin-6 via STAT3 signaling in synovial tissues Content: The severe acute respiratory syndrome-coronavirus-2 (SARS-CoV-2) has spread explosively worldwide and resulted in a pandemic of a new respiratory disease called coronavirus disease 2019 (COVID-19) in 2020. Symptoms of COVID-19 include fever, malaise, cough, and in severe cases, pneumonia and acute respiratory distress syndrome (1,2).", "qid": 26, "docid": "acw2fhi8", "rank": 21, "score": 0.8414214253425598}, {"content": "Title: Angiotensin-converting enzyme 2, a SARS-CoV-2 receptor, is upregulated by interleukin-6 via STAT3 signaling in synovial tissues. Content: The severe acute respiratory syndrome-coronavirus-2 (SARS-CoV-2) has spread explosively worldwide and resulted in a pandemic of a new respiratory disease called coronavirus disease 2019 (COVID-19) in 2020. Symptoms of COVID-19 include fever, malaise, cough, and in severe cases, pneumonia and acute respiratory distress syndrome (1,2).", "qid": 26, "docid": "zcjam19p", "rank": 22, "score": 0.8414214253425598}, {"content": "Title: Comment on \u201cCutaneous manifestations in COVID\u201019: a first perspective \u201d by Recalcati S Content: Since the coronavirus disease 2019 (COVID 19) outbreak was first reported in the Chinese city of Wuhan on December 31, 2019, it has stricken more than 1,000,000 persons worldwide, of whom over 50,000 have died (1). Having been infected by severe acute respiratory syndrome coronavirus 2 (SARS\u2010COV\u20102), patients with COVID\u201019 mainly present with fever and respiratory symptoms (2). Isolated sudden onset anosmia has also frequently been reported (3). Less frequently, rhinorrhea, diarrhoea and dysgeusia may be associated. While only a few reports have evoked cutaneous manifestations (4), we read with interest an initial study on the topic entitled \u201cCutaneous manifestations in COVID\u201019: a first perspective \u201d by Recalcati S. (5).", "qid": 26, "docid": "9pn2hvph", "rank": 23, "score": 0.84110426902771}, {"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": 24, "score": 0.8407683372497559}, {"content": "Title: Atypical and novel presentations of Coronavirus Disease 2019: a case series of three children. Content: Typical presentations of Coronavirus Disease 2019 (COVID19) including respiratory symptoms (cough, respiratory distress and hypoxia), fever and dyspnea are considered main symptoms in adults, but atypical presentation children could be a diagnostic challenge We report three children whose initial presentation was gastrointestinal, and in whom COVID-19 infection was found, concluding that cases of acute appendicitis, mesenteric adenitis and flank tenderness may mask and infection with this virus, which should therefore be investigated.", "qid": 26, "docid": "1wyh7mrw", "rank": 25, "score": 0.840764045715332}, {"content": "Title: Cerebral Venous Sinus Thrombosis as a Presentation of COVID-19 Content: Coronavirus disease 19 (COVID-19) is caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). We describe the case of a 59-year-old man who presented with headache, hypertension and a single episode of fever with no other symptoms. He subsequently developed unilateral weakness. Computer tomography identified a cerebral venous sinus thrombosis (CVST). A subsequent test for COVID-19 was positive. This is the first report of CVST as a presenting symptom of COVID-19 infection. LEARNING POINTS: Thrombotic events may be the initial presenting symptom of COVID-19. These thrombotic events include stroke, venous thromboembolism, pulmonary embolism and cardiac complications. Clinicians should carefully consider the risk of thrombosis in patients positive for COVID-19, including prophylaxis and treatment beyond discharge.", "qid": 26, "docid": "udybki7w", "rank": 26, "score": 0.8407243490219116}, {"content": "Title: Time scale for resolution of olfactory dysfunction in COVID-19 Content: By now, the 2019 novel coronavirus disease (COVID-19), caused by the SARS-CoV-2 virus, is widely recognized around the world as a pandemic that has infected millions and claimed the lives of hundreds of thousands (1). Despite months of mitigation strategies, COVID-19 continues to spread and ascertainment of new knowledge about the disease process continues to be a priority of the medical community. Originally described by characteristic symptoms of fever, cough and/or shortness of breath that can rapidly progress to acute respiratory distress syndrome, it has become clear that COVID-19 has manifold clinical presentations (2-4). Notably, olfactory dysfunction (OD)-decreased sense of smell-has been reported to occur in up to 85.6% of COVID-19 patients (2,5).", "qid": 26, "docid": "90aguztr", "rank": 27, "score": 0.8407198786735535}, {"content": "Title: Time scale for resolution of olfactory dysfunction in COVID-19. Content: By now, the 2019 novel coronavirus disease (COVID-19), caused by the SARS-CoV-2 virus, is widely recognized around the world as a pandemic that has infected millions and claimed the lives of hundreds of thousands (1). Despite months of mitigation strategies, COVID-19 continues to spread and ascertainment of new knowledge about the disease process continues to be a priority of the medical community. Originally described by characteristic symptoms of fever, cough and/or shortness of breath that can rapidly progress to acute respiratory distress syndrome, it has become clear that COVID-19 has manifold clinical presentations (2-4). Notably, olfactory dysfunction (OD)-decreased sense of smell-has been reported to occur in up to 85.6% of COVID-19 patients (2,5).", "qid": 26, "docid": "kwpj3sbh", "rank": 28, "score": 0.8407198786735535}, {"content": "Title: Explanation for COVID\u201019 infection neurological damage and reactivations Content: A new pathogenic virus, COVID-19, appeared in 2019, in Wuhan, China, typically causing fever, cough, diarrhea and fatigue and significant mortality (Mao, 2020). From mid-January to mid-February in 2020, 214 patients with both non-severe and severe COVID-19 infections confirmed by nucleic acid tests, were examined by a panel of neurologists. Seventy-eight patients (36.4%) displayed neurological symptoms, including central nervous system symptoms of dizziness, headache, impaired consciousness, acute cerebrovascular disease with either ischemic stroke or cerebral hemorrhage, ataxia, seizures; peripheral nervous system symptoms of taste impairment, smell impairment, vision impairment, and nerve pain; and skeletal muscle injury (Mao, 2020).", "qid": 26, "docid": "s3wo3ten", "rank": 29, "score": 0.8400671482086182}, {"content": "Title: Oral cavity lesions as a manifestation of the novel virus (COVID-19): a letter-to-editor. Content: In early December 2019, the acute respiratory illness began in the Wuhan, China, which quickly spread around the world, that today known as COVID-19. (Sun, Qie, Liu, Ren, & Xi, 2020) Preliminary studies have shown that hospitalized patients have different symptoms, including myalgia, whooping cough, fatigue, and dyspnea and gastrointestinal complains. (Guo et al., 2020; Zhang et al., 2020) In more recent studies, skin manifestations have also been reported in covid-19 patients.", "qid": 26, "docid": "ncp2tphr", "rank": 30, "score": 0.8399954438209534}, {"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": 31, "score": 0.8394094109535217}, {"content": "Title: New emerging dermatological symptoms in coronavirus pandemic Content: COVID\u201019 (Coronavirus Disease 2019) is a fatal disease that could lead to a serious respiratory illness. It is caused by SARS\u2010CoV\u20102 virus. In December 2019, the first of human cases were identified in China and the infection spread quickly around the world. The World Health Organisation (WHO) declared the disease, a global pandemic on 11 March 2020, even as COVID\u201019 rapidly spread across the world. According to clinical reports, fever, headache, cough and myalgia are common clinical symptoms. Many symptoms also occur, such as sputum formation, haemoptysis and diarrhea.", "qid": 26, "docid": "46njnlct", "rank": 32, "score": 0.8377705812454224}, {"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": 26, "docid": "dn7iuzq1", "rank": 33, "score": 0.8376529216766357}, {"content": "Title: COVID-19 presenting with diarrhoea and hyponatraemia Content: COVID-19 is a viral disease with a high infectivity rate. The full spectrum of the disease is not yet understood. This understanding may help in limiting potential exposure. We present a young man with diarrhoea, abdominal pain and hyponatraemia who turned out to be positive for COVID-19.", "qid": 26, "docid": "2bfh73a8", "rank": 34, "score": 0.8373681902885437}, {"content": "Title: Preparing a neurology department for SARS-CoV-2 (COVID-19): Early experiences at Columbia University Irving Medical Center and the New York Presbyterian Hospital in New York City. Content: Beginning in December 2019, a novel coronavirus, SARS-CoV-2 (COVID-19), began spreading rapidly throughout China and now is a global pandemic with cases reported in over 192 countries and territories worldwide. Clinically, COVID-19 ranges from a mild, self-limiting respiratory illness to severe progressive pneumonia and multiorgan failure. The first COVID-19 case was reported at the beginning of March in New York City (NYC), and now just three weeks later, NYC and its suburbs have over 5% of global cases. Worldwide, there is a rapid increase in the number of cases daily, including the number of patients requiring hospitalization and intensive care support.", "qid": 26, "docid": "h661u7t6", "rank": 35, "score": 0.837168276309967}, {"content": "Title: Coronavirus 101 Content: COVID-2019 emerged from China in late December. It follows two other coronavirus outbreaks, the SARS-CoV and the MERS-CoV. Coronaviruses usually circulate among animals but sometimes can jump to humans. These three strains have caused severe disease in humans and global transmission concerns. Symptoms of COVID-2019 include cough, fever, and shortness of breath. Related illnesses can range from mild to severe to fatal. Primary care providers must be alert to respiratory symptoms they encounter that are associated with pertinent travel history, be prepared to safely screen, examine and possibly test and/or report suspicions to the health department for further evaluation.", "qid": 26, "docid": "9zetheol", "rank": 36, "score": 0.8371568322181702}, {"content": "Title: Characteristics and Clinical Course and Outcome of COVID\u201019 in Hispanic/Latino Patients in a Community Setting: A Retrospective Cohort Study Content: Severe acute respiratory syndrome coronavirus 2 (SARS\u2010CoV\u20102), the virus which causes coronavirus disease 2019 (COVID\u201019), has caused significant morbidity and mortality worldwide. The Centers for Disease Control and Prevention (CDC) suggest several possible symptoms associated with coronavirus disease 2019 (COVID\u201019), including cough, shortness of breath or difficulty breathing, fever, chills, muscle pain, sore throat, new loss of taste or smell, and less commonly nausea/vomiting/diarrhea.(1) This article is protected by copyright. All rights reserved.", "qid": 26, "docid": "pt5kemp2", "rank": 37, "score": 0.8369954824447632}, {"content": "Title: Cutaneous manifestations of hospitalized coronavirus disease 2019 patients: a report of six cases with clinicopathologic features and viral RNA in situ hybridization Content: Novel coronavirus disease 2019 (COVID-19) caused by the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) was declared a global pandemic on March, 2020.1 Recalcati et al. reported cutaneous manifestations in 20.4% of COVID-19 patients.2 We identified six patients (five female, one male) with COVID-19-associated cutaneous manifestations in April 2020 on the inpatient dermatology consultation service. The mean age was 51 years (range, 28-71 years).", "qid": 26, "docid": "yswhgbz1", "rank": 38, "score": 0.8361513614654541}, {"content": "Title: The neurological manifestations of COVID-19: a review article Content: RESULTS: Various neurological manifestations have been reported in the literature associated with COVID-19, which in the current study are classified into Central Nervous System (CNS) related manifestations including headache, dizziness, impaired consciousness, acute cerebrovascular disease, epilepsy, and Peripheral Nervous System (PNS) related manifestations such as hyposmia/anosmia, hypogeusia/ageusia, muscle pain, and Guillain-Barre syndrome. CONCLUSION: During the current context of COVID-19 pandemic, physicians should be aware of wide spectrum of neurological COVID-19 sign and symptoms for early diagnosis and isolation of patients. In this regard, COVID-19 has been associated with many neurological manifestations such as confusion, anosmia, and ageusia. Also, various evidences support the possible CNS roles in the COVID-19 pathophysiology. In this regard, further investigation of CNS involvement of SARS-COV-2 is suggested.", "qid": 26, "docid": "c9eye986", "rank": 39, "score": 0.8359788656234741}, {"content": "Title: Neurological manifestations of COVID-19 Content: The COVID-19 pandemic, which started in China, has spread rapidly to affect the entire world in a matter of months. Main manifestations of the disease include a febrile syndrome accompanied by respiratory symptoms; however, cases of systemic involvement are increasingly being reported, including cardiac and central nervous system compromise. In the series by Ling M. et al., 214 patients with COVID-19 were studied; 78 (36.4 %) had neurologic manifestations, which were classified into four main groups: acute cerebrovascular disease, impaired consciousness, peripheral nervous system involvement and muscular manifestations. Another report published by Li et al. describes that, out of 221 patients with COVID-19, 13 developed acute cerebrovascular disease with cerebral infarction, venous thrombosis and intracerebral hemorrhage.", "qid": 26, "docid": "c34c2kqs", "rank": 40, "score": 0.835779070854187}, {"content": "Title: Neurological manifestations of COVID-19. Content: The COVID-19 pandemic, which started in China, has spread rapidly to affect the entire world in a matter of months. Main manifestations of the disease include a febrile syndrome accompanied by respiratory symptoms; however, cases of systemic involvement are increasingly being reported, including cardiac and central nervous system compromise. In the series by Ling M. et al., 214 patients with COVID-19 were studied; 78 (36.4 %) had neurologic manifestations, which were classified into four main groups: acute cerebrovascular disease, impaired consciousness, peripheral nervous system involvement and muscular manifestations. Another report published by Li et al. describes that, out of 221 patients with COVID-19, 13 developed acute cerebrovascular disease with cerebral infarction, venous thrombosis and intracerebral hemorrhage.", "qid": 26, "docid": "faitrc5v", "rank": 41, "score": 0.8357790112495422}, {"content": "Title: [Anosmia and ageusia as primary symptoms of COVID-19] Content: This case report describes a physician in the early 30ies with subjective anosmia and ageusia as the major presenting symptoms of COVID-19. Apart from a week of slightly runny nose when coming from cold to warm air, the only symptom was a sudden onset of persistent anosmia and ageusia. Two weeks after normalisation of the mild sino-nasal symptoms, the patient was tested positive for SARS-CoV-2, and anosmia was verified with Sniffin' Sticks tests. Hypogeusia was verified with taste screening and two validated taste tests. Olfactory and gustatory loss may be underestimated symptoms of COVID-19.", "qid": 26, "docid": "r9ovq1o2", "rank": 42, "score": 0.8356043100357056}, {"content": "Title: [Anosmia and ageusia as primary symptoms of COVID-19]. Content: This case report describes a physician in the early 30ies with subjective anosmia and ageusia as the major presenting symptoms of COVID-19. Apart from a week of slightly runny nose when coming from cold to warm air, the only symptom was a sudden onset of persistent anosmia and ageusia. Two weeks after normalisation of the mild sino-nasal symptoms, the patient was tested positive for SARS-CoV-2, and anosmia was verified with Sniffin' Sticks tests. Hypogeusia was verified with taste screening and two validated taste tests. Olfactory and gustatory loss may be underestimated symptoms of COVID-19.", "qid": 26, "docid": "6kne981m", "rank": 43, "score": 0.8356042504310608}, {"content": "Title: Anosmia as a prominent symptom of COVID-19 infection Content: According to WHO recommendations, everyone must protect themselves against Coronavirus disease 2019 (COVID-19), which will also protect others. Due to the lack of current effective treatment and vaccine for COVID-19, screening, rapid diagnosis and isolation of the patients are essential (1, 2). Therefore, identifying the early symptoms of COVID-19 is of particular importance and is a health system priority. Early studies from COVID-19 outbreak in China have illustrated several non-specific signs and symptoms in infected patients, including fever, dry cough, dyspnea, myalgia, fatigue, lymphopenia, and radiographic evidence of pneumonia (3, 4). Recently, a probability of association between COVID-19 and altered olfactory function has been reported in South Korea, Iran, Italy, France, UK and the United States (5-8). However, to our knowledge, the definite association between COVID-19 and anosmia has not been published.", "qid": 26, "docid": "ils991dx", "rank": 44, "score": 0.8353295922279358}, {"content": "Title: Anosmia as a prominent symptom of COVID-19 infection. Content: According to WHO recommendations, everyone must protect themselves against Coronavirus disease 2019 (COVID-19), which will also protect others. Due to the lack of current effective treatment and vaccine for COVID-19, screening, rapid diagnosis and isolation of the patients are essential (1, 2). Therefore, identifying the early symptoms of COVID-19 is of particular importance and is a health system priority. Early studies from COVID-19 outbreak in China have illustrated several non-specific signs and symptoms in infected patients, including fever, dry cough, dyspnea, myalgia, fatigue, lymphopenia, and radiographic evidence of pneumonia (3, 4). Recently, a probability of association between COVID-19 and altered olfactory function has been reported in South Korea, Iran, Italy, France, UK and the United States (5-8). However, to our knowledge, the definite association between COVID-19 and anosmia has not been published.", "qid": 26, "docid": "k23iyivp", "rank": 45, "score": 0.8353295922279358}, {"content": "Title: Fecal\u2010Oral Transmission of COVID\u201019: Could Hypochlorhydria Play a Role? Content: Coronavirus disease 2019 (COVID\u201019) is caused by severe acute respiratory syndrome coronavirus\u20102 (SARS\u2010CoV\u20102) which emerged in Wuhan, China in 2019 (1). Respiratory symptoms remain the most common clinical manifestations of COVID\u201019. However, non\u2010respiratory symptoms are increasingly being recognized. Gastrointestinal (GI) symptoms such as anorexia, nausea, vomiting, diarrhea, and abdominal pain are noted in COVID\u201019 patients either alone or in association with respiratory manifestations (2). Stool viral RNA can be detected by up to 50% in patients with diarrhea (3). This article is protected by copyright. All rights reserved.", "qid": 26, "docid": "qq5udws5", "rank": 46, "score": 0.8352401256561279}, {"content": "Title: SARS\u2010CoV\u20102 infection presenting as a febrile rash Content: The World Health Organization (WHO) has declared that Coronavirus disease 2019 (Covid-19) is a public health emergency of international concern as it continues to spread worldwide.1 After a median incubation period of 4 days, fever and cough are the two most common manifestations of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection.", "qid": 26, "docid": "tleh9323", "rank": 47, "score": 0.835218071937561}, {"content": "Title: Severe COVID-19 Cases: Is Respiratory Distress Partially Explained by Central Nervous System Involvement? Content: The main characteristics and challenging symptoms of COVID-19, caused by the novel coronavirus SARS-CoV-2, are related to re-spiratory distress. Although most patients have mild symptoms such as fever, headache, cough, myalgia and anosmia, some develop acute respiratory distress syndrome, leading to death in many cases. Human coronavirus (CoVs) were responsible for two previ-ous worldwide outbreaks: Severe Acute Respiratory Syndrome (SARS-CoV) and Middle East Respiratory Syndrome (MERS-CoV). Several reports of these outbreaks demonstrated that these diseases affected the central nervous system (CNS).[1] Thus, for the current COVID-19 pandemic, a crucial question arises: does CNS affection at least partially explain the respiratory distress commonly found in these patients?", "qid": 26, "docid": "qvdv095k", "rank": 48, "score": 0.8350052237510681}, {"content": "Title: Olfactory and Gustatory Dysfunction in Coronavirus Disease 19 (COVID-19) Content: Coronavirus-disease-2019 (COVID-19) caused by the severe-acute-respiratory-syndrome-coronavirus-2 (SARS-CoV-2) shows a rapid spread over-the-world. Given scarce resources, non-laboratory diagnostics is crucial. In this cross-sectional study, two-thirds of European patients with polymerase chain reaction confirmed COVID-19 reported olfactory and gustatory dysfunction, indicating the significance of this history in the early diagnostics.", "qid": 26, "docid": "ct67dmgg", "rank": 49, "score": 0.834648609161377}, {"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": 50, "score": 0.8345964550971985}, {"content": "Title: COVID-19 Psychosis: A potential new neuropsychiatric condition triggered by novel coronavirus infection and the inflammatory response? Content: BACKGROUND: A growing literature documents psychological distress related to the novel coronavirus (COVID-19 or SARS-CoV2) pandemic. METHOD: We describe new-onset psychotic symptoms in three patients with no prior history of psychosis who tested positive in the Emergency Department for COVID-19 and who were otherwise asymptomatic. RESULTS: Patients had similar presentations of agitation, disorganization, paranoid ideation and auditory hallucinations, with concurrent evidence of systemic inflammation as indicated by elevated C-reactive protein and other inflammatory markers. CONCLUSION: In addition to the possibility of a stress-related trigger, based on evidence of immune activation, we postulate a potential immune-mediated neuropsychiatric trigger to these new-onset psychotic symptoms that warrants further investigation.", "qid": 26, "docid": "vzrx2is2", "rank": 51, "score": 0.8345763683319092}, {"content": "Title: Corona Virus 101 Content: COVID-2019 emerged from China in late December of 2019. It follows 2 other coronavirus outbreaks, the SARS-CoV and the MERS-CoV. Coronaviruses usually circulate among animals but sometimes can jump to humans. These 3 strains have caused severe disease in humans and global transmission concerns. Symptoms of COVID-2019 include cough, fever, and shortness of breath. Related illnesses can range from mild to severe to fatal. Primary care providers must be alert to respiratory symptoms they encounter that are associated with pertinent travel history, be prepared to safely screen, examine, and possibly test and/or report suspicions to the health department for further evaluation.", "qid": 26, "docid": "4nho5wa0", "rank": 52, "score": 0.8342006206512451}, {"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": 53, "score": 0.8331451416015625}, {"content": "Title: Anosmia: A marker of infection by the new corona virus Content: The diagnosis of Coronavirus Disease 2019 (COVID-19) is based on the identification of common symptoms such as fever, tiredness and dry cough. Anosmia and ageusia are also in fact symptoms of the infection with the new coronavirus and recently were considered as symptoms by the World Health Organization. In this case report we present the new onset anosmia during the COVID-19 pandemic. The patient, 31-year-old, reported olfactory and gustatory dysfunctions as initial symptoms of mild-to-moderate form of the COVID-19. Therefore, chemosensory dysfunctions should serve as a warning to health professionals as a possible marker of infection with the new corona virus.", "qid": 26, "docid": "b4zwinh2", "rank": 54, "score": 0.8329201340675354}, {"content": "Title: COVID-19: The Case of Three Patients with the Same Diagnosis but Different Clinical and Laboratory Features Content: SARS-CoV-2 is an RNA virus that causes COVID-19, which has been responsible for the pandemic that was declared in early 2020. Its pathological effect is majorly in the respiratory tract, but its full pathogenicity remains a mystery. Symptoms associated with COVID-19 include fever, cough, and shortness of breath. Some patients develop other symptoms like diarrhea. However, it is possible for other organs to be affected including the central nervous system, liver, and blood cells. The purpose of this case series is to unravel other factors associated with this disease, so we report three cases of COVID-19 that were hospitalized during the pandemic.", "qid": 26, "docid": "cowt4c2c", "rank": 55, "score": 0.8328699469566345}, {"content": "Title: Symmetric cutaneous vasculitis in COVID\u201019 pneumonia Content: Fever, cough, breathing difficulties, digestive issues and loss of smell and taste are the most common symptoms of novel SARS-CoV2 infection but cutaneous manifestations have been highlighted by several dermatologists. We found reports (1-3) to be very interesting because it was underlined how the COVID19 infection can also give cutaneous manifestations vasculitis - like. It has already been described how purple in children, when accompanied by fever, can be a rare but possible manifestation of novel SARs-CoV2 infection(4).", "qid": 26, "docid": "0z10ahnz", "rank": 56, "score": 0.832709550857544}, {"content": "Title: SARS-CoV-2 Infection Leads to Neurological Dysfunction Content: A number of neurological disease complications have been seen following infection with the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). While most person with COVID-19 respiratory disease demonstrate headache, nausea and vomiting, up to 40% present also experience dizziness, confusion, cerebrovascular disease, muscle pain, ataxia and seizures. Loss of taste and smell, defects in visual acuity and pain occur in parallel. Such central nervous system (CNS) signs and symptoms linked to laboratory-confirmed SARS-CoV-2 infection is often life threatening. Health care providers currently evaluating patients with neurologic symptoms need consider COVID-19 in any differential diagnosis. These considerations will facilitate prompt testing, isolation and prevention of viral transmission speeding best clinical outcomes. Graphical Abstract.", "qid": 26, "docid": "126ut1cb", "rank": 57, "score": 0.8326824307441711}, {"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": 58, "score": 0.8325350284576416}, {"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": 59, "score": 0.8323347568511963}, {"content": "Title: Clinical Characteristics of 5 COVID-19 Cases With Non-respiratory Symptoms as the First Manifestation in Children Content: An outbreak of the novel coronavirus disease 2019 (COVID-19) occurred in Wuhan, China, in December 2019, which then rapidly spread to more than 80 countries. However, detailed information on the characteristics of COVID-19 in children is still scarce. Five patients with non-respiratory symptoms as the first manifestation were hospitalized from the emergency department, and were later confirmed to have COVID-19, between 23 January and 20 February 2020, at the Wuhan Children's Hospital. SARS-CoV-2 nucleic acid detection was positive for all the patients. Four of the patients were male and one was female, and their ages ranged from 2-months to 5.6 years. All lived in Wuhan. One patient had a clear history of exposure to SARS-CoV-2, one had a suspected history of exposure, while the others had no exposure history. For three of the five patients, the primary onset disease required an emergency operation or treatment, and included intussusception, acute suppurative appendicitis perforation with local peritonitis, and traumatic subdural hemorrhage with convulsion, while for the other two it was acute gastroenteritis (including one patient with hydronephrosis and a stone in his left kidney). During the course of the disease, four of the five patients had a fever, whereas one case had no fever or cough. Two patients had leukopenia, and one also had lymphopenia. In the two cases of severe COVID-19, the levels of CRP, PCT, serum ferritin, IL-6, and IL-10 were significantly increased, whereas the numbers of CD3+, CD4+, CD8+ T lymphocytes, and CD16 + CD56 natural killer cells were decreased. We also found impaired liver, kidney, and myocardial functions; the presence of hypoproteinemia, hyponatremia, and hypocalcemia; and, in one case, abnormal coagulation function. Except for one patient who had a rotavirus infection, all patients tested negative for common pathogens, including the influenza virus, parainfluenza virus, respiratory syncytial virus, adenovirus, enterovirus, mycoplasma, Chlamydia, and Legionella. Chest CT images of all the patients showed patches or ground-glass opacities in the lung periphery or near the pleura, even large consolidations. This case series is the first report to describe the clinical features of COVID-19 with non-respiratory symptoms as the first manifestation in children.", "qid": 26, "docid": "g4250q6l", "rank": 60, "score": 0.8323080539703369}, {"content": "Title: A prospective clinical study of detailed neurological manifestations in patients with COVID-19 Content: BACKGROUND: COVID-19 is a virus pandemic. According to the first obtained data, COVID-19 has defined with findings such as cough, fever, diarrhea, and fatigue although neurological symptoms of patients with COVID-19 have not been investigated in detail. This study aims to investigate the neurological findings via obtained face-to-face anamnesis and detailed neurological examination in patients with COVID-19. METHODS: Two hundred thirty-nine consecutive inpatients with COVID-19, supported with laboratory tests, were evaluated. Detailed neurological examinations and evaluations of all patients were performed. All evaluations and examinations were performed by two neurologists who have at least five-year experience. RESULTS: This study was carried out 239 patients (133 male + 106 female) with diagnosed COVID-19. Neurological findings were present in 83 of 239 patients (34.7%). The most common neurological finding was a headache (27.6%). D-dimer blood levels were detected to be significantly higher in patients with at least one neurological symptom than patients without the neurological symptom (p < 0.05). IL-6 level was found to be significantly higher in patients with headache than without headache (p < 0.05). Creatine kinase (CK) level was detected to be significantly higher in patients with muscle pain (p < 0.05). CONCLUSION: Neurological symptoms are often seen in patients with COVID-19. Headache was the most common seen neurological symptom in this disease. Dizziness, impaired consciousness, smell and gustation impairments, cerebrovascular disorders, epileptic seizures, and myalgia were detected as other findings apart from the headache. It is suggested that determining these neurological symptoms prevents the diagnosis delay and helps to prohibit virus spread.", "qid": 26, "docid": "rcguim61", "rank": 61, "score": 0.8322619199752808}, {"content": "Title: SARS-CoV-2 Infection Leads to Neurological Dysfunction Content: A number of neurological disease complications have been seen following infection with the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). While most person with COVID-19 respiratory disease demonstrate headache, nausea and vomiting, up to 40% present also experience dizziness, confusion, cerebrovascular disease, muscle pain, ataxia and seizures. Loss of taste and smell, defects in visual acuity and pain occur in parallel. Such central nervous system (CNS) signs and symptoms linked to laboratory-confirmed SARS-CoV-2 infection is often life threatening. Health care providers currently evaluating patients with neurologic symptoms need consider COVID-19 in any differential diagnosis. These considerations will facilitate prompt testing, isolation and prevention of viral transmission speeding best clinical outcomes. [Figure: see text]", "qid": 26, "docid": "nbxzyjvf", "rank": 62, "score": 0.832249104976654}, {"content": "Title: Symptom Course in COVID-19 Outpatients Content: Objective: To describe the symptom course in outpatients with coronavirus disease 2019 (COVID-19). Design: Retrospective chart review of standardized symptom checklist for patients followed at home by telephone calls during their acute COVID-19 illness. Compile results by day of illness into a single heatmap representation of symptoms. Setting: COVID-19 Virtual Outpatient Management Clinic (VOMC) in Atlanta, Georgia; a practice that follows patients with mild COVID-19 at home. Participants: 272 patients with confirmed COVID-19 by nasopharyngeal PCR, who presented to the VOMC within 10 days of symptom onset and within 5 days of screening PCR test. Main outcome measure: Each symptom is recorded as yes/no for each patient on each day. The total number of yes replies is divided by the total number of patients in VOMC to generate a result for each cell in the heatmap. Patients admitted to the hospital are censored from the denominator. Results: The mean duration of follow-up was 20.2 days. The most commonly reported symptoms in the course of illness were cough (83%), headache (73%) loss of smell or taste (71%), sinus congestion (71%), and body ache (67%). Symptoms remained common at 3 weeks, including cough (41%), shortness of breath on exertion (24%), loss of smell or taste (23%), sinus congestion (23%), and headache (20%). Conclusions: Symptoms of acute COVID-19 frequently last longer than the minimum duration of isolation and patients and healthcare providers should be aware that symptom resolution may be gradual.", "qid": 26, "docid": "dpyvu6ji", "rank": 63, "score": 0.8313032388687134}, {"content": "Title: First 12 patients with coronavirus disease 2019 (COVID-19) in the United States Content: Introduction: More than 93,000 cases of coronavirus disease (COVID-19) have been reported worldwide. We describe the epidemiology, clinical course, and virologic characteristics of the first 12 U.S. patients with COVID-19. Methods: We collected demographic, exposure, and clinical information from 12 patients confirmed by CDC during January 20-February 5, 2020 to have COVID-19. Respiratory, stool, serum, and urine specimens were submitted for SARS-CoV-2 rRT-PCR testing, virus culture, and whole genome sequencing. Results: Among the 12 patients, median age was 53 years (range: 21-68); 8 were male, 10 had traveled to China, and two were contacts of patients in this series. Commonly reported signs and symptoms at illness onset were fever (n=7) and cough (n=8). Seven patients were hospitalized with radiographic evidence of pneumonia and demonstrated clinical or laboratory signs of worsening during the second week of illness. Three were treated with the investigational antiviral remdesivir. All patients had SARS-CoV-2 RNA detected in respiratory specimens, typically for 2-3 weeks after illness onset, with lowest rRT-PCR Ct values often detected in the first week. SARS-CoV-2 RNA was detected after reported symptom resolution in seven patients. SARS-CoV-2 was cultured from respiratory specimens, and SARS-CoV-2 RNA was detected in stool from 7/10 patients. Conclusions: In 12 patients with mild to moderately severe illness, SARS-CoV-2 RNA and viable virus were detected early, and prolonged RNA detection suggests the window for diagnosis is long. Hospitalized patients showed signs of worsening in the second week after illness onset.", "qid": 26, "docid": "a66sszp2", "rank": 64, "score": 0.8313015699386597}, {"content": "Title: Clinical characteristics of 3062 COVID-19 patients: A meta-analysis Content: We aimed to systematically review the clinical characteristics of coronavirus disease 2019 (COVID-19). Seven databases were searched to collect studies about the clinical characteristics of COVID-19 from January 1, 2020 to February 28, 2020. Then, meta-analysis was performed by using Stata12.0 software. A total of 38 studies involving 3062 COVID-19 patients were included. Meta-analysis showed that a higher proportion of infected patients was male (56.9%). The incidence rate of respiratory failure or acute respiratory distress syndrome was 19.5% and the fatality rate was 5.5%. Fever (80.4%), fatigue (46%), cough (63.1%), and expectoration (41.8%) were the most common clinical manifestations. Other common symptoms included muscle soreness (33%), anorexia (38.8%), chest tightness (35.7%), shortness of breath (35%), dyspnea (33.9%). Minor symptoms included nausea and vomiting (10.2%), diarrhea (12.9%), headache (15.4%), pharyngalgia (13.1%), shivering (10.9%), and abdominal pain (4.4%). The proportion of patients that was asymptomatic was 11.9%. Normal leukocyte counts (69.7%), lymphopenia (56.5%), elevated C-reactive protein levels (73.6%), elevated ESR (65.6%), and oxygenation index decreased (63.6%) were observed in most patients. About 37.2% of patients were found with elevated D-dimer, 25.9% of patients with leukopenia, along with abnormal levels of liver function (29%), and renal function (25.5%). Other findings included leukocytosis (12.6%) and elevated procalcitonin (17.5%). Only 25.8% of patients had lesions involving a single lung and 75.7% of patients had lesions involving bilateral lungs. The most commonly experienced symptoms of COVID-19 patients were fever, fatigue, cough, and expectoration. A relatively small percentage of patients were asymptomatic. Most patients showed normal leucocytes counts, lymphopenia, elevated levels of C-reactive protein and ESR. Bilateral lung involvement was common.", "qid": 26, "docid": "qfxdydgp", "rank": 65, "score": 0.8306678533554077}, {"content": "Title: A case of COVID-19 with tuberculous meningitis/ \u65b0\u578b\u51a0\u72b6\u75c5\u6bd2\u80ba\u708e\u5408\u5e76\u7ed3\u6838\u6027\u8111\u819c\u708e\u4e00\u4f8b Content: COVID\u204319 is caused by a new coronavirus that infects the lungs. Although some patients with COVID\u204319 may be combined with neurological symptoms, there is no direct evidence that this new coronavirus can directly invade nerve system. A case of COVID\u204319 with tuberculous meningitis is reported to remind that when patients with COVID\u204319 present symptom of encephalitis or meningitis, a comprehensive pathogen examination is recommended.", "qid": 26, "docid": "yi4ymv4v", "rank": 66, "score": 0.8306314945220947}, {"content": "Title: Abdominal Pain: A Real Challenge in Novel COVID-19 Infection Content: COVID-19 (coronavirus disease 19) is an infectious disease caused by coronavirus 2019-nCoV. Since its detection in China at the end of 2019, the novel coronavirus has rapidly spread throughout the world and has caused an international public health emergency. The most common manifestation is flu-like symptoms. Mild infections usually improve within a few days, but COVID-19 can cause severe pneumonia with acute respiratory distress syndrome and death. Gastrointestinal symptoms are less common but possible and more difficult to recognize as part of a COVID-19 syndrome. In line with the current opinion of the WHO, we strongly believe that preventive measures and early diagnosis of COVID-19 are crucial to interrupt virus spread and avoid local outbreaks. We report the cases of COVID-19 patients admitted to our Emergency Department who complained of gastrointestinal symptoms at admission. LEARNING POINTS: The novel COVID-19 infection is a severe public health problem which is causing an increasing number of deaths worldwide. Although uncommon, there may be a relationship between gastrointestinal symptoms and COVID-19, as reported in recent studies. Early detection and isolation of patients with COVID-19 infection is the only way to control and limit the global spread of this virus.", "qid": 26, "docid": "gjigvjgv", "rank": 67, "score": 0.830316960811615}, {"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": 26, "docid": "tu36aisz", "rank": 68, "score": 0.8301012516021729}, {"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": 26, "docid": "qt02t6tf", "rank": 69, "score": 0.8301012516021729}, {"content": "Title: Neurological Manifestations of Hospitalized Patients with COVID-19 in Wuhan, China: a retrospective case series study Content: OBJECTIVE: To study the neurological manifestations of patients with coronavirus disease 2019 (COVID-19). DESIGN: Retrospective case series SETTING: Three designated COVID-19 care hospitals of the Union Hospital of Huazhong University of Science and Technology in Wuhan, China. PARTICIPANTS: Two hundred fourteen hospitalized patients with laboratory confirmed diagnosis of severe acute respiratory syndrome from coronavirus 2 (SARS-CoV-2) infection. Data were collected from 16 January 2020 to 19 February 2020. MAIN OUTCOME MEASURES: Clinical data were extracted from electronic medical records and reviewed by a trained team of physicians. Neurological symptoms fall into three categories: central nervous system (CNS) symptoms or diseases (headache, dizziness, impaired consciousness, ataxia, acute cerebrovascular disease, and epilepsy), peripheral nervous system (PNS) symptoms (hypogeusia, hyposmia, hypopsia, and neuralgia), and skeletal muscular symptoms. Data of all neurological symptoms were checked by two trained neurologists. RESULTS: Of 214 patients studied, 88 (41.1%) were severe and 126 (58.9%) were non-severe patients. Compared with non-severe patients, severe patients were older (58.7 \u00b1 15.0 years vs 48.9 \u00b1 14.7 years), had more underlying disorders (42 [47.7%] vs 41 [32.5%]), especially hypertension (32 [36.4%] vs 19 [15.1%]), and showed less typical symptoms such as fever (40 [45.5%] vs 92 [73%]) and cough (30 [34.1%] vs 77 [61.1%]). Seventy-eight (36.4%) patients had neurologic manifestations. More severe patients were likely to have neurologic symptoms (40 [45.5%] vs 38 [30.2%]), such as acute cerebrovascular diseases (5 [5.7%] vs 1 [0.8%]), impaired consciousness (13 [14.8%] vs 3 [2.4%]) and skeletal muscle injury (17 [19.3%] vs 6 [4.8%]). CONCLUSION: Compared with non-severe patients with COVID-19, severe patients commonly had neurologic symptoms manifested as acute cerebrovascular diseases, consciousness impairment and skeletal muscle symptoms.", "qid": 26, "docid": "niw61l9r", "rank": 70, "score": 0.8300603628158569}, {"content": "Title: Anosmia and olfactory tract neuropathy in a case of COVID-19 Content: Coronavirus Disease-19 (COVID-19) has been in a global pandemic currently and relating symptoms were reported variously around the world. We reported a previously healthy man of COVID-19 presenting with anosmia as the obvious symptom with relevant radiological findings on brain magnetic resonance imaging.", "qid": 26, "docid": "nnj117c8", "rank": 71, "score": 0.830012321472168}, {"content": "Title: Neurologic Manifestations of Hospitalized Patients With Coronavirus Disease 2019 in Wuhan, China Content: Importance: The outbreak of coronavirus disease 2019 (COVID-19) in Wuhan, China, is serious and has the potential to become an epidemic worldwide. Several studies have described typical clinical manifestations including fever, cough, diarrhea, and fatigue. However, to our knowledge, it has not been reported that patients with COVID-19 had any neurologic manifestations. Objective: To study the neurologic manifestations of patients with COVID-19. Design, Setting, and Participants: This is a retrospective, observational case series. Data were collected from January 16, 2020, to February 19, 2020, at 3 designated special care centers for COVID-19 (Main District, West Branch, and Tumor Center) of the Union Hospital of Huazhong University of Science and Technology in Wuhan, China. The study included 214 consecutive hospitalized patients with laboratory-confirmed diagnosis of severe acute respiratory syndrome coronavirus 2 infection. Main Outcomes and Measures: Clinical data were extracted from electronic medical records, and data of all neurologic symptoms were checked by 2 trained neurologists. Neurologic manifestations fell into 3 categories: central nervous system manifestations (dizziness, headache, impaired consciousness, acute cerebrovascular disease, ataxia, and seizure), peripheral nervous system manifestations (taste impairment, smell impairment, vision impairment, and nerve pain), and skeletal muscular injury manifestations. Results: Of 214 patients (mean [SD] age, 52.7 [15.5] years; 87 men [40.7%]) with COVID-19, 126 patients (58.9%) had nonsevere infection and 88 patients (41.1%) had severe infection according to their respiratory status. Overall, 78 patients (36.4%) had neurologic manifestations. Compared with patients with nonsevere infection, patients with severe infection were older, had more underlying disorders, especially hypertension, and showed fewer typical symptoms of COVID-19, such as fever and cough. Patients with more severe infection had neurologic manifestations, such as acute cerebrovascular diseases (5 [5.7%] vs 1 [0.8%]), impaired consciousness (13 [14.8%] vs 3 [2.4%]), and skeletal muscle injury (17 [19.3%] vs 6 [4.8%]). Conclusions and Relevance: Patients with COVID-19 commonly have neurologic manifestations. During the epidemic period of COVID-19, when seeing patients with neurologic manifestations, clinicians should suspect severe acute respiratory syndrome coronavirus 2 infection as a differential diagnosis to avoid delayed diagnosis or misdiagnosis and lose the chance to treat and prevent further transmission.", "qid": 26, "docid": "vr11maos", "rank": 72, "score": 0.8299787044525146}, {"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": 26, "docid": "c5dm1d6t", "rank": 73, "score": 0.829849362373352}, {"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": 26, "docid": "v5uz8rsu", "rank": 74, "score": 0.829849362373352}, {"content": "Title: SARS-COV-2 Presenting as New Onset Atrial Fibrillation: A Case Report Content: Current literature has documented numerous different presentations of SARS-COV-2 (COVID-19). Common symptoms include fever, cough and shortness of breath, however, lack of these symptoms does not exclude COVID-19. Given the incomplete understanding of the virus at this time, healthcare professionals must continue to remain informed of the vast number of clinical presentations of the virus to ensure early supportive treatment, ideally leading to improved outcomes.", "qid": 26, "docid": "bqivjudl", "rank": 75, "score": 0.8298200964927673}, {"content": "Title: SARS\u2010CoV\u20102: a new aetiology for atypical lymphocytes Content: Coronavirus disease 2019 (COVID-19) is an infectious disease caused by a newly emerging coronavirus, SARS-CoV-2. COVID-19 has a very variable clinical picture, ranging from asymptomatic to severe acute respiratory syndrome that can lead to death. Our case, a 74-year-old female patient, presented with fever, moderate dyspnoea and leucocytosis (white blood cell count 21.6 \u00d7 109 /l, neutrophils 16.8 \u00d7 109 /l, lymphocytes 3.67 \u00d7 109 /l). RT-PCR for SARS-CoV-2 was performed, which confirmed COVID-19.", "qid": 26, "docid": "oo2s307i", "rank": 76, "score": 0.829325258731842}, {"content": "Title: (18)F-FDG PET/CT and Serial Chest CT Findings in a COVID-19 Patient With Dynamic Clinical Characteristics in Different Period Content: Neurological symptoms and gastrointestinal symptoms were rare at onset in COVID-19. Here we report a 37-year-old man with vertigo, fever, and diarrhea symptoms as the first manifestation. (18)F-FDG PET/CT spotted multiple ground glass opacity (GGO) lesions in the lungs, with increased tracer uptake in both lung GGOs and the whole colon. Serial CT examinations showed the emersion and dissipation of lung GGOs. We illustrate the symptoms initiation, the laboratory test results, the imaging examination, and the treatment strategy in the duration of COVID-19 with a timeline chart.", "qid": 26, "docid": "i2mw9289", "rank": 77, "score": 0.8292189240455627}, {"content": "Title: Novel Coronavirus COVID-19: Current Evidence and Evolving Strategies Content: COVID-19 is a global pandemic that has currently infected &gt;300,000 globally. Fever and cough are the most common symptoms of the disease, and it is important to remember that the virus can even be transmitted by individuals who test positive for the disease but do not have any symptoms. Currently reported mortality rates vary because of the rapid spread of the disease and different approaches to calculating this estimate, but it is clear that the risk of death is associated with age and the presence of underlying conditions. Risk mitigation techniques (i.e., hand washing, social distancing, and self-isolation) have already been emphasized across major news outlets. It is essential that we continue these practices, as the outbreak is currently expected to last for many more months and we must be mindful of the lessons learned from past pandemics to prevent a second wave from occurring.", "qid": 26, "docid": "3ateeei3", "rank": 78, "score": 0.8291007280349731}, {"content": "Title: Clinical Characteristics and Differential Clinical Diagnosis of Novel Coronavirus Disease 2019 (COVID-19) Content: Novel Coronavirus Disease (COVID-19) has become a rapidly growing pandemic involving several nations. It is of serious concern and extreme challenge not only to the health personnel but also to the countries for containment. The causative organism is SARS-CoV-2, RNA virus of subgenus Sarbecovirus, similar to the SARS virus, and seventh member of the human coronavirus family responsible for this zoonotic infection. It binds to the human angiotensin converting enzyme (hACE-2) receptor and causes constitutional and respiratory symptoms. The major mode of transmission is human to human and the median incubation period is 4 days. The most common symptom as studied from various cohorts of COVID-19 patients are fever (83\u201398%) followed by fatigue (70%) and dry cough (59%); gastrointestinal symptoms are relatively uncommon differentiating it from SARS and MERS. Most of the SAR-CoV-2 infection are mild (80%) with a usual recovery period of 2 weeks. COVID-19 commonly affects males in the middle age and elderly age group, with highest case fatality (8\u201315%) among those aged >80 years. The disease begins with fever, dry cough, fatigue and myalgia progressing to dyspnoea and ARDS over 6 and 8 days post exposure, respectively. Underlying co-morbidities increase mortality in COVID-19. Poor prognostic factors are elderly, co-morbidities, severe lymphopaenia, high CRP and D-dimer >1 \u03bcg/L. The overall mortality rate ranges from 1.5 to 3.6%. COVID-19 has to be differentiated from other viral and bacterial pneumonias as they are more common among healthy adults. Despite constant and vigorous efforts by researchers and health agencies, we are far from containment, cure or prevention by vaccine; hence right information and stringent prevention and control measures are the only weapon in the armoury to combat the ongoing infection.", "qid": 26, "docid": "nzjz0q8b", "rank": 79, "score": 0.8289257287979126}, {"content": "Title: COVID-19 and outbreak of chilblains: are they related? Content: SARS-CoV-2 is a new coronavirus that causes COVID-19, a disease associated with severe pneumonia.1 Many other clinical manifestations have been associated with the disease (diarrhoea, anosmia, dysgeusia, etc.) and patients can be healthy carriers of the virus.2 Several dermatologic manifestations associated with COVID-19 have been reported.3 Among them are numerous cases of chilblain-like lesions (CBLL) in young patients in good general condition, often not tested, or tested negative, for the SARS-CoV-2.4,5 In a recent study on 375 Spanish patients with suspected or confirmed COVID-19, these CBLL accounted for 19% of all cutaneous lesions;3 they were observed in young patients with mild systemic symptoms and seemed to appear late in the course of the disease.", "qid": 26, "docid": "yx3wxrhh", "rank": 80, "score": 0.8287979960441589}, {"content": "Title: Fever with Rash in COVID\u201019: Viral Exanthema or Secondary Lesions? Content: COVID\u201019 originated in Wuhan, China and has developed into a pandemic since late 2019. The virus possesses powerful pathogenicity as well as transmissibility. Many open questions remain, including the description of potential involvement of other organs than the respiratory tract. Most patients have mild influenza\u2010like symptoms. A minority, especially patients with chronic lung disease, develops lethal disease including severe pneumonia, pulmonary edema, rapidly developing acute respiratory distress syndrome (ARDS), multiple organ failure and septic shock.", "qid": 26, "docid": "xo7l2iei", "rank": 81, "score": 0.8282405734062195}, {"content": "Title: Guillain-Barr\u00e9 syndrome in a patient with antibodies against SARS-COV-2 Content: There are now several reports on neurologic features of SARS-CoV-2 infection.1 2 In a recent study of 214 patients with COVID-19, 78 (36.4%) patients had neurological manifestations, including headache, dizziness, acute cerebrovascular diseases, and impaired consciousness.2.", "qid": 26, "docid": "t7qe4itx", "rank": 82, "score": 0.828238844871521}, {"content": "Title: Smell and taste dysfunction during the COVID-19 outbreak: a preliminary report Content: In late December 2019, in Wuhan (China), health authorities reported several clusters of pneumo- nia of unknown cause, subsequently attributed to a novel coronavirus, identified as Severe Acute Respiratory Syndrome-Coronavirus 2. Anosmia and dysgeusia have been reported as particular symptoms.4,5 Notably, these sensory symptoms seem to have a peculiar trend, such as usually precede the onset of respiratory symp- toms. So, they have been defined as \"sentinel\" symptoms. We presented a series of COVID-19 patients. Anos- mia and dysgeusia frequently preceded respiratory complaints. Anosmia and dysgeusia seem to be short-lived and self-resolving in COVID-19, thus a neurotoxic effect swiftly disappearing and/or cytopathic damage could be hypothesized similarly to other viral infections.", "qid": 26, "docid": "vayoebve", "rank": 83, "score": 0.828041672706604}, {"content": "Title: Smell and taste dysfunction during the COVID-19 outbreak: a preliminary report. Content: In late December 2019, in Wuhan (China), health authorities reported several clusters of pneumo- nia of unknown cause, subsequently attributed to a novel coronavirus, identified as Severe Acute Respiratory Syndrome-Coronavirus 2. Anosmia and dysgeusia have been reported as particular symptoms.4,5 Notably, these sensory symptoms seem to have a peculiar trend, such as usually precede the onset of respiratory symp- toms. So, they have been defined as \"sentinel\" symptoms. We presented a series of COVID-19 patients. Anos- mia and dysgeusia frequently preceded respiratory complaints. Anosmia and dysgeusia seem to be short-lived and self-resolving in COVID-19, thus a neurotoxic effect swiftly disappearing and/or cytopathic damage could be hypothesized similarly to other viral infections.", "qid": 26, "docid": "pn0gqxru", "rank": 84, "score": 0.828041672706604}, {"content": "Title: Anxiety and Depression Scores in Maternity Healthcare Workers during the Covid-19 Pandemic Content: While Severe-Acute-Respiratory-Syndrome-CoronaVirus-2 (SARSCoV-2/Covid-19) causes physical morbidity for healthcare workers (HCWs), Covid-19 also carries psychological morbidity for HCWs. This morbidity translates to anxiety and depressive symptomatology. To this end, we assessed anxiety and depression among HCWs during Covid-19 pandemic.", "qid": 26, "docid": "xmydvh4g", "rank": 85, "score": 0.8278322219848633}, {"content": "Title: Anxiety and Depression Scores in Maternity Healthcare Workers during the Covid-19 Pandemic. Content: While Severe-Acute-Respiratory-Syndrome-CoronaVirus-2 (SARSCoV-2/Covid-19) causes physical morbidity for healthcare workers (HCWs), Covid-19 also carries psychological morbidity for HCWs. This morbidity translates to anxiety and depressive symptomatology. To this end, we assessed anxiety and depression among HCWs during Covid-19 pandemic.", "qid": 26, "docid": "rroaast3", "rank": 86, "score": 0.8278322219848633}, {"content": "Title: Clinical presentation and course of COVID-19. Content: Information about the clinical presentation and course of COVID-19 is rapidly evolving. Data are emerging from retrospective clinical studies conducted in Wuhan, China, showing the symptoms and characteristics of COVID-19 caused by severe acute respiratory virus coronavirus 2 (SARS-CoV-2) infection, including fever, cough, and shortness of breath. Radiographic data on COVID-19 cases reveal bilateral opacities on chest radiography and ground-glass opacities on computed tomography. Data on laboratory markers and mortality and morbidity are also emerging.", "qid": 26, "docid": "g4luqtjv", "rank": 87, "score": 0.8278114795684814}, {"content": "Title: Chest Imaging in Patients Hospitalized With COVID-19 Infection - A Case Series Content: COVID-19 (Corona Virus Disease-19) is a zoonotic illness first reported in the city of Wuhan, China in December 2019, and is now officially a global pandemic as declared by the World Health Organization. The infection is caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). COVID-19 infected patients can be asymptomatic carriers or present with mild-to-severe respiratory symptoms. Imaging, including computed tomography is not recommended to screen/diagnose COVID-19 infections, but plays an important role in management of these patients, and to rule out alternative diagnoses or coexistent diseases. In our multicenter case series, we outline the clinical presentations and illustrate the most common imaging manifestations in patients hospitalized with COVID-19.", "qid": 26, "docid": "jx4mfw0w", "rank": 88, "score": 0.8274785280227661}, {"content": "Title: Affective psychosis after COVID-19 infection in a previously healthy patient: a case report Content: \u2022 Patients COVID19 new-onset psychiatric symptoms because treatments or virus itself.", "qid": 26, "docid": "jujk76a6", "rank": 89, "score": 0.8273583650588989}, {"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": 90, "score": 0.8273295164108276}, {"content": "Title: The first pediatric patients with coronavirus disease 2019 (COVID-19) in Japan; The risk of co-infection with other respiratory viruses Content: Coronavirus disease 2019 (COVID-19) is a severe infectious disease of the respiratory tract caused by a novel coronavirus, Severe Acute Respiratory Syndrome Coronavirus 2, and has a high mortality rate. The disease emerged from Wuhan, China, in late 2019, and spread to Japan, including Hokkaido, in January 2020. In February 2020, three children were diagnosed with COVID-19 in Furano, Hokkaido, Japan. During this period, influenza and human metapneumovirus infections were prevalent among children in the Furano region. Two of the three cases experienced co-infection with other respiratory viruses, including influenza virus A or human metapneumovirus. To the authors' knowledge, the cases described in the present report were the first pediatric patients with COVID-19 in Japan. In children with COVID-19, the possibility of co-infection with other respiratory pathogens should be considered.", "qid": 26, "docid": "3w1bvo6s", "rank": 91, "score": 0.827123761177063}, {"content": "Title: The first pediatric patients with coronavirus disease 2019 (COVID-19) in Japan; The risk of co-infection with other respiratory viruses. Content: Coronavirus disease 2019 (COVID-19) is a severe infectious disease of the respiratory tract caused by a novel coronavirus, Severe Acute Respiratory Syndrome Coronavirus 2, and has a high mortality rate. The disease emerged from Wuhan, China, in late 2019, and spread to Japan, including Hokkaido, in January 2020. In February 2020, three children were diagnosed with COVID-19 in Furano, Hokkaido, Japan. During this period, influenza and human metapneumovirus infections were prevalent among children in the Furano region. Two of the three cases experienced co-infection with other respiratory viruses, including influenza virus A or human metapneumovirus. To the authors' knowledge, the cases described in the present report were the first pediatric patients with COVID-19 in Japan. In children with COVID-19, the possibility of co-infection with other respiratory pathogens should be considered.", "qid": 26, "docid": "ii1t8xfg", "rank": 92, "score": 0.827123761177063}, {"content": "Title: 18F-FDG PET/CT and Serial Chest CT Findings in a COVID-19 Patient With Dynamic Clinical Characteristics in Different Period Content: Neurological symptoms and gastrointestinal symptoms were rare at onset in COVID-19. Here we report a 37-year-old man with vertigo, fever, and diarrhea symptoms as the first manifestation. F-FDG PET/CT spotted multiple ground glass opacity (GGO) lesions in the lungs, with increased tracer uptake in both lung GGOs and the whole colon. Serial CT examinations showed the emersion and dissipation of lung GGOs. We illustrate the symptoms initiation, the laboratory test results, the imaging examination, and the treatment strategy in the duration of COVID-19 with a timeline chart.", "qid": 26, "docid": "0ia8ocqv", "rank": 93, "score": 0.8268822431564331}, {"content": "Title: Loss of Taste and Smell as Distinguishing Symptoms of COVID-19 Content: Olfactory and taste dysfunctions have emerged as symptoms of COVID-19. Among individuals with COVID-19 enrolled in a household study, loss of taste and/or smell was the fourth most commonly reported symptom (26/42; 62%), and among household contacts, it had the highest positive predictive value (83%; 95% CI: 55-95%) for COVID-19. These findings support consideration of loss of taste and/or smell in possible case identification and testing prioritization for COVID-19.", "qid": 26, "docid": "04zbbyii", "rank": 94, "score": 0.8268241882324219}, {"content": "Title: Epidemiological and clinical characteristics of COVID-19 patients in Nantong, China Content: INTRODUCTION: COVID-19 is a newly emerging life-threatening respiratory disease caused by a newly identified coronavirus SARS-CoV-2. METHODOLOGY: We included 28 COVID-19 patients admitted to Nantong Third Hospital from January 23 to February 26, 2020. SARS-CoV-2 infection was confirmed using real-time RT-PCR. The demographic, epidemiological, clinical, laboratory parameters were obtained from each patient. RESULTS: The vast majority (71.4%) of confirmed COVID-19 patients were brought in from outside of the city, and all others had contact history with these confirmed cases. The median age of patients was 50 years old and half had underlying diseases. The most common symptoms at the onset of illness were fever (96.4%), cough (67.9%), and chilly (28.6%), and 75.0% patients had two or more symptoms. Increased erythrocyte sedimentation rate, serum ferritin and C-reactive protein levels, and reduced absolute counts of total lymphocytes and T lymphocyte subsets were observed among the patients. The vast majority (85.7%) of patients showed bilateral or unilateral pneumonia, and three symptomatic patients and one asymptomatic case did not show abnormalities in their CT image. Among the 28 admitted patients, 24 were discharged as of February 26, 2020, with an average hospital stay of 14.96 (\u00b14.27) days, which was not significantly associated with the interval between the onset of symptoms and admission. CONCLUSIONS: In the absence of specific antiviral drugs or a vaccine, quarantine or isolation is the most effective intervention strategy for preventing the spread of the virus. Adequate supportive medical care is crucial for good prognosis of COVID-19 patients.", "qid": 26, "docid": "xfei3wi0", "rank": 95, "score": 0.8267710208892822}, {"content": "Title: Subjective neurological symptoms frequently occur in patients with SARS-CoV2 infection Content: OBJECTIVE: Coronavirus disease 2019 (COVID-19) represents a novel pneumonia leading to severe acute respiratory syndrome (SARS). Recent studies documented that SARS-Coronavirus2 (SARS-CoV2), responsible for COVID-19, can affect the nervous system. The aim of the present observational study was to prospectively assess subjective neurological symptoms (sNS) in patients with SARS-CoV2 infection. METHODS: We included patients hospitalized at the University Hospital of Rome Tor Vergata, medical center dedicated to the treatment of patients with COVID-19 diagnosis, who underwent an anamnestic interview about sNS consisting of 13 items, each related to a specific symptom, requiring a dichotomized answer. RESULTS: We included 103 patients with SARS-CoV2 infection. Ninety-four patients (91.3%) reported at least one sNS. Sleep impairment was the most frequent symptom, followed by dysgeusia, headache, hyposmia, and depression. Women more frequently complained hyposmia, dysgeusia, dizziness, numbeness/paresthesias, daytime sleepiness, and muscle ache. Moreover, muscle ache and daytime sleepiness were more frequent in the first 2 days after admission. Conversely, sleep impairment was more frequent in patients with more than 7 days of hospitalization. In these patients we also documented higher white blood cells and lower C-reactive protein levels. These laboratory findings correlated with the occurrence of hyposmia, dysgeusia, headache, daytime sleepiness, and depression. CONCLUSIONS: Patients with SARS-CoV2 infection frequently present with sNS. These symptoms were present from the early phases of the disease. The possibly intrinsic neurotropic properties of SARS-CoV2 may justify the very high frequency of sNS. Further studies targeted at investigating the consequences of SARS-CoV2 infection on the CNS should be planned.", "qid": 26, "docid": "h5b7mncf", "rank": 96, "score": 0.8267596364021301}, {"content": "Title: Novel Coronavirus COVID-19 Strike on Arab Countries and Territories: A Situation Report I Content: The novel Coronavirus (COVID-19) is an infectious disease caused by a new virus called COVID-19 or 2019-nCoV that first identified in Wuhan, China. The disease causes respiratory illness (such as the flu) with other symptoms such as a cough, fever, and in more severe cases, difficulty breathing. This new Coronavirus seems to be very infectious and has spread quickly and globally. In this work, information about COVID-19 is provided and the situation in Arab countries and territories regarding the COVID-19 strike is presented. The next few weeks main expectations is also given.", "qid": 26, "docid": "9fngwsh3", "rank": 97, "score": 0.8267005681991577}, {"content": "Title: Subjective neurological symptoms frequently occur in patients with SARS-CoV2 infection Content: OBJECTIVE: Coronavirus disease 2019 (COVID-19) represents a novel pneumonia leading to severe acute respiratory syndrome (SARS). Recent studies documented that SARS-Coronavirus2 (SARS-CoV2), responsible for COVID-19, can affect the nervous system. The aim of the present observational study was to prospectively assess subjective neurological symptoms (sNS) in patients with SARS-CoV2 infection. METHODS: We included patients hospitalized at the University Hospital of Rome \"Tor Vergata\", medical center dedicated to the treatment of patients with COVID-19 diagnosis, who underwent an anamnestic interview about sNS consisting of 13 items, each related to a specific symptom, requiring a dichotomized answer. RESULTS: We included 103 patients with SARS-CoV2 infection. Ninety-four patients (91.3%) reported at least one sNS. Sleep impairment was the most frequent symptom, followed by dysgeusia, headache, hyposmia, and depression. Women more frequently complained hyposmia, dysgeusia, dizziness, numbeness/paresthesias, daytime sleepiness, and muscle ache. Moreover, muscle ache and daytime sleepiness were more frequent in the first 2 days after admission. Conversely, sleep impairment was more frequent in patients with more than 7 days of hospitalization. In these patients we also documented higher white blood cells and lower C-reactive protein levels. These laboratory findings correlated with the occurrence of hyposmia, dysgeusia, headache, daytime sleepiness, and depression. CONCLUSIONS: Patients with SARS-CoV2 infection frequently present with sNS. These symptoms are present from the early phases of the disease. The possibly intrinsic neurotropic properties of SARS-CoV2 may justify the very high frequency of sNS. Further studies targeted at investigating the consequences of SARS-CoV2 infection on the CNS should be planned.", "qid": 26, "docid": "ee92q6sw", "rank": 98, "score": 0.8265286684036255}, {"content": "Title: Two cases of COVID\u201019 presenting with a clinical picture resembling chilblains: first report from the Middle East Content: Clinical characteristics of COVID-19 disease were identified in a cohort study involving 1099 patients from China. COVID-19 most commonly present with fever, cough, fatigue, and congestion. Two out of 1099 patients were reported to have skin rash, but time of onset and clinical description of rash were missing (Reference B). Another study focused primarily on cutaneous manifestations associated with COVID-19 evaluated 88 patients from Italy. 18 out of the 88 patients developed cutaneous manifestations, but only 8 patients developed skin lesions at onset of disease.", "qid": 26, "docid": "y1ba8ffw", "rank": 99, "score": 0.8263494968414307}, {"content": "Title: Epidemiological and clinical characteristics of COVID-19 patients in Nantong, China. Content: INTRODUCTION COVID-19 is a newly emerging life-threatening respiratory disease caused by a newly identified coronavirus SARS-CoV-2. METHODOLOGY We included 28 COVID-19 patients admitted to Nantong Third Hospital from January 23 to February 26, 2020. SARS-CoV-2 infection was confirmed using real-time RT-PCR. The demographic, epidemiological, clinical, laboratory parameters were obtained from each patient. RESULTS The vast majority (71.4%) of confirmed COVID-19 patients were brought in from outside of the city, and all others had contact history with these confirmed cases. The median age of patients was 50 years old and half had underlying diseases. The most common symptoms at the onset of illness were fever (96.4%), cough (67.9%), and chilly (28.6%), and 75.0% patients had two or more symptoms. Increased erythrocyte sedimentation rate, serum ferritin and C-reactive protein levels, and reduced absolute counts of total lymphocytes and T lymphocyte subsets were observed among the patients. The vast majority (85.7%) of patients showed bilateral or unilateral pneumonia, and three symptomatic patients and one asymptomatic case did not show abnormalities in their CT image. Among the 28 admitted patients, 24 were discharged as of February 26, 2020, with an average hospital stay of 14.96 (\u00b14.27) days, which was not significantly associated with the interval between the onset of symptoms and admission. CONCLUSIONS In the absence of specific antiviral drugs or a vaccine, quarantine or isolation is the most effective intervention strategy for preventing the spread of the virus. Adequate supportive medical care is crucial for good prognosis of COVID-19 patients.", "qid": 26, "docid": "t5cfza23", "rank": 100, "score": 0.8261887431144714}]}
{"query": "what is known about those infected with Covid-19 but are asymptomatic?", "hits": [{"content": "Title: A systematic review of asymptomatic infections with COVID-19 Content: Since the outbreak of coronavirus disease 2019 (COVID-19) in late December 2019, it has brought significant harm and challenges to over 200 countries and regions around the world. However, there is increasing evidence that many patients with COVID-19 are asymptomatic or have only mild symptoms, but they are able to transmit the virus to others. There are difficulties in screening for asymptomatic infections, which makes it more difficult for national prevention and control of this epidemic. This article reviews the characteristics, treatment, and outcomes of asymptomatic infections with COVID-19, hoping it would be helpful for early prevention and control of this severe public health threat worldwide.", "qid": 27, "docid": "hv0cwf6d", "rank": 1, "score": 0.8949970006942749}, {"content": "Title: A Systematic Review of Asymptomatic Infections with COVID-19 Content: Since the outbreak of coronavirus disease 2019 (COVID-19) in late December 2019, it has brought significant harm and challenges to over 200 countries and regions around the world. However, there is increasing evidence that many patients with COVID-19 are asymptomatic or have only mild symptoms, but they are able to transmit the virus to others. There are difficulties in screening for asymptomatic infections, which makes it more difficult for national prevention and control of this epidemic. This article reviews the characteristics, treatment, and outcomes of asymptomatic infections with COVID-19, hoping it would be helpful for early prevention and control of this severe public health threat worldwide.", "qid": 27, "docid": "xz6pq0v3", "rank": 2, "score": 0.8949970006942749}, {"content": "Title: Asymptomatic patients and asymptomatic phases of Coronavirus Disease 2019 (COVID-19): a population-based surveillance study Content: In this population-based study, we identified 307 confirmed COVID-19 cases from massive surveillance, including 129,551 individuals screened at fever clinics or returning from Hubei and 3710 close contacts of confirmed COVID-19 patients. Among them, 17 patients were asymptomatic at initial clinical assessment. These asymptomatic patients on admission accounted for a small proportion of all patients (5.54%) with relatively weak transmissibility, and the detection rate was 0.35 per 100 close contacts. Moreover, the dynamics of symptoms of the 307 patients showed that the interval from symptom remission to the final negativity of viral nucleic acid was 5.0 days (IQR 2.0 to 11.0 days), with 14 patients (4.56%) having re-detectable viral RNA after discharge. Together, our findings suggested asymptomatic carriers and presymptomatic patients only accounted for a small proportion of COVID-19. Also, the asymptomatic phase in during recovery of COVID-19 urged that negativity in viral RNA is necessary as de-isolation criteria and follow-up is recommended.", "qid": 27, "docid": "l4n9hwcx", "rank": 3, "score": 0.8870476484298706}, {"content": "Title: Prevention of COVID-19 infection in the medical population: a possible help from anosmia? Content: COVID-19 asymptomatic cases increases the risks of disease dissemination with even greater risk for physicians given the shortage of personal protective equipment. Here we report on the consistent finding of frequent presentation of anosmia or hyposmia in COVID-19 patients, even in the absence of other symptoms and without other olfactory or nasal findings. In the uncertainty of the clinical characteristics of these patients, this symptom can be a tool to reduce the spread of the infection between medical population.", "qid": 27, "docid": "dgvizk1z", "rank": 4, "score": 0.8852606415748596}, {"content": "Title: Prevention of COVID-19 infection in the medical population: a possible help from anosmia?. Content: COVID-19 asymptomatic cases increases the risks of disease dissemination with even greater risk for physicians given the shortage of personal protective equipment. Here we report on the consistent finding of frequent presentation of anosmia or hyposmia in COVID-19 patients, even in the absence of other symptoms and without other olfactory or nasal findings. In the uncertainty of the clinical characteristics of these patients, this symptom can be a tool to reduce the spread of the infection between medical population.", "qid": 27, "docid": "lln8japc", "rank": 5, "score": 0.8852606415748596}, {"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": 6, "score": 0.8847023248672485}, {"content": "Title: [Advances on presymptomatic or asymptomatic carrier transmission of COVID-19] Content: COVID-19 is rapidly spreading. Patients in incubation period and healthy carriers are possible sources for transmission. However, such sources of infection cannot be effectively identified due to the symptoms absent. The research evidence is very lacking so far, although there are a few studies suggesting that presymptomatic or asymptomatic carrier may cause COVID-19 transmission. Nearly half of the literature is in the state of preprint without peer review. The question of \"the degree to which presymptomatic or asymptomatic infections can transmit\" is not fully understood. There is an urgent need to screen infected carriers in larger close contacts or in the general population, and assess their risk for transmission.", "qid": 27, "docid": "3fd81ovn", "rank": 7, "score": 0.8810514211654663}, {"content": "Title: [Advances on presymptomatic or asymptomatic carrier transmission of COVID-19]. Content: COVID-19 is rapidly spreading. Patients in incubation period and healthy carriers are possible sources for transmission. However, such sources of infection cannot be effectively identified due to the symptoms absent. The research evidence is very lacking so far, although there are a few studies suggesting that presymptomatic or asymptomatic carrier may cause COVID-19 transmission. Nearly half of the literature is in the state of preprint without peer review. The question of \"the degree to which presymptomatic or asymptomatic infections can transmit\" is not fully understood. There is an urgent need to screen infected carriers in larger close contacts or in the general population, and assess their risk for transmission.", "qid": 27, "docid": "xbv0b96w", "rank": 8, "score": 0.8810514211654663}, {"content": "Title: Viral dynamics in asymptomatic patients with COVID-19 Content: Data are limited on the viral load, viral shedding patterns, and potential infectivity of asymptomatic patients (APs) with coronavirus disease 2019 (COVID-19). This study included 31 adult patients who were virologically confirmed to have COVID-19 but were asymptomatic on admission. Among these 31 patients, 22 presented symptoms after admission and were defined as asymptomatic patients in the incubation period (APIs); the other nine patients remained asymptomatic during hospitalization and were defined as asymptomatic patients (APs). The median cycle threshold (Ct) value of APs (39.0, interquartile range (IQR) 37.5-39.5) was significantly higher than that of APIs (34.5, IQR 32.2-37.0), indicating a lower viral load in APs. However, the duration of viral shedding remained similar in the two groups (7 days, IQR 5-14 days vs. 8 days, IQR 5-16 days). The study findings demonstrated that although APs with COVID-19 have a lower viral load, they still have certain period of viral shedding, which suggests the possibility of transmission during their asymptomatic period. Further longitudinal surveillance of these asymptomatic cases via virus nucleic acid testing are warranted.", "qid": 27, "docid": "thftzde3", "rank": 9, "score": 0.8799641132354736}, {"content": "Title: The incidence of the novel coronavirus SARS-CoV-2 among asymptomatic patients: a systematic review Content: BACKGROUND: the recent outbreak of the coronavirus disease 2019 (COVID\u201019) has quickly spread globally since its discovery in Wuhan, China, in December 2019. A comprehensive strategy, including surveillance, diagnostics, research, and clinical treatment is urgently needed to win the battle against COVID-19. Recently, numerous studies reported the incidence of SARS-CoV-2 in asymptomatic patients. Yet, the incidence and viral transmission from the asymptomatic cases are not apparent yet. AIM: this study aims to systematically review the published literature on SARS-CoV-2 in the asymptomatic patients to estimate the incidence of COVID-19 among asymptomatic cases, as well as describe its epidemiological and clinical significance. METHOD: the literature was searched through four scientific databases: PubMed, Web of Science, Scopus, and Science Direct. RESULTS: a total of 63 studies satisfied the inclusion criteria where the majority of the reported studies were from China. However, there was a lack of SARS-CoV-2 epidemiological studies from several countries worldwide, tracing the actual incidence of COVID-19, especially in asymptomatic patients. Studies with a large sample size (n>1000) estimated that percentage of people contracting SARS-CoV-2 and are likely to be asymptomatic ranges from 1.2-12.9%. However, the other studies with a smaller sample size reported a much higher incidence and indicated that up to 87.9% of COVID-19 infected individuals could be asymptomatic. Most of these studies indicated that asymptopatics are a potential source of infection to the community. CONCLUSION: this review highlighted the need for more robust and well-designed studies to better estimate COVID-19 incidence among asymptomatic patients worldwide. The early identification of the asymptomatic cases, as well as monitoring and tracing close contact, could help in mitigating the spread of COVID-19.", "qid": 27, "docid": "lgze4zex", "rank": 10, "score": 0.8786835670471191}, {"content": "Title: Viral dynamics in asymptomatic patients with COVID-19 Content: Abstract Data are limited on the viral load, viral shedding patterns and potential infectivity of asymptomatic patients (APs) with coronavirus disease 2019 (COVID-19). We included 31 adult patients who were virologically confirmed to have COVID-19 but were asymptomatic on admission. Among these 31 patients, 22 presented symptoms after admission and were defined as asymptomatic patients in incubation period (APIs); the other 9 patients remained asymptomatic during hospitalization and were defined as asymptomatic patients (APs). The cycle threshold (Ct) values of APs (39.0, IQR 37.5-39.5) was significantly higher than those of APIs (34.5, IQR 32.2-37.0), which indicated a lower viral load in APs, but the duration of viral shedding remained similar between the two groups (7 days IQR 5-14 vs. 8 days IQR 5-16). The study findings demonstrated that although they have a lower viral load, APs with COVID-19 still have certain period of viral shedding, which suggests the possibility of transmission during their asymptomatic period. Further longitudinal surveillance of these asymptomatic cases via virus nucleic acid tests are warranted.", "qid": 27, "docid": "bi3bl5qt", "rank": 11, "score": 0.8785876631736755}, {"content": "Title: The incidence of the novel coronavirus SARS-CoV-2 among asymptomatic patients: a systematic review Content: BACKGROUND: the recent outbreak of the coronavirus disease 2019 (COVID-19) has quickly spread globally since its discovery in Wuhan, China, in December 2019. A comprehensive strategy, including surveillance, diagnostics, research, and clinical treatment is urgently needed to win the battle against COVID-19. Recently, numerous studies reported the incidence of SARS-CoV-2 in asymptomatic patients. Yet, the incidence and viral transmission from the asymptomatic cases are not apparent yet. AIM: this study aims to systematically review the published literature on SARS-CoV-2 in the asymptomatic patients to estimate the incidence of COVID-19 among asymptomatic cases, as well as describe its epidemiological and clinical significance. METHOD: the literature was searched through four scientific databases: PubMed, Web of Science, Scopus, and Science Direct. RESULTS: a total of 63 studies satisfied the inclusion criteria where the majority of the reported studies were from China. However, there was a lack of SARS-CoV-2 epidemiological studies from several countries worldwide, tracing the actual incidence of COVID-19, especially in asymptomatic patients. Studies with a large sample size (n>1000) estimated that percentage of people contracting SARS-CoV-2 and are likely to be asymptomatic ranges from 1.2-12.9%. However, the other studies with a smaller sample size reported a much higher incidence and indicated that up to 87.9% of COVID-19 infected individuals could be asymptomatic. Most of these studies indicated that asymptopatics are a potential source of infection to the community. CONCLUSION: this review highlighted the need for more robust and well-designed studies to better estimate COVID-19 incidence among asymptomatic patients worldwide. The early identification of the asymptomatic cases, as well as monitoring and tracing close contact, could help in mitigating the spread of COVID-19.", "qid": 27, "docid": "6sf5xepa", "rank": 12, "score": 0.8779911994934082}, {"content": "Title: Asymptomatic patients as a source of COVID-19 infections: A systematic review and meta-analysis Content: BACKGROUND: Coronavirus Disease 2019 (COVID-19) is characterised by an unpredictable disease course, ranging from asymptomatic infections to severe, life-threating manifestations. Asymptomatic COVID-19 infections have been described, and the aim of this systematic review was to summarise their presentation form. METHODS: We searched PubMed\u00ae and Google\u00ae (1 December 2019 to 29 March 2020) and extracted age, laboratory findings, and computed tomography (CT) investigations. Pooled incidence rates of clinical characteristics were analysed using random effects models. RESULTS: In total, 506 patients from 34 studies (68 single cases and 438 from case series) with an asymptomatic course were identified. Patients with normal radiology were younger (19.59 \u00b1 17.17 years) than patients with abnormal radiology (39.14 \u00b1 26.70 years) (p value = 0.013). Despite being asymptomatic, CT investigations revealed abnormalities in 62.2% of the cases and ground glass opacities were most frequently observed (43.09% by meta-analysis). Most studies reported normal laboratory findings (61.74% by meta-analysis). CONCLUSIONS: More than half of patients without any symptoms present with CT abnormalities. Asymptomatic patients may be contagious and thus a potential source of transmission of COVID-19.", "qid": 27, "docid": "59a0v3sg", "rank": 13, "score": 0.8742419481277466}, {"content": "Title: How the asymptomatic population is influencing the COVID-19 outbreak in India? Content: According to the current perception, symptomatic, presymptomatic, and asymptomatic infectious persons can infect the healthy population susceptible to the SARS-Cov-2. More importantly, various reports indicate that the number of asymptomatic cases can be several-fold higher than the reported symptomatic cases. In this article, we take the reported cases in India and various states within the country as the specimen to understand the progression of the COVID-19. Employing a modified SEIRD model, we predict the spread of COVID-19 by the symptomatic as well as asymptomatic infectious population. Considering reported infection primarily due to symptomatic we compare the model predicted results with the available data to estimate the dynamics of the asymptomatically infected population. Our data indicate that in the absence of the asymptomatic infectious population, the number of symptomatic cases would have been much less. Therefore, the current progress of the symptomatic infection can be reduced by quarantining the asymptomatically infectious population via extensive or random testing. This study is motivated strictly towards academic pursuit; this theoretical investigation is not meant for influencing policy decisions or public health practices.", "qid": 27, "docid": "2ohq74mq", "rank": 14, "score": 0.874066948890686}, {"content": "Title: Clinical characteristics of 24 asymptomatic infections with COVID-19 screened among close contacts in Nanjing, China Content: Previous studies have showed clinical characteristics of patients with the 2019 novel coronavirus disease (COVID-19) and the evidence of person-to-person transmission. Limited data are available for asymptomatic infections. This study aims to present the clinical characteristics of 24 cases with asymptomatic infection screened from close contacts and to show the transmission potential of asymptomatic COVID-19 virus carriers. Epidemiological investigations were conducted among all close contacts of COVID-19 patients (or suspected patients) in Nanjing, Jiangsu Province, China, from Jan 28 to Feb 9, 2020, both in clinic and in community. Asymptomatic carriers were laboratory-confirmed positive for the COVID-19 virus by testing the nucleic acid of the pharyngeal swab samples. Their clinical records, laboratory assessments, and chest CT scans were reviewed. As a result, none of the 24 asymptomatic cases presented any obvious symptoms while nucleic acid screening. Five cases (20.8%) developed symptoms (fever, cough, fatigue, etc.) during hospitalization. Twelve (50.0%) cases showed typical CT images of ground-glass chest and 5 (20.8%) presented stripe shadowing in the lungs. The remaining 7 (29.2%) cases showed normal CT image and had no symptoms during hospitalization. These 7 cases were younger (median age: 14.0 years; P=0.012) than the rest. None of the 24 cases developed severe COVID-19 pneumonia or died. The median communicable period, defined as the interval from the first day of positive nucleic acid tests to the first day of continuous negative tests, was 9.5 days (up to 21 days among the 24 asymptomatic cases). Through epidemiological investigation, we observed a typical asymptomatic transmission to the cohabiting family members, which even caused severe COVID-19 pneumonia. Overall, the asymptomatic carriers identified from close contacts were prone to be mildly ill during hospitalization. However, the communicable period could be up to three weeks and the communicated patients could develop severe illness. These results highlighted the importance of close contact tracing and longitudinally surveillance via virus nucleic acid tests. Further isolation recommendation and continuous nucleic acid tests may also be recommended to the patients discharged.", "qid": 27, "docid": "nubzfw13", "rank": 15, "score": 0.8736423254013062}, {"content": "Title: Asymptomatic patients as a source of COVID-19 infections: A systematic review and meta-analysis. Content: BACKGROUND Coronavirus Disease 2019 (COVID-19) is characterised by an unpredictable disease course, ranging from asymptomatic infections to severe, life-threating manifestations. Asymptomatic COVID-19 infections have been described, and the aim of this systematic review was to summarise their presentation form. METHODS We searched PubMed\u00ae and Google\u00ae (1 December 2019 to 29 March 2020) and extracted age, laboratory findings, and computed tomography (CT) investigations. Pooled incidence rates of clinical characteristics were analysed using random effects models. RESULTS In total, 506 patients from 34 studies (68 single cases and 438 from case series) with an asymptomatic course were identified. Patients with normal radiology were younger (19.59 \u00b1 17.17 years) than patients with abnormal radiology (39.14 \u00b1 26.70 years) (p value = 0.013). Despite being asymptomatic, CT investigations revealed abnormalities in 62.2% of the cases and ground glass opacities were most frequently observed (43.09% by meta-analysis). Most studies reported normal laboratory findings (61.74% by meta-analysis). CONCLUSIONS More than half of patients without any symptoms present with CT abnormalities. Asymptomatic patients may be contagious and thus a potential source of transmission of COVID-19.", "qid": 27, "docid": "szzd7acz", "rank": 16, "score": 0.8736103773117065}, {"content": "Title: Challenges of managing the asymptomatic carriers of SARS-CoV-2 Content: After an outbreak in Wuhan, China, a growing number of countries are now suffering from an epidemic by SARS-CoV-2, which causes COVID-19. Undoubtedly, reports of the skyrocketing global spread of COVID-19 has shocked people globally, from Japan to the United States. Presently, the World Health Organization indicates that the fatality rate due to COVID-19 is about 2%, inferring that many positive subjects may potentially overcome the illness with mild influenza-like symptoms and no need for hospitalization at intensive-care units. Because COVID-19 is completely new to the human immune system, many throughout the world are likely vulnerable to becoming sick after their initial exposure to SARS-CoV-2. Besides hospitalized cases, many individuals are likely asymptomatic but potentially carry the virus. While our knowledge about carriers and their virus shedding is deficient, some studies modelling the viral transmission have considered the potential contribution of the asymptomatic carriers. Protocols for managing asymptomatic cases, for example for controlling them to restrict their contact with healthy people at public places or private residences, have not been established. In-house quarantine may as well be applicable to asymptomatic cases if they could be identified and diagnosed. Presumably now, the asymptomatic subjects potentially contribute to the transmission of COVID-19 without their knowledge, intention, or being diagnosed as carriers. Thus, managing the asymptomatic subjects, who can carry and likely transmit the virus, is a major healthcare challenge while the pandemic is looming.", "qid": 27, "docid": "27z0z409", "rank": 17, "score": 0.8731539249420166}, {"content": "Title: Clinical characteristics of 24 asymptomatic infections with COVID-19 screened among close contacts in Nanjing, China Content: Previous studies have showed clinical characteristics of patients with the 2019 novel coronavirus disease (COVID-19) and the evidence of person-to-person transmission. Limited data are available for asymptomatic infections. This study aims to present the clinical characteristics of 24 cases with asymptomatic infection screened from close contacts and to show the transmission potential of asymptomatic COVID-19 virus carriers. Epidemiological investigations were conducted among all close contacts of COVID-19 patients (or suspected patients) in Nanjing, Jiangsu Province, China, from Jan 28 to Feb 9, 2020, both in clinic and in community. Asymptomatic carriers were laboratory-confirmed positive for the COVID-19 virus by testing the nucleic acid of the pharyngeal swab samples. Their clinical records, laboratory assessments, and chest CT scans were reviewed. As a result, none of the 24 asymptomatic cases presented any obvious symptoms while nucleic acid screening. Five cases (20.8%) developed symptoms (fever, cough, fatigue, etc.) during hospitalization. Twelve (50.0%) cases showed typical CT images of ground-glass chest and 5 (20.8%) presented stripe shadowing in the lungs. The remaining 7 (29.2%) cases showed normal CT image and had no symptoms during hospitalization. These 7 cases were younger (median age: 14.0 years; P=0.012) than the rest. None of the 24 cases developed severe COVID-19 pneumonia or died. The median communicable period, defined as the interval from the first day of positive nucleic acid tests to the first day of continuous negative tests, was 9.5 days (up to 21 days among the 24 asymptomatic cases). Through epidemiological investigation, we observed a typical asymptomatic transmission to the cohabiting family members, which even caused severe COVID-19 pneumonia. Overall, the asymptomatic carriers identified from close contacts were prone to be mildly ill during hospitalization. However, the communicable period could be up to three weeks and the communicated patients could develop severe illness. These results highlighted the importance of close contact tracing and longitudinally surveillance via virus nucleic acid tests. Further isolation recommendation and continuous nucleic acid tests may also be recommended to the patients discharged. ELECTRONIC SUPPLEMENTARY MATERIAL: Supplementary material is available for this article at 10.1007/s11427-020-1661-4 and is accessible for authorized users.", "qid": 27, "docid": "iff8cuum", "rank": 18, "score": 0.8730949759483337}, {"content": "Title: Estimating the extent of true asymptomatic COVID-19 and its potential for community transmission: systematic review and meta-analysis Content: Background: The prevalence of true asymptomatic COVID-19 cases is critical to policy makers considering the effectiveness of mitigation measures against the SARS-CoV-2 pandemic. We aimed to synthesize all available research on the asymptomatic rates and transmission rates where possible. Methods: We searched PubMed, Embase, Cochrane COVID-19 trials, and European PMC for pre-print platforms such as MedRxiv. We included primary studies reporting on asymptomatic prevalence where: (a) the sample frame includes at-risk population, and (b) there was sufficiently long follow up to identify pre-symptomatic cases. Meta-analysis used fixed effect and random effects models. Results: We screened 571 articles and included five low risk-of-bias studies from three countries (China (2), USA (2), Italy (1)) that tested 9,242 at-risk people, of which 413 were positive and 65 were asymptomatic. Diagnosis in all studies was confirmed using a RT-qPCR test. The proportion of asymptomatic cases ranged from 6% to 41%. Meta-analysis (fixed effect) found that the proportion of asymptomatic cases was 16% (95% CI: 12% - 20%) overall; higher in non-aged care 19% (15% - 24%), and lower in long-term aged care 8% (4% - 14%). Two studies provided direct evidence of forward transmission of the infection by asymptomatic cases but suggested lower rates than symptomatic cases. Conclusion: Our estimates of the prevalence of asymptomatic COVID-19 cases are lower than many highly publicized studies, but still substantial. Further robust epidemiological evidence is urgently needed, including in sub-populations such as children, to better understand the importance of asymptomatic cases for driving spread of the pandemic.", "qid": 27, "docid": "li8kvzdh", "rank": 19, "score": 0.8726442456245422}, {"content": "Title: Asymptomatic transmission and the infection fatality risk for COVID-19: Implications for school reopening Content: Asymptomatic infection occurs for numerous respiratory viral diseases, including influenza and COVID-19. We seek to clarify confusion in three areas: age-specific risks of transmission and/or disease; various definitions for the COVID-19 \u201cmortality rate\u201d, each useful for specific purposes; and implications for student return strategies from pre-school through university settings.", "qid": 27, "docid": "e995ev2w", "rank": 20, "score": 0.8720234632492065}, {"content": "Title: Asymptomatic transmission and the infection fatality risk for COVID-19: Implications for school reopening Content: Asymptomatic infection occurs for numerous respiratory viral diseases, including influenza and COVID-19. We seek to clarify confusion in three areas: age-specific risks of transmission and/or disease; various definitions for the COVID-19 \"mortality rate\", each useful for specific purposes; and implications for student return strategies from pre-school through university settings.", "qid": 27, "docid": "401kxcmi", "rank": 21, "score": 0.8711506128311157}, {"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": 22, "score": 0.8708472847938538}, {"content": "Title: Clinical Progression of COVID-19 Patient with Extended Incubation Period, Delayed RT-PCR Time-to-positivity, and Potential Role of Chest CT-scan Content: Coronavirus Disease 2019 (COVID-19), previously called 2019-nCoV, is a novel disease caused by SARS- CoV-2 which was first identified as outbreak of unknown respiratory illness in Wuhan, China. COVID- 19 was declared as global health emergency by WHO on March 11, 2020 and quickly elevated to global pandemic on 11 March 2020. COVID-19 symptom is highly various in each patient, with fever, fatigue, shortness of breath, and cough as the main presenting symptoms. Patient with COVID-19 may shows severe symptom with severe pneumonia and ARDS, mild symptom resembling simple upper respiration tract infection, or even completely asymptomatic. Approximately 80% of cases is mild. However the number may changes as more people are getting tested. Some experts are estimating that up to 50% of all cases may be asymptomatic carrier.", "qid": 27, "docid": "3njzz1yi", "rank": 23, "score": 0.8705733418464661}, {"content": "Title: Clinical Progression of COVID-19 Patient with Extended Incubation Period, Delayed RT-PCR Time-to-positivity, and Potential Role of Chest CT-scan. Content: Coronavirus Disease 2019 (COVID-19), previously called 2019-nCoV, is a novel disease caused by SARS- CoV-2 which was first identified as outbreak of unknown respiratory illness in Wuhan, China. COVID- 19 was declared as global health emergency by WHO on March 11, 2020 and quickly elevated to global pandemic on 11 March 2020. COVID-19 symptom is highly various in each patient, with fever, fatigue, shortness of breath, and cough as the main presenting symptoms. Patient with COVID-19 may shows severe symptom with severe pneumonia and ARDS, mild symptom resembling simple upper respiration tract infection, or even completely asymptomatic. Approximately 80% of cases is mild. However the number may changes as more people are getting tested. Some experts are estimating that up to 50% of all cases may be asymptomatic carrier.", "qid": 27, "docid": "e4uzvmmh", "rank": 24, "score": 0.8705733418464661}, {"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": 25, "score": 0.8705723285675049}, {"content": "Title: Challenges of managing the asymptomatic carriers of SARS-CoV-2 Content: Abstract After an outbreak in Wuhan, China, a growing number of countries are now suffering from an epidemic by SARS-CoV-2, which causes COVID-19. Undoubtedly, reports of the skyrocketing global spread of COVID-19 has shocked people globally, from Japan to the United States.Presently, the World Health Organization indicates that fatality due to COVID-19 is about 2%, inferring that many positive subjects may potentially overcome the illness with mild influenza-like symptoms and no need for hospitalization at intensive-care units. Because COVID-19 is completely new to the human immune system, many throughout the world are likely vulnerable to becoming sick after their initial exposure to SARSCoV-2. Besides hospitalized cases, many individuals are likely asymptomatic but potentially carry the virus. While our knowledge about carriers and their virus shedding is deficient, some studies modelling the viral transmission have considered the potential contribution of the asymptomatic carriers. Protocols for managing asymptomatic cases, for example for controlling them to restrict their contact with healthy people at public places or private residences, have not been established.In-house quarantine may as well be applicable to asymptomatic cases if they could be identified and diagnosed. Presumably now, the asymptomatic subjects potentially contribute to the transmission of COVID-19 without their knowledge, intention or being diagnosed as carriers. Thus, managing the asymptomatic cases, who can carry and likely transmit the virus, is a major healthcare challenge while a pandemic is looming.", "qid": 27, "docid": "c5q7l7en", "rank": 26, "score": 0.8705188632011414}, {"content": "Title: Clinical Characteristics of 24 Asymptomatic Infections with COVID-19 Screened among Close Contacts in Nanjing, China Content: Background: Previous studies have showed clinical characteristics of patients with the 2019 novel coronavirus disease (COVID-19) and the evidence of person-to-person transmission. Limited data are available for asymptomatic infections. This study aims to present the clinical characteristics of 24 cases with asymptomatic infection screened from close contacts and to show the transmission potential of asymptomatic COVID-19 virus carriers. Methods: Epidemiological investigations were conducted among all close contacts of COVID-19 patients (or suspected patients) in Nanjing, Jiangsu Province, China, from Jan 28 to Feb 9, 2020, both in clinic and in community. Asymptomatic carriers were laboratory-confirmed positive for the COVID-19 virus by testing the nucleic acid of the pharyngeal swab samples. Their clinical records, laboratory assessments, and chest CT scans were reviewed. Findings: None of the 24 asymptomatic cases presented any obvious symptoms before nucleic acid screening. Five cases (20.8%) developed symptoms (fever, cough, fatigue and etc.) during hospitalization. Twelve (50.0%) cases showed typical CT images of ground-glass chest and five (20.8%) presented stripe shadowing in the lungs. The remaining seven (29.2%) cases showed normal CT image and had no symptoms during hospitalization. These seven cases were younger (median age: 14.0 years; P = 0.012) than the rest. None of the 24 cases developed severe COVID-19 pneumonia or died. The median communicable period, defined as the interval from the first day of positive nucleic acid tests to the first day of continuous negative tests, was 9.5 days (up to 21 days among the 24 asymptomatic cases). Through epidemiological investigation, we observed a typical asymptomatic transmission to the cohabiting family members, which even caused severe COVID-19 pneumonia. Interpretation: The asymptomatic carriers identified from close contacts were prone to be mildly ill during hospitalization. However, the communicable period could be up to three weeks and the communicated patients could develop severe illness. These results highlighted the importance of close contact tracing and longitudinally surveillance via virus nucleic acid tests. Further isolation recommendation and continuous nucleic acid tests may also be recommended to the patients discharged.", "qid": 27, "docid": "ofoqk100", "rank": 27, "score": 0.8704565167427063}, {"content": "Title: Characteristics of asymptomatic patients with SARS-CoV-2 infection in Jinan, China Content: Coronavirus Disease 2019 (COVID-19) caused by severe acute respiratory syndrome coronavirus 2(SARS-CoV-2) is continuously and rapidly circulating at present. Asymptomatic patients have been proven to be contagious and thus pose a significant infection control challenge. Here we describe the characteristics of asymptomatic patients with SARS-CoV-2 infection in Jinan, Shandong province, China. A total of 47 patients with confirmed COVID-19 were recruited. Among them, 11 patients were categorized as asymptomatic cases. We found that the asymptomatic patients in Jinan were relatively young and were mainly clustered cases. The laboratory indicators and lung lesion on chest CT were mild. No special factors were found accounting for the presence or absence of symptoms. The presence of asymptomatic patients increased the difficulty of screening. It is necessary to strengthen the identification of such patients in the future.", "qid": 27, "docid": "ffs350f2", "rank": 28, "score": 0.8704399466514587}, {"content": "Title: Comparison of transmissibility of coronavirus between symptomatic and asymptomatic patients: Reanalysis of the Ningbo Covid-19 data Content: We investigate the transmissibility of coronavirus for symptomatic and asymptomatic patients using the Ningbo Covid-19 data1. Through more in-depth and comprehensive statistical analysis, we conclude that there is no difference in the transmission rates of coronavirus between the symptomatic and asymptomatic patients, which is consistent with the original findings in Chen et al.1", "qid": 27, "docid": "nlzdto1h", "rank": 29, "score": 0.8687170147895813}, {"content": "Title: Identification of RT-PCR-Negative Asymptomatic COVID-19 Patients via Serological Testing Content: Asymptomatic individuals with coronavirus disease (COVID-19) have been identified via nucleic acid testing for severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2); however, the epidemiologic characteristics and viral shedding pattern of asymptomatic patients remain largely unknown. In this study, serological testing was applied when identifying nine asymptomatic cases of COVID-19 who showed persistent negative RT-PCR test results for SARS-CoV-2 nucleic acid and no symptoms of COVID-19. Two asymptomatic cases were presumed to be index patients who had cleared the virus when their close contacts developed symptoms of COVID-19. Three of the asymptomatic cases were local individuals who spontaneously recovered before their presumed index patients developed symptoms of COVID-19. This report presents the epidemiologic and clinical characteristics of asymptomatic individuals with SARS-CoV-2 infection that were undetected on RT-PCR tests in previous epidemiologic investigations probably due to the transient viral shedding duration.", "qid": 27, "docid": "mu2v9o1p", "rank": 30, "score": 0.8686673641204834}, {"content": "Title: Characteristics of asymptomatic patients with SARS-CoV-2 infection in Jinan, China Content: Abstract Coronavirus Disease 2019 (COVID-19) caused by severe acute respiratory syndrome coronavirus 2(SARS-CoV-2) is continuously and rapidly circulating at present. Asymptomatic patients have been proven to be contagious and thus pose a significant infection control challenge. Here we describe the characteristics of asymptomatic patients with SARS-CoV-2 infection in Jinan, Shandong province, China. A total of 47 patients with confirmed COVID-19 were recruited. Among them, 11 patients were categorized as asymptomatic cases. We found that the asymptomatic patients in Jinan were relatively young and were mainly clustered cases. The laboratory indicators and lung lesion on chest CT were mild. No special factors were found accounting for the presence or absence of symptoms. The presence of asymptomatic patients increased the difficulty of screening. It is necessary to strengthen the identification of such patients in the future.", "qid": 27, "docid": "xwvtjm6s", "rank": 31, "score": 0.8684535026550293}, {"content": "Title: The relative transmissibility of asymptomatic COVID-19 infections among close contacts Content: Asymptomatic transmission of the coronavirus disease 2019 is an important topic. A recent study in China showed that transmissibility of the asymptomatic cases is comparable to that of symptomatic cases. Here, we discuss that the conclusion may depend on how we interpret the data. To the best of our knowledge, this is the first time the relative transmissibility of asymptomatic COVID-19 infections is quantified.", "qid": 27, "docid": "cca7gzjq", "rank": 32, "score": 0.868170440196991}, {"content": "Title: Estimating Hidden Asymptomatics, Herd Immunity Threshold and Lockdown Effects using a COVID-19 Specific Model Content: A quantitative COVID-19 model that incorporates hidden asymptomatic patients is developed, and an analytic solution in parametric form is given. The model incorporates the impact of lockdown and resulting spatial migration of population due to announcement of lockdown. A method is presented for estimating the model parameters from real-world data. It is shown that increase of infections slows down and herd immunity is achieved when symptomatic patients are 4-6\\% of the population for the European countries we studied, when the total infected fraction is between 50-56 \\%. Finally, a method for estimating the number of asymptomatic patients, who have been the key hidden link in the spread of the infections, is presented.", "qid": 27, "docid": "nd6l5x8d", "rank": 33, "score": 0.8661956191062927}, {"content": "Title: Otolaryngology Providers Must Be Alert for Patients with Mild and Asymptomatic COVID-19 Content: More than half of COVID-19 patients are afebrile early in the disease course, yet mildly ill or asymptomatic patients can still spread SARS-CoV-2 with high efficiency. Atypically presenting patients may be seen in noninfectious disease settings such as otolaryngology, which is a specialty prone to occupational exposure. Otolaryngologists have been infected with COVID-19 at higher rates than other specialties in China and other countries. Otolaryngology providers should maintain high clinical suspicion for mild and asymptomatic COVID-19 patients. Protective strategies should be implemented including preappointment screening, triaging, restriction of nonurgent visits and surgeries, telemedicine, and appropriate personal protective equipment use.", "qid": 27, "docid": "yy7lhl9z", "rank": 34, "score": 0.8651635646820068}, {"content": "Title: Otolaryngology Providers Must Be Alert for Patients with Mild and Asymptomatic COVID-19. Content: More than half of COVID-19 patients are afebrile early in the disease course, yet mildly ill or asymptomatic patients can still spread SARS-CoV-2 with high efficiency. Atypically presenting patients may be seen in noninfectious disease settings such as otolaryngology, which is a specialty prone to occupational exposure. Otolaryngologists have been infected with COVID-19 at higher rates than other specialties in China and other countries. Otolaryngology providers should maintain high clinical suspicion for mild and asymptomatic COVID-19 patients. Protective strategies should be implemented including preappointment screening, triaging, restriction of nonurgent visits and surgeries, telemedicine, and appropriate personal protective equipment use.", "qid": 27, "docid": "nhfjqdnh", "rank": 35, "score": 0.8651635646820068}, {"content": "Title: Advice regarding COVID\u201019 and use of immunomodulators, in patients with severe dermatological diseases Content: Coronavirus disease 2019 (COVID-19) is the disease caused by the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), as named by the International Committee on Taxonomy of Viruses (ICTV). There is very limited evidence base to formulate specific advice for dermatology patients on immunomodulators with regards to COVID-19. The following is based on expert opinion, taking into account known risks of influenza (a negative sense single-stranded RNA virus) and other, positive-sense single-stranded, RNA virus infections (such as SARS, MERS, and the common cold). An Australia/New Zealand consensus document is in development.", "qid": 27, "docid": "nfjxp783", "rank": 36, "score": 0.8647935390472412}, {"content": "Title: Transmission and clinical characteristics of asymptomatic patients with SARS-CoV-2 infection Content: The 2019 novel coronavirus disease, SARS-CoV-2, is now spreading globally and is characterized by person-to-person transmission. However, it has recently been found that individuals infected with SARS-CoV-2 can be asymptomatic, and simultaneously a source of infection in others. The viral load detected in nasopharyngeal swabs of asymptomatic carriers is relatively high, with a great potential for transmission. More attention should be paid to the insidious spread of disease and harm contributed by asymptomatic SARS-CoV-2 carriers. To provide a theoretical basis for the accurate and early clinical identification of asymptomatic patients, this review objectively summarizes the epidemic status, transmission characteristics and clinical features of asymptomatic patients with SARS-CoV-2 infection.", "qid": 27, "docid": "m9xifjth", "rank": 37, "score": 0.8647323250770569}, {"content": "Title: A study on infectivity of asymptomatic SARS-CoV-2 carriers. Content: BACKGROUND An ongoing outbreak of coronavirus disease 2019 (COVID-19) has spread around the world. It is debatable whether asymptomatic COVID-19 virus carriers are contagious. We report here a case of the asymptomatic patient and present clinical characteristics of 455 contacts, which aims to study the infectivity of asymptomatic carriers. MATERIAL AND METHODS 455 contacts who were exposed to the asymptomatic COVID-19 virus carrier became the subjects of our research. They were divided into three groups: 35 patients, 196 family members and 224 hospital staffs. We extracted their epidemiological information, clinical records, auxiliary examination results and therapeutic schedules. RESULTS The median contact time for patients was four days and that for family members was five days. Cardiovascular disease accounted for 25% among original diseases of patients. Apart from hospital staffs, both patients and family members were isolated medically. During the quarantine, seven patients plus one family member appeared new respiratory symptoms, where fever was the most common one. The blood counts in most contacts were within a normal range. All CT images showed no sign of COVID-19 infection. No severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infections was detected in 455 contacts by nucleic acid test. CONCLUSION In summary, all the 455 contacts were excluded from SARS-CoV-2 infection and we conclude that the infectivity of some asymptomatic SARS-CoV-2 carriers might be weak.", "qid": 27, "docid": "7xb7hj9u", "rank": 38, "score": 0.8633001446723938}, {"content": "Title: Emergence of a novel human coronavirus threatening human health Content: In late December 2019, a cluster of patients with \u2018atypical pneumonia\u2019 of unknown etiology was reported in Wuhan, China. A novel human coronavirus, now provisionally called \u2018SARS-CoV-2\u2019, was identified as the cause of this disease, now named \u2018COVID-19\u2019.", "qid": 27, "docid": "nugginc9", "rank": 39, "score": 0.8629570603370667}, {"content": "Title: A study on infectivity of asymptomatic SARS-CoV-2 carriers Content: BACKGROUND: An ongoing outbreak of coronavirus disease 2019 (COVID-19) has spread around the world. It is debatable whether asymptomatic COVID-19 virus carriers are contagious. We report here a case of the asymptomatic patient and present clinical characteristics of 455 contacts, which aims to study the infectivity of asymptomatic carriers. MATERIAL AND METHODS: 455 contacts who were exposed to the asymptomatic COVID-19 virus carrier became the subjects of our research. They were divided into three groups: 35 patients, 196 family members and 224 hospital staffs. We extracted their epidemiological information, clinical records, auxiliary examination results and therapeutic schedules. RESULTS: The median contact time for patients was four days and that for family members was five days. Cardiovascular disease accounted for 25% among original diseases of patients. Apart from hospital staffs, both patients and family members were isolated medically. During the quarantine, seven patients plus one family member appeared new respiratory symptoms, where fever was the most common one. The blood counts in most contacts were within a normal range. All CT images showed no sign of COVID-19 infection. No severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infections was detected in 455 contacts by nucleic acid test. CONCLUSION: In summary, all the 455 contacts were excluded from SARS-CoV-2 infection and we conclude that the infectivity of some asymptomatic SARS-CoV-2 carriers might be weak.", "qid": 27, "docid": "yz7goivp", "rank": 40, "score": 0.8628778457641602}, {"content": "Title: Severe inflammation in children - cause for awareness during the current pandemic/ Hyperinflammation hos barn kan ha samband med covid-19 Content: Clinical manifestations of COVID-19 in children are generally mild and many are asymptomatic However, recent international reports have described clusters of children presenting with an unusual syndrome of high, persistent fever, severe inflammation and single- or multiorgan dysfunction, with a suspected association to COVID-19 pandemic It is recommended that clinicians are aware of this rare syndrome and that suspected cases are treated in a multidisciplinary setting", "qid": 27, "docid": "byzgkhit", "rank": 41, "score": 0.8628485202789307}, {"content": "Title: [Severe inflammation in children - cause for awareness during the current pandemic] Content: Clinical manifestations of COVID-19 in children are generally mild and many are asymptomatic However, recent international reports have described clusters of children presenting with an unusual syndrome of high, persistent fever, severe inflammation and single- or multiorgan dysfunction, with a suspected association to COVID-19 pandemic It is recommended that clinicians are aware of this rare syndrome and that suspected cases are treated in a multidisciplinary setting", "qid": 27, "docid": "ak2up6al", "rank": 42, "score": 0.8628485202789307}, {"content": "Title: Why the immune system fails to mount an adaptive immune response to a Covid -19 infection. Content: The Covid-19 pandemic has already affected many thousands of people and has become the greatest health challenge worldwide [1]. The range of clinical presentations varies from asymptomatic and mild clinical symptoms to acute respiratory-distress syndrome (ARDS) and death. Due to the unknown number of asymptomatic viral-shedding and pauci-symptomatic people in the community, the total number of infections is uncertain. As yet, effective treatment is unavailable. However, the results of preliminary studies and clinical trials are improving our understanding of the pathogenesis and treatment of Covid-19. Herein, we share our personal opinions on the immunopathogenesis of this infection.", "qid": 27, "docid": "z2n51cet", "rank": 43, "score": 0.8626893758773804}, {"content": "Title: An unusual case of coronavirus disease 2019: Delayed chest CT evidence Content: Asymptomatic patients and infected patients with normal chest CT imaging are considered carriers of SARS-CoV-2. Before a diagnosis of coronavirus disease 2019 (COVID-19) is made, these patients with negative chest CT findings may be ignored, causing the possibility of virus transmission. For patients with suspected infections, reliable epidemiological information and clinical symptoms, clinical management is necessary even when the chest CT is negative.", "qid": 27, "docid": "23g413x3", "rank": 44, "score": 0.8626325130462646}, {"content": "Title: Diagn\u00f3stico De Neumon\u00eda Covid 19 En Pacientes Asintom\u00e1ticos Tras La Realizaci\u00f3n De Un Pet-tc Oncol\u00f3gico Content: INTRODUCTION: On January 30, 2020, the World Health Organization (WHO) declared an international emergency due to the pandemic caused by a new coronavirus. There are some oncological indications that have special priority and studies are still being carried out despite the current situation. In these studies we have found suspicious findings of COVID-19 pneumonia in asymptomatic patients. The objective of this work is to assess the incidence of these findings, describe their characteristics and the evolution of suspected patients. MATERIAL AND METHODS: Oncological PET studies carried out in asymptomatic patients between March 18 and April 8, 2020 have been reviewed. Patients who presented findings suggestive of corresponding to an pulmonary infectious process were selected. Clinical findings have been reviewed to confirm or rule out SARS-CoV2 infection. RESULTS: During the specified period, a total of 129 PET-CT studies were performed. Of these, 11 (8.5%) found suspicious findings of a pulmonary infectious process. These were 8 men and 3 women aged between 30 and 79 years (mean 62.2). CONCLUSIONS: Patients with COVID 19 can present few symptoms of the disease, and in PET-CT studies both presymptomatic and almost asymptomatic patients can be detected, so nuclear medicine physicians should take special attention to the pulmonary evaluation of PET-CT studies.", "qid": 27, "docid": "jjslw3lu", "rank": 45, "score": 0.8625748753547668}, {"content": "Title: [Severe inflammation in children - cause for awareness during the current pandemic]. Content: Clinical manifestations of COVID-19 in children are generally mild and many are asymptomatic. However, recent international reports have described clusters of children presenting with an unusual syndrome of high, persistent fever, severe inflammation and single- or multiorgan dysfunction, with a suspected association to COVID-19 pandemic. It is recommended that clinicians are aware of this rare syndrome and that suspected cases are treated in a multidisciplinary setting.", "qid": 27, "docid": "ccrs6c0p", "rank": 46, "score": 0.8622891306877136}, {"content": "Title: Clinical characteristics of asymptomatic and symptomatic patients with mild COVID-19 Content: OBJECTIVES: Detailed knowledge on the prevalence of asymptomatic cases of coronavirus disease 2019 (COVID-19) and the clinical characteristics of mild COVID-19 is essential for effective control of the COVID-19 pandemic. We determined the prevalence of asymptomatic cases of COVID-19 and characterized the symptoms of patients with mild COVID-19. METHODS: Study participants were recruited from a community facility designated for the isolation of patients without moderate-to-severe symptoms of COVID-19 in South Korea. The prevalence of asymptomatic patients at admission and the detailed symptoms of mild COVID-19 were evaluated through a questionnaire-based survey. Diagnosis of COVID-19 was confirmed by real-time RT-PCR. RESULTS: Of the 213 individuals with COVID-19, 41 (19.2%) were asymptomatic until admission. Among the remaining patients with mild COVID-19, the most common symptom was cough (40.1%; 69/172), followed by hyposmia (39.5%; 68/172) and sputum (39.5%; 68/172). Of the 68 individuals with hyposmia, 61 (90%) had accompanying symptoms such as hypogeusia, nasal congestion or rhinorrhoea. Fever (>37.5\u00b0C) was only observed in 20 (11.6%) individuals. CONCLUSIONS: As much as one-fifth of individuals with COVID-19 remained asymptomatic from exposure to admission. Hyposmia was quite frequent among individuals with mild COVID-19, but fever was not. Social distancing should be strongly implemented to prevent disease transmission from asymptomatic individuals or those with mild and inconspicuous symptoms.", "qid": 27, "docid": "p76gscn5", "rank": 47, "score": 0.8622668981552124}, {"content": "Title: Follow up investigation of asymptomatic COVID-19 cases at diagnosis in Busan, Korea Content: Objectives: The objective of the study was to conduct a follow-up investigation of 10 asymptomatic patients at diagnosis among the 98 confirmed COVID-19 cases reported in Busan between February 21 and March 13, 2020 to determine whether asymptomatic infection and transmission during asymptomatic period are possible. Methods: The study analyzed 10 asymptomatic, confirmed COVID-19 cases to determine whether asymptomatic infection is possible. We conducted in-depth interviews with patients and guardians; interviews with primary physicians; review of medical records and drug utilization review (DUR) reports; and base station-based location tracking. Results: Among the 98, confirmed COVID-19 cases reported in Busan, the study analyzed 10 (10.2%) asymptomatic patients at diagnosis. The Results confirmed that two (2.0%) patients reported to be asymptomatic during the initial epidemiological investigation, but turned symptomatic before diagnosis as per the in-depth interview results. Four cases (4.0%) of early detection led to confirmed diagnosis during the incubation period and presentation of symptoms after diagnosis. In addition, the remaining four patients (4.0%), having no subjective symptoms nor specific findings on chest radiography and Computed Tomography, remained asymptomatic until the isolation order was lifted. With regard to whether transmission during the asymptomatic period is possible, it was found that one out of 23 household contacts of the confirmed patients was identified as an additional confirmed case after coming in close contact with an index patient during the presymptomatic period. Conclusion: Among the 98 confirmed cases, asymptomatic infection was confirmed in four cases (4.0%). In addition, there was one additional confirmed case in which the patient was a family member who came in close contact with an index patient during the incubation period, thereby confirming that transmission during the asymptomatic period is possible. The possibility of transmission during the asymptomatic period has been confirmed; therefore, it is necessary to review the measures for expanding contact tracing that is currently being applied starting one day prior to the onset of symptoms.", "qid": 27, "docid": "op7ohlv3", "rank": 48, "score": 0.8620074987411499}, {"content": "Title: DIAGN\u00d3STICO DE NEUMON\u00cdA COVID 19 EN PACIENTES ASINTOM\u00c1TICOS TRAS LA REALIZACI\u00d3N DE UN PET-TC ONCOL\u00d3GICO Content: ABSTRACT INTRODUCTION: On January 30, 2020, the World Health Organization (WHO) declared an international emergency due to the pandemic caused by a new coronavirus. There are some oncological indications that have special priority and studies are still being carried out despite the current situation. In these studies we have found suspicious findings of COVID-19 pneumonia in asymptomatic patients. The objective of this work is to assess the incidence of these findings, describe their characteristics and the evolution of suspected patients. MATERIAL AND METHODS: Oncological PET studies carried out in asymptomatic patients between March 18 and April 8, 2020 have been reviewed. Patients who presented findings suggestive of corresponding to an pulmonary infectious process were selected. Clinical findings have been reviewed to confirm or rule out SARS-CoV2 infection. RESULTS: During the specified period, a total of 129 PET-CT studies were performed. Of these, 11 (8.5%) found suspicious findings of a pulmonary infectious process. These were 8 men and 3 women aged between 30 and 79 years (mean 62.2). CONCLUSIONS: Patients with COVID 19 can present few symptoms of the disease, and in PET-CT studies both presymptomatic and almost asymptomatic patients can be detected, so nuclear medicine physicians should take special attention to the pulmonary evaluation of PET-CT studies.", "qid": 27, "docid": "zjoyxioy", "rank": 49, "score": 0.8619945645332336}, {"content": "Title: Follow up investigation of asymptomatic COVID-19 cases at diagnosis in Busan, Korea. Content: Objectives The objective of the study was to conduct a follow-up investigation of 10 asymptomatic patients at diagnosis among the 98 confirmed COVID-19 cases reported in Busan between February 21 and March 13, 2020 to determine whether asymptomatic infection and transmission during asymptomatic period are possible. Methods The study analyzed 10 asymptomatic, confirmed COVID-19 cases to determine whether asymptomatic infection is possible. We conducted in-depth interviews with patients and guardians; interviews with primary physicians; review of medical records and drug utilization review (DUR) reports; and base station-based location tracking. Results Among the 98, confirmed COVID-19 cases reported in Busan, the study analyzed 10 (10.2%) asymptomatic patients at diagnosis. The Results confirmed that two (2.0%) patients reported to be asymptomatic during the initial epidemiological investigation, but turned symptomatic before diagnosis as per the in-depth interview results. Four cases (4.0%) of early detection led to confirmed diagnosis during the incubation period and presentation of symptoms after diagnosis. In addition, the remaining four patients (4.0%), having no subjective symptoms nor specific findings on chest radiography and Computed Tomography, remained asymptomatic until the isolation order was lifted. With regard to whether transmission during the asymptomatic period is possible, it was found that one out of 23 household contacts of the confirmed patients was identified as an additional confirmed case after coming in close contact with an index patient during the presymptomatic period. Conclusion Among the 98 confirmed cases, asymptomatic infection was confirmed in four cases (4.0%). In addition, there was one additional confirmed case in which the patient was a family member who came in close contact with an index patient during the incubation period, thereby confirming that transmission during the asymptomatic period is possible. The possibility of transmission during the asymptomatic period has been confirmed; therefore, it is necessary to review the measures for expanding contact tracing that is currently being applied starting one day prior to the onset of symptoms.", "qid": 27, "docid": "8zw79b2f", "rank": 50, "score": 0.8619899749755859}, {"content": "Title: The proportion of COVID-19 cases that are asymptomatic in South Korea: Comment on Nishiura et al Content: The Korean Centers for Disease Control & Prevention reports the asymptomatic case proportion for COVID-19 is 33.3%. The asymptomatic case proportion in South Korea closely approximates the rate of 30.8% reported by Nishiura et al. (2020) among Japanese nationals returning from abroad.", "qid": 27, "docid": "hzez9mj4", "rank": 51, "score": 0.8613107204437256}, {"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": 52, "score": 0.8610035181045532}, {"content": "Title: Anosmia and Ageusia: Common Findings in COVID-19 Patients Content: In a not negligible number of patients affected by COVID-19 (coronavirus disease 2019), especially if paucisymptomatic, anosmia and ageusia can represent the first or only symptomatology present. Laryngoscope, 130:1787-1787, 2020.", "qid": 27, "docid": "vdd3udnj", "rank": 53, "score": 0.8608124256134033}, {"content": "Title: Testing Asymptomatic Emergency Department Patients for Coronavirus of 2019 (COVID\u201019) in a Low Prevalence Region Content: The first cases of Coronavirus of 2019 (COVID\u201019) were reported in Wuhan, China in December 2019(1). The literature demonstrates geographical variation with regards to estimates of infection incidence, suggesting that COVID\u201019 has been underdiagnosed in certain regions(2,3). The rate of asymptomatic infection has been estimated to be as high as 30.8%, which may help explain variation in incidence, particularly in regions with differing screening practices (3). Transmission of COVID\u201019 by asymptomatic carriers has been reported in multiple family units, indicating that this mode of infection is important in understanding disease epidemiology and population risk(4,5).", "qid": 27, "docid": "wzb6qv7y", "rank": 54, "score": 0.8607573509216309}, {"content": "Title: COVID-19 Transmission Within a Family Cluster by Presymptomatic Carriers in China Content: We report a family cluster of coronavirus disease 2019 (COVID-19) caused by a presymptomatic case. There were 9 family members, including 8 laboratory-confirmed with COVID-19, and a 6-year-old child had no evidence of infection. Among the 8 patients, 1 adult and a 13-month-old infant were asymptomatic, and 1 adult was diagnosed as having severe pneumonia.", "qid": 27, "docid": "wxvy01cg", "rank": 55, "score": 0.8607186079025269}, {"content": "Title: Prevalence of Asymptomatic SARS-CoV-2 Infection: A Narrative Review Content: Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) has spread rapidly throughout the world since the first cases of coronavirus disease 2019 (COVID-19) were observed in December 2019 in Wuhan, China. It has been suspected that infected persons who remain asymptomatic play a significant role in the ongoing pandemic, but their relative number and effect have been uncertain. The authors sought to review and synthesize the available evidence on asymptomatic SARS-CoV-2 infection. Asymptomatic persons seem to account for approximately 40% to 45% of SARS-CoV-2 infections, and they can transmit the virus to others for an extended period, perhaps longer than 14 days. Asymptomatic infection may be associated with subclinical lung abnormalities, as detected by computed tomography. Because of the high risk for silent spread by asymptomatic persons, it is imperative that testing programs include those without symptoms. To supplement conventional diagnostic testing, which is constrained by capacity, cost, and its one-off nature, innovative tactics for public health surveillance, such as crowdsourcing digital wearable data and monitoring sewage sludge, might be helpful.", "qid": 27, "docid": "1ay60wzs", "rank": 56, "score": 0.860580325126648}, {"content": "Title: SARS-CoV-2 and COVID-19: The most important research questions Content: Coronavirus disease 2019 (COVID-19) caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) is an ongoing global health emergency. Here we highlight nine most important research questions concerning virus transmission, asymptomatic and presymptomatic virus shedding, diagnosis, treatment, vaccine development, origin of virus and viral pathogenesis.", "qid": 27, "docid": "hfkzu18p", "rank": 57, "score": 0.8603761196136475}, {"content": "Title: Early viral clearance and antibody kinetics of COVID-19 among asymptomatic carriers Content: Background Asymptomatic carriers contribute to the spread of Coronavirus Disease 2019 (COVID-19), but their clinical characteristics, viral kinetics, and antibody responses remain unclear. Methods A total of 56 COVID-19 patients without symptoms at admission and 19 age-matched symptomatic patients were enrolled. RNA of SARS-CoV-2 was tested using transcriptase quantitative PCR, and the total antibodies (Ab), IgG, IgA and IgM against the SARS-CoV-2 were tested using Chemiluminescence Microparticle Immuno Assay. Results Among 56 patients without symptoms at admission, 33 cases displayed symptoms and 23 remained asymptomatic throughout the follow-up period. 43.8% of the asymptomatic carriers were children and none of the asymptomatic cases had recognizable changes in C-reactive protein or interleukin-6, except one 64-year-old patient. The initial threshold cycle value of nasopharyngeal SARS-CoV-2 in asymptomatic carriers was similar to that in pre-symptomatic and symptomatic patients, but the communicable period of asymptomatic carriers (9.63 days) was shorter than pre-symptomatic patients (13.6 days). There was no obvious differences of the seropositive conversion rate of total Ab, IgG, and IgA among the three groups, though the rates of IgM varied largely. The average peak IgG and IgM COI of asymptomatic cases was 3.5 and 0.8, respectively, which is also lower than those in symptomatic patients with peaked IgG and IgM COI of 4.5 and 2.4 (p <0.05). Conclusion Young COVID-19 patients seem to be asymptomatic cases with early clearance of SARS-CoV-2 and low levels of IgM generation but high total Ab, IgG and IgA. Our findings provide empirical information for viral clearance and antibody kinetics of asymptomatic COVID-19 patients.", "qid": 27, "docid": "c6um6puc", "rank": 58, "score": 0.8601387739181519}, {"content": "Title: Characteristics of a family cluster of Severe Acute Respiratory Syndrome Coronavirus 2 in Henan, China Content: \u2022 The worldwide outbreak of SARS-CoV-2 called for more close investigations of the family transmission routes of infectious diseases. \u2022 We hypothesize that the likelihood to develop COVID-19 is probably associated with the duration of being exposed to SARS-CoV-2. \u2022 In a family cluster, asymptomatic infection carriers can be persons of all ages, from nine to sixty years old.", "qid": 27, "docid": "ojjzetc8", "rank": 59, "score": 0.8601230382919312}, {"content": "Title: Aktu\u00e1ln\u00ed problematika COVID-19 z pohledu imunologa./ COVID-19 from the perspective of an immunologist Content: COVID-19 is an infectious disease caused by a coronavirus SARS-CoV-2. COVID-19 has a number of similarities to SARS and MERS diseases. Its highly contagious nature is particularly due to the rapid spread of the disease through asymptomatic individuals; however, the worlds most contagious infectious disease is still considered measles. Scientific data have revealed the interactions between COVID-19 and the immune system. These findings may contribute to the development of novel preventive and therapeutic approaches. Just as coronavirus itself the reports about the disease have massively spread through media and public contributing to overall public fear and stress. This promotion of non-scientific evidence and misinformation through social media might have also a devastating impact on the individuals immune system. Data regarding the mortality rates of COVID-19 have achieved unprecedented media and public engagements, however, the true facts about the disease prevention, immunomodulation and novel treatments are often left unsaid. We present the most recent facts about COVID-19 disease and its interactions with the immune system.", "qid": 27, "docid": "pfyqjrwk", "rank": 60, "score": 0.8588182926177979}, {"content": "Title: COVID-19 from the perspective of an immunologist. Content: COVID-19 is an infectious disease caused by a coronavirus SARS-CoV-2. COVID-19 has a number of similarities to SARS and MERS diseases. Its highly contagious nature is particularly due to the rapid spread of the disease through asymptomatic individuals; however, the worlds most contagious infectious disease is still considered measles. Scientific data have revealed the interactions between COVID-19 and the immune system. These findings may contribute to the development of novel preventive and therapeutic approaches. Just as coronavirus itself the reports about the disease have massively spread through media and public contributing to overall public fear and stress. This promotion of non-scientific evidence and misinformation through social media might have also a devastating impact on the individuals immune system. Data regarding the mortality rates of COVID-19 have achieved unprecedented media and public engagements, however, the true facts about the disease prevention, immunomodulation and novel treatments are often left unsaid. We present the most recent facts about COVID-19 disease and its interactions with the immune system.", "qid": 27, "docid": "mwpbrbqu", "rank": 61, "score": 0.8588181734085083}, {"content": "Title: The Role of Chest Computed Tomography in Asymptomatic Patients of Positive Coronavirus Disease 2019: A Case and Literature Review Content: Coronavirus disease 2019 (COVID-19) caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) is an ongoing global health emergency. At present, patients are the primary source of infection. A randomly diagnosed confirmed case of COVID-19 highlights the importance of computerized tomography of thorax in diagnosing asymptomatic patients. In the early phase of COVID-19, routine screenings miss patients who are virus carriers, and tracking travel history is of paramount importance to early detection and isolation of SARS-CoV-2 cases.", "qid": 27, "docid": "38bzszr4", "rank": 62, "score": 0.8587903380393982}, {"content": "Title: Vascular skin symptoms in COVID-19: a french observational study Content: Coronavirus 19 (COVID-19) was declared as a pandemic viral infection by the World Health organization on March 11th 2020. Usual clinical manifestations of COVID-19 infection include fever, fatigue, myalgia, headache, diarrhea, dry cough, dyspnea that may lead to acute respiratory distress syndrome and death (1). Skin symptoms of COVID-19 have been poorly described but may include erythematous rash, urticaria and chicken pox like lesions (2-7). Angiotensin-converting enzyme 2 (ACE2) is a cellular receptor for COVID-19.", "qid": 27, "docid": "vp5xj8m5", "rank": 63, "score": 0.8587802648544312}, {"content": "Title: Thrombocytopenia as an initial manifestation of Covid-19; Case Series and Literature review. Content: Covid-19 has emerged as a global threat that has claimed millions of lives until now. Haematological manifestation as an initial presentation of this deadly virus is not frequently reported in the literature. We hereby report a case series of asymptomatic patients with severe thrombocytopenia which was later found to be Covid induced.", "qid": 27, "docid": "ydyde5mr", "rank": 64, "score": 0.8583416938781738}, {"content": "Title: Post-donation COVID-19 identification in blood donors. Content: The coronavirus disease 19 (COVID-19) outbreak, which was characterized as a pandemic on 11 March 2020 by the WHO, started in December 2019 with the emergence of pneumonia cases of unknown cause in Wuhan, Hubei, China [1]. SARS-CoV-2, the causative agent of COVID-19, are enveloped, non-segmented, single stranded positive sense RNA viruses and are classified as a sister clade to the prototype human and bat severe acute respiratory syndrome coronaviruses (SARS-CoVs) of the species Severe acute respiratory syndrome-related coronavirus [2]. So far, no respiratory virus, including SARS-CoV and the Middle East Respiratory Syndrome (MERS)-CoV, has been confirmed as transfusion-transmissible [3,4].", "qid": 27, "docid": "82sc928x", "rank": 65, "score": 0.8579742908477783}, {"content": "Title: Sudden hyposmia as a prevalent symptom of COVID-19 infection. Content: Severe Acute Respiratory Syndrome Coronavirus-2 (SARS-CoV-2) has recently caused a pandemic that has involved Italy as the second worldwide nation in terms of infected patients and deaths. The clinical manifestation of Covid-19 ranges from asymptomatic carrier status to severe pneumonia. Asymptomatic individuals in Covid-19 are those who are carriers of the virus but do not show clinical symptoms and are able to transmit the disease in the same degree as symptomatic carriers. In order to contain contagions is of supreme importance to identify asymptomatic patients because this subpopulation is one of the main factors contributing to the spread of this disease. We report on six Italian patients with COVID-19 who presented sudden hyposmia as the only or most prominent disease manifestation, without upper or lower respiratory tract involvement or other major features of the disease. A supra-threshold olfaction test confirmed the hyposmia in all patients. The onset of hyposmia during a Covid-19 outbreak should be considered as a warning sign of an infection that requires a diagnostic test for Covid-19", "qid": 27, "docid": "vde6vm2a", "rank": 66, "score": 0.8579630851745605}, {"content": "Title: The relative transmissibility of asymptomatic cases among close contacts Content: Abstract Asymptomatic transmission of the coronavirus disease 2019 is an important topic. A recent study in China showed that transmissibility of the asymptomatic cases is comparable to that of symptomatic cases. Here we showed that the conclusion may depend on how we interpret the data. To the best of our knowledge, this is the first time the relative transmissibility of asymptomatic COVID-19 cases is quantified.", "qid": 27, "docid": "8pjoz64q", "rank": 67, "score": 0.8576654195785522}, {"content": "Title: COVID-19 presenting with diarrhoea and hyponatraemia Content: COVID-19 is a viral disease with a high infectivity rate. The full spectrum of the disease is not yet understood. This understanding may help in limiting potential exposure. We present a young man with diarrhoea, abdominal pain and hyponatraemia who turned out to be positive for COVID-19.", "qid": 27, "docid": "2bfh73a8", "rank": 68, "score": 0.8571462631225586}, {"content": "Title: The need for neurologists in the care of COVID\u201019 patients Content: Coronavirus disease 2019 (COVID-19) is an infectious disease caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) resulting in severe acute respiratory syndrome in a substantial number of patients. Approximately 5% to 10% of patients need intensive care unit (ICU) admission and mechanical ventilation [1]. The primary symptoms of COVID-19 include fever, dry cough and fatigue [2]. However, a recent report from Shandong, China, disclosed that a subset of patients did not suffer from respiratory symptoms but had neurologic signs and symptoms [3]. Moreover, in a retrospective study from Wuhan, China, neurologic symptoms were observed in 36.4% of the hospitalized patients with COVID-19 infection and pertained to both the central and peripheral nervous system [4].", "qid": 27, "docid": "l21fin9q", "rank": 69, "score": 0.8571338653564453}, {"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": 70, "score": 0.8568788766860962}, {"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": 27, "docid": "dn7iuzq1", "rank": 71, "score": 0.8567907810211182}, {"content": "Title: Unclear issues regarding COVID-19 Content: Scientists from all over the world have been intensively working to discover different aspects of Coronavi-rus disease 2019 (COVID-19) since the first cluster of cases was reported in China. Herein, we aimed to investigate unclear issues related to transmission and pathogenesis of disease as well as accuracy of diagnostic tests and treatment modalities. A literature search on PubMed, Ovid, and EMBASE databases was con-ducted, and articles pertinent to identified search terms were extracted. A snow-ball search strategy was followed in order to retrieve additional relevant articles. It was reported that viral spread may occur during the asymptomatic phase of infection, and viral load was suggested to be a useful marker to assess disease severity. In contrast to immune response against viral infections, cytotoxic T lymphocytes decline in SARS-CoV-2 infection, which can be partially explained by direct invasion of T lymphocytes or apoptosis activated by SARS-CoV-2. Dysregulation of the urokinase pathway, cleavage of the SARS-CoV-2 Spike protein by FXa and FIIa, and consumption coagulopathy were the proposed mechanisms of the coagulation dysfunction in COVID-19. False-negative rates of reverse transcriptase polymerase chain reaction varied between 3% and 41% across studies. The probability of the positive test was proposed to decrease with the number of days past from symptom onset. Safety issues related to infection spread limit the use of high flow nasal oxygen (HFNO) and continuous positive airway pressure (CPAP) in hypoxic patients. Further studies are required to elucidate the challenging issues, thus enhancing the management of COVID-19 patients.", "qid": 27, "docid": "r43h5i23", "rank": 72, "score": 0.8567232489585876}, {"content": "Title: Viral kinetics of SARS-CoV-2 in asymptomatic carriers and presymptomatic patients Content: From a total of 71 laboratory-confirmed cases, three presymptomatic patients and 10 patients with entirely asymptomatic infections were identified. In two of the three incubation period patients, the viral titer in the presymptomatic period was very high (Ct value<20). The median number of days to first negative RT-PCR in the asymptomatic carriers was 4.5 (range 2.5-9), and all asymptomatic carriers reached a first RT-PCR Ct>35 within 14 days after diagnosis. Patients who have COVID-19 may already be infectious before there are symptoms, and 14 days of isolation after diagnosis may be sufficient in entirely asymptomatic cases.", "qid": 27, "docid": "1cqqfk0u", "rank": 73, "score": 0.8562784194946289}, {"content": "Title: A COVID-19 Transmission within a family cluster by presymptomatic infectors in China Content: We report a COVID-19 family cluster caused by a presymptomatic case. There were 9 family members, including 8 laboratory-confirmed with COVID-19, and a 6-year-old child had no evidence of infection. Amongst the 8 patients, one adult and one 13-month-old infant were asymptomatic, one adult was diagnosed as having severe pneumonia.", "qid": 27, "docid": "scb7yot1", "rank": 74, "score": 0.8553391098976135}, {"content": "Title: Severe Acute Respiratory Syndrome\u2013associated Coronavirus Infection Content: Whether severe acute respiratory syndrome\u2013associated coronavirus (SARS-CoV) infection can be asymptomatic is unclear. We examined the seroprevalence of SARS-CoV among 674 healthcare workers from a hospital in which a SARS outbreak had occurred. A total of 353 (52%) experienced mild self-limiting illnesses, and 321 (48%) were asymptomatic throughout the course of these observations. None of these healthcare workers had antibody to SARS CoV, indicating that subclinical or mild infection attributable to SARS CoV in adults is rare.", "qid": 27, "docid": "wivzfv6t", "rank": 75, "score": 0.8553136587142944}, {"content": "Title: Viral kinetics of SARS-CoV-2 in asymptomatic carriers and presymptomatic patients Content: Abstract From 71 laboratory-confirmed cases, we found three presymptomatic patients and 10 entirely asymptomatic infections. In two of the three incubation period patients, the viral titer in the presymptomatic period was very high (Ct value <20). The median days to first negative RT-PCR in the entirely asymptomatic carriers was 4.5 (range 2.5\u20139) days and all asymptomatic carriers reached a first Ct>35 RT-PCR within 14 days after diagnosis. Patients who have COVID-19 may already be infectious before there are symptoms, and 14 days of isolation after diagnosis may be sufficient in entirely asymptomatic cases.", "qid": 27, "docid": "ngfrf912", "rank": 76, "score": 0.8551411628723145}, {"content": "Title: Clinical display, diagnostics and genetic implication of novel Coronavirus (COVID-19) epidemic. Content: COVID-19 pandemic can cause irreparable damage to the involved society. This study aimed to provide a summary of the up-to-dated clinical display, diagnostics, molecular and genetic implications for COVID-19 infected patients. In this review, 73 research articles published before 25 March 2020 were analyzed to better understand the clinical characteristics of patients and to introduce the available serological, hematology and molecular diagnostic methods. Apart from articles extracted from PubMed and Google Scholar, WHO (https://www.who.int/), NHC (National Health Commission of the People's Republic of China (http://www.nhc.gov.cn/), NICE (National Institute for Health and Clinical Excellence, https://www.nice.org.uk/), CDC (Centers for Disease Control and Prevention, https://www.cdc.gov/), and National Administration of Traditional Chinese Medicine (http://www.satcm.gov.cn/) were also accessed to search for eligible studies. Papers published between January 1, 2020, and 25 March 2020 were searched in English and the terms \"2019-nCoV, Covid-19, Clinical Characteristics OR manifestation, method of detection, COVID-19 Genome and molecular test\" were used. As the pandemic continues to evolve, there have been reports about the possibility of asymptomatic transmission of this newly emerged pneumonia virus. We highlighted the role of HLA haplotype in virus infection as HLA typing will provide susceptibility information for personalized prevention, diagnosis, and treatment in future studies. All the data in this article will assist researchers and clinicians to develop their clinical views regarding infected patients and to emphasize the origin of SARS-CoV-2 for diagnostics.", "qid": 27, "docid": "kpw8brqk", "rank": 77, "score": 0.8544085621833801}, {"content": "Title: Clinical display, diagnostics and genetic implication of novel Coronavirus (COVID-19) epidemic Content: COVID-19 pandemic can cause irreparable damage to the involved society. This study aimed to provide a summary of the up-to-dated clinical display, diagnostics, molecular and genetic implications for COVID-19 infected patients. In this review, 73 research articles published before 25 March 2020 were analyzed to better understand the clinical characteristics of patients and to introduce the available serological, hematology and molecular diagnostic methods. Apart from articles extracted from PubMed and Google Scholar, WHO (https://www.who.int/), NHC (National Health Commission of the People's Republic of China (http://www.nhc.gov.cn/), NICE (National Institute for Health and Clinical Excellence, https://www.nice.org.uk/), CDC (Centers for Disease Control and Prevention, https://www.cdc.gov/), and National Administration of Traditional Chinese Medicine (http://www.satcm.gov.cn/) were also accessed to search for eligible studies. Papers published between January 1, 2020, and 25 March 2020 were searched in English and the terms \"2019-nCoV, Covid-19, Clinical Characteristics OR manifestation, method of detection, COVID-19 Genome and molecular test\" were used. As the pandemic continues to evolve, there have been reports about the possibility of asymptomatic transmission of this newly emerged pneumonia virus. We highlighted the role of HLA haplotype in virus infection as HLA typing will provide susceptibility information for personalized prevention, diagnosis, and treatment in future studies. All the data in this article will assist researchers and clinicians to develop their clinical views regarding infected patients and to emphasize the origin of SARS-CoV-2 for diagnostics.", "qid": 27, "docid": "nz95gp0s", "rank": 78, "score": 0.8544085025787354}, {"content": "Title: COVID-19 masquerading as Chikungunya fever Content: The COVID-19 outbreak is an unprecedented global public health challenge. It has a myriad of clinical presentations including fever, cough, vomiting, and diarrhea. Here, we present a unique case of COVID-19, with an atypical presentation of arthralgias and false-positive results for the chikungunya virus. By highlighting the importance of this rare association, we want physicians to be vigilant in the time of this pandemic and to have a high suspicion for this novel disease.", "qid": 27, "docid": "njeuur7g", "rank": 79, "score": 0.8543088436126709}, {"content": "Title: Intraoperative Diagnosis of Coronavirus Disease 2019 in an Asymptomatic Patient: A Case Report Content: Patients with coronavirus disease 2019 (COVID-19) with variable clinical presentations are encountered in the perioperative setting. While some have already been diagnosed and are symptomatic, others have undiagnosed, asymptomatic COVID-19. The latter group poses the greatest risk of transmission. Given limited capacities in most health care systems, diagnostic testing is mainly performed in symptomatic patients or those with relevant exposure. We report an intraoperative diagnosis of COVID-19 in an asymptomatic patient, prompted by clinical signs. To control a pandemic such as COVID-19, a high index of suspicion is pivotal when caring for asymptomatic patients in the perioperative setting.", "qid": 27, "docid": "d06wt817", "rank": 80, "score": 0.8540142178535461}, {"content": "Title: Cutaneous manifestations of hospitalized coronavirus disease 2019 patients: a report of six cases with clinicopathologic features and viral RNA in situ hybridization Content: Novel coronavirus disease 2019 (COVID-19) caused by the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) was declared a global pandemic on March, 2020.1 Recalcati et al. reported cutaneous manifestations in 20.4% of COVID-19 patients.2 We identified six patients (five female, one male) with COVID-19-associated cutaneous manifestations in April 2020 on the inpatient dermatology consultation service. The mean age was 51 years (range, 28-71 years).", "qid": 27, "docid": "yswhgbz1", "rank": 81, "score": 0.8539219498634338}, {"content": "Title: COVID-19: Specific and non-specific clinical manifestations and symptoms: The current state of knowledge Content: Coronavirus disease 2019 (COVID-19), due to the severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2), has become an epidemiological threat and a worldwide concern. SARS-CoV-2 has spread to 210 countries worldwide and more than 6,500,000 confirmed cases and 384,643 deaths have been reported, while the number of both confirmed and fatal cases is continually increasing. COVID-19 is a viral disease that can affect every age group\u2014from infants to the elderly\u2014resulting in a wide spectrum of various clinical manifestations. COVID-19 might present different degrees of severity\u2014from mild or even asymptomatic carriers, even to fatal cases. The most common complications include pneumonia and acute respiratory distress syndrome. Fever, dry cough, muscle weakness, and chest pain are the most prevalent and typical symptoms of COVID-19. However, patients might also present atypical symptoms that can occur alone, which might indicate the possible SARS-CoV-2 infection. The aim of this paper is to review and summarize all of the findings regarding clinical manifestations of COVID-19 patients, which include respiratory, neurological, olfactory and gustatory, gastrointestinal, ophthalmic, dermatological, cardiac, and rheumatologic manifestations, as well as specific symptoms in pediatric patients.", "qid": 27, "docid": "s7b3sw74", "rank": 82, "score": 0.8538906574249268}, {"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": 83, "score": 0.8536795377731323}, {"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": 84, "score": 0.8533551692962646}, {"content": "Title: Clinical characteristics of COVID-19 in 104 people with SARS-CoV-2 infection on the Diamond Princess cruise ship: a retrospective analysis Content: BACKGROUND: The ongoing COVID-19 pandemic is a global threat. Identification of markers for symptom onset and disease progression is a pressing issue. We described the clinical features of people infected on board the Diamond Princess cruise ship who were diagnosed with asymptomatic severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection or mild or severe COVID-19, on admission to the Self-Defense Forces Central Hospital (Tokyo, Japan) and at the end of observation. METHODS: This retrospective, single-centre study included participants with laboratory-detected SARS-CoV-2 infection who were admitted to the Self-Defense Forces Central Hospital from Feb 11 to Feb 25, 2020. Clinical records, laboratory data, and radiological findings were analysed. Clinical outcomes were followed up until discharge or Feb 26, 2020, whichever came first. We defined asymptomatic infection as SARS-CoV-2 infection with no history of clinical signs and symptoms, severe COVID-19 as clinical symptoms of pneumonia (dyspnoea, tachypnoea, peripheral capillary oxygen saturation <93%, and need for oxygen therapy), and mild COVID-19 as all other symptoms. Clinical features on admission were compared among patients with different disease severity, including asymptomatic infection, at the end of observation. We used univariable analysis to identify factors associated with symptomatic illness among asymptomatic people infected with SARS-CoV-2 and disease progression in patients with COVID-19. FINDINGS: Among the 104 participants included in the final analysis, the median age was 68 years (IQR 47\u201375) and 54 (52%) were male. On admission, 43 (41%) participants were classified as asymptomatic, 41 (39%) as having mild COVID-10, and 20 (19%) as having severe COVID-19. At the end of observation, 33 (32%) participants were confirmed as being asymptomatic, 43 (41%) as having mild COVID-19, and 28 (27%) as having severe COVID-19. Serum lactate hydrogenase concentrations were significantly higher in the ten participants who were asymptomatic on admission but developed symptomatic COVID-19 compared with the 33 participants who remained asymptomatic throughout the observation period (five [50%] vs four [12%] participants; odds ratio 7\u00b725, 95% CI 1\u00b743\u201336\u00b770; p=0\u00b7020). Compared with patients with mild disease at the end of observation, patients with severe COVID-19 were older (median age 73 years [IQR 55\u201377] vs 60 years [40\u201371]; p=0\u00b7028) and had more frequent consolidation on chest CT (13 [46%] of 28 vs nine [21%] of 43; p=0\u00b7035) and lymphopenia (16 [57%] vs ten [23%]; p=0\u00b70055) on admission. INTERPRETATION: Older age, consolidation on chest CT images, and lymphopenia might be risk factors for disease progression of COVID-19 and contribute to improved clinical management. FUNDING: None.", "qid": 27, "docid": "11rd64fp", "rank": 85, "score": 0.85334312915802}, {"content": "Title: Influenza and COVID-19 Co-infection: Report of 6 cases and review of the Literature. Content: COVID-19 pandemic caused infection in a season when influenza is still prevalent. Both viruses have similar transmission characteristics and common clinical manifestations. Influenza has been described to cause respiratory infection with some other respiratory pathogens. However the information of COVID-19 and influenza co-infection is limited. In this study, we reported our co-infected cases and reviewed the literature. We included all COVID-19 diagnosed patients. All patients with a presumed diagnosis of COVID-19 were routinely screened for influenza. Their thorax radiology was reviewed for COVID-19 -influenza differentiation. During the study period, 1103 patients have been diagnosed COVID-19. Among them, 6 patients (0.54%) were diagnosed co-infected with influenza. There have been 28 more co-infected patients reported. Laboratory-based, screening studies reported more patients. Thorax radiology findings were compatible with COVID-19 in 5 and with influenza in 1 one of our patients. Our cases were mild-to-moderate in severity. The reported cases in the literature included patients died (n=2) and those living ventilator dependent or under mechanical ventilation. COVID-19 and influenza co-infection is rare. Screening studies report more cases, suggesting that unless screening COVID-19 patients, the co-infection remains undiagnosed and underestimated. Increasing experience in thoracic radiology may contribute to diagnose the responsible virus(es) from the clinical illness. Influenza vaccine for larger population groups can be recommended to simplify clinicians' work. This article is protected by copyright. All rights reserved.", "qid": 27, "docid": "dt75j2u6", "rank": 86, "score": 0.8531978130340576}, {"content": "Title: COVID-19: A New Virus as a Potential Rapidly Spreading in the Worldwide Content: Covid-19 is a novel virus with high affinity to spread in the community In December 2019, it was first identified in Wuhan, China The symptoms are non-specific, so fever, cough, dyspnea, are prominent features Respiratory failure and mortality have also been reported The most common lung CT scan findings are bilateral ground glass opacities", "qid": 27, "docid": "0em5sf3g", "rank": 87, "score": 0.8531124591827393}, {"content": "Title: Clinical characteristics of COVID-19 in 104 people with SARS-CoV-2 infection on the Diamond Princess cruise ship: a retrospective analysis Content: BACKGROUND: The ongoing COVID-19 pandemic is a global threat. Identification of markers for symptom onset and disease progression is a pressing issue. We described the clinical features of people infected on board the Diamond Princess cruise ship who were diagnosed with asymptomatic severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection or mild or severe COVID-19, on admission to the Self-Defense Forces Central Hospital (Tokyo, Japan) and at the end of observation. METHODS: This retrospective, single-centre study included participants with laboratory-detected SARS-CoV-2 infection who were admitted to the Self-Defense Forces Central Hospital from Feb 11 to Feb 25, 2020. Clinical records, laboratory data, and radiological findings were analysed. Clinical outcomes were followed up until discharge or Feb 26, 2020, whichever came first. We defined asymptomatic infection as SARS-CoV-2 infection with no history of clinical signs and symptoms, severe COVID-19 as clinical symptoms of pneumonia (dyspnoea, tachypnoea, peripheral capillary oxygen saturation <93%, and need for oxygen therapy), and mild COVID-19 as all other symptoms. Clinical features on admission were compared among patients with different disease severity, including asymptomatic infection, at the end of observation. We used univariable analysis to identify factors associated with symptomatic illness among asymptomatic people infected with SARS-CoV-2 and disease progression in patients with COVID-19. FINDINGS: Among the 104 participants included in the final analysis, the median age was 68 years (IQR 47-75) and 54 (52%) were male. On admission, 43 (41%) participants were classified as asymptomatic, 41 (39%) as having mild COVID-10, and 20 (19%) as having severe COVID-19. At the end of observation, 33 (32%) participants were confirmed as being asymptomatic, 43 (41%) as having mild COVID-19, and 28 (27%) as having severe COVID-19. Serum lactate hydrogenase concentrations were significantly higher in the ten participants who were asymptomatic on admission but developed symptomatic COVID-19 compared with the 33 participants who remained asymptomatic throughout the observation period (five [50%] vs four [12%] participants; odds ratio 7\u00b725, 95% CI 1\u00b743-36\u00b770; p=0\u00b7020). Compared with patients with mild disease at the end of observation, patients with severe COVID-19 were older (median age 73 years [IQR 55-77] vs 60 years [40-71]; p=0\u00b7028) and had more frequent consolidation on chest CT (13 [46%] of 28 vs nine [21%] of 43; p=0\u00b7035) and lymphopenia (16 [57%] vs ten [23%]; p=0\u00b70055) on admission. INTERPRETATION: Older age, consolidation on chest CT images, and lymphopenia might be risk factors for disease progression of COVID-19 and contribute to improved clinical management. FUNDING: None.", "qid": 27, "docid": "2i1q54nd", "rank": 88, "score": 0.8528900742530823}, {"content": "Title: Proportion of COVID-19 Cases that Are Asymptomatic in South Korea: Comment on Nishiura et al Content: \u2022 The Korean Centers for Disease Control & Prevention reports the asymptomatic case proportion for COVID-19 is 33.3%. \u2022 The asymptomatic case proportion in South Korea closely approximates the rate of 30.8% reported by Nishiura et al. (2020) among Japanese nationals returning from abroad. \u2022 The asymptomatic case proportion in South Korea is higher (56.1%) among those who re-test positive for COVID-19.", "qid": 27, "docid": "sbuwquvm", "rank": 89, "score": 0.8525121212005615}, {"content": "Title: [Screening and management of asymptomatic infection of 2019-novel coronavirus] Content: At present, the prevention and control of COVID-19 in China has entered a critical period. Recently, various areas outside Hubei Province have gradually begun to resume work and production, but the development of the epidemic situation is still uncertain and complex. A few days ago, researchers gradually began to pay attention to asymptomatic infection of 2019-novel coronavirus and described the disease process of asymptomatic infection and the possibility of being a source of infection. This provided a scientific basis for further optimizing and improving epidemic prevention and control measures. Paying attention to the screening and self-protection of high-risk groups and strengthening the level of detection should be helpful to the detection and management of asymptomatic infection.", "qid": 27, "docid": "s28hef1o", "rank": 90, "score": 0.8520641326904297}, {"content": "Title: [Screening and management of asymptomatic infection of 2019-novel coronavirus]. Content: At present, the prevention and control of COVID-19 in China has entered a critical period. Recently, various areas outside Hubei Province have gradually begun to resume work and production, but the development of the epidemic situation is still uncertain and complex. A few days ago, researchers gradually began to pay attention to asymptomatic infection of 2019-novel coronavirus and described the disease process of asymptomatic infection and the possibility of being a source of infection. This provided a scientific basis for further optimizing and improving epidemic prevention and control measures. Paying attention to the screening and self-protection of high-risk groups and strengthening the level of detection should be helpful to the detection and management of asymptomatic infection.", "qid": 27, "docid": "hkm8yspk", "rank": 91, "score": 0.8520641326904297}, {"content": "Title: Asymptomatic transmission during the COVID-19 pandemic and implications for public health strategies Content: SARS-CoV-2 spread rapidly within months despite global public health strategies to curb transmission by testing symptomatic patients and encouraging social distancing. Here, we summarize rapidly emerging evidence highlighting transmission by asymptomatic and pre-symptomatic individuals. Viral load of asymptomatic carriers is comparable to symptomatic patients, viral shedding is highest before symptom onset suggesting high transmissibility before symptoms. Within universally tested subgroups, surprisingly high percentages of COVID-19 positive asymptomatic individuals were found. Asymptomatic transmission was reported in several clusters. A Wuhan study showed an alarming rate of intrahospital transmission, and several countries reported higher prevalence among healthcare workers than the general population. This raises concern that health workers could act as silent disease vectors. Therefore, current public health strategies relying solely on 'symptom onset' for infection identification need urgent reassessment. Extensive universal testing irrespective of symptoms may be considered with priority placed on groups with high frequency exposure to positive patients.", "qid": 27, "docid": "6ua5txjc", "rank": 92, "score": 0.8519721031188965}, {"content": "Title: The 2019 Novel Coronavirus Outbreak - A Global Threat Content: The 2019 Novel Corona virus infection (COVID 19) is an ongoing public health emergency of international significance. There are significant knowledge gaps in the epidemiology, transmission dynamics, investigation tools and management. In this article, we review the available evidence about this disease. Every decade has witnessed the evolution of a new coronavirus epidemic since the last three decades. The varying transmission patterns, namely, nosocomial transmission and spread through mildly symptomatic cases is an area of concern. There is a spectrum of clinical features from mild to severe life threatening disease with major complications like severe pneumonia, ARDS, acute cardiac injury and septic shock. Presence of bilateral ground glass opacity and consolidation on imaging in appropriate clinical background should raise a suspicion about COVID 19. Poor prognostic factors include Multilobular infiltration on chest imaging, Lymphopenia, Bacterial co-infection, Smoking history, Chronic medical conditions like Hypertension and age >60 years (MuLBSTA score). Diagnosis is confirmed with PCR based testing of appropriate respiratory samples. Management is primarily supportive, with newer antivirals (lopinavir ritonavir and Remdesivir) under investigation. Role of steroids is still inconclusive. Standard infection control and prevention techniques should be followed. Vigilant screening of suspected cases and their contacts is important. Isolation of symptomatic cases and home quarantine of asymptomatic contacts is recommended. To conclude, controlling this highly transmissible disease requires international co-ordination.", "qid": 27, "docid": "umkg8n5q", "rank": 93, "score": 0.8517477512359619}, {"content": "Title: The 2019 Novel Coronavirus Outbreak - A Global Threat. Content: The 2019 Novel Corona virus infection (COVID 19) is an ongoing public health emergency of international significance. There are significant knowledge gaps in the epidemiology, transmission dynamics, investigation tools and management. In this article, we review the available evidence about this disease. Every decade has witnessed the evolution of a new coronavirus epidemic since the last three decades. The varying transmission patterns, namely, nosocomial transmission and spread through mildly symptomatic cases is an area of concern. There is a spectrum of clinical features from mild to severe life threatening disease with major complications like severe pneumonia, ARDS, acute cardiac injury and septic shock. Presence of bilateral ground glass opacity and consolidation on imaging in appropriate clinical background should raise a suspicion about COVID 19. Poor prognostic factors include Multilobular infiltration on chest imaging, Lymphopenia, Bacterial co-infection, Smoking history, Chronic medical conditions like Hypertension and age >60 years (MuLBSTA score). Diagnosis is confirmed with PCR based testing of appropriate respiratory samples. Management is primarily supportive, with newer antivirals (lopinavir ritonavir and Remdesivir) under investigation. Role of steroids is still inconclusive. Standard infection control and prevention techniques should be followed. Vigilant screening of suspected cases and their contacts is important. Isolation of symptomatic cases and home quarantine of asymptomatic contacts is recommended. To conclude, controlling this highly transmissible disease requires international co-ordination.", "qid": 27, "docid": "u8i3kbl4", "rank": 94, "score": 0.8517477512359619}, {"content": "Title: Novel Coronavirus COVID-19: Current Evidence and Evolving Strategies Content: COVID-19 is a global pandemic that has currently infected &gt;300,000 globally. Fever and cough are the most common symptoms of the disease, and it is important to remember that the virus can even be transmitted by individuals who test positive for the disease but do not have any symptoms. Currently reported mortality rates vary because of the rapid spread of the disease and different approaches to calculating this estimate, but it is clear that the risk of death is associated with age and the presence of underlying conditions. Risk mitigation techniques (i.e., hand washing, social distancing, and self-isolation) have already been emphasized across major news outlets. It is essential that we continue these practices, as the outbreak is currently expected to last for many more months and we must be mindful of the lessons learned from past pandemics to prevent a second wave from occurring.", "qid": 27, "docid": "3ateeei3", "rank": 95, "score": 0.8517072200775146}, {"content": "Title: Asymptomatic transmission during the COVID-19 pandemic and implications for public health strategies Content: SARS-CoV-2 spread rapidly within months despite global public health strategies to curb transmission by testing symptomatic patients and encouraging social distancing. Here, we summarize rapidly emerging evidence highlighting transmission by asymptomatic and pre-symptomatic individuals. Viral load of asymptomatic carriers is comparable to symptomatic patients, viral shedding is highest before symptom onset suggesting high transmissibility before symptoms. Within universally tested subgroups, surprisingly high percentages of COVID-19 positive asymptomatic individuals were found. Asymptomatic transmission was reported in several clusters. A Wuhan study showed an alarming rate of intrahospital transmission, and several countries reported higher prevalence among healthcare workers than the general population. This raises concern that health workers could act as silent disease vectors. Therefore, current public health strategies relying solely on \u2018symptom onset\u2019 for infection identification need urgent reassessment. Extensive universal testing irrespective of symptoms may be considered with priority placed on groups with high frequency exposure to positive patients.", "qid": 27, "docid": "f99itvu9", "rank": 96, "score": 0.851426899433136}, {"content": "Title: Coronavirus (COVID-19) Infection-Induced Chilblains: A Brisk Perieccrine Inflammatory Response Content: The varying cutaneous and pathological manifestations of coronavirus 2 (SARS-CoV-2 or COVID-19) may have prognostic implications. Acral ischemic findings present with a hypercoagulable state in critically ill COVID-19 patients. Pathologically confirmed varicella-like exanthem and perniosis COVID-19 cases have correlated with paucisymptomatic and asymptomatic patients in previous reports. We present the second case of biopsy-proven COVID-19 infection-induced chilblains (pernio) in a paucisymptomatic patient with a brisk perieccrine lymphocytic response. Based on an antecedent pathological study, we know coronavirus particles have been seen in the eccrine gland associated with a brisk peri-inflammatory response. The prominent perieccrine inflammation is helpful in the diagnosis of COVID-19 infections. Currently, nonischemic pathological findings correlate with a good prognosis based on the paucisymptomatic or asymptomatic nature of their disease courses. Patients presenting with suspected COVID-19 infection-induced chilblains who are paucisymptomatic or asymptomatic should be isolated and immediately tested with polymerase chain reaction (PCR) testing (as there is a delay in diagnosis based on the poor sensitivity of the current rapid test). We continue to stress the importance of early diagnosis and quarantining to prevent spread to the older and immunocompromised patients.", "qid": 27, "docid": "2mlu8evo", "rank": 97, "score": 0.851401150226593}, {"content": "Title: Coronavirus (COVID-19) Infection-Induced Chilblains: A Brisk Perieccrine Inflammatory Response. Content: The varying cutaneous and pathological manifestations of coronavirus 2 (SARS-CoV-2 or COVID-19) may have prognostic implications. Acral ischemic findings present with a hypercoagulable state in critically ill COVID-19 patients. Pathologically confirmed varicella-like exanthem and perniosis COVID-19 cases have correlated with paucisymptomatic and asymptomatic patients in previous reports. We present the second case of biopsy-proven COVID-19 infection-induced chilblains (pernio) in a paucisymptomatic patient with a brisk perieccrine lymphocytic response. Based on an antecedent pathological study, we know coronavirus particles have been seen in the eccrine gland associated with a brisk peri-inflammatory response. The prominent perieccrine inflammation is helpful in the diagnosis of COVID-19 infections. Currently, nonischemic pathological findings correlate with a good prognosis based on the paucisymptomatic or asymptomatic nature of their disease courses. Patients presenting with suspected COVID-19 infection-induced chilblains who are paucisymptomatic or asymptomatic should be isolated and immediately tested with polymerase chain reaction (PCR) testing (as there is a delay in diagnosis based on the poor sensitivity of the current rapid test). We continue to stress the importance of early diagnosis and quarantining to prevent spread to the older and immunocompromised patients.", "qid": 27, "docid": "priiggyi", "rank": 98, "score": 0.851401150226593}, {"content": "Title: SnapShot: COVID-19 Content: Coronavirus disease 2019 (COVID-19) is a novel respiratory illness caused by SARS-CoV-2. Viral entry is mediated through viral spike protein and host ACE2 enzyme interaction. Most cases are mild; severe disease often involves cytokine storm and organ failure. Therapeutics including antivirals, immunomodulators, and vaccines are in development. To view this SnapShot, open or download the PDF.", "qid": 27, "docid": "q3jeu45r", "rank": 99, "score": 0.851368248462677}, {"content": "Title: High COVID\u201019 virus replication rates, the creation of antigen\u2013antibody immune complexes and indirect haemagglutination resulting in thrombosis Content: A new pathogenic virus, COVID-19, appeared in 2019, in Wuhan, China, typically causing fever, cough, diarrhea and fatigue and significant mortality (Mao, 2020). COVID-19 has also shown about 80% genetic similarity to the Severe Acute Respiratory Symptom (SARS) virus, which is already known to be derived from a bat virus (Ye, 2020). Arterial thrombosis and venous thrombosis, variously attributed to long term patient immobilizations, inflammation, autoimmune reactions or endothelial cell damage to the blood vessels, have also been reported for COVID-19 infections (Bikdeli, 2020; Kollas, 2020). However, another explanation for thrombosis (blood clots) in some patients infected with COVID-19 is discussed.", "qid": 27, "docid": "ukgrkfd7", "rank": 100, "score": 0.851240336894989}]}
{"query": "what evidence is there for the value of hydroxychloroquine in treating Covid-19?", "hits": [{"content": "Title: Hydroxychloroquine for Treatment of SARS\u2010CoV\u20102 Infection? Improving Our Confidence in a Model\u2010Based Approach to Dose Selection Content: In less than six months, COVID-19 has spread from a marketplace in Wuhan, China to over 150 countries and territories of the world. Therapeutics are desperately needed to reduce the morbidity and mortality of this pandemic disease. It has been reported that hydroxychloroquine (HCQ) is active against SARS-CoV-2 in vitro, and this finding was quickly supported by an open label non-randomized clinical trial that provided the first published clinical evidence HCQ may be a treatment option.", "qid": 28, "docid": "248de4cj", "rank": 1, "score": 0.923355221748352}, {"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": 2, "score": 0.9223628640174866}, {"content": "Title: Hydroxychloroquine use in the COVID-19 patient Content: Hydroxychloroquine (HCQ) has multiple potential antiviral mechanisms of action that differ according to the pathogen studied (eg, Chikungunya, Dengue virus, human immunodeficiency virus, poliovirus, Zika virus). Data on HCQ for treatment of coronavirus disease 2019 (COVID-19) are rapidly evolving. To date, there is no evidence from randomized controlled trials that HCQ, or any single therapy, improves outcomes in patients infected with COVID-19. There are also no clinical trial data supporting prophylactic HCQ therapy in COVID-19. Use of HCQ in patients with COVID-19 is being investigated for prophylaxis, postexposure prophylaxis, and treatment.", "qid": 28, "docid": "1x9vqepb", "rank": 3, "score": 0.9213452339172363}, {"content": "Title: Hydroxychloroquine use in the COVID-19 patient. Content: Hydroxychloroquine (HCQ) has multiple potential antiviral mechanisms of action that differ according to the pathogen studied (eg, Chikungunya, Dengue virus, human immunodeficiency virus, poliovirus, Zika virus). Data on HCQ for treatment of coronavirus disease 2019 (COVID-19) are rapidly evolving. To date there is no evidence from randomized controlled trials that any single therapy improves outcomes in patients infected with COVID-19. There are also no clinical trial data supporting prophylactic HCQ therapy in COVID-19. Hydroxychloroquine (HCQ) use in patients with COVID-19 is being investigated examining prophylaxis, postexposure prophylaxis, and treatment regimens.", "qid": 28, "docid": "7ttesiuu", "rank": 4, "score": 0.9197079539299011}, {"content": "Title: Towards Optimization of Hydroxychloroquine Dosing in Intensive Care Unit COVID-19 Patients Content: Hydroxychloroquine (HCQ) appears to be a promising treatment for COVID-19. However, all ongoing clinical trials with HCQ use different dosing regimens, resulting on various concentrations PK studies are therefore needed to define the optimal dosing regimen.", "qid": 28, "docid": "onqy21w5", "rank": 5, "score": 0.9164410829544067}, {"content": "Title: Chloroquine and COVID-19 - a potential game changer? Content: The novel coronavirus SARS-CoV-2, causing the disease COVID-19, first emerged in Wuhan, China in December 2019 and has now spread to 203 countries or territories, infected over 2 million people and caused over 133,000 deaths. There is an urgent need for specific treatments. One potential treatment is chloroquine and its derivatives, including hydroxychloroquine, which have both antiviral and anti-inflammatory effects. These compounds are effective against SARS-CoV-2 in vitro, but in vivo data are lacking. Although some encouraging outcomes have been reported, and these results have been received enthusiastically, we recommend careful and critical evaluation of current evidence only when all methods and data are available for peer review. Chloroquine is safe and cheap. However, further evidence from coordinated multicentre trials is required before it can be confidently said whether it is effective against the current pandemic.", "qid": 28, "docid": "zrx4x5sa", "rank": 6, "score": 0.9161282777786255}, {"content": "Title: Off-label prescribing in the midst of a pandemic: The case of hydroxychloroquine Content: There is currently no robust evidence to support prescribing hydroxychloroquine as a treatment or prophylaxis for COVID-19.", "qid": 28, "docid": "lh5g8vl7", "rank": 7, "score": 0.9142070412635803}, {"content": "Title: Off-label prescribing in the midst of a pandemic: The case of hydroxychloroquine. Content: There is currently no robust evidence to support prescribing hydroxychloroquine as a treatment or prophylaxis for COVID-19.", "qid": 28, "docid": "0eizsamh", "rank": 8, "score": 0.9142070412635803}, {"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": 9, "score": 0.9140291810035706}, {"content": "Title: A Rush to Judgment? Rapid Reporting and Dissemination of Results and Its Consequences Regarding the Use of Hydroxychloroquine for COVID-19 Content: Hydroxychloroquine, an essential treatment for many patients with rheumatologic conditions, has recently garnered widespread attention as a potential treatment for COVID-19 infection. The authors appraise the study generating this interest and highlight the potential consequences of rapid dissemination of overinterpreted data, particularly for people with conditions for which hydroxychloroquine has demonstrated benefits in preventing organ damage and life-threatening disease flares.", "qid": 28, "docid": "amhj8ljl", "rank": 10, "score": 0.9139847755432129}, {"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": 11, "score": 0.9121581315994263}, {"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": 12, "score": 0.9121580719947815}, {"content": "Title: Smooth or Risky Revisit of an Old Malaria Drug for COVID-19? Content: Hydroxychloroquine (HCQ) is an old medication for malaria. In addition to handling this parasitic disease, HCQ is also used to treat a number of autoimmune disorders including rheumatoid arthritis and systemic lupus erythematosus when other medications are not effective. Recently a new viral infection (COVID-19) is rocking the entire world so much that it has already taken more than 200,000 lives throughout the world within the last two months and the World Health Organization was forced to declare it as a pandemic on March 11, 2020. Interestingly, some reports indicate that this wonder drug may be also beneficial for COVID-19 and accordingly, many clinical trials have begun. Here, we discuss different modes of action (anti-inflammatory, antioxidant, inhibition of endosomal acidification, suppression of angiotensin-converting enzyme 2 or ACE2 glycosylation, etc.) of HCQ that might be responsible for its possible anti-COVID-19 effect. On the other hand, this review also makes an honest attempt to delineate mechanisms (increase in vasoconstriction, inhibition of autophagy, depletion of T cells, etc.) indicating how it may aggravate certain conditions and why caution should be taken before granting widespread repurposing of HCQ for COVID-19. Graphical Abstract.", "qid": 28, "docid": "kmic4j3q", "rank": 13, "score": 0.9110615253448486}, {"content": "Title: Smooth or Risky Revisit of an Old Malaria Drug for COVID-19? Content: Hydroxychloroquine (HCQ) is an old medication for malaria. In addition to handling this parasitic disease, HCQ is also used to treat a number of autoimmune disorders including rheumatoid arthritis and systemic lupus erythematosus when other medications are not effective. Recently a new viral infection (COVID-19) is rocking the entire world so much that it has already taken more than 200,000 lives throughout the world within the last two months and the World Health Organization was forced to declare it as a pandemic on March 11, 2020. Interestingly, some reports indicate that this wonder drug may be also beneficial for COVID-19 and accordingly, many clinical trials have begun. Here, we discuss different modes of action (anti-inflammatory, antioxidant, inhibition of endosomal acidification, suppression of angiotensin-converting enzyme 2 or ACE2 glycosylation, etc.) of HCQ that might be responsible for its possible anti-COVID-19 effect. On the other hand, this review also makes an honest attempt to delineate mechanisms (increase in vasoconstriction, inhibition of autophagy, depletion of T cells, etc.) indicating how it may aggravate certain conditions and why caution should be taken before granting widespread repurposing of HCQ for COVID-19. [Figure: see text]", "qid": 28, "docid": "pnpsn6dr", "rank": 14, "score": 0.9097678065299988}, {"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": 15, "score": 0.9096812009811401}, {"content": "Title: An Updated Systematic Review of the Therapeutic Role of Hydroxychloroquine in Coronavirus Disease-19 (COVID-19) Content: BACKGROUND AND OBJECTIVE: The world is currently experiencing the Coronavirus Disease-19 (COVID-19) pandemic. There is no approved drug for the definitive treatment of the disease. Various drugs are being tried for the treatment of COVID-19, including hydroxychloroquine (HCQ). This study was performed to systematically review the therapeutic role of HCQ in COVID-19 from the available literature. METHODS: PubMed, Embase, ClinicalTrials.gov, ICTRP (WHO), Cochrane Library databases, and two pre-print servers (medRxiv.org and Research Square) were searched for clinical studies that evaluated the therapeutic role of HCQ on COVID-19 until 10 May 2020. The available studies were critically analyzed and the data were extracted. RESULTS: A total of 663 articles were screened and 12 clinical studies (seven peer-reviewed and published studies and five non-peer-reviewed studies from pre-print servers) with a total sample size of 3543 patients were included. Some of the clinical studies demonstrated good virological and clinical outcomes with HCQ alone or in combination with azithromycin in COVID-19 patients, although the studies had major methodological limitations. Some of the other studies showed negative results with HCQ therapy along with the risk of adverse reactions. CONCLUSION: The results of efficacy and safety of HCQ in COVID-19, as obtained from the clinical studies, are not satisfactory, although many of these studies had major methodological limitations. Stronger evidence from well-designed robust randomized clinical trials is required before conclusively determining the role of HCQ in the treatment of COVID-19. Clinical prudence is required in advocating HCQ as a therapeutic armamentarium in COVID-19. ELECTRONIC SUPPLEMENTARY MATERIAL: The online version of this article (10.1007/s40261-020-00927-1) contains supplementary material, which is available to authorized users.", "qid": 28, "docid": "ne8k1vez", "rank": 16, "score": 0.9095280170440674}, {"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": 17, "score": 0.908901572227478}, {"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": 18, "score": 0.90869140625}, {"content": "Title: An Updated Systematic Review of the Therapeutic Role of Hydroxychloroquine in Coronavirus Disease-19 (COVID-19) Content: BACKGROUND AND OBJECTIVE: The world is currently experiencing the Coronavirus Disease-19 (COVID-19) pandemic. There is no approved drug for the definitive treatment of the disease. Various drugs are being tried for the treatment of COVID-19, including hydroxychloroquine (HCQ). This study was performed to systematically review the therapeutic role of HCQ in COVID-19 from the available literature. METHODS: PubMed, Embase, ClinicalTrials.gov, ICTRP (WHO), Cochrane Library databases, and two pre-print servers (medRxiv.org and Research Square) were searched for clinical studies that evaluated the therapeutic role of HCQ on COVID-19 until 10 May 2020. The available studies were critically analyzed and the data were extracted. RESULTS: A total of 663 articles were screened and 12 clinical studies (seven peer-reviewed and published studies and five non-peer-reviewed studies from pre-print servers) with a total sample size of 3543 patients were included. Some of the clinical studies demonstrated good virological and clinical outcomes with HCQ alone or in combination with azithromycin in COVID-19 patients, although the studies had major methodological limitations. Some of the other studies showed negative results with HCQ therapy along with the risk of adverse reactions. CONCLUSION: The results of efficacy and safety of HCQ in COVID-19, as obtained from the clinical studies, are not satisfactory, although many of these studies had major methodological limitations. Stronger evidence from well-designed robust randomized clinical trials is required before conclusively determining the role of HCQ in the treatment of COVID-19. Clinical prudence is required in advocating HCQ as a therapeutic armamentarium in COVID-19.", "qid": 28, "docid": "5gvdddeh", "rank": 19, "score": 0.9084833860397339}, {"content": "Title: Behandling med 4-aminokinoliner vid covid-19 kan ge allvarliga biverkningar./ [Potential harms associated with 4-aminoquinoline treatment] Content: Hydroxychloroquine and chloroquine are currently being evaluated as treatment against COVID-19. These drugs are associated with some potential harms, including QTc-interval prolongation, hypoglycaemia, severe skin reactions and psychiatric effects. Use of hydroxychloroquine or chloroquine should be reserved to current indications or clinical trials, as recommended by several governmental medical products agencies.", "qid": 28, "docid": "x09n56na", "rank": 20, "score": 0.9073789119720459}, {"content": "Title: [Potential harms associated with 4-aminoquinoline treatment]. Content: Hydroxychloroquine and chloroquine are currently being evaluated as treatment against COVID-19. These drugs are associated with some potential harms, including QTc-interval prolongation, hypoglycaemia, severe skin reactions and psychiatric effects. Use of hydroxychloroquine or chloroquine should be reserved to current indications or clinical trials, as recommended by several governmental medical products agencies.", "qid": 28, "docid": "8wgg86qc", "rank": 21, "score": 0.9073789119720459}, {"content": "Title: Dr. Balevic, et al, reply Content: We read with great interest the very thoughtful commentary by Joob and Wiwanitkit1 We agree with the authors that, despite conflicting clinical data to date, it is possible that hydroxychloroquine (HCQ) may have a protective effect in the setting of the coronavirus disease 2019 (COVID\u00ad19).", "qid": 28, "docid": "s4wa298y", "rank": 22, "score": 0.9070006608963013}, {"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": 23, "score": 0.9061731100082397}, {"content": "Title: Hydroxychloroquine use during the COVID-19 pandemic 2020 Content: At present, there are no studies demonstrating the clinical efficacy of hydroxychloroquine for the prophylaxis or treatment of COVID-19 infection.", "qid": 28, "docid": "o3ggu5qf", "rank": 24, "score": 0.9057711362838745}, {"content": "Title: Hydroxychloroquine use during the COVID-19 pandemic 2020. Content: At present, there are no studies demonstrating the clinical efficacy of hydroxychloroquine for the prophylaxis or treatment of COVID-19 infection.", "qid": 28, "docid": "svwkpcme", "rank": 25, "score": 0.9057711362838745}, {"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": 26, "score": 0.9057311415672302}, {"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": 27, "score": 0.9054408073425293}, {"content": "Title: Rapid systematic review on clinical evidence of chloroquine and hydroxychloroquine in COVID-19: critical assessment and recommendation for future clinical trials Content: Purpose: This study aims to critically assess the published studies of Chloroquine (CQ) and hydroxychloroquine (HCQ) for the treatment of COVID-19 and provide recommendations for future clinical trials for the COVID-19 pandemic. Method: A rapid systematic review was conducted by searching the PubMed, Embase, and China National Knowledge Infrastructure databases on April 13, 2020. Three clinical trial registry platforms, including ClinicalTrials.gov, the EU Clinical Trials Register, and the Chinese Clinical Trial Register were also complementarily searched. Results: A total of 10 clinical studies were identified, including 3 randomized controlled trials (RCTs), 1 comparative nonrandomized trial, 5 single-arm trials, and 1 interim analysis. The heterogeneity among studies of the baseline disease severity and reported endpoints made a pooled analysis impossible. CQ and HCQ (with or without azithromycin) showed significant therapeutic benefit in terms of virologic clearance rate, improvement in symptoms and imaging findings, time to clinical recovery, and length of hospital stay in 1 RCT, 4 single-arm trials, and the interim analysis, whereas no treatment benefit of CQ or HCQ was observed in the remaining 4 studies. Limitations of the included studies ranged from small sample size, to insufficient information concerning baseline patient characteristics, to potential for selection bias without detailing the rationale for exclusion, and presence of confounding factors. Conclusion: Based on the studies evaluated, there still lacked solid evidence supporting the efficacy and safety of HCQ and CQ as a treatment for COVID-19 with or without azithromycin. This emphasized the importance of robust RCTs investing HCQ/CQ to address the evidence uncertainties. Keywords: COVID-19, Systematic review, Clinical trial, Chloroquine, Hydroxychloroquine", "qid": 28, "docid": "y9wuszu5", "rank": 28, "score": 0.9052783250808716}, {"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": 29, "score": 0.9045051336288452}, {"content": "Title: Hydroxychloroquine plus standard care compared with the standard care alone in COVID-19: a meta-analysis of randomized controlled trials Content: Background & Objective: The efficacy and safety of Hydroxychloroquine (HCQ) in treating coronavirus disease COVID-19 pandemic is disputed. This study aimed to examine the efficacy and safety of HCQ plus standard of care in COVID-19 patients. Methods: PubMed, The Cochrane Library, Embase, and web of sciences were searched up to June 1, 2020. The references list of the key studies was reviewed for additional relevant resources. Clinical studies registry databases were searched for identifying potential clinical trials. The quality of the included studies was evaluated using the Cochrane Collaborations tool. Meta-analysis was performed using RevMan software (version 5.3). Results: Three randomized controlled trials with total number of 242 patients were identified eligible for meta-analysis. No significant differences were observed between HCQ and standard care in terms of viral clearance (Risk ratio [RR] = 1.03; 95% confidence interval [CI] = 0.91, 1.16; P= 0.68), disease progression (RR=0.92; 95% CI= 0.10, 0.81; P=0.94), Chest CT (RR=1.40; 95% CI= 1.03, 1.91; P=0.03). There is a significant difference between HCQ and standard care for adverse events (RR=2.88; 95% CI= 1.50, 5.54; P=0.002). Conclusion: Although the current meta-analysis failed to confirm the efficacy and safety of HCQ in the treatment of COVID-19 patients, further rigorous randomized clinical trials are necessary to evaluate conclusively the efficacy and safety of HCQ against COVID-19. Keyword: Coronavirus Disease; COVID-19; SARS-CoV-2; Hydroxychloroquine; Efficacy; Safety", "qid": 28, "docid": "n288cnap", "rank": 30, "score": 0.9043785333633423}, {"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": 31, "score": 0.9042282104492188}, {"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": 32, "score": 0.9036852717399597}, {"content": "Title: Chloroquine: Can it be a Novel Drug for COVID-19 Content: Coronavirus disease 2019 (COVID-19) has been declared a pandemic by the World Health Organization. The United States Food and Drug Administration has not approved any drug or vaccine for the treatment of COVID-19; however, reports have emerged from different parts of the world about the potential therapeutic benefits of existing drugs. Chloroquine and phosphate hydroxychloroquine are the drugs currently in the limelight, and recently, the National Task Force for COVID-19 constituted by the Indian Council of Medical Research has recommended the use of antimalarial drug hydroxychloroquine for prophylaxis of severe acute respiratory syndrome-coronavirus 2 infection in selected high-risk individuals. This short write-up explores the potential efficacy and established safety of chloroquine in COVID-19.", "qid": 28, "docid": "fxqseibh", "rank": 33, "score": 0.9032959342002869}, {"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": 34, "score": 0.9027328491210938}, {"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": 35, "score": 0.9027328491210938}, {"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": 36, "score": 0.9026222825050354}, {"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": 37, "score": 0.9026222825050354}, {"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": 38, "score": 0.9022537469863892}, {"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": 39, "score": 0.902174711227417}, {"content": "Title: Therapeutic use of chloroquine and hydroxychloroquine in COVID-19 and other viral infections: A narrative review Content: The rapidly spreading Coronavirus Disease (COVID-19) pandemic, caused by the severe acute respiratory syndrome coronavirus (SARS-CoV-2), represents an unprecedented serious challenge to the global public health community. The extremely rapid international spread of the disease with significant morbidity and mortality made finding possible therapeutic interventions a global priority. While approved specific antiviral drugs against SARS-CoV-2 are still lacking, a large number of existing drugs are being explored as a possible treatment for COVID-19 infected patients. Recent publications have re-examined the use of Chloroquine (CQ) and/or Hydroxychloroquine (HCQ) as a potential therapeutic option for these patients. In an attempt to explore the evidence that supports their use in COVID-19 patients, we comprehensively reviewed the previous studies which used CQ or HCQ as an antiviral treatment. Both CQ and HCQ demonstrated promising in vitro results, however, such data have not yet been translated into meaningful in vivo studies. While few clinical trials have suggested some beneficial effects of CQ and HCQ in COVID-19 patients, most of the reported data are still preliminary. Given the current uncertainty, it is worth being mindful of the potential risks and strictly rationalise the use of these drugs in COVID-19 patients until further high quality randomized clinical trials are available to clarify their role in the treatment or prevention of COVID-19.", "qid": 28, "docid": "7habtj4m", "rank": 40, "score": 0.9020839929580688}, {"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": 41, "score": 0.901901364326477}, {"content": "Title: Hydroxychloroquine is associated with slower viral clearance in clinical COVID-19 patients with mild to moderate disease: A retrospective study Content: Background: There is conflicting data regarding the use of hydroxychloroquine (HCQ) in COVID-19 hospitalized patients Objective: To assess the efficacy of HCQ in increasing SARS-CoV-2 viral clearance Design: Retrospective observational study Setting: Cleveland Clinic Abu Dhabi Participants: Hospitalized adult patients with confirmed SARS-CoV-2 infection Intervention: None Measurements: The primary outcome was the time from a confirmed positive nasopharyngeal swab to turn negative. A negative nasopharyngeal swab conversion was defined as a confirmed SARS-CoV-2 case followed by two negative results using RT-PCR assay with samples obtained 24 hours apart Results: 34 confirmed COVID-19 patients were included. Nineteen (55.9%) patients presented with symptoms, and 14 (41.2%) had pneumonia. Only 21 (61.8%) patients received HCQ. The time to SARS-CoV-2 negativity nasopharyngeal test was significantly longer in patients who received HCQ compared to those who did not receive HCQ (17 [13-21] vs. 10 [4-13] days, p=0.023). HCQ was independently associated with time to negativity test after adjustment for potential confounders (symptoms, pneumonia or oxygen therapy) in multivariable linear regression analysis. On day 14, 47.8% (14/23) patients tested negative in the HCQ group compared to 90.9% (10/11) patients who did not receive HCQ (p=0.016). Limitations: Small sample size and retrospective design with a potential risk of selection bias Conclusion: HCQ was associated with a slower viral clearance in COVID-19 patients with mild to moderate disease. Data from ongoing randomized clinical trials with HCQ should provide a definitive answer regarding the efficacy and safety of this treatment.", "qid": 28, "docid": "9b88lizj", "rank": 42, "score": 0.9016680717468262}, {"content": "Title: Chloroquine and Hydroxychloroquine for the treatment of COVID-19: A Systematic Review and Meta-analysis Content: Background: There is no effective therapy for COVID-19. Hydroxychloroquine (HCQ) and chloroquine (CQ) have been used for its treatment but their safety and efficacy remain uncertain. Objective: We performed a systematic review to synthesize the available data on the efficacy and safety of CQ and HCQ for the treatment of COVID-19. Methods: Two reviewers searched for published and pre-published relevant articles between December 2019 to 8th June 2020. The data from the selected studies were abstracted and analyzed for efficacy and safety outcomes. Critical appraisal of the evidence was done by Cochrane risk of bias tool and Newcastle Ottawa scale. The quality of evidence was graded as per the GRADE approach. Results: We reviewed 12 observational and 3 randomized trials which included 10659 patients of whom 5713 received CQ/HCQ and 4966 received only standard of care. The efficacy of CQ/HCQ for COVID-19 was inconsistent across the studies. Meta-analysis of included studies revealed no significant reduction in mortality with HCQ use [RR 0.98 95% CI 0.66-1.46] , time to fever resolution [mean difference -0.54 days (-1.19-011)] or clinical deterioration/development of ARDS with HCQ [RR 0.90 95% CI 0.47-1.71]. There was a higher risk of ECG abnormalities/arrhythmia with HCQ/CQ [RR 1.46 95% CI 1.04 to 2.06]. The quality of evidence was graded as very low for these outcomes. Conclusions: The available evidence suggests that CQ or HCQ does not improve clinical outcomes in COVID-19. Well-designed randomized trials are required for assessing the efficacy and safety of HCQ and CQ for COVID-19.", "qid": 28, "docid": "uf32cq68", "rank": 43, "score": 0.9012567400932312}, {"content": "Title: \u201cHydroxychloroquine in patients with COVID-19: A Systematic Review and meta-analysis.\u201d Content: BACKGROUNDS AND AIMS: The role of hydroxychloroquine (HCQ) in the treatment of COVID-19 is not fully known. We studied the efficacy of HCQ compared to the control in COVID-19 subjects on a. viral clearance measured by reverse transcriptase polymerase chain reaction (RT-PCR) and, b. death due to all cause. METHODS: PubMed, Scopus, Cochrane and MedRxiv database were searched using the specific keywords up to April 30, 2020. Studies that met our objectives were assessed for the risk of bias applying various tools as indicated. Three studies each that reported the outcome of viral clearance by RT-PCR and death due to all cause, were meta-analyzed by applying inverse variance-weighted averages of logarithmic risk ratio (RR) using a random effects model. Heterogeneity and publication bias were assessed using the I(2) statistic and funnel plots, respectively. RESULTS: Meta-analysis of 3 studies (n = 210) on viral clearance assessed by RT-PCR showed no benefit (RR, 1.05; 95% CI, 0.79 to 1.38; p = 0.74), although with a moderate heterogeneity (I(2) = 61.7%, p = 0.07). While meta-analysis of 3 studies (n = 474) showed a significant increase in death with HCQ, compared to the control (RR, 2.17; 95% 1.32 to 3.57; p = 0.002), without any heterogeneity (I(2) = 0.0%, p = 0.43). CONCLUSIONS: No benefit on viral clearance but a significant increase in mortality was observed with HCQ compared to control in patients with COVID-19.", "qid": 28, "docid": "95zrth5d", "rank": 44, "score": 0.9011951088905334}, {"content": "Title: Effect of Hydroxychloroquine in Hospitalized Patients with COVID-19: Preliminary results from a multi-centre, randomized, controlled trial. Content: Background: Hydroxychloroquine and chloroquine have been proposed as treatments for coronavirus disease 2019 (COVID-19) on the basis of in vitro activity, uncontrolled data, and small randomized studies. Methods: The Randomised Evaluation of COVID-19 therapy (RECOVERY) trial is a randomized, controlled, open-label, 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 hydroxychloroquine vs. usual care alone. The primary outcome was 28-day mortality. Results: 1561 patients randomly allocated to receive hydroxychloroquine were compared with 3155 patients concurrently allocated to usual care. Overall, 418 (26.8%) patients allocated hydroxychloroquine and 788 (25.0%) patients allocated usual care died within 28 days (rate ratio 1.09; 95% confidence interval [CI] 0.96 to 1.23; P=0.18). Consistent results were seen in all pre-specified subgroups of patients. Patients allocated to hydroxychloroquine were less likely to be discharged from hospital alive within 28 days (60.3% vs. 62.8%; rate ratio 0.92; 95% CI 0.85-0.99) and those not on invasive mechanical ventilation at baseline were more likely to reach the composite endpoint of invasive mechanical ventilation or death (29.8% vs. 26.5%; risk ratio 1.12; 95% CI 1.01-1.25). There was no excess of new major cardiac arrhythmia. Conclusions: In patients hospitalized with COVID-19, hydroxychloroquine was not associated with reductions in 28-day mortality but was associated with an increased length of hospital stay and increased risk of progressing to invasive mechanical ventilation or death.", "qid": 28, "docid": "36flecmg", "rank": 45, "score": 0.9010622501373291}, {"content": "Title: \"Hydroxychloroquine in patients with COVID-19: A Systematic Review and meta-analysis.\" Content: BACKGROUNDS AND AIMS: The role of hydroxychloroquine (HCQ) in the treatment of COVID-19 is not fully known. We studied the efficacy of HCQ compared to the control in COVID-19 subjects on - a. viral clearance measured by reverse transcriptase polymerase chain reaction (RT-PCR) and, b. death due to all cause. METHODS: PubMed, Scopus, Cochrane and MedRxiv database were searched using the specific keywords up to April 30, 2020. Studies that met our objectives were assessed for the risk of bias applying various tools as indicated. Three studies each that reported the outcome of viral clearance by RT-PCR and death due to all cause, were meta-analyzed by applying inverse variance-weighted averages of logarithmic risk ratio (RR) using a random effects model. Heterogeneity and publication bias were assessed using the I2 statistic and funnel plots, respectively. RESULTS: Meta-analysis of 3 studies (n = 210) on viral clearance assessed by RT-PCR showed no benefit (RR, 1.05; 95% CI, 0.79 to 1.38; p = 0.74), although with a moderate heterogeneity (I2 = 61.7%, p = 0.07). While meta-analysis of 3 studies (n = 474) showed a significant increase in death with HCQ, compared to the control (RR, 2.17; 95% 1.32 to 3.57; p = 0.002), without any heterogeneity (I2 = 0.0%, p = 0.43). CONCLUSIONS: No benefit on viral clearance but a significant increase in mortality was observed with HCQ compared to control in patients with COVID-19.", "qid": 28, "docid": "dapkxiyy", "rank": 46, "score": 0.9010319709777832}, {"content": "Title: Emergency Approval of Chloroquine and Hydroxychloroquine for Treatment of COVID-19. Content: The world is suffering a respiratory pandemic disease caused by a novel coronavirus (2019-nCoV), commonly known as COVID-19 (coronavirus disease 2019). The Food and Drug Administration issued an emergency authorization for chloroquine and hydroxychloroquine as experimental treatments for COVID-19 leading to a shortage of both medications. A literature review conducted in April 2020 shows a lack of high-quality data available, resulting in ambiguous guideline recommendations. Decisions to use either drug should be made with careful consideration of risks versus benefits along with proper monitoring. Because of its higher potency and better safety profile, hydroxychloroquine may be the more reasonable treatment option if treatment is initiated.", "qid": 28, "docid": "uzx5f0s4", "rank": 47, "score": 0.8996320962905884}, {"content": "Title: Emergency Authorization of Chloroquine and Hydroxychloroquine for Treatment of COVID-19 Content: The world is suffering a respiratory pandemic disease caused by a novel coronavirus (2019-nCoV), commonly known as COVID-19 (coronavirus disease 2019). The Food and Drug Administration issued an emergency authorization for chloroquine and hydroxychloroquine as experimental treatments for COVID-19 leading to a shortage of both medications. A literature review conducted in April 2020 shows a lack of high-quality data available, resulting in ambiguous guideline recommendations. Decisions to use either drug should be made with careful consideration of risks versus benefits along with proper monitoring. Because of its higher potency and better safety profile, hydroxychloroquine may be the more reasonable treatment option if treatment is initiated.", "qid": 28, "docid": "i3h4gflo", "rank": 48, "score": 0.8996320366859436}, {"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": 49, "score": 0.8995320796966553}, {"content": "Title: Therapeutic Application of Chloroquine in Clinical Trials for COVID-19 Content: The novel corona virus disease -2019 (COVID-19) pandemic has caused a massive global public health havoc. Recent clinical trials carried out in China has found a promising therapeutic application of chloroquine and hydroxychloroquine for COVID-19. This study meticulously evaluated the various dosages of chloroquine and hydroxychloroquine utilized in clinical trials registered in Chinese and US clinical trial registries for the treatment of pneumonia caused by SARS-CoV-2.", "qid": 28, "docid": "jc9ugexn", "rank": 50, "score": 0.8994982242584229}, {"content": "Title: COVID-19: a recommendation to examine the effect of hydroxychloroquine in preventing infection and progression ;Journal of Antimicrobial Chemotherapy ;Oxford Academic Content: A novel coronavirus disease (COVID-19), caused by infection with SARS-CoV-2, has swept across 31 provinces in China and over 40 countries worldwide The transition from first symptoms to acute respiratory distress syndrome (ARDS) is highly likely to be due to uncontrolled cytokine release There is an urgent need to identify safe and effective drugs for treatment Chloroquine (CQ) exhibits a promising inhibitory effect However, the clinical use of CQ can cause severe side effects We propose that hydroxychloroquine (HCQ), which exhibits an antiviral effect highly similar to that of CQ, could serve as a better therapeutic approach HCQ is likely to attenuate the severe progression of COVID-19, inhibiting the cytokine storm by suppressing T cell activation It has a safer clinical profile and is suitable for those who are pregnant It is cheaper and more readily available in China We herein strongly urge that clinical trials are performed to assess the preventive effects of HCQ in both disease infection and progression", "qid": 28, "docid": "42ywl8gp", "rank": 51, "score": 0.8994303941726685}, {"content": "Title: Therapeutic use of chloroquine and hydroxychloroquine in COVID-19 and other viral infections: A narrative review Content: Abstract The rapidly spreading Coronavirus Disease (COVID-19) pandemic, caused by the severe acute respiratory syndrome coronavirus (SARS-CoV-2), represents an unprecedented serious challenge to the global public health community. The extremely rapid international spread of the disease with significant morbidity and mortality made finding possible therapeutic interventions a global priority. While approved specific antiviral drugs against SARS-CoV-2 are still lacking, a large number of existing drugs are being explored as a possible treatment for COVID-19 infected patients. Recent publications have re-examined the use of Chloroquine (CQ) and/or Hydroxychloroquine (HCQ) as a potential therapeutic option for these patients. In an attempt to explore the evidence that supports their use in COVID-19 patients, we comprehensively reviewed the previous studies which used CQ or HCQ as an antiviral treatment. Both CQ and HCQ demonstrated promising in vitro results, however, such data have not yet been translated into meaningful in vivo studies. While few clinical trials have suggested some beneficial effects of CQ and HCQ in COVID-19 patients, most of the reported data are still preliminary. Given the current uncertainty, it is worth being mindful of the potential risks and strictly rational the use of these drugs in COVID-19 patients until further high quality randomized clinical trials are available to clarify their role in the treatment or prevention of COVID-19.", "qid": 28, "docid": "5yvjbr5q", "rank": 52, "score": 0.899208664894104}, {"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": 53, "score": 0.8991140723228455}, {"content": "Title: Psychiatric adverse events with hydrochloroquine during COVID-19 Pandemic Content: \u2022 Hydrochloroquine, well known in rheumatology, dermatology and tropical medicine is now considered in the treatment and prophylaxy for the SARS-CoVid19. \u2022 Mental and neurological manifestations should be assessed following the use of hydrochloroquine particularly following prophylactic use. \u2022 For acute malaria studies, hydroxychloroquine was associated with high prevalence of mental neurological manifestations amongst anti-malaria drugs. \u2022 Recommendations of using hydrochloroquine in COVID are variable and sometimes contradictory depending on agencies and countries.", "qid": 28, "docid": "242yq90p", "rank": 54, "score": 0.8984680771827698}, {"content": "Title: Perspectives on repositioning chloroquine and hydroxychloroquine for the treatment of Covid-19 Content: Coronavirus disease 2019 (COVID-19) is now spreading as a pandemic ravaging the whole world In the absence of a vaccine and an effective antiviral chemotherapy, there is currently an intense global interest in repositioning chloroquine (CQ) and its derivative hydroxychloroquine (HCQ) to combat the pandemic CQ has been used for decades for the treatment and prophylaxis against malaria in endemic countries It is readily available and has also been manufactured in these countries CQ is cheap, stable under field conditions and has been well tolerated as an antimalarial This experience could be adapted to deploy CQ or HCQ for prophylaxis or treatment of COVID19 if strong evidence could be generated for these uses We believe that well-designed drug trials should be initiated in malaria-endemic countries, taking into account the local context of the epidemic and the capacity of the health system in combating it In this paper, we are presenting the current status of evidence for using CQ and HCQ against COVID19", "qid": 28, "docid": "85g1tp38", "rank": 55, "score": 0.898327112197876}, {"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": 56, "score": 0.8982154130935669}, {"content": "Title: Hydroxychloroquine Versus COVID-19: A Rapid Systematic Review and Meta-Analysis Content: Background: Coronavirus Disease 2019 (COVID-19) has become a major global issue with rising the number of infected individuals and mortality in recent months. Among all therapeutic approaches, arguments have raised about hydroxychloroquine efficacy in treatment of COVID-19. We aimed to overcome the controversies regarding effectiveness of hydroxychloroquine in treatment of COVID-19, using a systematic review and meta-analysis. Methods: A systematic search was performed in PubMed, Scopus, Embase, Cochrane Library, Web of Science, Google Scholar and medRxiv pre-print database using all available MeSH terms for COVID-19 and hydroxychloroquine. Two authors selected and assessed the quality of studies independently using related checklists. Data have been extracted from included studies and analyzed using CMA v. 2.2.064. heterogeneity was also assessed using I-squared test. Results: Seven studies including four clinical trials and three observational studies have entered into the study. The results of meta-analysis of clinical trials showed that there were no significant differences between patients who received the standard treatment with HCQ regimen and the patients that received the standard treatment without HCQ (RR: 1.44, 95% CI, 0.80-2.59). CT-Scan findings improved in 59% (95% CI 0.15-0.92) and nasopharyngeal culture following RT-PCR resulted negative in 76% (95% CI 0.56-0.89) of patients received hydroxychloroquine. Meta-analysis of observational studies showed 75% (95% CI, 0.54-0.88) of patients were discharged from the hospital, 34% (95% CI, 0.07-0.14) admitted to intensive care unit and 1.5% (95% CI, 0.03-0.83) have expired. Conclusion: This study indicated no clinical benefits regarding HCQ for treatment of COVID-19 patients. However, further large clinical trials should be taken into account in order to achieve more reliable findings.", "qid": 28, "docid": "ujomta30", "rank": 57, "score": 0.8971152901649475}, {"content": "Title: COVID-19: a recommendation to examine the effect of hydroxychloroquine in preventing infection and progression Content: A novel coronavirus disease (COVID-19), caused by infection with SARS-CoV-2, has swept across 31 provinces in China and over 40 countries worldwide. The transition from first symptoms to acute respiratory distress syndrome (ARDS) is highly likely to be due to uncontrolled cytokine release. There is an urgent need to identify safe and effective drugs for treatment. Chloroquine (CQ) exhibits a promising inhibitory effect. However, the clinical use of CQ can cause severe side effects. We propose that hydroxychloroquine (HCQ), which exhibits an antiviral effect highly similar to that of CQ, could serve as a better therapeutic approach. HCQ is likely to attenuate the severe progression of COVID-19, inhibiting the cytokine storm by suppressing T cell activation. It has a safer clinical profile and is suitable for those who are pregnant. It is cheaper and more readily available in China. We herein strongly urge that clinical trials are performed to assess the preventive effects of HCQ in both disease infection and progression.", "qid": 28, "docid": "q4m4q6p0", "rank": 58, "score": 0.8970437049865723}, {"content": "Title: Hydroxychloroquine in COVID-19: A systematic review and meta-analysis Content: Abstract Background Hydroxychloroquine is being administered among patients with COVID19 infection in many healthcare systems across the world considering its in vitro effect against the SARS CoV 2 virus. In spite of several observational studies and a few randomized controlled trials, the effect of hydroxychloroquine on patients with COVID 19 infection remains unclear. We undertook this systematic review with meta-analysis to evaluate the efficacy and safety of hydroxychloroquine among patients with COVID 19 infection. Methods We searched PubMed, Embase, the Cochrane Library, Web of Science, medRxiv, and other relevant resources until May 13, 2020. We included randomized controlled trials and observational studies in which hydroxychloroquine was adminstered and compared to a control group. Data were extracted, and quality assessment of the studies was carried out. We evaluated symptomatic progression, mortality, viral clearance, the evolution of changes on chest CT imaging, and adverse events. A fixed or random-effects model was used depending on outcome heterogeneity. Results We included eleven studies including, three randomized controlled trials and eight observational studies. Among these, 2354 patients received hydroxychloroquine alone or in combination, while 1952 did not. Mortality was reported at different points of time. The overall mortality was not significantly different among patients who received hydroxychloroquine compared to the control group (OR: 1.41, 95% CI: 0.76 to 2.62; p = 0.28). Clinical worsening or lack of symptomatic improvement did not differ between patients who received hydroxychloroquine compared to those who did not (OR 1.1, 95% CI: 0.6 to 2.02; p = 0.76). Viral clearance, assessed by RT-PCR, did not differ significantly between the hydroxychloroquine and the control groups (OR: 1.13, CI: 0.26 to 5.01; p = 0.87). The evolution of changes on chest CT imaging was reported only in two studies; a more pronounced improvement was observed with the use of hydroxychloroquine compared to standard care (OR: 2.68, CI: 1.1 to 6.6; P = 0.03). The incidence of adverse events was significantly higher with hydroxychloroquine (OR: 4.1, CI: 1.42 to 11.88; p = 0.009). Conclusions Our meta-analysis does not suggest improvement in clinical progression, mortality, or viral clearance by RT PCR among patients with COVID 19 infection who are treated with hydroxychloroquine. There was a significantly higher incidence of adverse events with hydroxychloroquine use.", "qid": 28, "docid": "qxgpehuy", "rank": 59, "score": 0.8970392346382141}, {"content": "Title: COVID-19 in Patient with Sarcoidosis Receiving Long-Term Hydroxychloroquine Treatment, France, 2020 Content: Because of in vitro studies, hydroxychloroquine is under evaluation as a preexposure or postexposure prophylaxis for coronavirus disease (COVID-19) and as a possible COVID-19 curative treatment. We report a case of COVID-19 in a patient with sarcoidosis who was receiving long-term hydroxychloroquine treatment, despite adequate plasma concentrations.", "qid": 28, "docid": "d612wsh3", "rank": 60, "score": 0.8955975770950317}, {"content": "Title: COVID-19 in Patient with Sarcoidosis Receiving Long-Term Hydroxychloroquine Treatment, France, 2020. Content: Because of in vitro studies, hydroxychloroquine is under evaluation as a preexposure or postexposure prophylaxis for coronavirus disease (COVID-19) and as a possible COVID-19 curative treatment. We report a case of COVID-19 in a patient with sarcoidosis who was receiving long-term hydroxychloroquine treatment, despite adequate plasma concentrations.", "qid": 28, "docid": "5moean7z", "rank": 61, "score": 0.8955975770950317}, {"content": "Title: Advances in the use of chloroquine and hydroxychloroquine for the treatment of COVID-19 Content: Coronavirus Disease 2019 (COVID-19), caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), is spreading worldwide. Antiviral therapy is the most important treatment for COVID-19. Among the drugs under investigation, anti-malarials, chloroquine (CQ) and hydroxychloroquine (HCQ), are being repurposed as treatment for COVID-19. CQ/HCQ were shown to prevent receptor recognition by coronaviruses, inhibit endosome acidification, which interferes with membrane fusion, and exhibit immunomodulatory activity. These multiple mechanisms may work together to exert a therapeutic effect on COVID-19. A number of in vitro studies revealed inhibitory effects of CQ/HCQ on various coronaviruses, including SARS-CoV-2 although conflicting results exist. Several clinical studies showed that CQ/HCQ alone or in combination with a macrolide may alleviate the clinical symptoms of COVID-19, promote viral conversion, and delay disease progression, with less serious adverse effects. However, recent studies indicated that the use of CQ/HCQ, alone or in combination with a macrolide, did not show any favorable effect on patients with COVID-19. Adverse effects, including prolonged QT interval after taking CQ/HCQ, may develop in COVID-19 patients. Therefore, current data are not sufficient enough to support the use of CQ/HCQ as therapies for COVID-19 and increasing caution should be taken about the application of CQ/HCQ in COVID-19 before conclusive findings are obtained by well-designed, multi-center, randomized, controlled studies.", "qid": 28, "docid": "s5xgbzx1", "rank": 62, "score": 0.8953906893730164}, {"content": "Title: Advances in the use of chloroquine and hydroxychloroquine for the treatment of COVID-19. Content: Coronavirus Disease 2019 (COVID-19), caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), is spreading worldwide. Antiviral therapy is the most important treatment for COVID-19. Among the drugs under investigation, anti-malarials, chloroquine (CQ) and hydroxychloroquine (HCQ), are being repurposed as treatment for COVID-19. CQ/HCQ were shown to prevent receptor recognition by coronaviruses, inhibit endosome acidification, which interferes with membrane fusion, and exhibit immunomodulatory activity. These multiple mechanisms may work together to exert a therapeutic effect on COVID-19. A number of in vitro studies revealed inhibitory effects of CQ/HCQ on various coronaviruses, including SARS-CoV-2 although conflicting results exist. Several clinical studies showed that CQ/HCQ alone or in combination with a macrolide may alleviate the clinical symptoms of COVID-19, promote viral conversion, and delay disease progression, with less serious adverse effects. However, recent studies indicated that the use of CQ/HCQ, alone or in combination with a macrolide, did not show any favorable effect on patients with COVID-19. Adverse effects, including prolonged QT interval after taking CQ/HCQ, may develop in COVID-19 patients. Therefore, current data are not sufficient enough to support the use of CQ/HCQ as therapies for COVID-19 and increasing caution should be taken about the application of CQ/HCQ in COVID-19 before conclusive findings are obtained by well-designed, multi-center, randomized, controlled studies.", "qid": 28, "docid": "q8d7rvnj", "rank": 63, "score": 0.8953906893730164}, {"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": 64, "score": 0.8951289057731628}, {"content": "Title: Efficacy of hydroxychloroquine in patients with COVID-19: results of a randomized clinical trial Content: Aims: Studies have indicated that chloroquine (CQ) shows antagonism against COVID-19 in vitro. However, evidence regarding its effects in patients is limited. This study aims to evaluate the efficacy of hydroxychloroquine (HCQ) in the treatment of patients with COVID-19. Main methods: From February 4 to February 28, 2020, 62 patients suffering from COVID-19 were diagnosed and admitted to Renmin Hospital of Wuhan University. All participants were randomized in a parallel-group trial, 31 patients were assigned to receive an additional 5-day HCQ (400 mg/d) treatment, Time to clinical recovery (TTCR), clinical characteristics, and radiological results were assessed at baseline and 5 days after treatment to evaluate the effect of HCQ. Key findings: For the 62 COVID-19 patients, 46.8% (29 of 62) were male and 53.2% (33 of 62) were female, the mean age was 44.7 (15.3) years. No difference in the age and sex distribution between the control group and the HCQ group. But for TTCR, the body temperature recovery time and the cough remission time were significantly shortened in the HCQ treatment group. Besides, a larger proportion of patients with improved pneumonia in the HCQ treatment group (80.6%, 25 of 31) compared with the control group (54.8%, 17 of 31). Notably, all 4 patients progressed to severe illness that occurred in the control group. However, there were 2 patients with mild adverse reactions in the HCQ treatment group. Significance: Among patients with COVID-19, the use of HCQ could significantly shorten TTCR and promote the absorption of pneumonia.", "qid": 28, "docid": "q8l3ra55", "rank": 65, "score": 0.8943936228752136}, {"content": "Title: Hydroxychloroquine and Covid-19: A Cellular and Molecular Biology Based Update Content: As the time for finding a definitive and safe cure as a vaccine for novel Corona Virus Disease 2019 (Covid-19) is still far, there is need to study in depth about the other potential drugs, which can save millions of lives due to Covid-19 pandemic. Right at the center of the debate is the use of drug \u201cHydroxychloroquine\u201d as a prophylaxis as well as a treatment strategy against Covid-19 in conjunction with azithromycin. In this review, we will study the cellular and molecular aspects of hydroxychloroquine, which had driven its use in Covid-19 patients, as well as its chemistry and pharmacokinetics along with clinical trials going on worldwide using hydroxychloroquine against Covid-19. ELECTRONIC SUPPLEMENTARY MATERIAL: The online version of this article (10.1007/s12291-020-00900-x) contains supplementary material, which is available to authorized users.", "qid": 28, "docid": "0gozdv43", "rank": 66, "score": 0.8943831920623779}, {"content": "Title: A Rapid Systematic Review of Clinical Trials Utilizing Chloroquine and Hydroxychloroquine as a Treatment for COVID-19 Content: OBJECTIVES: The emergence of SARS-CoV-2 has presented clinicians with a difficult therapeutic dilemma. With supportive care as the current mainstay of treatment, the fatality rate of COVID-19 is 6.9%. There are currently several trials assessing the efficacy of different antivirals as treatment. Of these, chloroquine (CQ) and its derivative hydroxychloroquine (HCQ) have garnered the most attention. METHODS: In this study, the literature currently available on CQ and HCQ as treatment of COVID-19 was surveyed using EMBASE, PubMed, Cochrane Library, MedRxiv, and one clinical trial registry. Upon gathering published and preprint trials, risk of bias was assessed using Cochrane Risk of Bias Tool 2.0. RESULTS: There are currently seven completed clinical trials and 29 registered clinical trials focusing on HCQ or CQ as a therapeutic avenue for COVID-19. Of these, five of seven trials have shown favorable outcomes for patients using CQ or HCQ and two of seven have shown no change compared to control. However, all seven trials carried varying degrees of bias and poor study design. CONCLUSION: There are currently not enough data available to support the routine use of HCQ and CQ as therapies for COVID-19. Pending further results from more extensive studies with more stringent study parameters, clinicians should defer from routine use of HCQ and CQ. There are several clinical trials currently under way with results expected soon.", "qid": 28, "docid": "bfui91w7", "rank": 67, "score": 0.8942540884017944}, {"content": "Title: RETRACTED: Hydroxychloroquine or chloroquine with or without a macrolide for treatment of COVID-19: a multinational registry analysis Content: BACKGROUND: Hydroxychloroquine or chloroquine, often in combination with a second-generation macrolide, are being widely used for treatment of COVID-19, despite no conclusive evidence of their benefit. Although generally safe when used for approved indications such as autoimmune disease or malaria, the safety and benefit of these treatment regimens are poorly evaluated in COVID-19. METHODS: We did a multinational registry analysis of the use of hydroxychloroquine or chloroquine with or without a macrolide for treatment of COVID-19. The registry comprised data from 671 hospitals in six continents. We included patients hospitalised between Dec 20, 2019, and April 14, 2020, with a positive laboratory finding for SARS-CoV-2. Patients who received one of the treatments of interest within 48 h of diagnosis were included in one of four treatment groups (chloroquine alone, chloroquine with a macrolide, hydroxychloroquine alone, or hydroxychloroquine with a macrolide), and patients who received none of these treatments formed the control group. Patients for whom one of the treatments of interest was initiated more than 48 h after diagnosis or while they were on mechanical ventilation, as well as patients who received remdesivir, were excluded. The main outcomes of interest were in-hospital mortality and the occurrence of de-novo ventricular arrhythmias (non-sustained or sustained ventricular tachycardia or ventricular fibrillation). FINDINGS: 96\u00e2\u0080\u0088032 patients (mean age 53\u00b78 years, 46\u00b73% women) with COVID-19 were hospitalised during the study period and met the inclusion criteria. Of these, 14\u00e2\u0080\u0088888 patients were in the treatment groups (1868 received chloroquine, 3783 received chloroquine with a macrolide, 3016 received hydroxychloroquine, and 6221 received hydroxychloroquine with a macrolide) and 81\u00e2\u0080\u0088144 patients were in the control group. 10\u00e2\u0080\u0088698 (11\u00b71%) patients died in hospital. After controlling for multiple confounding factors (age, sex, race or ethnicity, body-mass index, underlying cardiovascular disease and its risk factors, diabetes, underlying lung disease, smoking, immunosuppressed condition, and baseline disease severity), when compared with mortality in the control group (9\u00b73%), hydroxychloroquine (18\u00b70%; hazard ratio 1\u00b7335, 95% CI 1\u00b7223-1\u00b7457), hydroxychloroquine with a macrolide (23\u00b78%; 1\u00b7447, 1\u00b7368-1\u00b7531), chloroquine (16\u00b74%; 1\u00b7365, 1\u00b7218-1\u00b7531), and chloroquine with a macrolide (22\u00b72%; 1\u00b7368, 1\u00b7273-1\u00b7469) were each independently associated with an increased risk of in-hospital mortality. Compared with the control group (0\u00b73%), hydroxychloroquine (6\u00b71%; 2\u00b7369, 1\u00b7935-2\u00b7900), hydroxychloroquine with a macrolide (8\u00b71%; 5\u00b7106, 4\u00b7106-5\u00b7983), chloroquine (4\u00b73%; 3\u00b7561, 2\u00b7760-4\u00b7596), and chloroquine with a macrolide (6\u00b75%; 4\u00b7011, 3\u00b7344-4\u00b7812) were independently associated with an increased risk of de-novo ventricular arrhythmia during hospitalisation. INTERPRETATION: We were unable to confirm a benefit of hydroxychloroquine or chloroquine, when used alone or with a macrolide, on in-hospital outcomes for COVID-19. Each of these drug regimens was associated with decreased in-hospital survival and an increased frequency of ventricular arrhythmias when used for treatment of COVID-19. FUNDING: William Harvey Distinguished Chair in Advanced Cardiovascular Medicine at Brigham and Women's Hospital.", "qid": 28, "docid": "pscfmt4l", "rank": 68, "score": 0.8940327167510986}, {"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": 28, "docid": "lb2ybn0b", "rank": 69, "score": 0.8939679265022278}, {"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": 70, "score": 0.893646240234375}, {"content": "Title: Challenges and cares to promote rational use of chloroquine and hydroxychloroquine in the management of coronavirus disease 2019 (COVID-19) pandemic: a timely review Content: As a result of the 2019 coronavirus disease pandemic (COVID-19), there has been an urgent worldwide demand for treatments. Due to factors such as history of prescription for other infectious diseases, availability, and relatively low cost, the use of chloroquine (CQ) and hydroxychloroquine (HCQ) has been tested in vivo and in vitro for the ability to inhibit the causative virus, severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). However, even though investigators noted the therapeutic potential of these drugs, it is important to consider the toxicological risks and necessary care for rational use of CQ and HCQ. This study provides information on the main toxicological and epidemiological aspects to be considered for prophylaxis or treatment of COVID-19 using CQ but mainly HCQ, which is a less toxic derivative than CQ, and was shown to produce better results in inhibiting proliferation of SARS-CoV-2 based upon preliminary tests.", "qid": 28, "docid": "msz9d6cr", "rank": 71, "score": 0.893574059009552}, {"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": 72, "score": 0.8935575485229492}, {"content": "Title: A Case of Breakthrough COVID-19 during Hydroxychloroquine Maintenance Content: There have been controversies on the prophylactic effect of hydroxychloroquine against severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2). We describe a patient, 60-year old Korean woman, with coronavirus disease 2019 (COVID-19) who had been taking hydroxychloroquine for 6 months. Her serum and saliva concentrations of hydroxychloroquine were 280 \u00b5g/L and 4,890 \u00b5g/L, respectively. The present case raises concerns on hydroxychloroquine's role as a prophylactic agent for COVID-19.", "qid": 28, "docid": "ne42raez", "rank": 73, "score": 0.8932015299797058}, {"content": "Title: Hydroxychloroquine or chloroquine with or without a macrolide for treatment of COVID-19: a multinational registry analysis Content: BACKGROUND: Hydroxychloroquine or chloroquine, often in combination with a second-generation macrolide, are being widely used for treatment of COVID-19, despite no conclusive evidence of their benefit. Although generally safe when used for approved indications such as autoimmune disease or malaria, the safety and benefit of these treatment regimens are poorly evaluated in COVID-19. METHODS: We did a multinational registry analysis of the use of hydroxychloroquine or chloroquine with or without a macrolide for treatment of COVID-19. The registry comprised data from 671 hospitals in six continents. We included patients hospitalised between Dec 20, 2019, and April 14, 2020, with a positive laboratory finding for SARS-CoV-2. Patients who received one of the treatments of interest within 48 h of diagnosis were included in one of four treatment groups (chloroquine alone, chloroquine with a macrolide, hydroxychloroquine alone, or hydroxychloroquine with a macrolide), and patients who received none of these treatments formed the control group. Patients for whom one of the treatments of interest was initiated more than 48 h after diagnosis or while they were on mechanical ventilation, as well as patients who received remdesivir, were excluded. The main outcomes of interest were in-hospital mortality and the occurrence of de-novo ventricular arrhythmias (non-sustained or sustained ventricular tachycardia or ventricular fibrillation). FINDINGS: 96 032 patients (mean age 53\u00b78 years, 46\u00b73% women) with COVID-19 were hospitalised during the study period and met the inclusion criteria. Of these, 14 888 patients were in the treatment groups (1868 received chloroquine, 3783 received chloroquine with a macrolide, 3016 received hydroxychloroquine, and 6221 received hydroxychloroquine with a macrolide) and 81 144 patients were in the control group. 10 698 (11\u00b71%) patients died in hospital. After controlling for multiple confounding factors (age, sex, race or ethnicity, body-mass index, underlying cardiovascular disease and its risk factors, diabetes, underlying lung disease, smoking, immunosuppressed condition, and baseline disease severity), when compared with mortality in the control group (9\u00b73%), hydroxychloroquine (18\u00b70%; hazard ratio 1\u00b7335, 95% CI 1\u00b7223\u20131\u00b7457), hydroxychloroquine with a macrolide (23\u00b78%; 1\u00b7447, 1\u00b7368\u20131\u00b7531), chloroquine (16\u00b74%; 1\u00b7365, 1\u00b7218\u20131\u00b7531), and chloroquine with a macrolide (22\u00b72%; 1\u00b7368, 1\u00b7273\u20131\u00b7469) were each independently associated with an increased risk of in-hospital mortality. Compared with the control group (0\u00b73%), hydroxychloroquine (6\u00b71%; 2\u00b7369, 1\u00b7935\u20132\u00b7900), hydroxychloroquine with a macrolide (8\u00b71%; 5\u00b7106, 4\u00b7106\u20135\u00b7983), chloroquine (4\u00b73%; 3\u00b7561, 2\u00b7760\u20134\u00b7596), and chloroquine with a macrolide (6\u00b75%; 4\u00b7011, 3\u00b7344\u20134\u00b7812) were independently associated with an increased risk of de-novo ventricular arrhythmia during hospitalisation. INTERPRETATION: We were unable to confirm a benefit of hydroxychloroquine or chloroquine, when used alone or with a macrolide, on in-hospital outcomes for COVID-19. Each of these drug regimens was associated with decreased in-hospital survival and an increased frequency of ventricular arrhythmias when used for treatment of COVID-19. FUNDING: William Harvey Distinguished Chair in Advanced Cardiovascular Medicine at Brigham and Women's Hospital.", "qid": 28, "docid": "jisznsr3", "rank": 74, "score": 0.8929377794265747}, {"content": "Title: Hydroxychloroquine Proves Ineffective in Hamsters and Macaques Infected with SARS-CoV-2 Content: We remain largely without effective prophylactic/therapeutic interventions for COVID-19. Although many human clinical trials are ongoing, there remains a deficiency of supportive preclinical drug efficacy studies. Here we assessed the prophylactic/therapeutic efficacy of hydroxychloroquine (HCQ), a drug of interest for COVID-19 management, in two animal models. When used for prophylaxis or treatment neither the standard human malaria dose (6.5 mg/kg) nor a high dose (50 mg/kg) of HCQ had any beneficial effect on clinical disease or SARS-CoV-2 kinetics (replication/shedding) in the Syrian hamster disease model. Similarly, HCQ prophylaxis/treatment (6.5 mg/kg) did not significantly benefit clinical outcome nor reduce SARS-CoV-2 replication/shedding in the upper and lower respiratory tract in the rhesus macaque disease model. In conclusion, our preclinical animal studies do not support the use of HCQ in prophylaxis/treatment of COVID-19.", "qid": 28, "docid": "y5cbp2yz", "rank": 75, "score": 0.892903208732605}, {"content": "Title: A Randomized Trial of Hydroxychloroquine as Postexposure Prophylaxis for Covid-19 Content: BACKGROUND: Coronavirus disease 2019 (Covid-19) occurs after exposure to severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). For persons who are exposed, the standard of care is observation and quarantine. Whether hydroxychloroquine can prevent symptomatic infection after SARS-CoV-2 exposure is unknown. METHODS: We conducted a randomized, double-blind, placebo-controlled trial across the United States and parts of Canada testing hydroxychloroquine as postexposure prophylaxis. We enrolled adults who had household or occupational exposure to someone with confirmed Covid-19 at a distance of less than 6 ft for more than 10 minutes while wearing neither a face mask nor an eye shield (high-risk exposure) or while wearing a face mask but no eye shield (moderate-risk exposure). Within 4 days after exposure, we randomly assigned participants to receive either placebo or hydroxychloroquine (800 mg once, followed by 600 mg in 6 to 8 hours, then 600 mg daily for 4 additional days). The primary outcome was the incidence of either laboratory-confirmed Covid-19 or illness compatible with Covid-19 within 14 days. RESULTS: We enrolled 821 asymptomatic participants. Overall, 87.6% of the participants (719 of 821) reported a high-risk exposure to a confirmed Covid-19 contact. The incidence of new illness compatible with Covid-19 did not differ significantly between participants receiving hydroxychloroquine (49 of 414 [11.8%]) and those receiving placebo (58 of 407 [14.3%]); the absolute difference was -2.4 percentage points (95% confidence interval, -7.0 to 2.2; P = 0.35). Side effects were more common with hydroxychloroquine than with placebo (40.1% vs. 16.8%), but no serious adverse reactions were reported. CONCLUSIONS: After high-risk or moderate-risk exposure to Covid-19, hydroxychloroquine did not prevent illness compatible with Covid-19 or confirmed infection when used as postexposure prophylaxis within 4 days after exposure. (Funded by David Baszucki and Jan Ellison Baszucki and others; ClinicalTrials.gov number, NCT04308668.).", "qid": 28, "docid": "ian35wkd", "rank": 76, "score": 0.8922662734985352}, {"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": 77, "score": 0.8921077251434326}, {"content": "Title: A Randomized Trial of Hydroxychloroquine as Postexposure Prophylaxis for Covid-19 Content: BACKGROUND: Coronavirus disease 2019 (Covid-19) occurs after exposure to severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). For persons who are exposed, the standard of care is observation and quarantine. Whether hydroxychloroquine can prevent symptomatic infection after SARS-CoV-2 exposure is unknown. METHODS: We conducted a randomized, double-blind, placebo-controlled trial across the United States and parts of Canada testing hydroxychloroquine as postexposure prophylaxis. We enrolled adults who had household or occupational exposure to someone with confirmed Covid-19 at a distance of less than 6 ft for more than 10 minutes while wearing neither a face mask nor an eye shield (high-risk exposure) or while wearing a face mask but no eye shield (moderate-risk exposure). Within 4 days after exposure, we randomly assigned participants to receive either placebo or hydroxychloroquine (800 mg once, followed by 600 mg in 6 to 8 hours, then 600 mg daily for 4 additional days). The primary outcome was the incidence of either laboratory-confirmed Covid-19 or illness compatible with Covid-19 within 14 days. RESULTS: We enrolled 821 asymptomatic participants. Overall, 87.6% of the participants (719 of 821) reported a high-risk exposure to a confirmed Covid-19 contact. The incidence of new illness compatible with Covid-19 did not differ significantly between participants receiving hydroxychloroquine (49 of 414 [11.8%]) and those receiving placebo (58 of 407 [14.3%]); the absolute difference was \u22122.4 percentage points (95% confidence interval, \u22127.0 to 2.2; P=0.35). Side effects were more common with hydroxychloroquine than with placebo (40.1% vs. 16.8%), but no serious adverse reactions were reported. CONCLUSIONS: After high-risk or moderate-risk exposure to Covid-19, hydroxychloroquine did not prevent illness compatible with Covid-19 or confirmed infection when used as postexposure prophylaxis within 4 days after exposure. (Funded by David Baszucki and Jan Ellison Baszucki and others; ClinicalTrials.gov number, NCT04308668.)", "qid": 28, "docid": "wk61uyrt", "rank": 78, "score": 0.892004132270813}, {"content": "Title: Hydroxychloroquine (HCQ): an observational cohort study in primary and secondary prevention of pneumonia in an at-risk population Content: Background. Recent studies suggest that hydroxychloroquine (HCQ) could be effective against COVID-19. It is reasonable to expect that if HCQ can prevent or reduce the adverse effects of influenza, it may also reduce the effects of COVID-19 in humans. The objective of this study was to test whether HCQ can prevent or reduce the risk and severity of influenza. Methods. This is an observational cohort study using medico-administrative data from Quebec. Patients included had at least one emergency department (ED) visit in 2012 or 2013, with a prior diagnosis of chronic conditions, and were admissible to the public drug insurance plan. Two sub-cohorts were considered depending on reasons for ED visit: other than influenza or pneumonia (primary prevention) and influenza or pneumonia (secondary prevention). Results. In the primary prevention analysis (n=417,353), patients taking HCQ (n=3,659) had an increased risk of hospitalization for pneumonia in the following year compared to those who did not (5.2% vs. 2.9%; adjusted OR=1.25, p=0.0079). In the secondary prevention analysis (n=27,152), patients taking HCQ (n=392), compared to those who did not had a modest and non-significant increased risk of hospitalization for pneumonia after 30 days (25.8% vs. 22.6%; adjusted OR=1.14, p=0.3177). Interpretation: Based on the assumption that HCQ has similar effects on the COVID-19 as those observed on influenza, we can infer that it will not have positive effects on COVID-19. We should therefore act cautiously before initiating prospective interventional studies on the use of HCQ to reduce adverse effects of COVID-19.", "qid": 28, "docid": "8orcmz32", "rank": 79, "score": 0.8918213844299316}, {"content": "Title: Are hydroxychloroquine and chloroquine effective in the treatment of SARS-COV-2 (COVID-19)? Content: Data sources The authors of this rapid review did not disclose which electronic databases were included in their literature search. The inclusion and exclusion criteria for the data sources are not reported in the manuscript. Study selection The authors included six studies on the effectiveness of hydroxychloroquine or chloroquine for the prevention and treatment of COVID-19 in humans. Studies comprised of two randomised controlled trials, two non-randomised trials both of which were non-blinded and open-label and one that was uncontrolled, a prospective cohort study and an interim report. The authors did not report details of any studies that were excluded. Data extraction and synthesis The data extraction methodology was not reported and it is unclear if the Preferred Reporting Items for Systematic Review and Meta-Analysis (PRISMA) guidelines were followed. Treatment regimens and the study outcomes were extracted where available and overall findings were presented in a table. There were no comparable outcome measures; therefore, results were deemed unsuitable to combine and no statistical analyses were carried out. A narrative synthesis of each study is presented. Results The results of the studies in this rapid review are difficult to quantify as each study had different outcome parameters. Due to the heterogeneity of the studies, results were not combined, and no statistical analysis was carried out. Narrative synthesis of each of the included studies identified important and significant limitations, precluding the studies from demonstrating a statistically significant difference in outcomes. Conclusions This review highlights the urgent need for more high quality evidence on the use of hydroxychloroquine and chloroquine in the prevention and treatment of COVID-19. The results of the studies included should be interpreted with caution due to the weak supporting data and numerous methodological limitations. The authors suggested that the studies be viewed as hypothesis-generating and should not be used in decision making around the recommendations and guidelines in the prevention and treatment of COVID-19. There are currently several ongoing randomised controlled trials looking at the effectiveness and efficacy of these drugs on COVID-19. It is hoped the outcome of these studies can help guide future recommendations and national guidelines.", "qid": 28, "docid": "vn7nvsse", "rank": 80, "score": 0.8910872936248779}, {"content": "Title: Are hydroxychloroquine and chloroquine effective in the treatment of SARS-COV-2 (COVID-19)? Content: Data sources The authors of this rapid review did not disclose which electronic databases were included in their literature search. The inclusion and exclusion criteria for the data sources are not reported in the manuscript.Study selection The authors included six studies on the effectiveness of hydroxychloroquine or chloroquine for the prevention and treatment of COVID-19 in humans. Studies comprised of two randomised controlled trials, two non-randomised trials both of which were non-blinded and open-label and one that was uncontrolled, a prospective cohort study and an interim report. The authors did not report details of any studies that were excluded.Data extraction and synthesis The data extraction methodology was not reported and it is unclear if the Preferred Reporting Items for Systematic Review and Meta-Analysis (PRISMA) guidelines were followed. Treatment regimens and the study outcomes were extracted where available and overall findings were presented in a table. There were no comparable outcome measures; therefore, results were deemed unsuitable to combine and no statistical analyses were carried out. A narrative synthesis of each study is presented.Results The results of the studies in this rapid review are difficult to quantify as each study had different outcome parameters. Due to the heterogeneity of the studies, results were not combined, and no statistical analysis was carried out. Narrative synthesis of each of the included studies identified important and significant limitations, precluding the studies from demonstrating a statistically significant difference in outcomes.Conclusions This review highlights the urgent need for more high quality evidence on the use of hydroxychloroquine and chloroquine in the prevention and treatment of COVID-19. The results of the studies included should be interpreted with caution due to the weak supporting data and numerous methodological limitations. The authors suggested that the studies be viewed as hypothesis-generating and should not be used in decision making around the recommendations and guidelines in the prevention and treatment of COVID-19. There are currently several ongoing randomised controlled trials looking at the effectiveness and efficacy of these drugs on COVID-19. It is hoped the outcome of these studies can help guide future recommendations and national guidelines.", "qid": 28, "docid": "znv6yru8", "rank": 81, "score": 0.8910872936248779}, {"content": "Title: A systematic review on the efficacy and safety of chloroquine for the treatment of COVID-19 Content: PURPOSE: COVID-19 (coronavirus disease 2019) is a public health emergency of international concern. As of this time, there is no known effective pharmaceutical treatment, although it is much needed for patient contracting the severe form of the disease. The aim of this systematic review was to summarize the evidence regarding chloroquine for the treatment of COVID-19. METHODS: PubMed, EMBASE, and three trial Registries were searched for studies on the use of chloroquine in patients with COVID-19. RESULTS: We included six articles (one narrative letter, one in-vitro study, one editorial, expert consensus paper, two national guideline documents) and 23 ongoing clinical trials in China. Chloroquine seems to be effective in limiting the replication of SARS-CoV-2 (virus causing COVID-19) in vitro. CONCLUSIONS: There is rationale, pre-clinical evidence of effectiveness and evidence of safety from long-time clinical use for other indications to justify clinical research on chloroquine in patients with COVID-19. However, clinical use should either adhere to the Monitored Emergency Use of Unregistered Interventions (MEURI) framework or be ethically approved as a trial as stated by the World Health Organization. Safety data and data from high-quality clinical trials are urgently needed.", "qid": 28, "docid": "m7sawt31", "rank": 82, "score": 0.8907085657119751}, {"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": 83, "score": 0.8904855251312256}, {"content": "Title: Chloroquine and hydroxychloroquine in the treatment of COVID-19 with or without diabetes: A systematic search and a narrative review with a special reference to India and other developing countries Content: BACKGROUND AND AIMS: No drugs are currently approved for Coronavirus Disease-2019 (COVID-19), although some have been tried. In view of recent studies and discussion on chloroquine and hydroxychloroquine (HCQ), we aimed to review existing literature and relevant websites regarding these drugs and COVID-19, adverse effects related to drugs, and related guidelines. AIMS AND METHODS: We systematically searched the PubMed database up till March 21, 2020 and retrieved all the articles published on chloroquine and HCQ and COVID-19. RESULTS: Two small human studies have been conducted with both these drugs in COVID-19, and have shown significant improvement in some parameters in patients with COVID-19. CONCLUSION: Considering minimal risk upon use, a long experience of use in other diseases, cost-effectiveness and easy availability across India, we propose that both these drugs are worthy of fast track clinical trial for treatment, and may be carefully considered for clinical use as experimental drugs. Since HCQ has been approved for treatment of diabetes in India, it should be further researched in diabetes and COVID-19, a subgroup where significant mortality has been shown.", "qid": 28, "docid": "mn52exdm", "rank": 84, "score": 0.8903613686561584}, {"content": "Title: Swinging the pendulum: lessons learned from public discourse concerning hydroxychloroquine and COVID-19 Content: INTRODUCTION: Several months into the COVID-19 pandemic, safe and effective treatments against this global health disaster have yet to be identified. Clinical research trials around the world are underway testing a wide array of possible medications. In particular, the off-label use of hydroxychloroquine for COVID-19 prophylaxis and treatment has created many unprecedented challenges for the scientific community and the public. AREAS COVERED: We critically assessed major events from February - May 2020 that contributed to widespread use of hydroxychloroquine for the treatment and prophylaxis of COVID-19. We aimed to explore how opinions towards hydroxychloroquine may shift from early enthusiasm (based on in vitro and preliminary clinical data) to the hope for a miracle cure (through communication and promotion of questionable results) and, finally, to a rise of skepticism as more in-depth analyses are emerging. EXPERT OPINION: Mindful and rigorous acquisition of data, as well as its interpretation, are essential to an effective pandemic response. The rapid and premature promotion of results has had major implications for global crisis management, even creating distrust among the public. It is crucial for the medical and scientific community to incorporate the lessons learned from this situation.", "qid": 28, "docid": "salxq8ir", "rank": 85, "score": 0.8900045156478882}, {"content": "Title: Hydroxychloroquine and covid-19 Content: Hydroxychloroquine and chloroquine are medications that have been used for a long time. Their most common use is for the treatment and prophylaxis of malaria. However, these antimalarial drugs are known to also have anti-inflammatory and antiviral effects and are used for several chronic diseases such as systemic lupus erythematosus with low adverse effects. The antiviral action of hydroxychloroquine and chloroquine has been a point of interest to different researchers due to its mechanism of action. Several in vitro studies have proven their effectiveness on severe acute respiratory syndrome virus and currently both in vitro and in vivo studies have been conducted on 2019 novel coronavirus (covid-19). The purpose of this article is to review the history and mechanism of actions of these drugs and the potential use they can have on the current covid-19 pandemic.", "qid": 28, "docid": "fg2yt2o0", "rank": 86, "score": 0.889909565448761}, {"content": "Title: Hydroxychloroquine and covid-19. Content: Hydroxychloroquine and chloroquine are medications that have been used for a long time. Their most common use is for the treatment and prophylaxis of malaria. However, these antimalarial drugs are known to also have anti-inflammatory and antiviral effects and are used for several chronic diseases such as systemic lupus erythematosus with low adverse effects. The antiviral action of hydroxychloroquine and chloroquine has been a point of interest to different researchers due to its mechanism of action. Several in vitro studies have proven their effectiveness on severe acute respiratory syndrome virus and currently both in vitro and in vivo studies have been conducted on 2019 novel coronavirus (covid-19). The purpose of this article is to review the history and mechanism of actions of these drugs and the potential use they can have on the current covid-19 pandemic.", "qid": 28, "docid": "qv2wup1o", "rank": 87, "score": 0.889909565448761}, {"content": "Title: Chloroquine and hydroxychloroquine in the context of COVID-19 Content: Chloroquine and closely related structural analogs, employed initially for the treatment of malaria, are now gaining worldwide attention due to the rapidly spreading pandemic caused by severe acute respiratory syndrome-coronavirus-2, named coronavirus disease (COVID) of 2019 (COVID-19). Although much of this attention has a mechanistic basis, the hard efficacy data for chloroquine/hydroxychloroquine in the management of the clinical syndrome of COVID-19 have been limited thus far. This review aims to present the available in vitro and clinical data for the role of chloroquine/hydroxychloroquine in COVID-19 and attempts to put them into perspective, especially in relation to the different risks/benefits particular to each patient who may require treatment.", "qid": 28, "docid": "tkqmu1va", "rank": 88, "score": 0.8894716501235962}, {"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": 89, "score": 0.889313280582428}, {"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": 90, "score": 0.8888293504714966}, {"content": "Title: A Multicenter, randomized, open-label, controlled trial to evaluate the efficacy and tolerability of hydroxychloroquine and a retrospective study in adult patients with mild to moderate Coronavirus disease 2019 (COVID-19) Content: Objective In this study, we evaluated the efficacy of hydroxychloroquine (HCQ) against coronavirus disease 2019 (COVID-19) via a randomized controlled trial (RCT) and a retrospective study. Methods Subjects admitted to 11 designated public hospitals in Taiwan between April 1 and May 31, 2020, with COVID-19 diagnosis confirmed by pharyngeal real-time RT-PCR for SARS-CoV-2, were randomized at a 2:1 ratio and stratified by mild or moderate illness. HCQ 400 mg twice for 1 d and HCQ 200 mg twice daily for 6 days were administered. Both study group and controlled group received standard of care (SOC). Pharyngeal swabs and sputum were collected every other day. The proportion and time to negative viral PCR were assessed on day 14. In the retrospective study, medical records were reviewed for patients admitted before March 31, 2020. Results There were 33 and 37 cases in the RCT and retrospective study, respectively. In the RCT, the median times to negative rRT-PCR from randomization to hospital day 14 were 5 days (95% CI; 1-9 days) and 10 days (95% CI; 2-12 days) for the HCQ and SOC groups, respectively (p = 0.40). On day 14, 81.0% (17/21) and 75.0% (9/12) of the subjects in the HCQ and SOC groups, respectively, had undetected virus (p = 0.36). In the retrospective study, 12 (42.9%) in the HCQ group and 5 (55.6%) in the control group had negative rRT-PCR results on hospital day 14 (p = 0.70). Conclusions Neither study demonstrated that HCQ shortened viral shedding in mild to moderate COVID-19 subjects.", "qid": 28, "docid": "9yql0qbr", "rank": 91, "score": 0.8886497616767883}, {"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": 92, "score": 0.8881958723068237}, {"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": 93, "score": 0.8879362344741821}, {"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": 28, "docid": "1q9bhwpb", "rank": 94, "score": 0.8874778747558594}, {"content": "Title: A systematic review of the prophylactic role of chloroquine and hydroxychloroquine in coronavirus disease-19 (COVID-19) Content: OBJECTIVE: The pandemic coronavirus disease-19 (COVID-19) has pushed the global healthcare system to a crisis and amounted to a huge economic burden. Different drugs for prophylaxis against COVID-19 including chloroquine (CQ) or hydroxychloroquine (HCQ) have been tried. This study was performed to systematically review the role of CQ and HCQ in preventing the spread of COVID-19. METHODS: PubMed, EMBASE, ClinicalTrials.gov, International Clinical Trials Registry Platform and Cochrane Library databases were searched for studies that evaluated the prophylactic role of CQ or HCQ on SARS-CoV-2 (pre-clinical studies) or COVID-19 (clinical studies) until 30 March 2020. The available literature was critically appraised. RESULTS: A total of 45 articles were screened and 5 (3 in vitro pre-clinical studies and 2 clinical opinions) were included. The pre-clinical studies showed the prophylactic effects of CQ and HCQ against SARS-CoV-2. On the other hand, the clinical opinions advocated the prophylactic use of CQ and HCQ against COVID-19. However, no original clinical studies on the prophylactic role of CQ or HCQ on COVID-19 were available. CONCLUSION: Although pre-clinical results are promising, to date there is a dearth of evidence to support the efficacy of CQ or HCQ in preventing COVID-19. Considering potential safety issues and the likelihood of imparting a false sense of security, prophylaxis with CQ or HCQ against COVID-19 needs to be thoroughly evaluated in observational studies or high-quality randomized controlled studies.", "qid": 28, "docid": "6rnko6tl", "rank": 95, "score": 0.8873504996299744}, {"content": "Title: Review on the clinical pharmacology of hydroxychloroquine sulfate for the treatment of COVID-19 Content: BACKGROUND: As the number of severe acute respiratory syndrome coronavirus 2 (SARS-COV-2) infected people is skyrocketing worldwide, the international medical situation becomes very serious. Potential therapeutic drugs, vaccine and stem cell replacement methods are emerging, it is urgent to find specific therapeutic drugs and the best treatment regimens. After the publication of hydroxychloroquine (HCQ) with anti-SARS-COV-2 activity in vitro, a small, non-randomized, open-label clinical trial showed that HCQ treatment was significantly associated with reduced viral load in patients with coronavirus disease-19 (COVID-19). Meanwhile, a large prophylaxis study of HCQ sulfate for COVID-19 has been initiated in the United States. HCQ offered a promising efficacy in the treatment of COVID-19, but the optimal administration is still being explored. METHODS: Use the keyword 'Hydroxychloroquine' to conduct a literature search in PubMed to collect relevant literature on the mechanism of action of HCQ, clinical efficacy and safety, pharmacokinetic characteristics, precautions for clinical use and drug interactions, and extract and organize information. RESULTS: This paper reviews the mechanism, clinical efficacy and safety, pharmacokinetic characteristics, exposure-response relationship and precautions and drug interactions of HCQ, and summarized dosage recommendations for HCQ sulfate. CONCLUSION: It has been proved that HCQ, which has an established safety profile, is effective against SARS-CoV-2 with sufficient pre-clinical rationale and evidence. Data from high-quality clinical trials are urgently needed worldwide.", "qid": 28, "docid": "u2zu2oet", "rank": 96, "score": 0.8873163461685181}, {"content": "Title: Efficacy, safety and cost\u2010effectiveness of hydroxychloroquine in children with COVID\u201019: A call for evidence Content: The novel severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) pandemic poses a serious threat to public health and local economies around the globe. This has created an urgent need to identify effective medications for its prevention and treatment (1). Among these treatments, the off-label use of hydroxychloroquine (HCQ), a less toxic derivate of chloroquine, has become a common practice among clinicians, including pediatricians, despite lack of evidence of its clinical efficacy for this indication (especially for pediatric patients) at present time (2).", "qid": 28, "docid": "tovty20e", "rank": 97, "score": 0.887295126914978}, {"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": 28, "docid": "k96byjze", "rank": 98, "score": 0.8871276378631592}, {"content": "Title: SARS-CoV-2 infection in a patient on chronic hydroxychloroquine therapy: Implications for prophylaxis Content: People exposed to COVID-19 have a risk of developing disease, and health care workers are at risk at a time when they are badly needed during a health care crisis. Hydroxychloroquine and chloroquine have been used as treatment and are being considered as prophylaxis. Our patient developed COVID-19 while on hydroxychloroquine and although more work is needed, this calls into question the role of these medications as preventive therapy.", "qid": 28, "docid": "i3xukl9g", "rank": 99, "score": 0.8870055079460144}, {"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": 100, "score": 0.8865256905555725}]}
{"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: 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": 1, "score": 0.8973001837730408}, {"content": "Title: Tackling SARS-CoV-2: proposed targets and repurposed drugs Content: The SARS-CoV-2 pandemic, declared as a global health emergency by the WHO in February 2020, has currently infected more than 6 million people with fatalities near 371,000 and increasing exponentially, in absence of vaccines and drugs. The pathogenesis of SARS-CoV-2 is still being elucidated. Identifying potential targets and repurposing drugs as therapeutic options is the need of the hour. In this review, we focus on potential druggable targets and suitable therapeutics, currently being explored in clinical trials, to treat SARS-CoV-2 infection. A brief understanding of the complex interactions of both viral as well as host targets, and the possible repurposed drug candidates are described with an emphasis on understanding the mechanisms at the molecular level.", "qid": 29, "docid": "4tis2he4", "rank": 2, "score": 0.890993595123291}, {"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": 3, "score": 0.8905619382858276}, {"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": 4, "score": 0.8876572251319885}, {"content": "Title: Analysis of therapeutic targets for SARS-CoV-2 and discovery of potential drugs by computational methods Content: SARS-CoV-2 has caused tens of thousands of infections and more than one thousand deaths. There are currently no registered therapies for treating coronavirus infections. Because of time consuming process of new drug development, drug repositioning may be the only solution to the epidemic of sudden infectious diseases. We systematically analyzed all the proteins encoded by SARS-CoV-2 genes, compared them with proteins from other coronaviruses, predicted their structures, and built 19 structures that could be done by homology modeling. By performing target-based virtual ligand screening, a total of 21 targets (including two human targets) were screened against compound libraries including ZINC drug database and our own database of natural products. Structure and screening results of important targets such as 3-chymotrypsin-like protease (3CLpro), Spike, RNA-dependent RNA polymerase (RdRp), and papain like protease (PLpro) were discussed in detail. In addition, a database of 78 commonly used anti-viral drugs including those currently on the market and undergoing clinical trials for SARS-CoV-2 was constructed. Possible targets of these compounds and potential drugs acting on a certain target were predicted. This study will provide new lead compounds and targets for further in vitro and in vivo studies of SARS-CoV-2, new insights for those drugs currently ongoing clinical studies, and also possible new strategies for drug repositioning to treat SARS-CoV-2 infections.", "qid": 29, "docid": "i1lyno9g", "rank": 5, "score": 0.883185863494873}, {"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": 6, "score": 0.8804050087928772}, {"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": 7, "score": 0.8773729801177979}, {"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": 8, "score": 0.8762173652648926}, {"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": 0.874543309211731}, {"content": "Title: Homology Modeling of TMPRSS2 Yields Candidate Drugs That May Inhibit Entry of SARS-CoV-2 into Human Cells. Content: The most rapid path to discovering treatment options for the novel coronavirus SARS-CoV-2 is to find existing medications that are active against the virus. We have focused on identifying repurposing candidates for the transmembrane serine protease family member II (TMPRSS2), which is critical for entry of coronaviruses into cells. Using known 3D structures of close homologs, we created seven homology models. We also identified a set of serine protease inhibitor drugs, generated several conformations of each, and docked them into our models. We used three known chemical (non-drug) inhibitors and one validated inhibitor of TMPRSS2 in MERS as benchmark compounds and found six compounds with predicted high binding affinity in the range of the known inhibitors. We also showed that a previously published weak inhibitor, Camostat, had a significantly lower binding score than our six compounds. All six compounds are anticoagulants with significant and potentially dangerous clinical effects and side effects. Nonetheless, if these compounds significantly inhibit SARS-CoV-2 infection, they could represent a potentially useful clinical tool.", "qid": 29, "docid": "97l3r5tv", "rank": 10, "score": 0.8713416457176208}, {"content": "Title: The SARS-CoV-2 main protease as drug target Content: The unprecedented pandemic of the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) is threatening global health. The virus emerged in late 2019 and can cause a severe disease associated with significant mortality. Several vaccine development and drug discovery campaigns are underway. The SARS-CoV-2 main protease is considered a promising drug target, as it is dissimilar to human proteases. Sequence and structure of the main protease are closely related to those from other betacoronaviruses, facilitating drug discovery attempts based on previous lead compounds. Covalently binding peptidomimetics and small molecules are investigated. Various compounds show antiviral activity in infected human cells.", "qid": 29, "docid": "f8aolprb", "rank": 11, "score": 0.8706220388412476}, {"content": "Title: Perspectives on the development of neutralizing antibodies against SARS-CoV-2 Content: SARS-CoV-2 gains entry to human cells through its spike (S) protein binding to angiotensin-converting enzyme 2 (ACE2). Therefore, the receptor binding domain (RBD) of the S protein is the primary target for neutralizing antibodies. Selection of broad-neutralizing antibodies against SARS-CoV-2 and SARS-CoV is attractive and might be useful for treating not only COVID-19 but also future SARS-related CoV infections. Broad-neutralizing antibodies, such as 47D11, S309, and VHH-72, have been reported to target a conserved region in the RBD of the S1 subunit. The S2 subunit required for viral membrane fusion might be another target. Due to their small size and high stability, single-domain antibodies might have the ability to be administered by an inhaler making them potentially attractive therapeutics for respiratory infections. A cocktail strategy combining two (or more) antibodies that recognize different parts of the viral surface that interact with human cells might be the most effective.", "qid": 29, "docid": "tj4m01s4", "rank": 12, "score": 0.8699454069137573}, {"content": "Title: Hypothetical targets and plausible drugs of Coronavirus infection caused by SARS-CoV-2. Content: The world is confronting a dire situation due to the recent pandemic of the novel coronavirus disease (SARS-CoV-2) with the mortality rate passed over 470,000. Attaining efficient drugs evolve in parallel to the understanding of the SARS-CoV-2 pathogenesis. The current drugs in the pipeline and some plausible drugs are overviewed in this paper. Although different types of antiviral targets are applicable for SARS-CoV-2 drug screenings, the more promising targets can be considered as 3C-like main protease (3CL protease) and RNA polymerase. The remdesivir could be considered the closest bifunctional drug to the provisional clinical administration for SARS-CoV-2. The known molecular targets of the SARS-CoV-2 include fourteen targets while four molecules of angiotensin-converting enzyme 2 (ACE2), cathepsin L, 3CL protease and RNA-dependent RNA polymerase (RdRp) are suggested as more promising potential targets. Accordingly, dual-acting drugs as an encouraging solution in drug discovery are suggested. Emphasizing the potential route of SARS-CoV-2 infection and virus entry related factors like integrins, cathepsin and ACE2 seems valuable. The potential molecular targets of each phase of the SARS-CoV-2 life cycle are discussed and highlighted in this paper. Much progress in understanding the SARS-CoV-2 and molecular details of its life cycle followed by the identification of new therapeutic targets are needed to lead us to an efficient approach in anti-SARS-CoV-2 drug discovery.", "qid": 29, "docid": "bq0hm89l", "rank": 13, "score": 0.8691263198852539}, {"content": "Title: Novel Drugs Targeting the SARS-CoV-2/COVID-19 Machinery Content: Like other human pathogenic viruses, coronavirus SARS-CoV-2 employs sophisticated macromolecular machines for viral host cell entry, genome replication and protein processing. Such machinery encompasses SARS-CoV-2 envelope spike (S) glycoprotein required for host cell entry by binding to the ACE2 receptor, viral RNA-dependent RNA polymerase (RdRp) and 3-chymotrypsin-like main protease (3Clpro/Mpro). Under the pressure of the accelerating COVID-19 pandemic caused by the outbreak of SARSCoV- 2 in Wuhan, China in December 2019, novel and repurposed drugs were recently designed and identified for targeting the SARS-CoV-2 reproduction machinery, with the aim to limit spread of SARS-CoV-2 and morbidity and mortality of the COVID-19 pandemic.", "qid": 29, "docid": "pqooh65g", "rank": 14, "score": 0.8691022396087646}, {"content": "Title: Novel Drugs Targeting the SARS-CoV-2/COVID-19 Machinery. Content: Like other human pathogenic viruses, coronavirus SARS-CoV-2 employs sophisticated macromolecular machines for viral host cell entry, genome replication and protein processing. Such machinery encompasses SARS-CoV-2 envelope spike (S) glycoprotein required for host cell entry by binding to the ACE2 receptor, viral RNA-dependent RNA polymerase (RdRp) and 3-chymotrypsin-like main protease (3Clpro/Mpro). Under the pressure of the accelerating COVID-19 pandemic caused by the outbreak of SARSCoV- 2 in Wuhan, China in December 2019, novel and repurposed drugs were recently designed and identified for targeting the SARS-CoV-2 reproduction machinery, with the aim to limit spread of SARS-CoV-2 and morbidity and mortality of the COVID-19 pandemic.", "qid": 29, "docid": "91pm9ffj", "rank": 15, "score": 0.8691022396087646}, {"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": 29, "docid": "nhq0oq8y", "rank": 16, "score": 0.8688945770263672}, {"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": 17, "score": 0.867964506149292}, {"content": "Title: Oral drug repositioning candidates and synergistic remdesivir combinations for the prophylaxis and treatment of COVID-19 Content: The ongoing pandemic caused by the novel severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), necessitates strategies to identify prophylactic and therapeutic drug candidates for rapid clinical deployment. A high-throughput, high-content imaging assay of human HeLa cells expressing the SARS-CoV-2 receptor ACE2 was used to screen ReFRAME, a best-in-class drug repurposing library. From nearly 12,000 compounds, we identified 66 compounds capable of selectively inhibiting SARS-CoV-2 replication in human cells. Twenty-four of these drugs show additive activity in combination with the RNA-dependent RNA polymerase inhibitor remdesivir and may afford increased in vivo efficacy. We also identified synergistic interaction of the nucleoside analog riboprine and a folate antagonist 10-deazaaminopterin with remdesivir. Overall, seven clinically approved drugs (halofantrine, amiodarone, nelfinavir, simeprevir, manidipine, ozanimod, osimertinib) and 19 compounds in other stages of development may have the potential to be repurposed as SARS-CoV-2 oral therapeutics based on their potency, pharmacokinetic and human safety profiles.", "qid": 29, "docid": "9od553a6", "rank": 18, "score": 0.8676945567131042}, {"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": 19, "score": 0.8660944104194641}, {"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": 20, "score": 0.865008533000946}, {"content": "Title: Repurposing of FDA-approved antivirals, antibiotics, anthelmintics, antioxidants, and cell protectives against SARS-CoV-2 papain-like protease Content: SARS-CoV-2 or Coronavirus disease 19 (COVID-19) is a rapidly spreading, highly contagious, and sometimes fatal disease for which drug discovery and vaccine development are critical. SARS-CoV-2 papain-like protease (PLpro) was used to virtually screen 1697 clinical FDA-approved drugs. Among the top results expected to bind with SARS-CoV-2 PLpro strongly were three cell protectives and antioxidants (NAD+, quercitrin, and oxiglutatione), three antivirals (ritonavir, moroxydine, and zanamivir), two antimicrobials (doripenem and sulfaguanidine), two anticancer drugs, three benzimidazole anthelmintics, one antacid (famotidine), three anti-hypertensive ACE receptor blockers (candesartan, losartan, and valsartan) and other miscellaneous systemically or topically acting drugs. The binding patterns of these drugs were superior to the previously identified SARS CoV PLpro inhibitor, 6-mercaptopurine (6-MP), suggesting a potential for repurposing these drugs to treat COVID-19. The objective of drug repurposing is the rapid relocation of safe and approved drugs by bypassing the lengthy pharmacokinetic, toxicity, and preclinical phases. The ten drugs with the highest estimated docking scores with favorable pharmacokinetics were subjected to molecular dynamics (MD) simulations followed by molecular mechanics/generalized Born surface area (MM/GBSA) binding energy calculations. Phenformin, quercetin, and ritonavir all demonstrated prospective binding affinities for COVID-19 PLpro over 50 ns MD simulations, with binding energy values of -56.6, -40.9, and -37.6 kcal/mol, respectively. Energetic and structural analyses showed phenformin was more stable than quercetin and ritonavir. The list of the drugs provided herein constitutes a primer for clinical application in COVID-19 patients and guidance for further antiviral studies.Communicated by Ramaswamy H. Sarma.", "qid": 29, "docid": "bkh2reye", "rank": 21, "score": 0.8644987344741821}, {"content": "Title: Knowledge-based repositioning of the anti-HCV direct antiviral agent Sofosbuvir as SARS-CoV-2 treatment Content: The new human coronavirus named SARS-CoV-2 is a positive-sense RNA virus for which no specific drugs are currently available. A knowledge-based analysis strongly suggests a possible repositioning of the anti-HCV direct antiviral agent (DAA) Sofosbuvir as treatment for SARS-CoV-2. Indeed, the RNA-dependent RNA-polymerases (RdRp) of the two viruses show high sequence and structural homology, supporting the likelihood of binding the Sofosbuvir molecule with similar efficiency. Such a repositioning would allow the containment of the SARS-CoV-2 pandemic and limit the progression of disease to potentially deadly COVID19.", "qid": 29, "docid": "fspxett8", "rank": 22, "score": 0.8644468784332275}, {"content": "Title: Repurposing of FDA-approved antivirals, antibiotics, anthelmintics, antioxidants, and cell protectives against SARS-CoV-2 papain-like protease Content: SARS-CoV-2 or Coronavirus disease 19 (COVID-19) is a rapidly spreading, highly contagious, and sometimes fatal disease for which drug discovery and vaccine development are critical. SARS-CoV-2 papain-like protease (PL(pro)) was used to virtually screen 1697 clinical FDA-approved drugs. Among the top results expected to bind with SARS-CoV-2 PL(pro) strongly were three cell protectives and antioxidants (NAD+, quercitrin, and oxiglutatione), three antivirals (ritonavir, moroxydine, and zanamivir), two antimicrobials (doripenem and sulfaguanidine), two anticancer drugs, three benzimidazole anthelmintics, one antacid (famotidine), three anti-hypertensive ACE receptor blockers (candesartan, losartan, and valsartan) and other miscellaneous systemically or topically acting drugs. The binding patterns of these drugs were superior to the previously identified SARS CoV PL(pro) inhibitor, 6-mercaptopurine (6-MP), suggesting a potential for repurposing these drugs to treat COVID-19. The objective of drug repurposing is the rapid relocation of safe and approved drugs by bypassing the lengthy pharmacokinetic, toxicity, and preclinical phases. The ten drugs with the highest estimated docking scores with favorable pharmacokinetics were subjected to molecular dynamics (MD) simulations followed by molecular mechanics/generalized Born surface area (MM/GBSA) binding energy calculations. Phenformin, quercetin, and ritonavir all demonstrated prospective binding affinities for COVID-19 PL(pro) over 50 ns MD simulations, with binding energy values of \u221256.6, \u221240.9, and \u221237.6 kcal/mol, respectively. Energetic and structural analyses showed phenformin was more stable than quercetin and ritonavir. The list of the drugs provided herein constitutes a primer for clinical application in COVID-19 patients and guidance for further antiviral studies. Communicated by Ramaswamy H. Sarma", "qid": 29, "docid": "y7dqoqa4", "rank": 23, "score": 0.8640854954719543}, {"content": "Title: Screening and testing for a suitable untransfected cell line for SARS-CoV-2 studies Content: At present, the novel pandemic coronavirus SARS-CoV-2 is a major global threat to human health and hence demands united research activities at different levels. Finding appropriate cell systems for drug screening and testing molecular interactions of the virus with the host cell is mandatory for drug development and understanding the mechanisms of viral entry and replication. For this, we selected human cell lines represented in the Cancer Cell Line Encyclopedia (CCLE) based on RNA-seq data determined transcript levels of ACE2 and TMPRSS2, two membrane proteins that have been identified to aid SARS-CoV-2 entry into the host cell. mRNA and protein expression of these host factors were verified via RQ-PCR and western blot. We then tested permissiveness of these cell lines towards SARS-CoV-2 infection, cytopathic effect, and viral replication finding limited correlation between receptor expression and infectability. One of the candidate cancer cell lines, the human colon cancer cell line CL-14, tested positive for SARS-CoV-2 infection. Our data argue that SARS-CoV-2 in vitro infection models need careful selection and validation since ACE2/TMPRSS2 receptor expression on its own does not guarantee permissiveness to the virus. Author summary In the midst of the pandemic outbreak of corona-virus SARS-CoV-2 therapeutics for disease treatment are still to be tested and the virus-host-interactions are to be elucidated. Drug testing and viral studies are commonly conducted with genetically manipulated cells. In order to find a cell model system without genetic modification we screened human cell lines for two proteins known to facilitate entry of SARS-CoV-2. We confirmed and quantified permissiveness of current cell line infection models, but dismissed a number of receptor-positive cell lines that did not support viral replication. Importantly, ACE2/TMPRSS2 co-expression seems to be necessary for viral entry but is not sufficient to predict permissiveness of various cancer cell lines. Moreover, the expression of specific splice variants and the absence of missense mutations of the host factors might hint on successful infection and virus replication of the cell lines.", "qid": 29, "docid": "wp3v00uk", "rank": 24, "score": 0.8630291223526001}, {"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": 25, "score": 0.8628805875778198}, {"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": 29, "docid": "hchioraj", "rank": 26, "score": 0.8623144626617432}, {"content": "Title: Potential RNA-dependent RNA polymerase inhibitors as prospective therapeutics against SARS-CoV-2 Content: Introduction. The emergence of SARS-CoV-2 has taken humanity off guard. Following an outbreak of SARS-CoV in 2002, and MERS-CoV about 10 years later, SARS-CoV-2 is the third coronavirus in less than 20 years to cross the species barrier and start spreading by human-to-human transmission. It is the most infectious of the three, currently causing the COVID-19 pandemic. No treatment has been approved for COVID-19. We previously proposed targets that can serve as binding sites for antiviral drugs for multiple coronaviruses, and here we set out to find current drugs that can be repurposed as COVID-19 therapeutics.Aim. To identify drugs against COVID-19, we performed an in silico virtual screen with the US Food and Drug Administration (FDA)-approved drugs targeting the RNA-dependent RNA polymerase (RdRP), a critical enzyme for coronavirus replication.Methodology. Initially, no RdRP structure of SARS-CoV-2 was available. We performed basic sequence and structural analysis to determine if RdRP from SARS-CoV was a suitable replacement. We performed molecular dynamics simulations to generate multiple starting conformations that were used for the in silico virtual screen. During this work, a structure of RdRP from SARS-CoV-2 became available and was also included in the in silico virtual screen.Results. The virtual screen identified several drugs predicted to bind in the conserved RNA tunnel of RdRP, where many of the proposed targets were located. Among these candidates, quinupristin is particularly interesting because it is expected to bind across the RNA tunnel, blocking access from both sides and suggesting that it has the potential to arrest viral replication by preventing viral RNA synthesis. Quinupristin is an antibiotic that has been in clinical use for two decades and is known to cause relatively minor side effects.Conclusion. Quinupristin represents a potential anti-SARS-CoV-2 therapeutic. At present, we have no evidence that this drug is effective against SARS-CoV-2 but expect that the biomedical community will expeditiously follow up on our in silico findings.", "qid": 29, "docid": "64bxnvdg", "rank": 27, "score": 0.862142026424408}, {"content": "Title: Potential RNA-dependent RNA polymerase inhibitors as prospective therapeutics against SARS-CoV-2. Content: Introduction. The emergence of SARS-CoV-2 has taken humanity off guard. Following an outbreak of SARS-CoV in 2002, and MERS-CoV about 10 years later, SARS-CoV-2 is the third coronavirus in less than 20 years to cross the species barrier and start spreading by human-to-human transmission. It is the most infectious of the three, currently causing the COVID-19 pandemic. No treatment has been approved for COVID-19. We previously proposed targets that can serve as binding sites for antiviral drugs for multiple coronaviruses, and here we set out to find current drugs that can be repurposed as COVID-19 therapeutics.Aim. To identify drugs against COVID-19, we performed an in silico virtual screen with the US Food and Drug Administration (FDA)-approved drugs targeting the RNA-dependent RNA polymerase (RdRP), a critical enzyme for coronavirus replication.Methodology. Initially, no RdRP structure of SARS-CoV-2 was available. We performed basic sequence and structural analysis to determine if RdRP from SARS-CoV was a suitable replacement. We performed molecular dynamics simulations to generate multiple starting conformations that were used for the in silico virtual screen. During this work, a structure of RdRP from SARS-CoV-2 became available and was also included in the in silico virtual screen.Results. The virtual screen identified several drugs predicted to bind in the conserved RNA tunnel of RdRP, where many of the proposed targets were located. Among these candidates, quinupristin is particularly interesting because it is expected to bind across the RNA tunnel, blocking access from both sides and suggesting that it has the potential to arrest viral replication by preventing viral RNA synthesis. Quinupristin is an antibiotic that has been in clinical use for two decades and is known to cause relatively minor side effects.Conclusion. Quinupristin represents a potential anti-SARS-CoV-2 therapeutic. At present, we have no evidence that this drug is effective against SARS-CoV-2 but expect that the biomedical community will expeditiously follow up on our in silico findings.", "qid": 29, "docid": "7xp3szhz", "rank": 28, "score": 0.862142026424408}, {"content": "Title: Potential therapeutic targets and promising drugs for combating SARS-CoV-2 Content: As of April 9, 2020, a novel coronavirus (SARS-CoV-2) had caused 89,931 deaths and 1,503,900 confirmed cases worldwide, which indicates an increasingly severe and uncontrollable situation. Initially, little was known about the virus. As research continues, we now know the genome structure, epidemiological and clinical characteristics, and pathogenic mechanisms of SARS-CoV-2. Based on this knowledge, potential targets involved in the processes of virus pathogenesis need to be identified, and the discovery or development of drugs based on these potential targets is the most pressing need. Here, we have summarized the potential therapeutic targets involved in virus pathogenesis and discuss the advances, possibilities, and significance of drugs based on these targets for treating SARS-CoV-2. This review will facilitate the identification of potential targets and provide clues for drug development that can be translated into clinical applications for combating SARS-CoV-2.", "qid": 29, "docid": "zl1d3gf2", "rank": 29, "score": 0.8613420724868774}, {"content": "Title: SARS-CoV-2 RNA polymerase as target for antiviral therapy Content: A new human coronavirus named SARS-CoV-2 was identified in several cases of acute respiratory syndrome in Wuhan, China in December 2019. On March 11 2020, WHO declared the SARS-CoV-2 infection to be a pandemic, based on the involvement of 169 nations. Specific drugs for SARS-CoV-2 are obviously not available. Currently, drugs originally developed for other viruses or parasites are currently in clinical trials based on empiric data. In the quest of an effective antiviral drug, the most specific target for an RNA virus is the RNA-dependent RNA-polymerase (RdRp) which shows significant differences between positive-sense and negative-sense RNA viruses. An accurate evaluation of RdRps from different viruses may guide the development of new drugs or the repositioning of already approved antiviral drugs as treatment of SARS-CoV-2. This can accelerate the containment of the SARS-CoV-2 pandemic and, hopefully, of future pandemics due to other emerging zoonotic RNA viruses.", "qid": 29, "docid": "c0jfa5jd", "rank": 30, "score": 0.8612697124481201}, {"content": "Title: In silico Study of Pharmacological Treatments against SARS-CoV2 Main Protease Content: The COVID-19 caused by a new type of coronavirus has emerged from China and led to thousands of death globally Despite the efforts engaged in studying this newly emerged virus and searching for its treatment, the understanding of the COVID-19 drug and target protein interactions still represent a key challenge Several molecules have demonstrated In-Vitro activity against the SARS-CoV-2 virus and/or potential clinical benefit in observational and non-randomized studies Randomized clinical trials of an appropriate size are currently ongoing to establish the efficacy of these therapeutic proposals Herein, concerning these diverse guidelines and therapeutic suggestions of different approaches to the treatment, this research aims to provide a molecular analysis of the interaction between the principal molecules cited in bibliography and the active protease site of the virus", "qid": 29, "docid": "krtcols6", "rank": 31, "score": 0.8610540628433228}, {"content": "Title: SARS-CoV-2 and SARS-CoV differ in their cell tropism and drug sensitivity profiles Content: SARS-CoV-2 is a novel coronavirus currently causing a pandemic. We show that the majority of amino acid positions, which differ between SARS-CoV-2 and the closely related SARS-CoV, are differentially conserved suggesting differences in biological behaviour. In agreement, novel cell culture models revealed differences between the tropism of SARS-CoV-2 and SARS-CoV. Moreover, cellular ACE2 (SARS-CoV-2 receptor) and TMPRSS2 (enables virus entry via S protein cleavage) levels did not reliably indicate cell susceptibility to SARS-CoV-2. SARS-CoV-2 and SARS-CoV further differed in their drug sensitivity profiles. Thus, only drug testing using SARS-CoV-2 reliably identifies therapy candidates. Therapeutic concentrations of the approved protease inhibitor aprotinin displayed anti-SARS-CoV-2 activity. The efficacy of aprotinin and of remdesivir (currently under clinical investigation against SARS-CoV-2) were further enhanced by therapeutic concentrations of the proton pump inhibitor omeprazole (aprotinin 2.7-fold, remdesivir 10-fold). Hence, our study has also identified anti-SARS-CoV-2 therapy candidates that can be readily tested in patients.", "qid": 29, "docid": "gpr86lxe", "rank": 32, "score": 0.8609755039215088}, {"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": 33, "score": 0.8599022626876831}, {"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": 34, "score": 0.859822154045105}, {"content": "Title: In Silico Evaluation of the Effectivity of Approved Protease Inhibitors against the Main Protease of the Novel SARS-CoV-2 Virus Content: The coronavirus disease, COVID-19, caused by the novel coronavirus SARS-CoV-2, which first emerged in Wuhan, China and was made known to the World in December 2019 turned into a pandemic causing more than 126,124 deaths worldwide up to April 16th, 2020. It has 79.5% sequence identity with SARS-CoV-1 and the same strategy for host cell invasion through the ACE-2 surface protein. Since the development of novel drugs is a long-lasting process, researchers look for effective substances among drugs already approved or developed for other purposes. The 3D structure of the SARS-CoV-2 main protease was compared with the 3D structures of seven proteases, which are drug targets, and docking analysis to the SARS-CoV-2 protease structure of thirty four approved and on-trial protease inhibitors was performed. Increased 3D structural similarity between the SARS-CoV-2 main protease, the HCV protease and &#945;-thrombin was found. According to docking analysis the most promising results were found for HCV protease, DPP-4, &#945;-thrombin and coagulation Factor Xa known inhibitors, with several of them exhibiting estimated free binding energy lower than -8.00 kcal/mol and better prediction results than reference compounds. Since some of the compounds are well-tolerated drugs, the promising in silico results may warrant further evaluation for viral anticipation. DPP-4 inhibitors with anti-viral action may be more useful for infected patients with diabetes, while anti-coagulant treatment is proposed in severe SARS-CoV-2 induced pneumonia.", "qid": 29, "docid": "sdx64c1k", "rank": 35, "score": 0.8598160743713379}, {"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": 29, "docid": "yzb8pouz", "rank": 36, "score": 0.8594356775283813}, {"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": 29, "docid": "h2xn9n20", "rank": 37, "score": 0.8594356775283813}, {"content": "Title: CD209L/L-SIGN and CD209/DC-SIGN act as receptors for SARS-CoV-2 and are differentially expressed in lung and kidney epithelial and endothelial cells Content: The spike protein (S) of SARS-CoV-2 mediates entry into human cells by interacting with human angiotensin-converting enzyme 2 (ACE2) through its receptor-binding domain (RBD). Here, we report identification of CD209L/L-SIGN and a related protein, CD209/DSIGN as alternative receptors capable of mediating SARS-CoV-2 entry into human cells. Immunofluorescence staining of human tissues revealed a prominent expression of CD209L in the lung and kidney epithelial and endothelial cells of small and medium-sized vessels, whereas CD209 was detected only in a limited number of cell types. Biochemical assays revealed that ectopically expressed CD209L and CD209 bind to S-RBD and mediate SARS-CoV-2 S-pseudotyped virus entry. Furthermore, we demonstrate that human endothelial cells endogenously express CD209L and are permissive to SARS-CoV-2 infection. Soluble CD209L-Fc neutralized virus entry. Our observations show that CD209L and CD209 serve as alternative receptors for SARS-CoV-2 in disease-relevant cell types, including the vascular system. This may have implications for antiviral drug development.", "qid": 29, "docid": "kp7lxt4z", "rank": 38, "score": 0.8591713905334473}, {"content": "Title: Discovery of clinically approved drugs capable of inhibiting SARS-CoV-2 in vitro infection using a phenotypic screening strategy and network-analysis to predict their potential to treat covid-19 Content: The disease caused by SARS-CoV2, covid-19, rapidly spreads worldwide, causing the greatest threat to global public health in the last 100 years. This scenario has become catastrophic as there are no approved vaccines to prevent the disease, and the main measures to contain the virus transmission are confinement and social distancing. One priority strategy is based on drug repurposing by pursuing antiviral chemotherapy that can control transmission and prevent complications associated with covid-19. With this aim, we performed a high content screening assay for the discovery of anti-SARS-CoV-2 compounds. From the 65 screened compounds, we have found four drugs capable to selectively inhibit SARS-CoV-2 in vitro infection: brequinar, abiraterone acetate, neomycin, and the extract of Hedera helix. Brequinar and abiraterone acetate had higher inhibition potency against SARS-CoV-2 than neomycin and Hedera helix extract, respectively. Drugs with reported antiviral activity and in clinical trials for covid-19, chloroquine, ivermectin, and nitazoxanide, were also included in the screening, and the last two were found to be non-selective. We used a data mining approach to build drug-host molecules-biological function-disease networks to show in a holistic way how each compound is interconnected with host node molecules and virus infection, replication, inflammatory response, and cell apoptosis. In summary, the present manuscript identified four drugs with active inhibition effect on SARS-CoV-2 in vitro infection, and by network analysis, we provided new insights and starting points for the clinical evaluation and repurposing process to treat SARS-CoV-2 infection. Summary sentence Discovery of drug repurposing candidates, inhibitors of SARS-CoV-2 infection in vitro, using a phenotypic screening strategy and network analysis.", "qid": 29, "docid": "40fz5r90", "rank": 39, "score": 0.8591262102127075}, {"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": 40, "score": 0.8589363694190979}, {"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": 29, "docid": "c08ptb1o", "rank": 41, "score": 0.8586530685424805}, {"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": 42, "score": 0.8583773374557495}, {"content": "Title: Drug repositioning is an alternative for the treatment of coronavirus COVID-19 Content: Given the extreme importance of the current pandemic caused by COVID-19, and as scientists agree there is no identified pharmacological treatment, where possible, therapeutic alternatives are raised through drug repositioning. This paper presents a selection of studies involving drugs from different pharmaceutical classes with activity against SARS-CoV-2 and SARS-CoV, with the potential for use in the treatment of COVID-19 disease.", "qid": 29, "docid": "ij8wk06v", "rank": 43, "score": 0.8583256006240845}, {"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": 29, "docid": "w9mij6c6", "rank": 44, "score": 0.858048677444458}, {"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": 45, "score": 0.8580152988433838}, {"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": 46, "score": 0.8573472499847412}, {"content": "Title: In Silico Evaluation of the Effectivity of Approved Protease Inhibitors against the Main Protease of the Novel SARS-CoV-2 Virus Content: The coronavirus disease, COVID-19, caused by the novel coronavirus SARS-CoV-2, which first emerged in Wuhan, China and was made known to the World in December 2019 turned into a pandemic causing more than 126,124 deaths worldwide up to April 16th, 2020. It has 79.5% sequence identity with SARS-CoV-1 and the same strategy for host cell invasion through the ACE-2 surface protein. Since the development of novel drugs is a long-lasting process, researchers look for effective substances among drugs already approved or developed for other purposes. The 3D structure of the SARS-CoV-2 main protease was compared with the 3D structures of seven proteases, which are drug targets, and docking analysis to the SARS-CoV-2 protease structure of thirty four approved and on-trial protease inhibitors was performed. Increased 3D structural similarity between the SARS-CoV-2 main protease, the HCV protease and \u03b1-thrombin was found. According to docking analysis the most promising results were found for HCV protease, DPP-4, \u03b1-thrombin and coagulation Factor Xa known inhibitors, with several of them exhibiting estimated free binding energy lower than \u22128.00 kcal/mol and better prediction results than reference compounds. Since some of the compounds are well-tolerated drugs, the promising in silico results may warrant further evaluation for viral anticipation. DPP-4 inhibitors with anti-viral action may be more useful for infected patients with diabetes, while anti-coagulant treatment is proposed in severe SARS-CoV-2 induced pneumonia.", "qid": 29, "docid": "teahway7", "rank": 47, "score": 0.856976330280304}, {"content": "Title: Fragment tailoring strategy to design novel chemical entities as potential binders of novel corona virus main protease Content: The recent pandemic of severe acute respiratory syndrome-coronavirus2 (SARS-CoV-2) infection (COVID-19) has put the world on serious alert. The main protease of SARS-CoV-2 (SARS-CoV-2-MPro) cleaves the long polyprotein chains to release functional proteins required for replication of the virus and thus is a potential drug target to design new chemical entities in order to inhibit the viral replication in human cells. The current study employs state of art computational methods to design novel molecules by linking molecular fragments which specifically bind to different constituent sub-pockets of the SARS-CoV-2-MPro binding site. A huge library of 191678 fragments was screened against the binding cavity of SARS-CoV-2-MPro and high affinity fragments binding to adjacent sub-pockets were tailored to generate new molecules. These newly formed molecules were further subjected to molecular docking, ADMET filters and MM-GBSA binding energy calculations to select 17 best molecules (named as MP-In1 to MP-In17), which showed comparable binding affinities and interactions with the key binding site residues as the reference ligand. The complexes of these 17 molecules and the reference molecule with SARS-CoV-2-MPro, were subjected to molecular dynamics simulations, which assessed the stabilities of their binding with SARS-CoV-2-MPro. Fifteen molecules were found to form stable complexes with SARS-CoV-2-MPro. These novel chemical entities designed specifically according to the pharmacophoric requirements of SARS-CoV-2-MPro binding pockets showed good synthetic feasibility and returned no exact match when searched against chemical databases. Considering their interactions, binding efficiencies and novel chemotypes, they can be further evaluated as potential starting points for SARS-CoV-2 drug discovery. [Formula: see text]Communicated by Ramaswamy H. Sarma.", "qid": 29, "docid": "84h7nqbs", "rank": 48, "score": 0.8565578460693359}, {"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": 29, "docid": "24m4rh9w", "rank": 49, "score": 0.8562625646591187}, {"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": 29, "docid": "yigj0u3n", "rank": 50, "score": 0.856229305267334}, {"content": "Title: Structure-based drug designing and immunoinformatics approach for SARS-CoV-2 Content: The prevalence of respiratory illness caused by the novel SARS-CoV-2 associated with multiple organ failures is spreading rapidly due to its contagious human-to-human transmission and inadequate global healthcare systems. Pharmaceutical re-use, reflecting an effective drug development technique using existing drugs, could shorten the time and reduce the costs relative to de novo drug discovery. We have performed virtual screening of antiviral compounds targeting the spike glycoprotein (S), main protease (M(pro)), and the SARS-CoV-2 RBD-ACE2 complex of SARS-CoV-2. PC786, an antiviral polymerase inhibitor, showed improved binding affinity toward all the targets. Furthermore, the post-fusion conformation of the trimeric S protein RBD domain with ACE2 revealed conformational changes associated with the PC786 drug binding. The proposed T cell and B cell epitope identification using the immunoinformatics approach could direct the experimental study with a higher probability of discovering appropriate vaccine candidates with fewer experiments and higher reliability.", "qid": 29, "docid": "ty27die9", "rank": 51, "score": 0.8561413288116455}, {"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": 29, "docid": "vvf3ei6v", "rank": 52, "score": 0.8558974862098694}, {"content": "Title: Computational Prediction of the Comprehensive SARS-CoV-2 vs. Human Interactome to Guide the Design of Therapeutics Content: Understanding the disease pathogenesis of the novel coronavirus, denoted SARS-CoV-2, is critical to the development of anti-SARS-CoV-2 therapeutics. The global propagation of the viral disease, denoted COVID-19 (\u201ccoronavirus disease 2019\u201d), has unified the scientific community in searching for possible inhibitory small molecules or polypeptides. Given the known interaction between the human ACE2 (\u201cAngiotensin-converting enzyme 2\u201d) protein and the SARS-CoV virus (responsible for the coronavirus outbreak circa. 2003), considerable focus has been directed towards the putative interaction between the SARS-CoV-2 Spike protein and ACE2. However, a more holistic understanding of the SARS-CoV-2 vs. human inter-species interactome promises additional putative protein-protein interactions (PPI) that may be considered targets for the development of inhibitory therapeutics. To that end, we leverage two state-of-the-art, sequence-based PPI predictors (PIPE4 & SPRINT) capable of generating the comprehensive SARS-CoV-2 vs. human interactome, comprising approximately 285,000 pairwise predictions. Of these, we identify the high-scoring subset of human proteins predicted to interact with each of the 14 SARS-CoV-2 proteins by both methods, comprising 279 high-confidence putative interactions involving 225 human proteins. Notably, the Spike-ACE2 interaction was the highest ranked for both the PIPE4 and SPRINT predictors, corroborating existing evidence for this PPI. Furthermore, the PIPE-Sites algorithm was used to predict the putative subsequence that might mediate each interaction and thereby inform the design of inhibitory polypeptides intended to disrupt the corresponding host-pathogen interactions. We hereby publicly release the comprehensive set of PPI predictions and their corresponding PIPE-Sites landscapes in the following DataVerse repository: 10.5683/SP2/JZ77XA. All data and metadata are released under a CC-BY 4.0 licence. The information provided represents theoretical modeling only and caution should be exercised in its use. It is intended as a resource for the scientific community at large in furthering our understanding of SARS-CoV-2.", "qid": 29, "docid": "dxabs45r", "rank": 53, "score": 0.8558670282363892}, {"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": 54, "score": 0.855761706829071}, {"content": "Title: SARS-CoV-2: Repurposed Drugs and Novel Therapeutic Approaches-Insights into Chemical Structure-Biological Activity and Toxicological Screening Content: SARS-CoV-2 (severe acute respiratory syndrome coronavirus 2) pandemic represents the primary public health concern nowadays, and great efforts are made worldwide for efficient management of this crisis Considerable scientific progress was recorded regarding SARS-CoV-2 infection in terms of genomic structure, diagnostic tools, viral transmission, mechanism of viral infection, symptomatology, clinical impact, and complications, but these data evolve constantly Up to date, neither an effective vaccine nor SARS-CoV-2 specific antiviral agents have been approved, but significant advances were enlisted in this direction by investigating repurposed approved drugs (ongoing clinical trials) or developing innovative antiviral drugs (preclinical and clinical studies) This review presents a thorough analysis of repurposed drug admitted for compassionate use from a chemical structure-biological activity perspective highlighting the ADME (absorption, distribution, metabolism, and excretion) properties and the toxicophore groups linked to potential adverse effects A detailed pharmacological description of the novel potential anti-COVID-19 therapeutics was also included In addition, a comprehensible overview of SARS-CoV-2 infection in terms of general description and structure, mechanism of viral infection, and clinical impact was portrayed", "qid": 29, "docid": "ip092sys", "rank": 55, "score": 0.8554435968399048}, {"content": "Title: En route to Peptide Therapeutics for COVID 19: Harnessing Potential Antigenic Mimicry Between Viral and Human Proteins Content: Molecular mimicry is a general strategy used by pathogens to infect the host cells. The emergence of SARS-CoV-2 virus has resulted in more than 6,700,000 infections and 390,000 deaths worldwide. Coronavirus disease (COVID-19) is an infectious disease caused by this virus. In this project concept, we aim to focus on the peptide-protein interaction analysis using two important drug targets in SARS-CoV-2 such as spike (S) protein and nucleocapsid (N) protein. These proteins play an important role in the virus entry and encapsidation of the viral particles. Motifs or functional regions in these two proteins must be sharing sequence homology with human protein (ACE2) which may be involved in the binding mechanism. The results will show a set of motif regions which can disrupt the viral infection. Once we identify these sets of antigenic determinant regions, antibody binding activity studies can be performed by in vitro methods. Our results from this study may suggest the existence of antigenic mimicry between SARS-CoV-2 and host proteins. The hit peptide components will have therapeutic applications to be developed into a wide variety of medicinal formulations against SARS-CoV-2 such as vaccine, intranasal and inhalation formulations. Also, the choice of conserved regions will lead to development of cross protective therapeutics against wide range of coronaviruses.", "qid": 29, "docid": "qj81xbn0", "rank": 56, "score": 0.855374276638031}, {"content": "Title: A data-driven hypothesis on the epigenetic dysregulation of host metabolism by SARS coronaviral infection: Potential implications for the SARS-CoV-2 modus operandi Content: COVID-19, the disease caused by the novel SARS-CoV-2, a betacoronavirus structurally similar to SARS-CoV. Based on both structural and syndromic similarities with SARS-CoV, a hypothesis is formed on SARS-CoV-2 potential to affect the host's metabolism as part of its lifecycle. This hypothesis is evaluated by (a) exploratory analysis of SARS-CoV/human transcriptomic interaction data and gene set enrichment analysis (b) a confirmatory, focused review of the literature based on the findings by (a). A STRING Viruses (available search for human - SARS-CoV (NCBI taxonomy Id: 9606 vs. NCBI taxonomy Id: 694009) genomic interactions reveals ten human proteins, interacting with SARS-CoV: SGTA, FGL2, SPECC1, STAT3, PHB, BCL2L1, PPP1CA, CAV1, JUN, XPO1. Gene set enrichment analyses (GSEA) with STRING on this network revealed their role as a putative protein - protein interaction network (PPI; Enrichment p-value = 0.0296) mediating, viral parasitism, interleukin as well as insulin signaling, diabetes and triglyceride catabolism. In the literature, SARS-CoV has been known to cause de novo diabetes by ACE2-dependent uptake on pancreatic isle cells, and furthermore dysregulate lipid autophagy in favor of the viral lifecycle. Conversely, currently there are only non-causative, observational evidence of worse outcomes for COVID-19 patients with comorbid diabetes or hyperglycemia. No study has reported on the lipid profiles of COVID-19 patients; however, lipid-targeting molecules have been proposed as agents against SARS-CoV-2. Future studies, reporting on lipid and glucose metabolism of COVID-19 patients could help elucidate the disease's seculae and aid drug design.", "qid": 29, "docid": "8hrqedig", "rank": 57, "score": 0.855329155921936}, {"content": "Title: Potential targets for anti-SARS drugs in the structural proteins from SARS related coronavirus Content: This is a further study on the severe acute respiratory syndrome (SARS) using the probabilistic models. The purpose was to define the potential targets for anti-SARS drugs in the structural proteins from human SARS related coronavirus (SARS-CoV) while knowing little about the functional sites and possible mutations in these proteins. From a probabilistic viewpoint, we can theoretically select the amino acid pairs as potential candidates for anti-SARS drugs. These candidates have a greater chance of colliding with anti-SARS drugs, are more likely to link with the protein functions and are less vulnerable to mutations.", "qid": 29, "docid": "amzmyqys", "rank": 58, "score": 0.8552097082138062}, {"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": 29, "docid": "phxu6usy", "rank": 59, "score": 0.8548885583877563}, {"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": 60, "score": 0.8547248840332031}, {"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": 61, "score": 0.8544209003448486}, {"content": "Title: Drug repositioning is an alternative for the treatment of coronavirus COVID-19 Content: Abstract Given the extreme importance of the current pandemic caused by COVID-19, and as scientists agree there is no identified pharmacological treatment, where possible, therapeutic alternatives are raised through drug repositioning. This paper presents a selection of studies involving drugs from different pharmaceutical classes with activity against SARS-CoV-2 and SARS-CoV, with the potential for use in the treatment of COVID-19 disease.", "qid": 29, "docid": "agc89fqv", "rank": 62, "score": 0.8542203903198242}, {"content": "Title: Reconstructing SARS-CoV-2 response signaling and regulatory networks Content: Several molecular datasets have been recently compiled to characterize the activity of SARS-CoV-2 within human cells. Here we extend computational methods to integrate several different types of sequence, functional and interaction data to reconstruct networks and pathways activated by the virus in host cells. We identify the key proteins in these networks and further intersect them with genes differentially expressed at conditions that are known to impact viral activity. Several of the top ranked genes do not directly interact with virus proteins though some were shown to impact other coronaviruses highlighting the importance of large scale data integration for understanding virus and host activity.", "qid": 29, "docid": "m8yyntls", "rank": 63, "score": 0.8541007041931152}, {"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": 64, "score": 0.8540341258049011}, {"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": 65, "score": 0.8537789583206177}, {"content": "Title: Clinical trials of repurposed antivirals for SARS-CoV-2 Content: The coronavirus disease 2019 (COVID-19) pandemic caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) has prompted the repurposing of drugs on the basis of promising in vitro and therapeutic results with other human coronavirus diseases such as severe acute respiratory syndrome (SARS) and Middle East respiratory syndrome (MERS). These repurposed drugs have mainly included remdesivir, favipiravir, lopinavir/ritonavir, ribavirin, interferons, and hydroxychloroquine. Unfortunately, the first open-label, randomized controlled trials are showing the poor efficacy of these repurposed drugs. These results highlight the necessity of identifying and characterizing specific and potent SARS-CoV-2 antivirals.", "qid": 29, "docid": "yvlcorrg", "rank": 66, "score": 0.8537536859512329}, {"content": "Title: Clinical trials of repurposed antivirals for SARS-CoV-2. Content: The coronavirus disease 2019 (COVID-19) pandemic caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) has prompted the repurposing of drugs on the basis of promising in vitro and therapeutic results with other human coronavirus diseases such as severe acute respiratory syndrome (SARS) and Middle East respiratory syndrome (MERS). These repurposed drugs have mainly included remdesivir, favipiravir, lopinavir/ritonavir, ribavirin, interferons, and hydroxychloroquine. Unfortunately, the first open-label, randomized controlled trials are showing the poor efficacy of these repurposed drugs. These results highlight the necessity of identifying and characterizing specific and potent SARS-CoV-2 antivirals.", "qid": 29, "docid": "5q5mele8", "rank": 67, "score": 0.8537536859512329}, {"content": "Title: Fragment tailoring strategy to design novel chemical entities as potential binders of novel corona virus main protease Content: The recent pandemic of severe acute respiratory syndrome\u2013coronavirus2 (SARS-CoV-2) infection (COVID-19) has put the world on serious alert. The main protease of SARS-CoV-2 (SARS-CoV-2-M(Pro)) cleaves the long polyprotein chains to release functional proteins required for replication of the virus and thus is a potential drug target to design new chemical entities in order to inhibit the viral replication in human cells. The current study employs state of art computational methods to design novel molecules by linking molecular fragments which specifically bind to different constituent sub-pockets of the SARS-CoV-2-M(Pro) binding site. A huge library of 191678 fragments was screened against the binding cavity of SARS-CoV-2-M(Pro) and high affinity fragments binding to adjacent sub-pockets were tailored to generate new molecules. These newly formed molecules were further subjected to molecular docking, ADMET filters and MM-GBSA binding energy calculations to select 17 best molecules (named as MP-In1 to MP-In17), which showed comparable binding affinities and interactions with the key binding site residues as the reference ligand. The complexes of these 17 molecules and the reference molecule with SARS-CoV-2-M(Pro), were subjected to molecular dynamics simulations, which assessed the stabilities of their binding with SARS-CoV-2-M(Pro). Fifteen molecules were found to form stable complexes with SARS-CoV-2-M(Pro). These novel chemical entities designed specifically according to the pharmacophoric requirements of SARS-CoV-2-M(Pro) binding pockets showed good synthetic feasibility and returned no exact match when searched against chemical databases. Considering their interactions, binding efficiencies and novel chemotypes, they can be further evaluated as potential starting points for SARS-CoV-2 drug discovery. [Image: see text] Communicated by Ramaswamy H. Sarma", "qid": 29, "docid": "lr3wj8we", "rank": 68, "score": 0.853355884552002}, {"content": "Title: Computational methods to develop potential neutralizing antibody Fab region against SARS-CoV-2 as therapeutic and diagnostic tool Content: SARS-CoV-2, a global pandemic originated from Wuhan city of China in the month of December 2019. There is an urgency to identify potential antibodies to neutralize the virus and also as a diagnostic tool candidate. At present palliative treatments using existing antiviral drugs are under trails to treat SARS-CoV-2.Whole Genome sequence of Wuhan market sample of SARS-CoV-2 was obtained from NCBI Gene ID MN908947.3.Spike protein sequence PDB ID 6VSB obtained from RCSB database. Spike protein sequence had shown top V gene match with IGLV1-44*01, IGLV1-47*02 and has VL type chain. Whole Genome sequence had shown top V gene match with IGHV1-38-4*01 and has VH type chain. VD chain had shown link to allele HLA-A0206 80%, HLA-A0217 80%, HLA-A2301 75%, HLA-A0203 75%, HLA-A0202 70% and HLA-A0201 55% of binding levels. Some conserved regions of spike protein had shown strong binding affinity with HLA-A-0*201, HLA-A24, HLA-B-5701 and HLA-B-5703 alpha chains. Synthetic Fab construct BCR type antibody IgG (CR5840) had shown Polyspecific binding activity with spike glycoprotein when compared with available Anti-SARS antibody CR3022.Thus we propose CR5840 Fab constructed antibody as potential neutralizing antibody for SARS-CoV-2. Based on germline analysis we also propose cytotoxic T lymphocyte epitope peptide selective system as effective tool for the development of SARS-CoV-2 vaccine.", "qid": 29, "docid": "2jrichn5", "rank": 69, "score": 0.853290319442749}, {"content": "Title: Interferon-Induced Transmembrane Protein (IFITM3) Is Upregulated Explicitly in SARS-CoV-2 Infected Lung Epithelial Cells Content: Current guidelines for COVID-19 management recommend the utilization of various repurposed drugs. Despite ongoing research toward the development of a vaccine against SARS-CoV-2, such a vaccine will not be available in time to contribute to the containment of the ongoing pandemic. Therefore, there is an urgent need to develop a framework for the rapid identification of novel targets for diagnostic and therapeutic interventions. We analyzed publicly available transcriptomic datasets of SARS-CoV infected humans and mammals to identify consistent differentially expressed genes then validated in SARS-CoV-2 infected epithelial cells transcriptomic datasets. Comprehensive toxicogenomic analysis of the identified genes to identify possible interactions with clinically proven drugs was carried out. We identified IFITM3 as an early upregulated gene, and valproic acid was found to enhance its mRNA expression as well as induce its antiviral action. These findings indicate that analysis of publicly available transcriptomic and toxicogenomic data represents a rapid approach for the identification of novel targets and molecules that can modify the action of such targets during the early phases of emerging infections like COVID-19.", "qid": 29, "docid": "cmfo60z0", "rank": 70, "score": 0.8530802130699158}, {"content": "Title: Lessons Learned to Date on COVID-19 Hyperinflammatory Syndrome: Considerations for Interventions to Mitigate SARS-CoV-2 Viral Infection and Detrimental Hyperinflammation Content: The first case of human transmission of SARS-CoV-2 was reported in China in December 2019. A few months later, this viral infection had spread worldwide and became a pandemic. The disease caused by SARS-CoV-2, termed COVID-19, is multifactorial and associated with both specific antiviral as well as inflammatory responses, the extent of which may determine why some individuals are asymptomatic while others develop serious complications. Here we review possible life-threating immune events that can occur during disease progression to uncover key factors behind COVID-19 severity and provide suggestions for interventions with repurposed drugs in well-controlled and randomized clinical trials. These drugs include therapeutics with potential to inhibit SARS-CoV-2 entry into host cells such as serine protease inhibitors of the cellular protease TMPS2 and drugs targeting the renin-angiotensin system; antivirals with potential to block SARS-CoV-2 replication or factors that could boost the antiviral response; monoclonal antibodies targeting pro-inflammatory cytokines that drive the hyperinflammatory response during COVID-19 progression toward the severe stage and therapeutics that could ameliorate the function of the lungs. Furthermore, in order to help make more informed decisions on the timing of the intervention with the drugs listed in this review, we have grouped these therapeutics according to the stage of COVID-19 progression that we considered most appropriate for their mechanism of action.", "qid": 29, "docid": "2qugltxu", "rank": 71, "score": 0.8530253767967224}, {"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": 72, "score": 0.8524247407913208}, {"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": 29, "docid": "ddt5qmls", "rank": 73, "score": 0.8523454666137695}, {"content": "Title: COVID-19: a new virus, but an old cytokine release syndrome Content: Understanding the cell entry mechanism of pandemic coronavirus SARS-CoV-2 is crucial for treating the disease Zhou et al (Nature) and Hoffmann et al (Cell) identify ACE2 as a SARS-CoV-2 receptor, and the latter show its entry mechanism depends on cellular serine protease TMPRSS2 These results suggest several possible therapeutic targets, including the IL-6-STAT3 axis previously associated with cytokine release syndromes", "qid": 29, "docid": "muzqgk95", "rank": 74, "score": 0.8522879481315613}, {"content": "Title: Current Insight into the Novel Coronavirus Disease 2019 (COVID-19) Content: SARS-CoV-2 is a novel strain of coronavirus that has not been previously identified in humans. It has been declared a pandemic and has infected at least 1,844,683 individuals and caused 117,021 deaths as of 14th April 2020. Transmission among humans occurs via close contact with an infected individual that produces respiratory droplets. Patients have been shown to undergo acute respiratory distress syndrome, which is defined as cytokine storm. The diagnosis relies on detection of nucleic acid, IgG/IgM antibodies, and a chest radiograph of the suspected individuals. The genome of SARS-CoV-2 is similar to other coronaviruses that comprise of ten open reading frames (ORFs). SARS-CoV-2 spike protein exhibits higher affinity to ACE2 receptor as compared with SARS-CoV. Repurposing drugs like favipiravir, remdesivir, chloroquine, and TMPRSS2 protease inhibitors have been shown to be effective for the treatment of COVID-19. Personal protective measures should be followed to prevent SARS-CoV-2 infection. In addition, a clinical trial of SARS-CoV-2 vaccine, mRNA-1273, has been started. This chapter provides a glimpse of advancements made in the area of SARS-CoV-2 infection by proving recent clinical and research trials in the field.", "qid": 29, "docid": "zv0ysi8m", "rank": 75, "score": 0.8522687554359436}, {"content": "Title: Taking aim at a fast-moving target: Targets to watch for SARS-CoV-2 and COVID-19 Content: Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) is characterized as a betacoronavirus and recognized as the seventh discrete coronavirus species capable of causing human disease. This new coronavirus causes febrile respiratory illness and on March 11, 2020, was characterized as a global pandemic. Investigators have accelerated the search for a vaccine to prevent infection and for agents to treat it. This article presents those drug targets that (as of March 20, 2020) are currently under active investigation for the treatment of COVID-19, the disease caused by SARS-CoV-2 infection.", "qid": 29, "docid": "ybzfhp8p", "rank": 76, "score": 0.8522353172302246}, {"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": 77, "score": 0.8522254228591919}, {"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": 78, "score": 0.8522254228591919}, {"content": "Title: Potential Inhibitors for Novel Coronavirus Protease Identified by Virtual Screening of 606 Million Compounds Content: The rapid outbreak of the novel severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) in China followed by its spread around the world poses a serious global concern for public health. To this date, no specific drugs or vaccines are available to treat SARS-CoV-2 despite its close relation to the SARS-CoV virus that caused a similar epidemic in 2003. Thus, there remains an urgent need for the identification and development of specific antiviral therapeutics against SARS-CoV-2. To conquer viral infections, the inhibition of proteases essential for proteolytic processing of viral polyproteins is a conventional therapeutic strategy. In order to find novel inhibitors, we computationally screened a compound library of over 606 million compounds for binding at the recently solved crystal structure of the main protease (Mpro) of SARS-CoV-2. A screening of such a vast chemical space for SARS-CoV-2 Mpro inhibitors has not been reported before. After shape screening, two docking protocols were applied followed by the determination of molecular descriptors relevant for pharmacokinetics to narrow down the number of initial hits. Next, molecular dynamics simulations were conducted to validate the stability of docked binding modes and comprehensively quantify ligand binding energies. After evaluation of potential off-target binding, we report a list of 12 purchasable compounds, with binding affinity to the target protease that is predicted to be more favorable than that of the cocrystallized peptidomimetic compound. In order to quickly advise ongoing therapeutic intervention for patients, we evaluated approved antiviral drugs and other protease inhibitors to provide a list of nine compounds for drug repurposing. Furthermore, we identified the natural compounds (-)-taxifolin and rhamnetin as potential inhibitors of Mpro. Rhamnetin is already commercially available in pharmacies.", "qid": 29, "docid": "b7n8jadp", "rank": 79, "score": 0.852027416229248}, {"content": "Title: Severe respiratory SARS-CoV2 infection: Does ACE2 receptor matter? Content: SARS-CoV-2 is a novel virus of the Coronaviridiae family that represents a major global health issue. Mechanisms implicated in virus/host cells interaction are central for cell infection and replication that in turn lead to disease onset and local damage. To enter airway and lung epithelia, SARS-CoV-2 attaches to ACE2 receptors by spike (S) glycoproteins. Molecular mechanisms that promote interaction between SARS-CoV-2 virus and host with particular focus on virus cell entry receptor ACE2 are described. We further explore the impact of underlying medical conditions and therapies including renin-angiotensin inhibitors on modulating ACE 2, which is the major SARS-CoV-2 cell entry receptor.", "qid": 29, "docid": "7ow3bzfh", "rank": 80, "score": 0.8518372178077698}, {"content": "Title: Risk of drug-induced Long QT Syndrome associated with the use of repurposed COVID-19 drugs: a systematic review Content: Background: The World Health Organization first declared SARS-CoV-2 (COVID-19) a pandemic on March 11, 2020. There are currently no vaccines or therapeutic agents proven efficacious to treat COVID-19. So, whether existing approved drugs could be repurposed and used off-label for the treatment of novel COVID-19 disease is being explored. Methods: A thorough literature search was performed to gather information on the pharmacological properties and toxicity of 6 drugs (azithromycin, chloroquine, favipiravir, hydroxychloroquine, lopinavir/ritonavir, remdesivir) proposed to be repurposed to treat COVID-19. Researchers emphasized affinity of these drugs to block the rapid component of the delayed rectifier cardiac potassium current (IKr) encoded by the human ether-a-go-go gene (hERG), their propensity to prolong cardiac repolarization (QT interval) and cause torsade de pointes (TdP). Risk of drug-induced Long QT Syndrome (LQTS) for these drugs was quantified by comparing six indices used to assess such risk and by querying the U.S. Food and Drug Administration (FDA) Adverse Event Reporting System database with specific key words. Data are also provided to compare the level of risk for drug-induced LQTS by these drugs to 23 other, well-recognized, torsadogenic compounds. Results: Estimators of LQTS risk levels indicated a very-high or high risk for all COVID-19 repurposed drugs except for azithromycin, although cases of TdP have been reported following the administration of this drug. There was an excellent agreement among the various indices used to assess risk of drug-induced LQTS for the six repurposed drugs and the 23 torsadogenic compounds. Conclusion: The risk-benefit assessment for the use of repurposed drugs to treat COVID-19 is complicated since benefits are currently anticipated, not proven. Mandatory monitoring of the QT interval shall be performed as such monitoring is possible for hospitalized patients or by the use of biodevices for outpatients initiated on these drugs.", "qid": 29, "docid": "jcqhxzih", "rank": 81, "score": 0.8516238927841187}, {"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": 82, "score": 0.8515982031822205}, {"content": "Title: Candidate drugs against SARS-CoV-2 and COVID-19 Content: Outbreak and pandemic of coronavirus SARS-CoV-2 in 2019/2020 will challenge global health for the future. Because a vaccine against the virus will not be available in the near future, we herein try to offer a pharmacological strategy to combat the virus. There exists a number of candidate drugs that may inhibit infection with and replication of SARS-CoV-2. Such drugs comprise inhibitors of TMPRSS2 serine protease and inhibitors of angiotensin-converting enzyme 2 (ACE2). Blockade of ACE2, the host cell receptor for the S protein of SARS-CoV-2 and inhibition of TMPRSS2, which is required for S protein priming may prevent cell entry of SARS-CoV-2. Further, chloroquine and hydroxychloroquine, and off-label antiviral drugs, such as the nucleotide analogue remdesivir, HIV protease inhibitors lopinavir and ritonavir, broad-spectrum antiviral drugs arbidol and favipiravir as well as antiviral phytochemicals available to date may limit spread of SARS-CoV-2 and morbidity and mortality of COVID-19 pandemic.", "qid": 29, "docid": "xef6fr39", "rank": 83, "score": 0.8515378832817078}, {"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": 29, "docid": "jbc74lcu", "rank": 84, "score": 0.851457953453064}, {"content": "Title: ACE2 fragment as a decoy for novel SARS-Cov-2 virus Content: Novel SARS-Cov-2 enters human cells via interaction between the surface spike (S) glycoprotein and the cellular membrane receptor angiotensin-converting enzyme 2 (ACE2). Using a combination of comparative structural analyses of the binding surface of the S protein to ACE2, docking experiments, and molecular dynamics simulations we computationally identified a minimal, stable fragment of ACE2. This fragment binds to the S protein, is soluble, and appears not to bind to the physiological ligand angiotensinII. These results suggest a possible use of the ACE2 fragment as a decoy that could interfere with viral binding by competition.", "qid": 29, "docid": "77ku0164", "rank": 85, "score": 0.8512393236160278}, {"content": "Title: Coagulation modifiers targeting SARS-CoV-2 main protease Mpro for COVID-19 treatment: an in silico approach Content: Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection depends on viral polyprotein processing, catalysed by the main proteinase (Mpro). The solution of the SARS-CoV-2 Mpro structure allowed the investigation of potential inhibitors. This work aims to provide first evidences of the applicability of commercially approved drugs to treat coronavirus disease-19 (COVID-19). We screened 4,334 compounds to found potential inhibitors of SARS-CoV-2 replication using an in silico approach. Our results evidenced the potential use of coagulation modifiers in COVID-19 treatment due to the structural similarity of SARS-CoV-2 Mpro and human coagulation factors thrombin and Factor Xa. Further in vitro and in vivo analysis are needed to corroborate these results.", "qid": 29, "docid": "jxha9b65", "rank": 86, "score": 0.8511152863502502}, {"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": 29, "docid": "pgxew3yk", "rank": 87, "score": 0.8510997891426086}, {"content": "Title: Roles of spike protein in the pathogenesis of SARS coronavirus. Content: 1. Infection with SARS coronavirus (SARS-CoV) induces a cellular stress condition known as the unfolded protein response (UPR). UPR induction is mediated primarily by viral spike (S) protein. The modulation of UPR by S protein involves activation of PERK protein kinase. Other branches of the UPR pathways controlled by IRE1 and ATF6 proteins, respectively, are not involved. 2. The protease inhibitor Ben-HCl effectively suppresses SARS-CoV infection by blocking virus entry. Viral infectivity is associated with the cleavage of S protein by the cellular protease factor Xa. 3. Two new aspects of the interaction between SARS-CoV S protein and the cell have been defined. These have important implications in the pathogenesis of SARS, providing opportunities for developing vaccines and antivirals against SARS-CoV. 4. Counteracting the UPR and targeting the cleavage of S protein with small molecule pharmaceutical agents represent two new anti-SARS-CoV strategies. 5. The receptor-binding domain of S protein delivered via adeno-associated virus can efficiently induce mucosal immunity and provide long-term protection against SARS-CoV infection.", "qid": 29, "docid": "wg9i32ob", "rank": 88, "score": 0.8510655760765076}, {"content": "Title: Old drugs as lead compounds for a new disease? Binding analysis of SARS coronavirus main proteinase with HIV, psychotic and parasite drugs Content: Abstract The SARS-associated coronavirus (SARS-CoV) main proteinase is a key enzyme in viral polyprotein processing. To allow structure-based design of drugs directed at SARS-CoV main proteinase, we predicted its binding pockets and affinities with existing HIV, psychotic and parasite drugs (lopinavir, ritonavir, niclosamide and promazine), which show signs of inhibiting the replication of SARS-CoV. Our results suggest that these drugs and another two HIV inhibitors (PNU and UC2) could be used as templates for designing SARS-CoV proteinase inhibitors.", "qid": 29, "docid": "d4loia11", "rank": 89, "score": 0.8509877324104309}, {"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": 90, "score": 0.8509711027145386}, {"content": "Title: ACE-2 och coronavirus \u00ad en fr\u00e5ga om balans och dynamik?/ [ACE2 and coronavirus - a question of balance and dynamics?] Content: The new SARS-CoV-2 virus enters cells via angiotensin-converting enzyme 2 (ACE2). ACE2 counteracts ACE and angiotensin II in the renin-angiotensin-aldosterone system (RAAS) and has critical functions in the lung and cardiovascular system. SARS-CoV was found to down-regulate ACE2, leaving angiotensin II unbalanced in affected organs. A similar effect of SARS-CoV-2 could partly explain risk factors and symptoms, and could potentially be treatable.", "qid": 29, "docid": "wqpt073e", "rank": 91, "score": 0.8509136438369751}, {"content": "Title: [ACE2 and coronavirus - a question of balance and dynamics?] Content: The new SARS-CoV-2 virus enters cells via angiotensin-converting enzyme 2 (ACE2). ACE2 counteracts ACE and angiotensin II in the renin-angiotensin-aldosterone system (RAAS) and has critical functions in the lung and cardiovascular system. SARS-CoV was found to down-regulate ACE2, leaving angiotensin II unbalanced in affected organs. A similar effect of SARS-CoV-2 could partly explain risk factors and symptoms, and could potentially be treatable.", "qid": 29, "docid": "e97zvah8", "rank": 92, "score": 0.8509136438369751}, {"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": 93, "score": 0.8508143424987793}, {"content": "Title: SARS-CoV-2 Cell Entry Depends on ACE2 and TMPRSS2 and Is Blocked by a Clinically Proven Protease Inhibitor Content: The recent emergence of the novel, pathogenic SARS-coronavirus 2 (SARS-CoV-2) in China and its rapid national and international spread pose a global health emergency. Cell entry of coronaviruses depends on binding of the viral spike (S) proteins to cellular receptors and on S protein priming by host cell proteases. Unravelling which cellular factors are used by SARS-CoV-2 for entry might provide insights into viral transmission and reveal therapeutic targets. Here, we demonstrate that SARS-CoV-2 uses the SARS-CoV receptor ACE2 for entry and the serine protease TMPRSS2 for S protein priming. A TMPRSS2 inhibitor approved for clinical use blocked entry and might constitute a treatment option. Finally, we show that the sera from convalescent SARS patients cross-neutralized SARS-2-S-driven entry. Our results reveal important commonalities between SARS-CoV-2 and SARS-CoV infection and identify a potential target for antiviral intervention.", "qid": 29, "docid": "a5phwzxh", "rank": 94, "score": 0.8506734371185303}, {"content": "Title: Genomics-guided molecular maps of coronavirus targets in human cells: a path toward the repurposing of existing drugs to mitigate the pandemic Content: Human genes required for SARS-CoV-2 entry into human cells, ACE2 and FURIN, were employed as baits to build genomics-guided maps of up-stream regulatory elements, their expression and functions in human body, including pathophysiologically-relevant cell types. Genes acting as 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) were then employed to identify existing drugs that could be repurposed to mitigate the coronavirus infection. Present analyses identify Vitamin D and Quercetin as promising pandemic mitigation agents. Gene expression profiles of Vitamin D and Quercetin activities and their established safety records as over-the-counter medicinal substances suggest that they may represent viable candidates for further assessment and considerations of their potential as coronavirus pandemic mitigation agents. Notably, gene set enrichment analyses and expression profiling experiments identify multiple drugs, most notably testosterone, dexamethasone, and doxorubicin, smoking, and many disease conditions that appear to act as putative coronavirus infection-promoting agents. Discordant patterns of Testosterone versus Estradiol impacts on SCARS-CoV-2 targets suggest a plausible molecular explanation of the apparently higher male mortality during coronavirus pandemic.", "qid": 29, "docid": "uxs9tiuk", "rank": 95, "score": 0.8505544662475586}, {"content": "Title: Computational Prediction of Mutational Effects on the SARS-CoV-2 Binding by Relative Free Energy Calculations Content: The ability of coronaviruses to infect humans is invariably associated with their binding strengths to human receptor proteins Both SARS-CoV-2, initially named 2019-nCoV, and SARS-CoV were reported to utilize angiotensin-converting enzyme 2 (ACE2) as an entry receptor in human cells To better understand the interplay between SARS-CoV-2 and ACE2, we performed computational alanine scanning mutagenesis on the \u201chotspot\u201d residues at protein-protein interfaces using relative free energy calculations Our data suggest that the mutations in SARS-CoV-2 lead to a greater binding affinity relative to SARS-CoV In addition, our free energy calculations provide insight into the infectious ability of viruses on a physical basis, and also provide useful information for the design of antiviral drugs", "qid": 29, "docid": "nhxnz86n", "rank": 96, "score": 0.850525975227356}, {"content": "Title: Study of combining virtual screening and antiviral treatments of the Sars-CoV-2 (Covid-19) Content: The recent epidemic outbreak of a novel human coronavirus called SARS-CoV-2 and causing the respiratory tract disease COVID-19 has reached worldwide resonance and a global effort is being undertaken to characterize the molecular features and evolutionary origins of this virus. Therefore, rapid and accurate identification of pathogenic viruses plays a vital role in selecting appropriate treatments, saving people's lives and preventing epidemics. Additionally, general treatments, coronavirus-specific treatments, and antiviral treatments useful in fighting COVID-19 are addressed. This review sets out to shed light on the SARS-CoV-2 and host receptor recognition, a crucial factor for successful virus infection and taking immune-informatics approaches to identify B- and T-cell epitopes for surface glycoprotein of SARS-CoV-2. A variety of improved or new approaches also have been developed. It is anticipated that this will assist researchers and clinicians in developing better techniques for timely and effective detection of coronavirus infection. Moreover, the genomic sequence of the virus responsible for COVID-19, as well as the experimentally determined three-dimensional structure of the Main protease (Mpro) is available. The reported structure of the target Mpro was described in this review to identify potential drugs for COVID-19 using virtual high throughput screening.", "qid": 29, "docid": "ribspvyf", "rank": 97, "score": 0.8503026962280273}, {"content": "Title: Considerations for interactions of drugs used for the treatment of COVID-19 with anti-Cancer treatments Content: SARS-CoV2 infection is an emerging issue worldwide. Cancer patient are at increased risk of infection compared to general population. On the other hand, these patients are at major risk of drug interactions caused by renal and hepatic impairment background. Because of the long-term use of chemotherapy drugs, drug interactions are important in these patients especially with SARS-CoV2 treatments now. This paper is review of reported drug interactions of current treatments for COVID-19 and anticancer agents.", "qid": 29, "docid": "8tldrtcb", "rank": 98, "score": 0.8502873778343201}, {"content": "Title: Considerations for interactions of drugs used for the treatment of COVID-19 with anti-cancer treatments Content: SARS-CoV2 infection is an emerging issue worldwide. Cancer patient are at increased risk of infection compared to general population. On the other hand, these patients are at major risk of drug interactions caused by renal and hepatic impairment background. Because of the long-term use of chemotherapy drugs, drug interactions are important in these patients especially with SARS-CoV2 treatments now. This paper is review of reported drug interactions of current treatments for COVID-19 and anticancer agents.", "qid": 29, "docid": "wsqjwszz", "rank": 99, "score": 0.8502873182296753}, {"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": 100, "score": 0.8501449823379517}]}
{"query": "is remdesivir an effective treatment for COVID-19", "hits": [{"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": 1, "score": 0.9317511916160583}, {"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": 2, "score": 0.9232834577560425}, {"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": 3, "score": 0.9231747984886169}, {"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": 4, "score": 0.9231747984886169}, {"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": 5, "score": 0.9224447011947632}, {"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": 6, "score": 0.9216969609260559}, {"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": 7, "score": 0.9208962917327881}, {"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": 8, "score": 0.9208903312683105}, {"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": 9, "score": 0.9208145141601562}, {"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": 10, "score": 0.9206463098526001}, {"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": 11, "score": 0.9202927350997925}, {"content": "Title: Remdesivir for 5 or 10 Days in Patients with Severe Covid-19 Content: BACKGROUND: Remdesivir is an RNA polymerase inhibitor with potent antiviral activity in vitro and efficacy in animal models of coronavirus disease 2019 (Covid-19). METHODS: We conducted a randomized, open-label, phase 3 trial involving hospitalized patients with confirmed SARS-CoV-2 infection, oxygen saturation of 94% or less while they were breathing ambient air, and radiologic evidence of pneumonia. Patients were randomly assigned in a 1:1 ratio to receive intravenous remdesivir for either 5 days or 10 days. All patients received 200 mg of remdesivir on day 1 and 100 mg once daily on subsequent days. The primary end point was clinical status on day 14, assessed on a 7-point ordinal scale. RESULTS: In total, 397 patients underwent randomization and began treatment (200 patients for 5 days and 197 for 10 days). The median duration of treatment was 5 days (interquartile range, 5 to 5) in the 5-day group and 9 days (interquartile range, 5 to 10) in the 10-day group. At baseline, patients randomly assigned to the 10-day group had significantly worse clinical status than those assigned to the 5-day group (P = 0.02). By day 14, a clinical improvement of 2 points or more on the ordinal scale occurred in 64% of patients in the 5-day group and in 54% in the 10-day group. After adjustment for baseline clinical status, patients in the 10-day group had a distribution in clinical status at day 14 that was similar to that among patients in the 5-day group (P = 0.14). The most common adverse events were nausea (9% of patients), worsening respiratory failure (8%), elevated alanine aminotransferase level (7%), and constipation (7%). CONCLUSIONS: In patients with severe Covid-19 not requiring mechanical ventilation, our trial did not show a significant difference between a 5-day course and a 10-day course of remdesivir. With no placebo control, however, the magnitude of benefit cannot be determined. (Funded by Gilead Sciences; GS-US-540-5773 ClinicalTrials.gov number, NCT04292899.).", "qid": 30, "docid": "pibcxe1x", "rank": 12, "score": 0.9175769090652466}, {"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": 30, "docid": "w3ido97l", "rank": 13, "score": 0.9168127775192261}, {"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": 30, "docid": "ntozf7ba", "rank": 14, "score": 0.9168127775192261}, {"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": 0.9148215055465698}, {"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": 16, "score": 0.9125029444694519}, {"content": "Title: Remdesivir for 5 or 10 Days in Patients with Severe Covid-19. Content: BACKGROUND Remdesivir is an RNA polymerase inhibitor with potent antiviral activity in vitro and efficacy in animal models of coronavirus disease 2019 (Covid-19). METHODS We conducted a randomized, open-label, phase 3 trial involving hospitalized patients with confirmed SARS-CoV-2 infection, oxygen saturation of 94% or less while they were breathing ambient air, and radiologic evidence of pneumonia. Patients were randomly assigned in a 1:1 ratio to receive intravenous remdesivir for either 5 days or 10 days. All patients received 200 mg of remdesivir on day 1 and 100 mg once daily on subsequent days. The primary end point was clinical status on day 14, assessed on a 7-point ordinal scale. RESULTS In total, 397 patients underwent randomization and began treatment (200 patients for 5 days and 197 for 10 days). The median duration of treatment was 5 days (interquartile range, 5 to 5) in the 5-day group and 9 days (interquartile range, 5 to 10) in the 10-day group. At baseline, patients randomly assigned to the 10-day group had significantly worse clinical status than those assigned to the 5-day group (P = 0.02). By day 14, a clinical improvement of 2 points or more on the ordinal scale occurred in 64% of patients in the 5-day group and in 54% in the 10-day group. After adjustment for baseline clinical status, patients in the 10-day group had a distribution in clinical status at day 14 that was similar to that among patients in the 5-day group (P = 0.14). The most common adverse events were nausea (9% of patients), worsening respiratory failure (8%), elevated alanine aminotransferase level (7%), and constipation (7%). CONCLUSIONS In patients with severe Covid-19 not requiring mechanical ventilation, our trial did not show a significant difference between a 5-day course and a 10-day course of remdesivir. With no placebo control, however, the magnitude of benefit cannot be determined. (Funded by Gilead Sciences; GS-US-540-5773 ClinicalTrials.gov number, NCT04292899.).", "qid": 30, "docid": "zbi0llig", "rank": 17, "score": 0.9123543500900269}, {"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": 18, "score": 0.909590482711792}, {"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": 19, "score": 0.909590482711792}, {"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": 20, "score": 0.9095436930656433}, {"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": 21, "score": 0.9075607061386108}, {"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": 22, "score": 0.9064421653747559}, {"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": 23, "score": 0.9057663679122925}, {"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": 24, "score": 0.9032156467437744}, {"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": 25, "score": 0.9029693603515625}, {"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": 26, "score": 0.9021021127700806}, {"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": 27, "score": 0.902101993560791}, {"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": 28, "score": 0.901546061038971}, {"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": 30, "docid": "tasbdhs1", "rank": 29, "score": 0.9009872674942017}, {"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": 30, "score": 0.8993780612945557}, {"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": 31, "score": 0.8953611850738525}, {"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": 32, "score": 0.8953325152397156}, {"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": 33, "score": 0.8924909830093384}, {"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": 34, "score": 0.889137864112854}, {"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": 35, "score": 0.8887598514556885}, {"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": 36, "score": 0.887784481048584}, {"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": 37, "score": 0.8877289295196533}, {"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": 38, "score": 0.8873851299285889}, {"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": 39, "score": 0.8858777284622192}, {"content": "Title: Remdesivir investigational trials in COVID-19: a critical reappraisal Content: Abstract During outbreak of emerging disease, the most important aim is to discover an effective drug to save life. Consequently, a lot of effort are generally made by the industry to promote clinical trials with new drugs. Here we review evidence of the 8 most recent reports including 3 randomized controlled trials on the clinical efficacy of remdesivir in treating COVID-19 patient. We conclude that it is far too premature to identify remdesivir as a curative or life-saving intervention.", "qid": 30, "docid": "pkklt77i", "rank": 40, "score": 0.8858623504638672}, {"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": 41, "score": 0.8857917785644531}, {"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": 42, "score": 0.8850327730178833}, {"content": "Title: Remdesivir: Review of Pharmacology, Pre-clinical Data, and Emerging Clinical Experience for COVID-19 Content: The global pandemic of novel coronavirus disease 2019 (COVID-19) caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) has created an urgent need for effective antivirals. Remdesivir (formerly GS-5734) is a nucleoside analogue pro-drug currently being evaluated in COVID-19 clinical trials. Its unique structural features allow high concentrations of the active triphosphate metabolite to be delivered intracellularly and it evades proofreading to successfully inhibit viral RNA synthesis. In pre-clinical models, remdesivir has demonstrated potent antiviral activity against diverse human and zoonotic \u00df-coronaviruses, including SARS-CoV-2. In this article, we critically review available data on remdesivir with an emphasis on biochemistry, pharmacology, pharmacokinetics, and in vitro activity against coronaviruses as well as clinical experience and current progress in COVID-19 clinical trials.", "qid": 30, "docid": "gk2p9w2d", "rank": 43, "score": 0.8828999996185303}, {"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": 30, "docid": "x89iy0m2", "rank": 44, "score": 0.8824865221977234}, {"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": 45, "score": 0.8814399242401123}, {"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": 46, "score": 0.8779933452606201}, {"content": "Title: Coronavirus drug, water warning and virus-research funding. Content: One of the world\u2019s best hopes for treating COVID-19 \u2014 a compound called remdesivir \u2014 has been authorized as a therapy against the disease On 1 May, the US Food and Drug Administration (FDA) granted an \u2018emergency-use authorization\u2019 for clinicians to use the drug, which is administered intravenously, in hospitals for people with severe COVID-19", "qid": 30, "docid": "5kcl80sj", "rank": 47, "score": 0.877892017364502}, {"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": 48, "score": 0.8778884410858154}, {"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": 49, "score": 0.8771409392356873}, {"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": 50, "score": 0.8771148920059204}, {"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": 51, "score": 0.8765075206756592}, {"content": "Title: Safety, Tolerability, and Pharmacokinetics of Remdesivir, an Antiviral for Treatment of COVID-19, in Healthy Subjects Content: Remdesivir (RDV), a single diastereomeric monophosphoroamidate prodrug that inhibits viral RNA polymerases, has potent in vitro antiviral activity against SARS-CoV2. RDV received FDA's emergency use authorization in United States and approval in Japan for treatment of severe COVID-19 patients. This report describes two phase 1 studies that evaluated the safety and pharmacokinetics (PK) of single escalating and multiple intravenous (IV) doses of RDV (solution or lyophilized formulation) in healthy subjects. Lyophilized formulation was evaluated for potential future use in clinical trials due to its storage stability in resource-limited settings. All adverse events were Grade 1 or 2 in severity. Overall, RDV exhibited a linear profile following single-dose IV administration over 2 hours of RDV solution formulation across the dose range of 3 to 225mg. Both lyophilized and solution formulations provided comparable PK parameters. High intracellular concentrations of the active triphosphate (approximately 220 to 370- fold higher than the in vitro EC50 against SARS-CoV-2 clinical isolate) were achieved following infusion of 75 mg or 150 mg lyophilized formulation over 30 minutes or 2 hours. Following multiple-doses of RDV 150mg once daily for 7 or 14 days, RDV exhibited a PK profile similar to single-dose administration. Metabolite GS-441524 accumulated approximately 1.9-fold after daily dosing. Overall, RDV exhibited favorable safety and PK profiles that supported once-daily dosing.", "qid": 30, "docid": "6ywijk3d", "rank": 52, "score": 0.8763256072998047}, {"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": 53, "score": 0.8754884600639343}, {"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": 54, "score": 0.8744463920593262}, {"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": 55, "score": 0.8741084337234497}, {"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": 56, "score": 0.8724145889282227}, {"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": 57, "score": 0.871469259262085}, {"content": "Title: Lack of antiviral activity of darunavir against SARS-CoV-2 Content: OBJECTIVES: Given the high need and the absence of specific antivirals for treatment of COVID-19 (the disease caused by severe acute respiratory syndrome-associated coronavirus-2 [SARS-CoV-2]), human immunodeficiency virus (HIV) protease inhibitors are being considered as therapeutic alternatives. METHODS: Prezcobix/Rezolsta is a fixed-dose combination of 800 mg of the HIV protease inhibitor darunavir (DRV) and 150 mg cobicistat, a CYP3A4 inhibitor, which is indicated in combination with other antiretroviral agents for the treatment of HIV infection. There are currently no definitive data on the safety and efficacy of DRV/cobicistat for the treatment of COVID-19. The in vitro antiviral activity of darunavir against a clinical isolate from a patient infected with SARS-CoV-2 was assessed. RESULTS: DRV showed no antiviral activity against SARS-CoV-2 at clinically relevant concentrations (EC50 > 100 \u00b5M). Remdesivir, used as a positive control, demonstrated potent antiviral activity (EC50 = 0.38 \u00b5M). CONCLUSIONS: Overall, the data do not support the use of DRV for the treatment of COVID-19.", "qid": 30, "docid": "roxiohnm", "rank": 58, "score": 0.871188759803772}, {"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": 59, "score": 0.8706147074699402}, {"content": "Title: Efficacy of remdesivir in COVID-19 patients with a simulated two-arm controlled study Content: While the recent study on the compassionate use of remdesivir for COVID-19 patients has shown a 68% clinical improvement7 it is a one-arm study that renders the evaluation of the efficacy in reducing death and the length of stay of hospitalization intractable due to a lacking of the control group. We came up with a two-arm controlled study design to simulate the treated and the untreated (control group) group by applying two respective transition models to the empirical data on dynamics of the disease severity (Figure 2 of the original article7) that are classified into low- (no and low oxygen supplement), medium- (non-invasive ventilator and high oxygen supplement), and high-(ECMO and invasive ventilator) from enrolment until discharge, death or the end of follow-up. By using a simulated two-arm controlled study, the remdesivir treatment group as opposed to the control group led to a statistically significantly 29% (95% CI: 22-35%) reduction of death from COVID-19. The treated group also revealed a 33% (95% CI 28-38%) significantly higher odds of discharge than the control group. The median time to discharge for the treated group (5.5 days, 16.5 days, and 29.5 days for low-, medium-, and high-risk state, respectively) was around half of those of the control arm. Our results with a simulated two-arm controlled study have not only corroborated the efficacy of remdesivir but also made great contribution to designing a further large-scale randomized controlled trial. They have significant implications for reducing transmission probability and infectious time of COVID-19 patients when contacting with susceptible health care workers during hospitalization.", "qid": 30, "docid": "qpa6tk6v", "rank": 60, "score": 0.8697390556335449}, {"content": "Title: Remdesivir potently inhibits SARS-CoV-2 in human lung cells and chimeric SARS-CoV expressing the SARS-CoV-2 RNA polymerase in mice Content: Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) emerged in 2019 as the causative agent of the novel pandemic viral disease COVID-19. With no approved therapies, this pandemic illustrates the urgent need for safe, broad-spectrum antiviral countermeasures against SARS-CoV-2 and future emerging CoVs. We report that remdesivir (RDV), a monophosphoramidate prodrug of an adenosine analog, potently inhibits SARS-CoV-2 replication in human lung cells and primary human airway epithelial cultures (EC50 = 0.01 \u03bcM). Weaker activity was observed in Vero E6 cells (EC50 = 1.65 \u03bcM) due to their low capacity to metabolize RDV. To rapidly evaluate in vivo efficacy, we engineered a chimeric SARS-CoV encoding the viral target of RDV, the RNA-dependent RNA polymerase, of SARS-CoV-2. In mice infected with chimeric virus, therapeutic RDV administration diminished lung viral load and improved pulmonary function as compared to vehicle treated animals. These data provide evidence that RDV is potently active against SARS-CoV-2 in vitro and in vivo, supporting its further clinical testing for treatment of COVID-19.", "qid": 30, "docid": "ghrlj6b2", "rank": 61, "score": 0.8694586753845215}, {"content": "Title: Compounds with Therapeutic Potential against Novel Respiratory 2019 Coronavirus Content: Currently, the expansion of the novel human respiratory coronavirus (known as SARS-CoV-2 [severe acute respiratory syndrome coronavirus 2], COVID-2019 [coronavirus disease 2019], or 2019-nCoV [2019 novel coronavirus]) has stressed the need for therapeutic alternatives to alleviate and stop this new epidemic. The previous epidemics of infections by high-morbidity human coronaviruses, such as SARS-CoV in 2003 and the Middle East respiratory syndrome coronavirus (MERS-CoV) in 2012, prompted the characterization of compounds that could be potentially active against the currently emerging novel coronavirus, SARS-CoV-2. The most promising compound is remdesivir (GS-5734), a nucleotide analog prodrug currently in clinical trials for treating Ebola virus infections. Remdesivir inhibited the replication of SARS-CoV and MERS-CoV in tissue cultures, and it displayed efficacy in nonhuman animal models. In addition, a combination of the human immunodeficiency virus type 1 (HIV-1) protease inhibitors lopinavir/ritonavir and interferon beta (LPV/RTV\u2013IFN-\u03b2) was shown to be effective in patients infected with SARS-CoV. LPV/RTV\u2013IFN-\u03b2 also improved clinical parameters in marmosets and mice infected with MERS-CoV. Remarkably, the therapeutic efficacy of remdesivir appeared to be superior to that of LPV/RTV\u2013IFN-\u03b2 against MERS-CoV in a transgenic humanized mouse model. The relatively high mortality rates associated with these three novel human coronavirus infections, SARS-CoV, MERS-CoV, and SARS-CoV-2, have suggested that proinflammatory responses might play a role in the pathogenesis. It remains unknown whether the generated inflammatory state should be targeted. Therapeutics that target the coronavirus alone might not be able to reverse highly pathogenic infections. This minireview aims to provide a summary of therapeutic compounds that have shown potential in fighting SARS-CoV-2 infections.", "qid": 30, "docid": "nz8qvuw6", "rank": 62, "score": 0.8684325218200684}, {"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 (C(0)) and at 1 (C(1)) and 24 h (C(24)) 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 C(0) (6- to 7-fold higher than EC(50) from in vitro studies) and a notable decay at C(1). GS-441524 plasma concentrations reached a peak at C(1) 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": "9gnjh45x", "rank": 63, "score": 0.8683331608772278}, {"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": 64, "score": 0.8682607412338257}, {"content": "Title: Comparative Antiviral Activity of Remdesivir and Anti-HIV Nucleoside Analogs Against Human Coronavirus 229E (HCoV-229E) Content: Remdesivir is a nucleotide prodrug that is currently undergoing extensive clinical trials for the treatment of COVID-19. The prodrug is metabolized to its active triphosphate form and interferes with the action of RNA-dependent RNA polymerase of SARS-COV-2. Herein, we report the antiviral activity of remdesivir against human coronavirus 229E (HCoV-229E) compared to known anti-HIV agents. These agents included tenofovir (TFV), 4'-ethynyl-2-fluoro-2'-deoxyadenosine (EFdA), alovudine (FLT), lamivudine (3TC), and emtricitabine (FTC), known as nucleoside reverse-transcriptase inhibitors (NRTIs), and a number of 5'-O-fatty acylated anti-HIV nucleoside conjugates. The anti-HIV nucleosides interfere with HIV RNA-dependent DNA polymerase and/or act as chain terminators. Normal human fibroblast lung cells (MRC-5) were used to determine the cytotoxicity of the compounds. The study revealed that remdesivir exhibited an EC50 value of 0.07 \u00b5M against HCoV-229E with TC50 of > 2.00 \u00b5M against MRC-5 cells. Parent NRTIs were found to be inactive against (HCoV-229E) at tested concentrations. Among all the NRTIs and 5'-O-fatty acyl conjugates of NRTIs, 5'-O-tetradecanoyl ester conjugate of FTC showed modest activity with EC50 and TC50 values of 72.8 \u00b5M and 87.5 \u00b5M, respectively. These data can be used for the design of potential compounds against other coronaviruses.", "qid": 30, "docid": "7wiirvox", "rank": 65, "score": 0.8682178258895874}, {"content": "Title: Comparative Antiviral Activity of Remdesivir and Anti-HIV Nucleoside Analogs against Human Coronavirus 229E (HCoV-229E) Content: Remdesivir is a nucleotide prodrug that is currently undergoing extensive clinical trials for the treatment of COVID-19. The prodrug is metabolized to its active triphosphate form and interferes with the action of RNA-dependent RNA polymerase of SARS-COV-2. Herein, we report the antiviral activity of remdesivir against human coronavirus 229E (HCoV-229E) compared to known anti-HIV agents. These agents included tenofovir (TFV), 4\u2032-ethynyl-2-fluoro-2\u2032-deoxyadenosine (EFdA), alovudine (FLT), lamivudine (3TC), and emtricitabine (FTC), known as nucleoside reverse-transcriptase inhibitors (NRTIs), and a number of 5\u2032-O-fatty acylated anti-HIV nucleoside conjugates. The anti-HIV nucleosides interfere with HIV RNA-dependent DNA polymerase and/or act as chain terminators. Normal human fibroblast lung cells (MRC-5) were used to determine the cytotoxicity of the compounds. The study revealed that remdesivir exhibited an EC(50) value of 0.07 \u00b5M against HCoV-229E with TC(50) of > 2.00 \u00b5M against MRC-5 cells. Parent NRTIs were found to be inactive against (HCoV-229E) at tested concentrations. Among all the NRTIs and 5\u2032-O-fatty acyl conjugates of NRTIs, 5\u2032-O-tetradecanoyl ester conjugate of FTC showed modest activity with EC(50) and TC(50) values of 72.8 \u00b5M and 87.5 \u00b5M, respectively. These data can be used for the design of potential compounds against other coronaviruses.", "qid": 30, "docid": "ljmkqdzx", "rank": 66, "score": 0.8679943084716797}, {"content": "Title: Compounds with Therapeutic Potential against Novel Respiratory 2019 Coronavirus Content: Currently, the expansion of the novel human respiratory coronavirus (known as SARS-CoV-2 [severe acute respiratory syndrome coronavirus 2], COVID-2019 [coronavirus disease 2019], or 2019-nCoV [2019 novel coronavirus]) has stressed the need for therapeutic alternatives to alleviate and stop this new epidemic. The previous epidemics of infections by high-morbidity human coronaviruses, such as SARS-CoV in 2003 and the Middle East respiratory syndrome coronavirus (MERS-CoV) in 2012, prompted the characterization of compounds that could be potentially active against the currently emerging novel coronavirus, SARS-CoV-2. The most promising compound is remdesivir (GS-5734), a nucleotide analog prodrug currently in clinical trials for treating Ebola virus infections. Remdesivir inhibited the replication of SARS-CoV and MERS-CoV in tissue cultures, and it displayed efficacy in nonhuman animal models. In addition, a combination of the human immunodeficiency virus type 1 (HIV-1) protease inhibitors lopinavir/ritonavir and interferon beta (LPV/RTV-IFN-\u00df) was shown to be effective in patients infected with SARS-CoV. LPV/RTV-IFN-\u00df also improved clinical parameters in marmosets and mice infected with MERS-CoV. Remarkably, the therapeutic efficacy of remdesivir appeared to be superior to that of LPV/RTV-IFN-\u00df against MERS-CoV in a transgenic humanized mouse model. The relatively high mortality rates associated with these three novel human coronavirus infections, SARS-CoV, MERS-CoV, and SARS-CoV-2, have suggested that proinflammatory responses might play a role in the pathogenesis. It remains unknown whether the generated inflammatory state should be targeted. Therapeutics that target the coronavirus alone might not be able to reverse highly pathogenic infections. This minireview aims to provide a summary of therapeutic compounds that have shown potential in fighting SARS-CoV-2 infections.", "qid": 30, "docid": "anen3dor", "rank": 67, "score": 0.8676357269287109}, {"content": "Title: Halting coronavirus polymerase. Content: The nucleotide analogue remdesivir is an investigational drug for the treatment of human coronavirus infection. Remdesivir is a phosphoramidate prodrug and is known to target viral RNA-dependent RNA polymerases. In this issue, Gordon et al. identify that remdesivir acts as a delayed RNA chain terminator for MERS-CoV polymerase complexes.", "qid": 30, "docid": "b8tknq05", "rank": 68, "score": 0.867466151714325}, {"content": "Title: Remdesivir inhibits SARS-CoV-2 in human lung cells and chimeric SARS-CoV expressing the SARS-CoV-2 RNA polymerase in mice. Content: Summary Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) is the causative agent of the novel viral disease COVID-19. With no approved therapies, this pandemic illustrates the urgent need for broad-spectrum antiviral countermeasures against SARS-CoV-2 and future emerging CoVs. We report that remdesivir (RDV) potently inhibits SARS-CoV-2 replication in human lung cells and primary human airway epithelial cultures (EC50 = 0.01 \u03bcM). Weaker activity is observed in Vero E6 cells (EC50 = 1.65 \u03bcM) due to their low capacity to metabolize RDV. To rapidly evaluate in vivo efficacy, we engineered a chimeric SARS-CoV encoding the viral target of RDV, the RNA-dependent RNA polymerase, of SARS-CoV-2. In mice infected with chimeric virus, therapeutic RDV administration diminishes lung viral load and improves pulmonary function compared to vehicle treated animals. These data demonstrate that RDV is potently active against SARS-CoV-2 in vitro and in vivo, supporting its further clinical testing for treatment of COVID-19.", "qid": 30, "docid": "9sjdb7f3", "rank": 69, "score": 0.8661873936653137}, {"content": "Title: Large trial yields strongest evidence yet that antiviral drug can help COVID-19 patients Content: A candidate treatment for COVID-19 has shown convincing\u2014albeit modest\u2014benefit for the first time in a large, carefully controlled clinical trial in hospitalized patients The infected people who received remdesivir, an experimental drug made by Gilead Sciences that cripples an enzyme several viruses use to copy their RNA, recovered in an average of 11 days versus 15 in patients who received a placebo \u201cAlthough a 31% improvement doesn\u2019t seem like a knockout, 100% [success], it is a very important proof of concept,\u201d said Anthony Fauci, head of the National Institute of Allergy and Infectious Diseases (NIAID), during an Oval Office meeting in which President Donald Trump was asked by media about a statement Gilead had released on the results The patients treated with remdesivir also had a lower mortality rate\u20148% versus 11 6% in the group given the placebo\u2014but this positive trend did not reach statistical significance, Fauci noted (The full results from the trial have not been made public in a preprint or peer-reviewed paper )", "qid": 30, "docid": "bjgy98r8", "rank": 70, "score": 0.8654828667640686}, {"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": 71, "score": 0.8649264574050903}, {"content": "Title: Remdesivir: Review of pharmacology, pre\u2010clinical data and emerging clinical experience for COVID\u201019 Content: The global pandemic of novel coronavirus disease 2019 (COVID\u201019) caused by severe acute respiratory syndrome coronavirus 2 (SARS\u2010CoV\u20102) has created an urgent need for effective antivirals. Remdesivir (formerly GS\u20105734) is a nucleoside analogue pro\u2010drug currently being evaluated in COVID\u201019 clinical trials. Its unique structural features allow high concentrations of the active triphosphate metabolite to be delivered intracellularly and it evades proofreading to successfully inhibit viral RNA synthesis. In pre\u2010clinical models, remdesivir has demonstrated potent antiviral activity against diverse human and zoonotic \u03b2\u2010coronaviruses, including SARS\u2010CoV\u20102. In this article we critically review available data on remdesivir with an emphasis on biochemistry, pharmacology, pharmacokinetics and in vitro activity against coronaviruses as well as clinical experience and current progress in COVID\u201019 clinical trials.", "qid": 30, "docid": "uo8k6qic", "rank": 72, "score": 0.8648404479026794}, {"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": 73, "score": 0.8646223545074463}, {"content": "Title: Safety, Tolerability, and Pharmacokinetics of Remdesivir, an Antiviral for Treatment of COVID\u201019, in Healthy Subjects Content: Remdesivir (RDV), a single diastereomeric monophosphoroamidate prodrug that inhibits viral RNA polymerases, has potent in vitro antiviral activity against SARS\u2010CoV2. RDV received FDA\u2019s emergency use authorization in United States and approval in Japan for treatment of severe COVID\u201019 patients. This report describes two phase 1 studies that evaluated the safety and pharmacokinetics (PK) of single escalating and multiple intravenous (IV) doses of RDV (solution or lyophilized formulation) in healthy subjects. Lyophilized formulation was evaluated for potential future use in clinical trials due to its storage stability in resource\u2010limited settings. All adverse events were Grade 1 or 2 in severity. Overall, RDV exhibited a linear profile following single\u2010dose IV administration over 2 hours of RDV solution formulation across the dose range of 3 to 225mg. Both lyophilized and solution formulations provided comparable PK parameters. High intracellular concentrations of the active triphosphate (approximately 220 to 370\u2010 fold higher than the in vitro EC50 against SARS\u2010CoV\u20102 clinical isolate) were achieved following infusion of 75 mg or 150 mg lyophilized formulation over 30 minutes or 2 hours. Following multiple\u2010doses of RDV 150mg once daily for 7 or 14 days, RDV exhibited a PK profile similar to single\u2010dose administration. Metabolite GS\u2010441524 accumulated approximately 1.9\u2010fold after daily dosing. Overall, RDV exhibited favorable safety and PK profiles that supported once\u2010daily dosing.", "qid": 30, "docid": "uu4h5hdh", "rank": 74, "score": 0.8636677265167236}, {"content": "Title: Vytr hypothesis for the prophylactic and therapeutic efficacy of GS-5734 treatment in humans with COVID-19 Content: In December 2019, many pneumonia cases were reported without an appar-ent cause but were associated with seafood and wet markets in Wuhan, China Clinical features were similar to pneumonia, and SARS-CoV-2 (formerly 2019-nCoV) was determined as the causative pathogen. To date, there are no effective antiviral drugs for the targeted treatment of coronavirus disease 2019 (COVID-19). We provide the VITYALA YETHINDRA (VYTR) hypothesis for the prophylactic and therapeutic efficacy of GS-5734 treatment in humans with COVID-19. Prophylactic GS-5734 treatment may prevent SARS-CoV-2 induced disease and lung lesions in participants inoculated with SARS-CoV-2 and potentially inhibit SARS-CoV-2 replication. Therapeutic GS-5734 treatment may show a reduction in the severity of symptoms, reduce viral repli-cation, the complete eradication of lung lesions in some participants and decrease in the extent of lesions in 50% of participants may be possible. As broad-spectrum drugs are capable of inhibiting coronavirus infections, GS-5734 should be considered a broad-spectrum, first-line drug and may inhibit coronavirus infections and COVID-19. More clinical trials are needed to prove that GS-5734 (Remdesivir) is a safe and effective drug for the treatment of COVID-19.", "qid": 30, "docid": "7ovfb4mm", "rank": 75, "score": 0.860920250415802}, {"content": "Title: Lack of Antiviral Activity of Darunavir against SARS-CoV-2 Content: Abstract Objectives Given the high need and the absence of specific antivirals for treatment of COVID-19 (the disease caused by severe acute respiratory syndrome-associated coronavirus-2 [SARS-CoV-2]), human immunodeficiency virus (HIV) protease inhibitors are being considered as therapeutic alternatives. Methods Prezcobix/Rezolsta is a fixed-dose combination of 800mg of the HIV protease inhibitor darunavir (DRV) and 150mg cobicistat, a CYP3A4 inhibitor, which is indicated in combination with other antiretroviral agents for the treatment of HIV infection. There are currently no definitive data on the safety and efficacy of DRV/cobicistat for treatment of COVID-19. The in vitro antiviral activity of darunavir against a clinical isolate from a patient infected with SARS-CoV-2 was assessed. Results DRV showed no activity against SARS-CoV-2 at clinically relevant concentrations (EC50 >100\u03bcM). Remdesivir, used as a positive control, showed potent antiviral activity (EC50 =0.38\u03bcM). Conclusions Overall, the data do not support the use of DRV for treatment of COVID-19.", "qid": 30, "docid": "8dlxnpcn", "rank": 76, "score": 0.8580430746078491}, {"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": 77, "score": 0.8550961017608643}, {"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": 78, "score": 0.8548824787139893}, {"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": 79, "score": 0.8547046184539795}, {"content": "Title: COVID-19: An Update about the Discovery Clinical Trial Content: Finding efficacious and safe treatments for COVID-19 emerges as a crucial need in order to control the spread of the pandemic. Whereas plasma therapy attracts much interest, the European project Discovery focuses on the potentialities of small molecules like remdesivir, the combination of lopinavir/ritonavir, hydroxychloroquine, and chloroquine. Results recently published on the clinical evaluation of those drugs are compiled in this brief report, although complete data are still impatiently awaited.", "qid": 30, "docid": "sqrbj5r4", "rank": 80, "score": 0.854674220085144}, {"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": 81, "score": 0.8539405465126038}, {"content": "Title: Lack of Antiviral Activity of Darunavir against SARS-CoV-2 Content: Given the high need and the absence of specific antivirals for treatment of COVID-19 (the disease caused by severe acute respiratory syndrome-associated coronavirus-2 [SARS-CoV-2]), human immunodeficiency virus (HIV) protease inhibitors are being considered as therapeutic alternatives. Prezcobix/Rezolsta is a fixed-dose combination of 800 mg of the HIV protease inhibitor darunavir (DRV) and 150 mg cobicistat, a CYP3A4 inhibitor, which is indicated in combination with other antiretroviral agents for the treatment of HIV infection. There are currently no definitive data on the safety and efficacy of DRV/cobicistat for treatment of COVID-19. The in vitro antiviral activity of darunavir against a clinical isolate from a patient infected with SARS-CoV-2 was assessed. DRV showed no activity against SARS-CoV-2 at clinically relevant concentrations (EC50 >100 \u03bcM). Remdesivir, used as a positive control, showed potent antiviral activity (EC50 = 0.38 \u03bcM). Overall, the data do not support the use of DRV for treatment of COVID-19.", "qid": 30, "docid": "679qfp2s", "rank": 82, "score": 0.8537514209747314}, {"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": 83, "score": 0.8535401821136475}, {"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": 84, "score": 0.853326678276062}, {"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": 0.8531160354614258}, {"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": 30, "docid": "puc13jf1", "rank": 86, "score": 0.8530257344245911}, {"content": "Title: An exploratory randomized controlled study on the efficacy and safety of lopinavir/ritonavir or arbidol treating adult patients hospitalized with mild/moderate COVID-19 (ELACOI) Content: Background: Antiviral therapies against the novel coronavirus SARS-CoV-2, which has caused a global pandemic of respiratory illness called COVID-19, are still lacking. Methods: Our study (NCT04252885, named ELACOI), was an exploratory randomized (2:2:1) controlled trial assessing the efficacy and safety of lopinavir/ritonavir (LPV/r) or arbidol monotherapy for treating patients with mild/moderate COVID-19. Findings: This study successfully enrolled 86 patients with mild/moderate COVID-19 with 34 randomly assigned to receive LPV/r, 35 to arbidol and 17 with no antiviral medication as control. Baseline characteristics of the three groups were comparable. The primary endpoints, the average time of positive-to-negative conversion of SARS-CoV-2 nucleic acid and conversion rates at days 7 and 14, were similar between groups (all P>0.05). There were no differences between groups in the secondary endpoints, the rates of antipyresis, cough alleviation, or improvement of chest CT at days 7 or 14 (all P>0.05). At day 7, eight (23.5%) patients in the LPV/r group, 3 (8.6%) in the arbidol group and 2(11.8%) in the control group showed a deterioration in clinical status from moderate to severe/critical(P =0.206). Overall, 12 (35.3%) patients in the LPV/r group and 5 (14.3%) in the arbidol group experienced adverse events during the follow-up period. No apparent adverse event occurred in the control group. Conclusions: LPV/r or arbidol monotherapy present little benefit for improving the clinical outcome of patients hospitalized with mild/moderate COVID-19 over supportive care.", "qid": 30, "docid": "9hknw4ws", "rank": 87, "score": 0.8524914979934692}, {"content": "Title: Systematic and Statistical Review of COVID19 Treatment Trials Content: Objective: The following systematic review and meta-analysis compiles the current data regarding human controlled COVID-19 treatment trials. Methods: An electronic search of the literature compiled studies pertaining to human controlled treatment trials with COVID-19. Medications assessed included lopinavir/ritonavir, arbidol, hydroxychloroquine, favipiravir, and heparin. Statistical analyzes were performed for common viral clearance endpoints whenever possible. Results: Lopinavir/ritonavir showed no significant effect on viral clearance for COVID-19 cases (OR 0.95 [95% CI 0.50-1.83]). Hydroxychloroquine also showed no significant effect on COVID-19 viral clearance rates (OR 2.16 [95% CI 0.80-5.84]). Arbidol showed no seven-day (OR 1.63 [95% CI 0.76-3.50]) or 14-day viral (OR 5.37 [95% CI 0.35-83.30]) clearance difference compared to lopinavir/ritonavir. Review of literature showed no significant clinical improvement with lopinavir/ritonavir, arbidol, hydroxychloroquine, or remdesivir. Favipiravir showed quicker symptom improvement compared to lopinavir/ritonavir and arbidol. Heparin showed improvement with severe COVID-19 cases. Conclusion: Current medications do not show significant effect on COVID-19 viral clearance rates. Favipiravir shows favorable results compared to other tested medications. Heparin shows benefit for severe cases of COVID-19.", "qid": 30, "docid": "suo3syr1", "rank": 88, "score": 0.8522547483444214}, {"content": "Title: Favipiravir versus Arbidol for COVID-19: A Randomized Clinical Trial Content: Background No clinically proven effective antiviral strategy exists for the epidemic Coronavirus Disease 2019 (COVID-19). Methods We conducted a prospective, randomized, controlled, open-label multicenter trial involving adult patients with COVID-19. Patients were randomly assigned in a 1:1 ratio to receive conventional therapy plus Umifenovir (Arbidol) (200mg*3/day) or Favipiravir (1600mg*2/first day followed by 600mg*2/day) for 10 days. The primary outcome was clinical recovery rate of Day 7. Latency to relief for pyrexia and cough, the rate of auxiliary oxygen therapy (AOT) or noninvasive mechanical ventilation (NMV) were the secondary outcomes. Safety data were collected for 17 days. Results 240 enrolled COVID-19 patients underwent randomization; 120 patients were assigned to receive Favipiravir (116 assessed), and 120 to receive Arbidol (120 assessed). Clinical recovery rate of Day 7 does not significantly differ between Favipiravir group (71/116) and Arbidol group (62/120) (P=0.1396, difference of recovery rate: 0.0954; 95% CI: -0.0305 to 0.2213). Favipiravir led to shorter latencies to relief for both pyrexia (difference: 1.70 days, P<0.0001) and cough (difference: 1.75 days, P<0.0001). No difference was observed of AOT or NMV rate (both P>0.05). The most frequently observed Favipiravir-associated adverse event was raised serum uric acid (16/116, OR: 5.52, P=0.0014). Conclusions Among patients with COVID-19, Favipiravir, compared to Arbidol, did not significantly improve the clinically recovery rate at Day 7. Favipiravir significantly improved the latency to relief for pyrexia and cough. Adverse effects caused Favipiravir are mild and manageable. This trial is registered with Chictr.org.cn (ChiCTR2000030254).", "qid": 30, "docid": "14he8n3u", "rank": 89, "score": 0.8522533774375916}, {"content": "Title: Target Virus or Target Ourselves for COVID-19 Drugs Discovery?-Lessons learned from anti-influenzas virus therapies Content: The COVID-19 pandemic, after it was reported in December 2019, is a highly contagious and now spreading to over 190 countries, causing a severe public health burden. Currently, there is no vaccine or specific drug to treat COVID-19, which is caused by a novel coronavirus, SARS-2-CoV. For this emergency, the FDA has approved Remdesivir and Hydroxychloroquine for treatment of COVID-19 as Emergency Use Authorization. However, even after this pandemic, COVID-19 may still have a chance to come back. Therefore, we need to come out with new strategies for drug discovery for combating COVID-19 in the future.", "qid": 30, "docid": "dblg9wfk", "rank": 90, "score": 0.8516795635223389}, {"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": 30, "docid": "9ikgkpds", "rank": 91, "score": 0.8512061834335327}, {"content": "Title: Remdesivir and Tocilizumab: Mix or Match Content: To date, no therapy has demonstrated definite efficacy for patients with COVID\u201019. Antiviral, as well as, anti\u2010inflammatory approaches, as these represented by remdesivir (RDV) and tocilizumab (TCZ) use, have been recently put forward. However, data upon optimal choice of one over the other, or potential need for regimen combination, remains an open question. We hereby report two well\u2010matched cases of SARS\u2010CoV\u20102 (+) patients, developing respiratory failure, both receiving TCZ following severe inflammatory response, with or without RDV. We argue that, RDV administration is pivotal early in the course of the disease, since TCZ use alone cannot ensure inflammation control. This article is protected by copyright. All rights reserved.", "qid": 30, "docid": "i6r419kp", "rank": 92, "score": 0.8511244654655457}, {"content": "Title: Clinical Outcomes and Plasma Concentrations of Baloxavir Marboxil and Favipiravir in COVID-19 Patients: an Exploratory Randomized, Controlled Trial Content: Background: Effective antiviral drugs for COVID-19 are still lacking. This study aims to evaluate the clinical outcomes and plasma concentrations of baloxavir marboxil and favipiravir in COVID-19 patients. Methods: Favipiravir and baloxavir acid were evaluated for their antiviral activity against SARS-CoV-2 in vitro before the trial initiation. We conducted an exploratory trial with 3 arms involving hospitalized adult patients with COVID-19. Patients were randomized assigned in a 1:1:1 ratio into baloxavir marboxil group, favipiravir group, and control group. The primary outcome was the percentage of subjects with viral negative by Day 14 and the time from randomization to clinical improvement. Virus load reduction, blood drug concentration and clinical presentation were also observed. The trial was registered with Chinese Clinical Trial Registry (ChiCTR 2000029544). Results: Baloxavir showed antiviral activity in vitro with the half-maximal effective concentration (EC50) of 5.48 M comparable to arbidol and lopinavir, but favipiravir did not demonstrate significant antiviral activity up to 100 M. Thirty patients were enrolled. The percentage of patients who turned viral negative after 14-day treatment was 70%, 77%, and 100% in the baloxavir, favipiravir, and control group respectively, with the medians of time from randomization to clinical improvement was 14, 14 and 15 days, respectively. One reason for the lack of virological effect and clinical benefits may be due to insufficient concentrations of these drugs relative to their antiviral activities. Conclusions: Our findings do not support that adding either baloxavir or favipiravir under the trial dosages to the existing standard treatment.", "qid": 30, "docid": "qujtxkxn", "rank": 93, "score": 0.8511164784431458}, {"content": "Title: Evaluation of 19 antiviral drugs against SARS-CoV-2 Infection Content: The global pandemic of the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2 or 2019-nCoV) has prompted multiple clinical trials to jumpstart search for anti-SARS-CoV-2 therapies from existing drugs, including those with reported in vitro efficacies as well as those ones that are not known to inhibit SARS-CoV-2, such as ritonavir/lopinavir and favilavir. Here we report that after screening 19 antiviral drugs that are either in clinical trials or with proposed activity against SARS-CoV-2, remdesivir was the most effective. Chloroquine only effectively protected virus-induced cytopathic effect at around 30 \u00b5M with a therapeutic index of 1.5. Our findings also suggest that velpatasvir, ledipasvir, ritonavir, litonavir, lopinavir, favilavir, sofosbuvir, danoprevir, and pocapavir do not have direct antiviral effect.", "qid": 30, "docid": "ai2zcke5", "rank": 94, "score": 0.8510314226150513}, {"content": "Title: Medical Management of COVID-19: Evidence and Experience Content: Coronavirus disease 2019 is caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), and this infectious disease is termed COVID-19 in short. On a global scale, as of June 1, 2020, the World Health Organization (WHO) published statistics of 6,057,853 infected patients and 371,166 deaths worldwide. Despite reported observational data about the experimental use of certain drugs, there is no conclusively proven curative therapy for COVID-19 as of now; however, remdesivir received emergency use authorization (EUA) by the Food and Drug Administration (FDA) recently for use in patients hospitalized with COVID-19. There are several ongoing clinical trials related to the pharmacological choices of therapy for COVID-19 patients; however, drug trials related to observational studies so far have yielded mixed results and therefore have created a sense of confusion among healthcare professionals (HCPs). In this review article, we seek to collate and provide a summary of treatment strategies for COVID-19 patients with a variable degree of illness and discuss pharmacologic and other therapies intended to be used either as experimental medicine/therapy or as part of supportive care in complicated cases of COVID-19.", "qid": 30, "docid": "svnz1ghh", "rank": 95, "score": 0.8506340384483337}, {"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": 30, "docid": "ocguwlam", "rank": 96, "score": 0.850616455078125}, {"content": "Title: Development of remdesivir repositioning as a nucleotide analog against COVID-19 RNA dependent RNA polymerase Content: Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) is the causative representative of a severe respiratory illness resulted in widespread human infections and deaths in nearly all of the countries since late 2019. There is no therapeutic FDA-approved drug against SARS-CoV-2 infection, although a combination of anti-viral drugs is directly being practiced in some countries. A broad-spectrum of antiviral agents are being currently evaluated in clinical trials, and in this review, we specifically focus on the application of Remdesivir (RVD) as a potential anti-viral compound against Middle East respiratory syndrome (MERS) -CoV, SARS-CoV and SARS-CoV-2. First, we overview the general information about SARS-CoV-2, followed by application of RDV as a nucleotide analogue which can potentially inhibits RNA-dependent RNA polymerase of COVs. Afterwards, we discussed the kinetics of SARS- or MERS-CoV proliferation in animal models which is significantly different compared to that in humans. Finally, some ongoing challenges and future perspective on the application of RDV either alone or in combination with other anti-viral agents against CoVs infection were surveyed to determine the efficiency of RDV in preclinical trials. As a result, this paper provides crucial evidence of the potency of RDV to prevent SARS-CoV-2 infections.Communicated by Ramaswamy H. Sarma.", "qid": 30, "docid": "kjc3j7yz", "rank": 97, "score": 0.8503255844116211}, {"content": "Title: Development of remdesivir repositioning as a nucleotide analog against COVID-19 RNA dependent RNA polymerase Content: Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) is the causative representative of a severe respiratory illness resulted in widespread human infections and deaths in nearly all of the countries since late 2019. There is no therapeutic FDA-approved drug against SARS-CoV-2 infection, although a combination of anti-viral drugs is directly being practiced in some countries. A broad-spectrum of antiviral agents are being currently evaluated in clinical trials, and in this review, we specifically focus on the application of Remdesivir (RVD) as a potential anti-viral compound against Middle East respiratory syndrome (MERS) -CoV, SARS-CoV and SARS-CoV-2. First, we overview the general information about SARS-CoV-2, followed by application of RDV as a nucleotide analogue which can potentially inhibits RNA-dependent RNA polymerase of COVs. Afterwards, we discussed the kinetics of SARS- or MERS-CoV proliferation in animal models which is significantly different compared to that in humans. Finally, some ongoing challenges and future perspective on the application of RDV either alone or in combination with other anti-viral agents against CoVs infection were surveyed to determine the efficiency of RDV in preclinical trials. As a result, this paper provides crucial evidence of the potency of RDV to prevent SARS-CoV-2 infections. Communicated by Ramaswamy H. Sarma", "qid": 30, "docid": "2ro2p77q", "rank": 98, "score": 0.8502895832061768}, {"content": "Title: Antiviral therapy in management of COVID-19: a systematic review on current evidence Content: BACKGROUND: The purpose of the current systematic review is to evaluate the efficacy of antiviral therapies in treatment of COVID-19. In addition, clinical trials on the efficacy of antiviral therapies in the management of Severe Acute Respiratory Syndrome coronavirus (SARS-Cov) or Middle East Respiratory Syndrome coronavirus (MERS-CoV) have also been reviewed, in order to identify potential treatment options for COVID-19. METHOD: An extensive search was performed in Medline, Embase, Scopus, Web of Science and CENTRAL databases until the end of March 15, 2020. Two independent researchers performed the screening, and finally the related studies were included. RESULTS: Only one clinical trial on the efficacy of antiviral therapy in management of COVID-19 was found. The results depicted that adding Lopinavir-Ritonavir to the standard treatment regimen of patients with severe COVID-19 has no benefits. Moreover, 21 case-series and case-report studies reported the prescription of antiviral agents in COVID-19, none of which can be used to determine the efficacy of antiviral therapies in confronting COVID-19. In addition, no clinical trials were found to be performed on the efficacy of antiviral agents in the management of SARS-CoV and MERS-CoV. CONCLUSION: The current evidence impede researchers from proposing an appropriate antiviral therapy against COVID-19, making the current situation a serious concern for international organizations such as World Health Organization (WHO). In the time of the current pandemic and future epidemics, organizations such as WHO should pursue more proactive actions and plan well-designed clinical trials so that their results can be used in managing future epidemics.", "qid": 30, "docid": "jlqee1b8", "rank": 99, "score": 0.8502695560455322}, {"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": 100, "score": 0.8501396179199219}]}
{"query": "How does the coronavirus differ from seasonal flu?", "hits": [{"content": "Title: Coronavirus, as a source of pandemic pathogens Content: The coronavirus and the influenza virus have similarities and differences. In order to comprehensively compare them, their genome sequencing data were examined by principal component analysis. Variations in coronavirus were smaller than those in a subclass of the influenza virus. In addition, differences among coronaviruses in a variety of hosts were small. These characteristics may have facilitated the infection of different hosts. Although many of the coronaviruses were more conservative, those repeatedly found among humans showed annual changes. If SARS-CoV-2 changes its genome like the Influenza H type, it will repeatedly spread every few years. In addition, the coronavirus family has many other candidates for subsequent pandemics. One Sentence Summary The genome data of coronavirus were compared to influenza virus, to investigate its spreading mechanism and future status. Coronavirus would repeatedly spread every few years. In addition, the coronavirus family has many other candidates for subsequent pandemics.", "qid": 31, "docid": "431ksdno", "rank": 1, "score": 0.8500283360481262}, {"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": 2, "score": 0.8486118912696838}, {"content": "Title: A Case Series of Patients Coinfected With Influenza and COVID-19 Content: Coronavirus disease 2019, also called COVID-19, is a global pandemic resulting in significant morbidity and mortality worldwide. In the United States, influenza infection occurs mainly during winter and several factors influence the burden of the disease, including circulating virus characteristics, vaccine effectiveness that season, and the duration of the season. We present a case series of 3 patients with coinfection of COVID-19 and influenza, with 2 of them treated successfully and discharged home. We reviewed the literature of patients coinfected with both viruses and discussed the characteristics, as well as treatment options.", "qid": 31, "docid": "u6grnk7p", "rank": 3, "score": 0.8369093537330627}, {"content": "Title: The Seasonal End of Human Coronavirus Hospital Admissions with Implications for SARS-CoV-2 Content: The seasonality of influenza viruses and endemic human coronaviruses was tracked over an 8-year period to assess key epidemiologic reduction points in disease incidence for an urban area in the northeast United States. Patients admitted to a pediatric hospital with worsening respiratory symptoms were tested using a multiplex PCR assay from nasopharyngeal swabs. The additive seasonal effects of outdoor temperatures and indoor relative humidity (RH) were evaluated. The 8-year average peak activity of human coronaviruses occurred in the first week of January, when droplet and contact transmission was enabled by the low indoor RH of 20-30%. Previous studies have shown that an increase in RH to 50% has been associated with markedly reduced viability and transmission of influenza virus and animal coronaviruses. As disease incidence was reduced by 50% in early March, to 75% in early April, to greater than 99% at the end of April, a relationship was observed from colder temperatures in January with a low indoor RH to a gradual increase in outdoor temperatures in April with an indoor RH of 45-50%. As a lipid-bound, enveloped virus with similar size characteristics to endemic human coronaviruses, SARS-CoV-2 should be subject to the same dynamics of reduced viability and transmission with increased humidity. In addition to the major role of social distancing, the transition from lower to higher indoor RH with increasing outdoor temperatures could have an additive effect on the decrease in SARS-CoV-2 cases in May. Over the 8-year period of this study, human coronavirus activity was either zero or >99% reduction in the months of June through September, and the implication would be that SARS-Cov-2 may follow a similar pattern.", "qid": 31, "docid": "3xw4qjoy", "rank": 4, "score": 0.834200382232666}, {"content": "Title: Will the COVID-19 pandemic slow down in the Northern hemisphere by the onset of summer? An epidemiological hypothesis Content: The COVID-19 pandemic has affected most countries of the world. As corona viruses are highly prevalent in the cold season, the question remains whether or not the pandemic will improve with increasing temperatures in the Northern hemisphere. We use data from a primary care registry of almost 15,000 patients over 20 years to retrieve information on viral respiratory infection outbreaks. Our analysis suggests that the severity of the pandemic will be softened by the seasonal change to summer.", "qid": 31, "docid": "iztm1z6g", "rank": 5, "score": 0.8341269493103027}, {"content": "Title: Species\u2010specific clinical characteristics of human coronavirus infection among otherwise healthy adolescents and adults Content: Human coronavirus (HCoV) is a known cause of influenza\u2010like illness (ILI). In a multisite, observational, longitudinal study of ILI among otherwise healthy adolescents and adults, 12% of subjects were PCR\u2010positive for HCoV. The distribution of species was as follows: HCoV\u2010OC43 (34%), HCoV\u2010229E (28%), HCoV\u2010NL63 (22%), and HCoV\u2010HKU1 (16%). We did not observe species\u2010specific differences in the clinical characteristics of HCoV infection, with the exception of HCoV\u2010HKU1, for which the severity of gastrointestinal symptoms trended higher on the fourth day of illness.", "qid": 31, "docid": "6sq1d5jt", "rank": 6, "score": 0.8333553671836853}, {"content": "Title: Influenza Virus Infections Content: Abstract Influenza, commonly known as flu, is a contagious, febrile viral disease. Common symptoms are chills, fever, sore throat, coughing, sneezing, muscle pains, headache, myalgia, etc. Influenza viruses (IVs) belonging to orthomyxovirus group are of three types (types A, B, and C). IVs are enveloped, segmented, negative-stranded RNA viruses containing eight distinct RNA segments (types A and B) and seven RNA segments (type C). Only type A viruses exhibit different subtypes. Currently, 18 hemagglutination (HA) subtypes (H1 to H18) and 11 neuraminidase (NA) subtypes (N1 to N11) are known in humans and other warm-blooded animals. Flu outbreaks occur as annual epidemics in fall and winter and infrequently, as worldwide pandemics. Annual epidemics are caused by antigenic drift due to mutations in HA and NA antigens, whereas pandemics are caused by antigenic shift due to genetic reassortment among different subtype viruses. The first pandemic of the twenty-first century, declared by the World Health Organization (WHO) in 2009, was caused by an H1N1 virus, derived from quadruple reassortment among swine, avian, and human IVs. Currently, two types of antiinfluenza drugs, based on either blocking the M2 proton channel (amantadine and rimantadine) or inhibiting NA (oseltamivir or Tamiflu by Roche and zanamivir or Relanza by GlaxoSmithKline) are available. The virus is commonly spread by aerosol droplets and by fingertips. Therefore, washing hands and avoiding contact with infected persons are the first lines of defense. Indoor living and closeness of people in an enclosed environment in winter facilitate virus transmission leading to epidemics. Annual vaccination is the best preventative measure. Currently, two types of vaccines (subunit vaccine by injection and live attenuated vaccine by nasal spray) are available and recommended by WHO and Centers for Disease Control.", "qid": 31, "docid": "skoeieb7", "rank": 7, "score": 0.8321739435195923}, {"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": 8, "score": 0.8304771184921265}, {"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": 9, "score": 0.8291248083114624}, {"content": "Title: Seasonality of Coronavirus 229E, HKU1, NL63 and OC43 from 2014-2020 Content: Abstract The possibility of seasonality of Covid-19 is being discussed; here we show clinical microbiology laboratory data illustrating seasonality of coronaviruses 229E, HKU1, NL63 and OC43. The data shown are specific to the four studied coronaviruses, and may or may not generalize to Covid-19.", "qid": 31, "docid": "clxza5zy", "rank": 10, "score": 0.8277228474617004}, {"content": "Title: Seasonality of infectious diseases and severe acute respiratory syndrome\u2013what we don't know can hurt us Content: Summary The novel severe acute respiratory syndrome (SARS) coronavirus caused severe disease and heavy economic losses before apparently coming under complete control. Our understanding of the forces driving seasonal disappearance and recurrence of infectious diseases remains fragmentary, thus limiting any predictions about whether, or when, SARS will recur. It is true that most established respiratory pathogens of human beings recur in wintertime, but a new appreciation for the high burden of disease in tropical areas reinforces questions about explanations resting solely on cold air or low humidity. Seasonal variation in host physiology may also contribute. Newly emergent zoonotic diseases such as ebola or pandemic strains of influenza have recurred in unpredictable patterns. Most established coronaviruses exhibit winter seasonality, with a unique ability to establish persistent infections in a minority of infected animals. Because SARS coronavirus RNA can be detected in the stool of some individuals for at least 9 weeks, recurrence of SARS from persistently shedding human or animal reservoirs is biologically plausible.", "qid": 31, "docid": "ax87r0bj", "rank": 11, "score": 0.8263405561447144}, {"content": "Title: Comparative review of respiratory diseases caused by coronaviruses and influenza A viruses during epidemic season Content: Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) continues to sweep the world, causing infection of millions and death of hundreds of thousands. The respiratory disease that it caused, COVID-19 (stands for coronavirus disease in 2019), has similar clinical symptoms with other two CoV diseases, severe acute respiratory syndrome and Middle East respiratory syndrome (SARS and MERS), of which causative viruses are SARS-CoV and MERS-CoV, respectively. These three CoVs resulting diseases also share many clinical symptoms with other respiratory diseases caused by influenza A viruses (IAVs). Since both CoVs and IAVs are general pathogens responsible for seasonal cold, in the next few months, during the changing of seasons, clinicians and public heath may have to distinguish COVID-19 pneumonia from other kinds of viral pneumonia. This is a discussion and comparison of the virus structures, transmission characteristics, clinical symptoms, diagnosis, pathological changes, treatment and prevention of the two kinds of viruses, CoVs and IAVs. It hopes to provide information for practitioners in the medical field during the epidemic season.", "qid": 31, "docid": "gc3iq0wp", "rank": 12, "score": 0.8260622620582581}, {"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": 13, "score": 0.8258830308914185}, {"content": "Title: Seasonality and selective trends in viral acute respiratory tract infections Content: Abstract Influenza A and B, and many unrelated viruses including rhinovirus, RSV, adenovirus, metapneumovirus and coronavirus share the same seasonality, since these viral acute respiratory tract infections (vARIs) are much more common in winter than summer. Unfortunately, early investigations that used recycled \u201cpedigree\u201d virus strains seem to have led microbiologists to dismiss the common folk belief that vARIs often follow chilling. Today, incontrovertible evidence shows that ambient temperature dips and host chilling increase the incidence and severity of vARIs. This review considers four possible mechanisms, M1 - 4, that can explain this link: (M1) increased crowding in winter may enhance viral transmission; (M2) lower temperatures may increase the stability of virions outside the body; (M3) chilling may increase host susceptibility; (M4) lower temperatures or host chilling may activate dormant virions. There is little evidence for M1 or M2, which are incompatible with tropical observations. Epidemiological anomalies such as the repeated simultaneous arrival of vARIs over wide geographical areas, the rapid cessation of influenza epidemics, and the low attack rate of influenza within families are compatible with M4, but not M3 (in its simple form). M4 seems to be the main driver of seasonality, but M3 may also play an important role.", "qid": 31, "docid": "zg17f7bd", "rank": 14, "score": 0.8239238262176514}, {"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": 15, "score": 0.8237401247024536}, {"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": 16, "score": 0.8233187794685364}, {"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": 17, "score": 0.8233187794685364}, {"content": "Title: The impact of the SARS\u2010CoV\u20102 outbreak on the safety and availability of blood transfusions in Italy Content: Coronaviruses are enveloped single-stranded RNA viruses belonging to the family of Coronaviridae. While initial research focused on their ability to cause enzootic infections, infections which have emerged in the past two decades demonstrate their ability to cross the species barrier and infect humans [1,2]. The ensuing epidemics have included Severe Acute Respiratory Syndrome (SARS) in 2002 and the more recent Middle East Respiratory Syndrome (MERS) in 2012, and have resulted in severe disease burden, mortality and economic disruption [3]. A novel flu-like coronavirus, emerging towards the end of 2019 and subsequently named SARS-CoV-2, has been associated with an epidemic initially focused in Wuhan, China.", "qid": 31, "docid": "7imgvale", "rank": 18, "score": 0.8230844140052795}, {"content": "Title: Epidemiology of coronavirus-associated respiratory tract infections and the role of rapid diagnostic tests: a prospective study. Content: 1. Coronaviruses accounted for 1.6% (98/6272) of respiratory tract infections based on nasopharyngeal aspirate samples. 2. HCoV-OC43 was the most common coronavirus detected,followed by HCoV-NL63, CoVHKU1,and HCoV-229E. 3. Although CoV-HKU1 infections were most often associated with the upper respiratory tract, more severe illness (pneumonia,acute bronchiolitis, and asthmatic exacerbation) may occur, especially in those with underlying disease. In young children, CoV-HKU1 infection is associated with a high rate of febrile seizures (50%). 4. CoV-HKU1 and HCoV-OC43 infections peaked in winter, in contrast to HCoV-NL63, which mainly occurred in early summer and autumn, but was absent in winter. 5. Reverse transcriptase polymerase chain reaction is useful for the rapid diagnosis of coronavirus infections.", "qid": 31, "docid": "vbq2jyxp", "rank": 19, "score": 0.8225723505020142}, {"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": 20, "score": 0.8205140829086304}, {"content": "Title: Understanding dynamics of pandemics Content: Along the centuries, novel strain of virus such as influenza produces pandemics which increase illness, death and disruption in the countries. Spanish flu in 1918, Asian flu in 1957, Hong Kong flu in 1968 and swine flu in 2009 were known pandemic which had various characteristics in terms of morbidity and mortality. A current pandemic is caused by novel corona virus originated from China. COVID-19 pandemic is very similar to Spanish, Hong Kong, Asian and swine influenza pandemics in terms of spreading to world by the mobilized people. Burden of pandemic is considered in terms of disease transmissibility and the growth rate of epidemic and duration of pandemic can be calculated by transmissibility characteristic. The case definition, finding out cases and first case cluster, proper treatment, sufficient stockpiles of medicine and population cooperation with the containment strategy should be considered for reduction of burden of pandemic.", "qid": 31, "docid": "rjdb1qrt", "rank": 21, "score": 0.8204743266105652}, {"content": "Title: Preliminary evidence that higher temperatures are associated with lower incidence of COVID-19, for cases reported globally up to 29th February 2020 Content: Seasonal variation in COVID-19 incidence could impact the trajectory of the pandemic. Using global line-list data on COVID-19 cases reported until 29th February 2020 and global gridded temperature data, and after adjusting for surveillance capacity and time since first imported case, higher average temperature was strongly associated with lower COVID-19 incidence for temperatures of 1\u00b0C and higher. However, temperature explained a relatively modest amount of the total variation in COVID-19 incidence. These preliminary findings support stringent containment efforts in Europe and elsewhere.", "qid": 31, "docid": "drzphrqj", "rank": 22, "score": 0.8195099830627441}, {"content": "Title: Influenza vaccination in the COVID-19 era Content: Influenza spreads globally annually with significant paediatric and adult attack rates and considerable morbidity, mortality and the exacerbation of extant chronic disease. In the northern and southern hemispheres, outbreaks occur mainly in the respective winter seasons. Influenza vaccination is available but only partially effective. In the absence of a vaccine, in winter, novel coronavirus COVID-19 will also circulate in parallel with seasonal influenza. Thus far it appears that with the current strains of these two viruses, the clinical outcome of co-infection is not significantly worse than infection with COVID-19 alone. However, several strains of influenza circulate, including strains still to come. Similarly, COVID-19 has several strains, with probably more to come. This paper discusses these issues and estimates ideal minimum influenza vaccination coverage based on an estimated influenza Basic Reproduction Number (R0) of 0.9-2.1 so as to obtain herd immunity or approach it. There is a strong argument for attempting near universal population coverage with the annual influenza vaccine leading up to next winter.", "qid": 31, "docid": "fm0dwft0", "rank": 23, "score": 0.8193275928497314}, {"content": "Title: Seroepidemiological analysis of influenza pandemics in Shizuoka Prefecture and all Japan Content: Abstract (1) Seroepidemiological analysis of influenza pandemics (1986\u20132003) in Shizuoka Prefecture and all Japan revealed differences in geographical, annual, seasonal, and age distributions. (2) For 17 years, the pandemics generally began at the 50th week every year showing over 1.0 patient/clinic, reached the peak at 5th week the following year, and ended over 10\u201315th week. Two big A/H3N2 pandemics were seen in 1989/1990 and 1997/1998 seasons, claiming over 1 million patients in Japan. (3) As herald strains, A/H3N2 strains (A/Sydney-like) were found in October 1999, and B strains (B/Victoria- and B/Yamagata-like) were detected in July and November 1998 and, in August and December 2000 in Shizuoka. B/Shizuoka/1/98 strain was registered internationally as a vaccine-recommended strain. (4) A/H3N2 and B viruses were detected in 55\u201378% of flu patients (almost under 10 years) with encephalopathy in 1999/2000 and 78\u201391% in 2000/2001 by MDCK and reverse transcription polymerase chain reaction (RT-PCR) methods. (5) High hemagglutination inhibition (HI) titers over 40 in 250 persons were shown against A/Sydney/5/97 (H3N2), A/Yokohama/8/98 (H3N2), A/Panama/2007/99 (H3N2) and A/Moscow/10/99 (H1N1) strains, while low titers showed against A/Beijing/262/95 (H1N1) and A/New Caledonia/20/99 (H1N1), and B/Beijing/243/97, B/Shangdong/7/97 and B/Yamanashi/106/98 strains in 1998\u20132000. (6) In anti-HA titers against A/H3N2, A/H1N1 and B subtypes, clear generation gaps were observed between children (0\u201319 years), adults (20\u201359 years) and old men (over 60 years). (7) The pandemics are dependent on host immunity (acquired and vaccinated) and climatic conditions (low temperature, low humidity and limited rainfall), considering highly pathogenic avian influenza (HPAI) viruses (A/H5N1, A/H7N7) like severe acute respiratory syndrome (SARS) corona virus in 2002\u20132003.", "qid": 31, "docid": "xgczt523", "rank": 24, "score": 0.819233775138855}, {"content": "Title: Characteristics of respiratory virus infection during the outbreak of 2019 novel coronavirus in Beijing Content: BACKGROUND: Coronavirus disease 2019 (COVID-19) is spreading. Here, we summarized the composition of pathogens in fever clinic patients and analyzed the characteristics of different respiratory viral infections. METHODS: Retrospectively collected patients with definite etiological results using nasal and pharyngeal swabs in a fever clinic. RESULTS: Overall, 1860 patients were screened, and 136 patients were enrolled. 72 (52.94%) of them were diagnosed as influenza (Flu) A virus infection. 32 (23.53%) of them were diagnosed as Flu B virus infection. 18 (13.24%) and 14 (10.29%) of them were diagnosed as COVID-19 and respiratory syncytial virus (RSV) infections, respectively. The COVID-19 group had a higher rate of contact with the epidemic area within 14 days and of clustering onset than other groups. Fever was the most common symptom in these patients. The ratio of fever to the highest temperature was higher in Flu A virus infection patients than in COVID-19 patients. COVID-19 patients had a lower white blood cell count and neutrophil count than Flu A virus and RSV infection groups, but higher lymphocyte count than Flu A and B virus infection groups. The COVID-19 group (83.33%) had a higher rate of pneumonia in chest CT scans than Flu A and B virus infection groups. CONCLUSIONS: Influenza viruses accounted for a large proportion of respiratory virus infection even during the epidemic of COVID-19 in Beijing. No single symptom or laboratory finding was suggestive of a specific respiratory virus; however, epidemic history was significant for the screening of COVID-19.", "qid": 31, "docid": "eu79h4ee", "rank": 25, "score": 0.8190610408782959}, {"content": "Title: The dissemination of COVID-19: an expectant and preventive role in global health Content: Backgroung: Coronaviruses (CoV) make up a large family of viruses, known since the mid-1960s, which received this name due to the spikes on its surface, which resemble a crown (from the Latin corona). CoV infections can cause everything from a common cold to severe respiratory syndromes, such as severe acute respiratory syndrome (SARS-CoV) and Middle Eastern respiratory syndrome (MERS-CoV).COVID-19 (SARS-CoV2) is a new variant of the coronavirus, and its isolation occurred in China on January 7th, 2020. COVID-19 has stood out with a high impact on public health due to the high number of cases with infection in a short period of time. However, it is possible to observe that 17% of patients confirmed with COVID-19 have severe infections and about 2.5% of these patients die. Current studies have shown that the number of mild and asymptomatic cases may be even greater. Thus, the challenges for controlling unreported cases of patients with mild symptoms that are spreading the virus and interfering with the magnitude and real data of the cases stand out. The transmission of the coronavirus occurs between humans, and it can occur from person to person through the air, through coughing or sneezing, by touching or shaking hands or by contact with contaminated objects or surfaces, followed by contact with the mouth, nose or eyes. Given the fluctuation in the incidence and the lethality rate, it is essential to stand out the precepts of health promotion in search of reorienting hygiene practices, considering that there is validity in health care models, still with a curative approach and the current situation experienced by the world population requires a preventive stance.(AU)", "qid": 31, "docid": "9efi8hf9", "rank": 26, "score": 0.8183993697166443}, {"content": "Title: The most eagerly awaited summer of the Anthropocene: A perspective of SARS-CoV-2 decay and seasonal change Content: To date, the world perhaps has never waited for the summer so impatiently in the entire Anthropocene, owing to the debate whether increasing temperature and humidity will decrease the environmental endurance of SARS-CoV-2. We present the perspective on the seasonal change on SARS-CoV-2 decay and COVID-19 spread. Our arguments are based on: i) structural similarity of coronavirus with several enteric viruses, and its vulnerability; ii) reports related to decay of those similar transmissible gastroenteritis viruses (TGEV) like norovirus and iii) improvement in the human immunity during summer with respect to winter. We present reasons why we can be optimistic about the slowdown of corona in the upcoming summer.", "qid": 31, "docid": "9v83g7dj", "rank": 27, "score": 0.8179594278335571}, {"content": "Title: Incubation period as part of the case definition of severe respiratory illness caused by a novel coronavirus. Content: Non-specific symptoms of acute respiratory viral infections make it difficult for many countries without ongoing transmission of a novel coronavirus to rule out other possibilities including influenza before isolating imported febrile individuals with a possible exposure history. The incubation period helps differential diagnosis, and up to two days is suggestive of influenza. It is worth including the incubation period in the case definition of novel coronavirus infection.", "qid": 31, "docid": "xfiqlck4", "rank": 28, "score": 0.817570686340332}, {"content": "Title: Influenza vaccination in the COVID-19 era Content: Abstract Influenza spreads globally annually with significant paediatric and adult attack rates and considerable morbidity, mortality and the exacerbation of extant chronic disease. In the northern and southern hemispheres, outbreaks occur mainly in the respective winter seasons. Influenza vaccination is available but only partially effective. In the absence of a vaccine, in winter, novel coronavirus COVID-19 will also circulate in parallel with seasonal influenza. Thus far it appears that with the current strains of these two viruses, the clinical outcome of co-infection is not significantly worse than infection with COVID-19 alone. However, several strains of influenza circulate, including strains still to come. Similarly, COVID-19 has several strains, with probably more to come. This paper discusses these issues and estimates ideal minimum influenza vaccination coverage based on an estimated influenza Basic Reproduction Number (R0) of 0.9\u20132.1 so as to obtain herd immunity or approach it. There is a strong argument for attempting near universal population coverage with the annual influenza vaccine leading up to next winter.", "qid": 31, "docid": "8ikiyqkp", "rank": 29, "score": 0.8169189095497131}, {"content": "Title: Global challenges to urology practice during the COVID\u201019 pandemic Content: Since the first report of coronavirus commonly termed as COVID-19 in China, it has progressed into a pandemic and Italy has been one of the countries worst hit. Coronaviruses are enveloped ribonucleic acid (RNA) viruses that cause respiratory, entero-hepatic, and neurologic diseases in humans and mammals. More specifically the coronavirus causing the current pandemic is severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). The common symptoms include a dry continuous cough, fever and shortness of breath; severe cases involve pneumonia which may require ventilatory support.", "qid": 31, "docid": "9sk8gdh8", "rank": 30, "score": 0.8164021968841553}, {"content": "Title: The need for neurologists in the care of COVID\u201019 patients Content: Coronavirus disease 2019 (COVID-19) is an infectious disease caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) resulting in severe acute respiratory syndrome in a substantial number of patients. Approximately 5% to 10% of patients need intensive care unit (ICU) admission and mechanical ventilation [1]. The primary symptoms of COVID-19 include fever, dry cough and fatigue [2]. However, a recent report from Shandong, China, disclosed that a subset of patients did not suffer from respiratory symptoms but had neurologic signs and symptoms [3]. Moreover, in a retrospective study from Wuhan, China, neurologic symptoms were observed in 36.4% of the hospitalized patients with COVID-19 infection and pertained to both the central and peripheral nervous system [4].", "qid": 31, "docid": "l21fin9q", "rank": 31, "score": 0.8160362243652344}, {"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": 32, "score": 0.8157774209976196}, {"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": 33, "score": 0.815348207950592}, {"content": "Title: Seasonality of Influenza A(H3N2) Virus: A Hong Kong Perspective (1997\u20132006) Content: BACKGROUND: The underlying basis for the seasonality of influenza A viruses is still uncertain. Phylogenetic studies investigated this phenomenon but have lacked sequences from more subtropical and tropical regions, particularly from Southeast Asia. METHODOLOGY/PRINCIPAL FINDINGS: 281 complete hemagglutinin (HA) and neuraminidase (NA) sequences were obtained from influenza A(H3N2) viruses, collected over 10 years (1997\u20132006) from Hong Kong. These dated sequences were analyzed with influenza A(H3N2) vaccine strain sequences (Syd/5/97, Mos/10/99, Fuj/411/02, Cal/7/04) and 315 other publicly available dated sequences from elsewhere, worldwide. In addition, the NA sequence alignment was inspected for the presence of any naturally occurring, known, neuraminidase inhibitor (NAI) resistance-associated amino acid mutations (R292K and E119V). Before 2001, the Hong Kong HA and NA sequences clustered more closely with the older vaccine sequences (Syd/5/97, Mos/10/99) than did sequences from elsewhere. After 2001, this trend reversed with significant clusters containing HA and NA sequences from different locations, isolated at different times, suggesting that viral migration may account for much of the influenza A(H3N2) seasonality during this 10-year period. However, at least one example from Hong Kong was found suggesting that in some years, influenza A(H3N2) viruses may persist in the same location, perhaps continuing to circulate, sub-clinically, at low levels between seasons, to re-emerge in the influenza season the following year, relatively unchanged. None of these Hong Kong influenza A(H3N2) NA sequences contained any of the known NAI-resistance associated mutations. CONCLUSIONS/SIGNIFICANCE: The seasonality of influenza A(H3N2) may be largely due to global migration, with similar viruses appearing in different countries at different times. However, occasionally, some viruses may remain within a single location and continue to circulate within that population, to re-emerge during the next influenza season, with relatively little genetic change. Naturally occurring NAI resistance mutations were absent or, at least, very rare in this population.", "qid": 31, "docid": "4z38v9rg", "rank": 34, "score": 0.8153230547904968}, {"content": "Title: The most eagerly awaited summer of the Anthropocene: A perspective of SARS-CoV-2 decay and seasonal change Content: Abstract To date, the world perhaps has never waited for the summer so impatiently in the entire Anthropocene, owing to the debate whether increasing temperature and humidity will decrease the environmental endurance of SARS-CoV-2. We present the perspective on the seasonal change on SARS-CoV-2 decay and COVID-19 spread. Our arguments are based on: i) structural similarity of coronavirus with several enteric viruses, and its vulnerability; ii) reports related to decay of those similar transmissible gastroenteritis viruses (TGEV) like norovirus and iii) improvement in the human immunity during summer with respect to winter. We present reasons why we can be optimistic about the slowdown of corona in the upcoming summer.", "qid": 31, "docid": "6exmxw6r", "rank": 35, "score": 0.81475830078125}, {"content": "Title: Seasonality of Respiratory Viral Infections Content: The seasonal cycle of respiratory viral diseases has been widely recognized for thousands of years, as annual epidemics of the common cold and influenza disease hit the human population like clockwork in the winter season in temperate regions. Moreover, epidemics caused by viruses such as severe acute respiratory syndrome coronavirus (SARS-CoV) and the newly emerging SARS-CoV-2 occur during the winter months. The mechanisms underlying the seasonal nature of respiratory viral infections have been examined and debated for many years. The two major contributing factors are the changes in environmental parameters and human behavior. Studies have revealed the effect of temperature and humidity on respiratory virus stability and transmission rates. More recent research highlights the importance of the environmental factors, especially temperature and humidity, in modulating host intrinsic, innate, and adaptive immune responses to viral infections in the respiratory tract. Here we review evidence of how outdoor and indoor climates are linked to the seasonality of viral respiratory infections. We further discuss determinants of host response in the seasonality of respiratory viruses by highlighting recent studies in the field. Expected final online publication date for the Annual Review of Virology, Volume 7 is September 29, 2020. Please see http://www.annualreviews.org/page/journal/pubdates for revised estimates.", "qid": 31, "docid": "5dfg0f5d", "rank": 36, "score": 0.8147262930870056}, {"content": "Title: Seasonality of Respiratory Viral Infections. Content: The seasonal cycle of respiratory viral diseases has been widely recognized for thousands of years, as annual epidemics of the common cold and influenza disease hit the human population like clockwork in the winter season in temperate regions. Moreover, epidemics caused by viruses such as severe acute respiratory syndrome coronavirus (SARS-CoV) and the newly emerging SARS-CoV-2 occur during the winter months. The mechanisms underlying the seasonal nature of respiratory viral infections have been examined and debated for many years. The two major contributing factors are the changes in environmental parameters and human behavior. Studies have revealed the effect of temperature and humidity on respiratory virus stability and transmission rates. More recent research highlights the importance of the environmental factors, especially temperature and humidity, in modulating host intrinsic, innate, and adaptive immune responses to viral infections in the respiratory tract. Here we review evidence of how outdoor and indoor climates are linked to the seasonality of viral respiratory infections. We further discuss determinants of host response in the seasonality of respiratory viruses by highlighting recent studies in the field. Expected final online publication date for the Annual Review of Virology, Volume 7 is September 29, 2020. Please see http://www.annualreviews.org/page/journal/pubdates for revised estimates.", "qid": 31, "docid": "1npav6m4", "rank": 37, "score": 0.8147262930870056}, {"content": "Title: Epidemiology and Clinical Symptoms Related to Seasonal Coronavirus Identified in Patients with Acute Respiratory Infections Consulting in Primary Care over Six Influenza Seasons (2014-2020) in France Content: There is currently debate about human coronavirus (HCoV) seasonality and pathogenicity, as epidemiological data are scarce. Here, we provide epidemiological and clinical features of HCoV patients with acute respiratory infection (ARI) examined in primary care general practice. We also describe HCoV seasonality over six influenza surveillance seasons (week 40 to 15 of each season) from the period 2014/2015 to 2019/2020 in Corsica (France). A sample of patients of all ages presenting for consultation for influenza-like illness (ILI) or ARI was included by physicians of the French Sentinelles Network during this period. Nasopharyngeal samples were tested for the presence of 21 respiratory pathogens by real-time RT-PCR. Among the 1389 ILI/ARI patients, 105 were positive for at least one HCoV (7.5%). On an annual basis, HCoVs circulated from week 48 (November) to weeks 14-15 (May) and peaked in week 6 (February). Overall, among the HCoV-positive patients detected in this study, HCoV-OC43 was the most commonly detected virus, followed by HCoV-NL63, HCoV-HKU1, and HCoV-229E. The HCoV detection rates varied significantly with age (p = 0.00005), with the age group 0-14 years accounting for 28.6% (n = 30) of HCoV-positive patients. Fever and malaise were less frequent in HCoV patients than in influenza patients, while sore throat, dyspnoea, rhinorrhoea, and conjunctivitis were more associated with HCoV positivity. In conclusion, this study demonstrates that HCoV subtypes appear in ARI/ILI patients seen in general practice, with characteristic outbreak patterns primarily in winter. This study also identified symptoms associated with HCoVs in patients with ARI/ILI. Further studies with representative samples should be conducted to provide additional insights into the epidemiology and clinical features of HCoVs.", "qid": 31, "docid": "5qhguue3", "rank": 38, "score": 0.8147063851356506}, {"content": "Title: Epidemiology and Clinical Symptoms Related to Seasonal Coronavirus Identified in Patients with Acute Respiratory Infections Consulting in Primary Care over Six Influenza Seasons (2014-2020) in France. Content: There is currently debate about human coronavirus (HCoV) seasonality and pathogenicity, as epidemiological data are scarce. Here, we provide epidemiological and clinical features of HCoV patients with acute respiratory infection (ARI) examined in primary care general practice. We also describe HCoV seasonality over six influenza surveillance seasons (week 40 to 15 of each season) from the period 2014/2015 to 2019/2020 in Corsica (France). A sample of patients of all ages presenting for consultation for influenza-like illness (ILI) or ARI was included by physicians of the French Sentinelles Network during this period. Nasopharyngeal samples were tested for the presence of 21 respiratory pathogens by real-time RT-PCR. Among the 1389 ILI/ARI patients, 105 were positive for at least one HCoV (7.5%). On an annual basis, HCoVs circulated from week 48 (November) to weeks 14-15 (May) and peaked in week 6 (February). Overall, among the HCoV-positive patients detected in this study, HCoV-OC43 was the most commonly detected virus, followed by HCoV-NL63, HCoV-HKU1, and HCoV-229E. The HCoV detection rates varied significantly with age (p = 0.00005), with the age group 0-14 years accounting for 28.6% (n = 30) of HCoV-positive patients. Fever and malaise were less frequent in HCoV patients than in influenza patients, while sore throat, dyspnoea, rhinorrhoea, and conjunctivitis were more associated with HCoV positivity. In conclusion, this study demonstrates that HCoV subtypes appear in ARI/ILI patients seen in general practice, with characteristic outbreak patterns primarily in winter. This study also identified symptoms associated with HCoVs in patients with ARI/ILI. Further studies with representative samples should be conducted to provide additional insights into the epidemiology and clinical features of HCoVs.", "qid": 31, "docid": "1n5ej08f", "rank": 39, "score": 0.8147063851356506}, {"content": "Title: Early occurrence of influenza A epidemics coincided with changes in occurrence of other respiratory virus infections Content: BACKGROUND: Viral interaction in which outbreaks of influenza and other common respiratory viruses might affect each other has been postulated by several short studies. Regarding longer time periods, influenza epidemics occasionally occur very early in the season, as during the 2009 pandemic. Whether early occurrence of influenza epidemics impacts outbreaks of other common seasonal viruses is not clear. OBJECTIVES: We investigated whether early occurrence of influenza outbreaks coincides with shifts in the occurrence of other common viruses, including both respiratory and non\u2010respiratory viruses. METHODS: We investigated time trends of and the correlation between positive laboratory diagnoses of eight common viruses in the Netherlands over a 10\u2010year time period (2003\u20132012): influenza viruses types A and B, respiratory syncytial virus (RSV), rhinovirus, coronavirus, norovirus, enterovirus, and rotavirus. We compared trends in viruses between early and late influenza seasons. RESULTS: Between 2003 and 2012, influenza B, RSV, and coronavirus showed shifts in their occurrence when influenza A epidemics occurred earlier than usual (before week 1). Although shifts were not always consistently of the same type, when influenza type A hit early, RSV outbreaks tended to be delayed, coronavirus outbreaks tended to be intensified, and influenza virus type B tended not to occur at all. Occurrence of rhinovirus, norovirus, rotavirus, and enterovirus did not change. CONCLUSION: When influenza A epidemics occured early, timing of the epidemics of several respiratory winter viruses usually occurring close in time to influenza A was affected, while trends in rhinoviruses (occurring in autumn) and trends in enteral viruses were not.", "qid": 31, "docid": "psog34u3", "rank": 40, "score": 0.8146818280220032}, {"content": "Title: Seasonality and uncertainty in COVID-19 growth rates Content: The virus causing COVID-19 has spread rapidly worldwide and threatens millions of lives. It remains unknown if summer weather will reduce its continued spread, thereby alleviating strains on hospitals and providing time for vaccine development. Early insights from laboratory studies of related coronaviruses predicted that COVID-19 would decline at higher temperatures, humidity, and ultraviolet light. Using current, fine-scaled weather data and global reports of infection we developed a model that explained 36% of variation in early growth rates before intervention, with 17% based on weather or demography and 19% based on country-specific effects. We found that ultraviolet light was most strongly associated with lower COVID-19 growth rates. Projections suggest that, in the absence of intervention, COVID-19 will decrease temporarily during summer, rebound by autumn, and peak next winter. However, uncertainty remains high and the probability of a weekly doubling rate remained >20% throughout the summer in the absence of control. Consequently, aggressive policy interventions will likely be needed in spite of seasonal trends.", "qid": 31, "docid": "0vlzwksu", "rank": 41, "score": 0.8145670890808105}, {"content": "Title: COVID-19: gastrointestinal symptoms and potential sources of 2019-nCoV transmission Content: A new type of coronavirus, i.e. se-vere acute respiratory syndrome coronavirus 2 (SARS-CoV-2; formerly known as 2019-nCoV) appeared in December 2019 in the province of Hubei, China, and over the past four months the number of cases of infection has exceeded 240,000 worldwide, leading to a pandemia [1]. At the genetic level, 2019-nCoV is closely related to the SARS-CoV and, to a lesser extent, to MERS-CoV, which appeared as epidemiological threats in recent years in China and the Middle East, respectively. Infections with the Coronaviridae virus family in a small percentage of patients, especially in those over 60 years of age with a positive clinical history, lead to severe acute respiratory syndrome [2].", "qid": 31, "docid": "q0wp7sba", "rank": 42, "score": 0.8144708871841431}, {"content": "Title: COVID-19: gastrointestinal symptoms and potential sources of 2019-nCoV transmission. Content: A new type of coronavirus, i.e. se-vere acute respiratory syndrome coronavirus 2 (SARS-CoV-2; formerly known as 2019-nCoV) appeared in December 2019 in the province of Hubei, China, and over the past four months the number of cases of infection has exceeded 240,000 worldwide, leading to a pandemia [1]. At the genetic level, 2019-nCoV is closely related to the SARS-CoV and, to a lesser extent, to MERS-CoV, which appeared as epidemiological threats in recent years in China and the Middle East, respectively. Infections with the Coronaviridae virus family in a small percentage of patients, especially in those over 60 years of age with a positive clinical history, lead to severe acute respiratory syndrome [2].", "qid": 31, "docid": "hebz8bi9", "rank": 43, "score": 0.8144708871841431}, {"content": "Title: Co-infection with Influenza A and COVID-19 Content: COVID-19, also called severe acute respiratory distress syndrome coronavirus 2 (SARS-CoV-2), originated in Wuhan, China. It has caused significant morbidity and mortality worldwide and has been declared a global pandemic by the WHO. Influenza occurs mainly during the winter, with the burden of disease determined by several factors, including the effectiveness of the vaccine that season, the characteristics of the circulating viruses, and how long the season lasts. We describe the case of a 66-year-old woman who was diagnosed with influenza A and COVID-19 co-infection. LEARNING POINTS: COVID-19 can co-occur with other viral infections. Some of these co-infections have active treatments, while supportive treatment is the mainstay of treatment for others.", "qid": 31, "docid": "9i024s08", "rank": 44, "score": 0.8142726421356201}, {"content": "Title: Coronavirus occurrence and transmission over 8 years in the HIVE cohort of households in Michigan Content: BACKGROUND: As part of the Household Influenza Vaccine Evaluation (HIVE) study, acute respiratory infections (ARI) have been identified in children and adults over 8 years. METHODS: Annually, 890 to 1441 individuals were followed and contacted weekly to report ARIs. Specimens collected during illness were tested for human coronaviruses (HCoV) types OC43, 229E, HKU1, and NL63. RESULTS: In total, 993 HCoV infections were identified over 8 years, with OC43 most commonly seen and 229E the least. HCoVs were detected in a limited time period, between December and April/May, and peaked in January/February. Highest infection frequency was in children <5 years (18 per 100 person-years), with little variation in older age groups (range: 7 to 11 per 100 person-years). Overall, 9% of adult cases and 20% of cases in children were associated with medical consultation. Of the 993 infections, 260 were acquired from an infected household contact. The serial interval between index and household-acquired cases ranged from 3.2 to 3.6 days and the secondary infection risk ranged from 7.2% to 12.6% by type. CONCLUSIONS: Coronaviruses are sharply seasonal. They appear, based on serial interval and secondary infection risk, to have similar transmission potential to influenza A(H3N2) in the same population.", "qid": 31, "docid": "u5q5ghrc", "rank": 45, "score": 0.8142490386962891}, {"content": "Title: Novel Coronavirus COVID-19 Strike on Arab Countries and Territories: A Situation Report I Content: The novel Coronavirus (COVID-19) is an infectious disease caused by a new virus called COVID-19 or 2019-nCoV that first identified in Wuhan, China. The disease causes respiratory illness (such as the flu) with other symptoms such as a cough, fever, and in more severe cases, difficulty breathing. This new Coronavirus seems to be very infectious and has spread quickly and globally. In this work, information about COVID-19 is provided and the situation in Arab countries and territories regarding the COVID-19 strike is presented. The next few weeks main expectations is also given.", "qid": 31, "docid": "9fngwsh3", "rank": 46, "score": 0.8142426013946533}, {"content": "Title: Direct Measurement of Rates of Asymptomatic Infection and Clinical Care-Seeking for Seasonal Coronavirus Content: The pandemic potential of the novel coronavirus (nCoV) that emerged in Wuhan, China, during December 2019 is strongly tied to the number and contagiousness of undocumented human infections. Here we present findings from a proactive longitudinal sampling study of acute viral respiratory infections that documents rates of asymptomatic infection and clinical care seeking for seasonal coronavirus. We find that the majority of infections are asymptomatic by most symptom definitions and that only 4% of individuals experiencing a seasonal coronavirus infection episode sought medical care for their symptoms. These numbers indicate that a very high percentage of seasonal coronavirus infections are undocumented and provide a reference for understanding the spread of the emergent nCoV.", "qid": 31, "docid": "90tccg03", "rank": 47, "score": 0.8141696453094482}, {"content": "Title: Age specificity of cases and attack rate of novel coronavirus disease (COVID-19) Content: Age distribution of the cases with novel coronavirus disease (COVID-19) is rather different from that of influenza. We examined the age distribution of COVID-19 cases in Japan from January to March, 2020. Children are less likely to be diagnosed as cases, and moreover, the risk of disease given exposure among children appears to be low. Both the overall risk and the conditional risk of disease given exposure are likely to be the highest among adults aged from 50-69 years. The most plausible explanation that we believe is immune imprinting to a similar virus among adults.", "qid": 31, "docid": "7kzaglt2", "rank": 48, "score": 0.814049243927002}, {"content": "Title: Tackling Corona Virus Disease 2019 (COVID 19) in Workplaces Content: Coronaviruses are zoonotic viruses and six species of Coronaviruses are known to cause human disease such as cause common cold, severe acute respiratory syndrome and the Middle East Respiratory Syndrome. In January 2020, scientists in Wuhan, China isolated a novel coronavirus (SARS-CoV-2), responsible for an outbreak of unknown pneumonia that had not been previously reported among humans. This virus spreads from person to person, through respiratory droplets, close contact, and by touching surfaces or objects contaminated by the virus. The incubation period varies between 2 days and 14 days. Symptoms usually include fever, cough, difficulty in breathing, pneumonia, severe acute respiratory syndrome. Older age and co-morbid conditions increase the fatality. Any person with a history of travel to and from COVID-19 affected countries in the past 14 days or any person who has had close contact with a laboratory confirmed COVID-19 are suspect cases and needs evaluation. Currently no vaccine is available and treatment is mainly supportive. Measures at workplace should include- avoiding non-essential travel, identifying and isolating sick employees at the earliest, hand hygiene, respiratory hygiene, environmental hygiene and social distancing.", "qid": 31, "docid": "rzr8qjw8", "rank": 49, "score": 0.8137104511260986}, {"content": "Title: Molecular epidemiology and characterization of human coronavirus in Thailand, 2012\u20132013 Content: BACKGROUND: Coronavirus causes respiratory infections in humans. To determine the prevalence of human coronavirus (HCoV) infection among patients with influenza-like illness, 5833 clinical samples from nasopharyngeal swabs and aspirates collected between January 2012 and December 2013 were examined. RESULTS: HCoV was found in 46 (0.79 %) samples. There were 19 (0.32 %) HCoV-HKU1, 19 (0.32 %) HCoV-NL63, 5 (0.09 %) HCoV-229E, and 3 (0.05 %) HCoV-OC43. None of the sample tested positive for MERS-CoV. The majority (54 %) of the HCoV-positive patients were between the ages of 0 and 5 years. HCoV was detected throughout the 2-year period and generally peaked from May to October, which coincided with the rainy season. Phylogenetic trees based on the alignment of the spike (S) gene sequences suggest an emergence of a new clade for HCoV-229E. CONCLUSIONS: The data in this study provide an insight into the prevalence of the recent circulating HCoVs in the region.", "qid": 31, "docid": "x6736prq", "rank": 50, "score": 0.813683271408081}, {"content": "Title: Pandemic Influenza Vaccines Content: Since their compositions remain uncertain, universal pandemic vaccines are yet to be created. They would aim to protect globally against pandemic influenza viruses that have not yet evolved. Thus they differ from seasonal vaccines to influenza virus, which are updated annually in spring to incorporate the latest circulating viruses, and are then produced and delivered before the peak influenza season starts in late fall and winter. The efficacy of seasonal vaccines is linked to their ability to induce virus-neutralizing antibodies, which provide subtype-specific protection against influenza A viruses. If pandemic vaccines were designed to resemble current vaccines in terms of composition and mode of action, they would have to be developed, tested, and mass-produced after the onset of a pandemic, once the causative virus had been identified. The logistic problems of generating a pandemic vaccine from scratch, conducting preclinical testing, and producing billions of doses within a few months for global distribution are enormous and may well be insurmountable. Alternatively, the scientific community could step up efforts to generate a universal vaccine against influenza A viruses that provides broadly cross-reactive protection through the induction of antibodies or T cells to conserved regions of the virus.", "qid": 31, "docid": "zh8e76w7", "rank": 51, "score": 0.8132768273353577}, {"content": "Title: Association between viral seasonality and meteorological factors Content: Numerous viruses can cause upper respiratory tract infections. They often precede serious lower respiratory tract infections. Each virus has a seasonal pattern, with peaks in activity in different seasons. We examined the effects of daily local meteorological data (temperature, relative humidity, \u201chumidity-range\u201d and dew point) from Edinburgh, Scotland on the seasonal variations in viral transmission. We identified the seasonality of rhinovirus, adenovirus, influenza A and B viruses, human parainfluenza viruses 1\u20133 (HPIV), respiratory syncytial virus (RSV) and human metapneumovirus (HMPV) from the 52060 respiratory samples tested between 2009 and 2015 and then confirmed the same by a generalised linear model. We also investigated the relationship between meteorological factors and viral seasonality. Non-enveloped viruses were present throughout the year. Following logistic regression adenovirus, influenza viruses A, B, RSV and HMPV preferred low temperatures; RSV and influenza A virus preferred a narrow \u201chumidity-range\u201d and HPIV type 3 preferred the season with lower humidity. A change (i.e. increase or decrease) in specific meteorological factors is associated with an increase in activity of specific viruses at certain times of the year.", "qid": 31, "docid": "ezrjey35", "rank": 52, "score": 0.8132714629173279}, {"content": "Title: Pain Management Under COVID-19 Coronavirus Infections in Children Including COVID-19: An Overview of the Epidemiology, Clinical Features, Diagnosis, Treatment and Prevention Options in Children Content: Coronaviruses (CoVs) are a large family of enveloped, single-stranded, zoonotic RNA viruses Four CoVs commonly circulate among humans: HCoV2-229E, -HKU1, -NL63 and -OC43 However, CoVs can rapidly mutate and recombine leading to novel CoVs that can spread from animals to humans The novel CoVs severe acute respiratory syndrome coronavirus (SARS-CoV) emerged in 2002 and Middle East respiratory syndrome coronavirus (MERS-CoV) in 2012 The 2019 novel coronavirus (SARS-CoV-2) is currently causing a severe outbreak of disease (termed COVID-19) in China and multiple other countries, threatening to cause a global pandemic In humans, CoVs mostly cause respiratory and gastrointestinal symptoms Clinical manifestations range from a common cold to more severe disease such as bronchitis, pneumonia, severe acute respiratory distress syndrome, multi-organ failure and even death SARS-CoV, MERS-CoV and SARS-CoV-2 seem to less commonly affect children and to cause fewer symptoms and less severe disease in this age group compared with adults, and are associated with much lower case-fatality rates Preliminary evidence suggests children are just as likely as adults to become infected with SARS-CoV-2 but are less likely to be symptomatic or develop severe symptoms However, the importance of children in transmitting the virus remains uncertain Children more often have gastrointestinal symptoms compared with adults Most children with SARS-CoV present with fever, but this is not the case for the other novel CoVs Many children affected by MERS-CoV are asymptomatic The majority of children infected by novel CoVs have a documented household contact, often showing symptoms before them In contrast, adults more often have a nosocomial exposure In this review, we summarize epidemiologic, clinical and diagnostic findings, as well as treatment and prevention options for common circulating and novel CoVs infections in humans with a focus on infections in children", "qid": 31, "docid": "jjdr14fe", "rank": 53, "score": 0.8132023811340332}, {"content": "Title: Respiratory virus shedding in exhaled breath and efficacy of face masks Content: We identified seasonal human coronaviruses, influenza viruses and rhinoviruses in exhaled breath and coughs of children and adults with acute respiratory illness. Surgical face masks significantly reduced detection of influenza virus RNA in respiratory droplets and coronavirus RNA in aerosols, with a trend toward reduced detection of coronavirus RNA in respiratory droplets. Our results indicate that surgical face masks could prevent transmission of human coronaviruses and influenza viruses from symptomatic individuals.", "qid": 31, "docid": "jvlun85u", "rank": 54, "score": 0.8127880096435547}, {"content": "Title: Respiratory virus shedding in exhaled breath and efficacy of face masks. Content: We identified seasonal human coronaviruses, influenza viruses and rhinoviruses in exhaled breath and coughs of children and adults with acute respiratory illness. Surgical face masks significantly reduced detection of influenza virus RNA in respiratory droplets and coronavirus RNA in aerosols, with a trend toward reduced detection of coronavirus RNA in respiratory droplets. Our results indicate that surgical face masks could prevent transmission of human coronaviruses and influenza viruses from symptomatic individuals.", "qid": 31, "docid": "g17lp8ch", "rank": 55, "score": 0.8127880096435547}, {"content": "Title: Infection by rhinovirus: Similarity of clinical signs included in the case definition of influenza IAn/H1N1 Content: INTRODUCTION: Although new influenza virus (IAn/H1N1) infections are mild and indistinguishable from any other seasonal influenza virus infections, there are few data on comparisons of the clinical features of infection with (IAn/H1N1) and with other respiratory viruses. The incidence, clinical aspects and temporal distribution of those respiratory viruses circulating during flu pandemic period were studied. METHODS: Respiratory samples from patients with acute influenza-like symptoms were collected from May 2009 to December 2009. Respiratory viruses were detected by conventional culture methods and genome amplification techniques. RESULTS: Although IAn/H1N1 was the virus most frequently detected, several other respiratory viruses co-circulated with IAn/H1N1 during the pandemic period, especially rhinovirus. The similarity between clinical signs included in the clinical case definition for influenza and those caused by other respiratory viruses, particularly rhinovirus, suggest that a high percentage of viral infections were clinically diagnosed as case of influenza. CONCLUSIONS: Our study offers useful information to face future pandemics caused by influenza virus, indicating that differential diagnoses are required in order to not overestimate the importance of the pandemic.", "qid": 31, "docid": "tww39tsu", "rank": 56, "score": 0.812782883644104}, {"content": "Title: Virus isolations from patients in general practice, 1961-71. Content: During the period 1961-71 of 1785 viruses isolated from patients in the general population 503 (28%) were rhinoviruses, 465 (26%) influenza viruses, 248 (14%) enteroviruses, 234 (13%) herpes simplex virus, 132 (7%) parainfluenza viruses, 129 (7%) adenoviruses and 49 (3%) respiratory syncytial virus. Also isolated were 18 strains of mumps virus, 7 coronaviruses and 295 streptococci of groups A, C or G.Fluctuations were observed in the frequency with which respiratory syncytial virus, parainfluenza virus type 2, and the adenoviruses were isolated over the 10-year period.Influenza viruses types A and B, parainfluenza viruses types 1 and 2, respiratory syncytial virus, adenoviruses types 3, 4, 6, 7 and 21, and many enteroviruses were all associated with outbreaks.Infections with influenza viruses A and B and parainfluenza viruses types 1 and 2 came during the winter, whereas those with parainfluenza virus type 3, enteroviruses, and rhinoviruses were more frequently seen in the summer and early autumn.", "qid": 31, "docid": "j5w9pslt", "rank": 57, "score": 0.8123542070388794}, {"content": "Title: Coronaviruses and SARS-COV-2 Content: Coronaviruses (CoVs) cause a broad spectrum of diseases in domestic and wild animals, poultry, and rodents, ranging from mild to severe enteric, respiratory, and systemic disease, and also cause the common cold or pneumonia in humans. Seven coronavirus species are known to cause human infection, 4 of which, HCoV 229E, HCoV NL63, HCoV HKU1 and HCoV OC43, typically cause cold symptoms in immunocompetent individuals. The others namely SARS-CoV (severe acute respiratory syndrome coronavirus), MERS-CoV (Middle East respiratory syndrome coronavirus) were zoonotic in origin and cause severe respiratory illness and fatalities. On 31 December 2019, the existence of patients with pneumonia of an unknown aetiology was reported to WHO by the national authorities in China. This virus was officially identified by the coronavirus study group as severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), and the present outbreak of a coronavirus-associated acute respiratory disease was labelled coronavirus disease 19 (COVID-19). COVID-19's first cases were seen in Turkey on March 10, 2020 and was number 47,029 cases and 1006 deaths after 1 month. Infections with SARS-CoV-2 are now widespread, and as of 10 April 2020, 1,727,602 cases have been confirmed in more than 210 countries, with 105,728 deaths.", "qid": 31, "docid": "lm9urlat", "rank": 58, "score": 0.8119461536407471}, {"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": 59, "score": 0.811809778213501}, {"content": "Title: Dramatic decrease of laboratory\u2010confirmed influenza A after school closure in response to COVID\u201019 Content: The novelty of the coronavirus disease 2019 (COVID-19) has led some researchers to use influenza models and changes in influenza activity to infer the impact of social distancing measures to mitigate the transmission of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2 This article is protected by copyright. All rights reserved.", "qid": 31, "docid": "x2g8gspz", "rank": 60, "score": 0.8116317987442017}, {"content": "Title: COVID-19: Emergence, Spread, Possible Treatments, and Global Burden Content: The Coronavirus (CoV) is a large family of viruses known to cause illnesses ranging from the common cold to acute respiratory tract infection. The severity of the infection may be visible as pneumonia, acute respiratory syndrome, and even death. Until the outbreak of SARS, this group of viruses was greatly overlooked. However, since the SARS and MERS outbreaks, these viruses have been studied in greater detail, propelling the vaccine research. On December 31, 2019, mysterious cases of pneumonia were detected in the city of Wuhan in China's Hubei Province. On January 7, 2020, the causative agent was identified as a new coronavirus (2019-nCoV), and the disease was later named as COVID-19 by the WHO. The virus spread extensively in the Wuhan region of China and has gained entry to over 210 countries and territories. Though experts suspected that the virus is transmitted from animals to humans, there are mixed reports on the origin of the virus. There are no treatment options available for the virus as such, limited to the use of anti-HIV drugs and/or other antivirals such as Remdesivir and Galidesivir. For the containment of the virus, it is recommended to quarantine the infected and to follow good hygiene practices. The virus has had a significant socio-economic impact globally. Economically, China is likely to experience a greater setback than other countries from the pandemic due to added trade war pressure, which have been discussed in this paper.", "qid": 31, "docid": "vx7ebtbp", "rank": 61, "score": 0.8114526271820068}, {"content": "Title: Coronavirus Occurrence and Transmission Over 8 Years in the HIVE Cohort of Households in Michigan Content: BACKGROUND: As part of the Household Influenza Vaccine Evaluation (HIVE) study, acute respiratory infections (ARI) have been identified in children and adults from 2010 to 2018. METHODS: Annually, 890 to 1441 individuals were followed and contacted weekly to report ARIs. Specimens collected during illness were tested for human coronaviruses (HCoV) types OC43, 229E, HKU1, and NL63. RESULTS: In total, 993 HCoV infections were identified during the 8 years, with OC43 most commonly seen and 229E the least. HCoVs were detected in a limited time period, between December and April/May and peaked in January/February. Highest infection frequency was in children <5 years (18 per 100 person-years), with little variation in older age groups (range, 7 to 11 per 100 person-years). Overall, 9% of adult cases and 20% of cases in children were associated with medical consultation. Of the 993 infections, 260 were acquired from an infected household contact. The serial interval between index and household-acquired cases ranged from 3.2 to 3.6 days and the secondary infection risk ranged from 7.2% to 12.6% by type. CONCLUSIONS: Coronaviruses are sharply seasonal. They appear, based on serial interval and secondary infection risk, to have similar transmission potential to influenza A(H3N2) in the same population.", "qid": 31, "docid": "gfztjt6p", "rank": 62, "score": 0.8112140893936157}, {"content": "Title: The association between severe COVID-19 and low platelet count: evidence from 31 observational studies involving 7613 participants. Content: A novel coronavirus disease 2019 (COVID-19) broke out at 2019 and had caused a pandemic around the world. This disease was found resulting from the infection of 2019 novel coronavirus (2019-nCoV) (Zhu, et al 2020). The severity of COVID-19 disease has a wide range and varies from asymptomatic to critical severe, clinical researches reported that 10-15% of the patients were in the severe situation and required a great deal of attention of treatment and nursing (WHO-China-Joint-Mission 2020).", "qid": 31, "docid": "nyfe0tnl", "rank": 63, "score": 0.811026930809021}, {"content": "Title: Other Respiratory Viruses Are Important Contributors to Adult Respiratory Hospitalizations and Mortality Even During Peak Weeks of the Influenza Season Content: BACKGROUND: During peak weeks of seasonal influenza epidemics, severe respiratory infections without laboratory confirmation are typically attributed to influenza. METHODS: In this prospective study, specimens and demographic and clinical data were collected from adults admitted with respiratory symptoms to 4 hospitals during the 8\u201310 peak weeks of 2 influenza seasons. Specimens were systematically tested for influenza and 13 other respiratory viruses (ORVs) by using the Luminex RVP FAST assay. RESULTS: At least 1 respiratory virus was identified in 46% (21% influenza, 25% noninfluenza; 2% coinfection) of the 286 enrolled patients in 2011\u20132012 and in 62% (46% influenza, 16% noninfluenza; 3% coinfection) of the 396 enrolled patients in 2012\u20132013. Among patients aged \u226575 years, twice as many ORVs (32%) as influenza viruses (14%) were detected in 2011\u20132012. During both seasons, the most frequently detected ORVs were enteroviruses/rhinoviruses (7%), respiratory syncytial virus (6%), human metapneumovirus (5%), coronaviruses (4%), and parainfluenza viruses (2%). Disease severity was similar for influenza and ORVs during both seasons. CONCLUSIONS: Although ORV contribution relative to influenza varies by age and season, during the peak weeks of certain influenza seasons, ORVs may be a more frequent cause of elderly hospitalization than influenza.", "qid": 31, "docid": "e32dzhij", "rank": 64, "score": 0.8109937310218811}, {"content": "Title: Seasonal influenza activity in Hong Kong and its association with meteorological variations. Content: Influenza seasons appear consistently in the temperate regions, but are more variable in tropical/subtropical regions. The determinant for such variation remains poorly understood. This study documented the activity of influenza over a 10-year period in Hong Kong; examining its association with changes in temperature and relative humidity. The two types of influenza exhibited different correlations with meteorological variations. Influenza A showed two seasonal peaks occurring respectively in winter/spring and summer months in most years. Influenza B showed a clear winter/spring peak, but its activity during summer months was more variable. Cold and humid conditions were associated with a higher activity of both influenza A and B. In contrast, hot and humid conditions were associated with a higher activity of influenza A, but were associated with only a moderate, less consistent increase in the activity of influenza B. A trend of increase in the magnitude of summer peaks of influenza A, but not influenza B, was observed. A hypothetical 2 degrees C rise in temperature would decrease the proportion of favorable days for influenza A in December-April from 78% to 57%, but an increase from 58% to 71% in May-November; with a similar effect (from 83% to 62%) for influenza B during December-April, but a modest change (from 17% to 18%) during May-November. The presence of two seasonal peaks of influenza annually emphasizes the need to evaluate the duration of protective immunity offered by vaccination. Further study on the effects of climate change and global warming on the activity of influenza is warranted.", "qid": 31, "docid": "sy53tfr6", "rank": 65, "score": 0.8108057975769043}, {"content": "Title: Evidence of an absence: the genetic origins of the 1918 pandemic influenza virus Content: Annual outbreaks of influenza A infection are an ongoing public health threat and novel influenza strains can periodically emerge to which humans have little immunity, resulting in devastating pandemics. The 1918 pandemic killed at least 40 million people worldwide and pandemics in 1957 and 1968 caused hundreds of thousands of deaths. The influenza A virus is capable of enormous genetic variation, both by continuous, gradual mutation and by reassortment of genome segments between viruses. Both the 1957 and 1968 pandemic strains are thought to have originated as reassortants in which one or both human-adapted viral surface proteins were replaced by proteins from avian influenza strains. Analyses of the genes of the 1918 pandemic virus, however, indicate that this strain might have had a different origin. The haemagglutinin and nucleoprotein genome segments in particular are unlikely to have come directly from an avian source that is similar to those that are currently being sequenced. Determining whether a pandemic influenza virus can emerge by different mechanisms will affect the scope and focus of surveillance and prevention efforts.", "qid": 31, "docid": "vy00r2b0", "rank": 66, "score": 0.8107645511627197}, {"content": "Title: Advice regarding COVID\u201019 and use of immunomodulators, in patients with severe dermatological diseases Content: Coronavirus disease 2019 (COVID-19) is the disease caused by the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), as named by the International Committee on Taxonomy of Viruses (ICTV). There is very limited evidence base to formulate specific advice for dermatology patients on immunomodulators with regards to COVID-19. The following is based on expert opinion, taking into account known risks of influenza (a negative sense single-stranded RNA virus) and other, positive-sense single-stranded, RNA virus infections (such as SARS, MERS, and the common cold). An Australia/New Zealand consensus document is in development.", "qid": 31, "docid": "nfjxp783", "rank": 67, "score": 0.8106098175048828}, {"content": "Title: The Role of Punctuated Evolution in the Pathogenicity of Influenza Viruses. Content: Influenza is an acute respiratory disease caused by influenza viruses. Evolutionarily, all influenza viruses are zoonoses, arising in the animal reservoir and spilling over into the human population. Several times a century, one of these zoonotic events results in a new influenza virus lineage becoming established in humans and circulating for years or decades as an endemic strain. The worldwide pandemic that occurs shortly after the nascent virus becomes established can have a profound impact on morbidity and mortality. Because influenza viruses continually evolve and the illness they engender can vary considerably based on characteristics of the strain, the weather, other circulating or endemic pathogens, as well as the number of susceptible hosts, the impact of each season on human health is unpredictable. Over time, the general pattern is for pandemic strains to adapt and gradually take on characteristics of seasonal strains with lower virulence and a diminished synergism with bacterial pathogens. Study of this punctuated evolution yields a number of insights into the overall pathogenicity of influenza viruses.", "qid": 31, "docid": "4huzn5jj", "rank": 68, "score": 0.8105621933937073}, {"content": "Title: [Coronaviruses]. Content: Corona viruses belong to a group of not yet well known viruses isolated in patients with infections of the upper respiratory organs, especially in winter months. It is presumed that they provoke about 15% - 20% of all infections. However, in the last years more attention has been paid to the role of human corona viruses in the provocation of sickness in man and they are becoming a special field of interest in scientific studies.", "qid": 31, "docid": "pkmkgppp", "rank": 69, "score": 0.8102835416793823}, {"content": "Title: Vascular skin symptoms in COVID-19: a french observational study Content: Coronavirus 19 (COVID-19) was declared as a pandemic viral infection by the World Health organization on March 11th 2020. Usual clinical manifestations of COVID-19 infection include fever, fatigue, myalgia, headache, diarrhea, dry cough, dyspnea that may lead to acute respiratory distress syndrome and death (1). Skin symptoms of COVID-19 have been poorly described but may include erythematous rash, urticaria and chicken pox like lesions (2-7). Angiotensin-converting enzyme 2 (ACE2) is a cellular receptor for COVID-19.", "qid": 31, "docid": "vp5xj8m5", "rank": 70, "score": 0.8102226257324219}, {"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": 71, "score": 0.8101857900619507}, {"content": "Title: No Evidence for Temperature-Dependence of the COVID-19 Epidemic Content: The pandemic of the COVID-19 disease extended from China across the north-temperate zone, and more recently to the tropics and southern hemisphere. We find no evidence that spread rates decline with temperatures above 20 oC, suggesting that the COVID-19 disease is unlikely to behave as a seasonal respiratory virus.", "qid": 31, "docid": "bnrmh1qs", "rank": 72, "score": 0.8101397752761841}, {"content": "Title: Circulation of other respiratory viruses and viral co-infection during the 2009 pandemic influenza Content: Abstract Coinciding with the pandemic wave of the influenza A(H1N1)pdm09 virus, other respiratory viruses have co-circulated in our area and were responsible for many acute respiratory infections and influenza-like illness (ILI). Apart from the pandemic virus that was responsible for most ILI cases, incidence rates of other viruses have varied among geographical areas. In general, human rhinovirus was the most frequent among individuals from the community, and respiratory syncytial virus among hospitalized patients. Detection rates of other respiratory viruses such as human metapneumovirus, adenovirus or parainfluenza viruses have been much lower. On the basis of an interference mechanism, human rhinovirus may contribute to modulate the pandemic wave, although available data are not conclusive to support this hypothesis. In contrast, the epidemic wave of respiratory syncytial virus during 2009\u20132010 was similar to previous seasons. Overall, incidence rates of respiratory viruses other than influenza did not change significantly during the pandemic season compared to other seasons. No association has been found between coinfection of pandemic influenza and other respiratory viruses with the prognosis of patients with influenza. The involvement of clinical virology laboratories in the etiological diagnosis of ILI cases has improved and has optimized diagnostic procedures.", "qid": 31, "docid": "5n8c9lzw", "rank": 73, "score": 0.810121476650238}, {"content": "Title: Genetic variability of human coronavirus OC43\u2010, 229E\u2010, and NL63\u2010like strains and their association with lower respiratory tract infections of hospitalized infants and immunocompromised patients Content: In the winter\u2013spring seasons 2003\u20132004 and 2004\u20132005, 47 (5.7%) patients with acute respiratory infection associated with human coronavirus (hCoV) 229E\u2010, NL63\u2010, and OC43\u2010like strains were identified among 823 (597 immunocompetent and 226 immunocompromised) patients admitted to hospital with acute respiratory syndromes. Viral infections were diagnosed by either immunological (monoclonal antibodies) or molecular (RT\u2010PCR) methods. Each of two sets of primer pairs developed for detection of all CoVs (panCoV) failed to detect 15 of the 53 (28.3%) hCoV strains identified. On the other hand, all hCoV strains could be detected by using type\u2010specific primers targeting genes 1ab and N. The HuH\u20107 cell line was found to be susceptible to isolation and identification of OC43\u2010 and 229E\u2010like strains. Overall, hCoV infection was caused by OC43\u2010like, 229E\u2010like, and NL63\u2010like strains in 25 (53.2%), 10 (21.3%), and 9 (19.1%) patients, respectively. In addition, three patients (6.4%) were infected by untypeable hCoV strains. NL63\u2010like strains were not found to circulate in 2003\u20132004, and 229E\u2010like strains did not circulate in 2004\u20132005, while OC43\u2010like strains were detected in both seasons. The monthly distribution reached a peak during January through March. Lower predominated over upper respiratory tract infections in each age group. In addition, hCoV infections interested only immunocompetent infants and young children during the first year of life, while all adults were immunocompromised patients. Coinfections of hCoVs and other respiratory viruses (mostly interesting the first year of life) were observed in 14 of the 47 (29.8%) patients and were associated with severe respiratory syndromes more frequently than hCoV single infections (P = 0.002). In conclusion, the use of multiple primer sets targeting different genes is recommended for diagnosis of all types of hCoV infection. In addition, the detection of still untypeable hCoV strains suggests that the number of hCoVs involved in human pathology might further increase. Finally, hCoVs should be screened routinely for in both infants and immunocompromised patients with acute respiratory infection. J. Med. Virol. 78:938\u2013949, 2006. \u00a9 2006 Wiley\u2010Liss, Inc.", "qid": 31, "docid": "cmjnb0al", "rank": 74, "score": 0.8101005554199219}, {"content": "Title: Overview: The history and pediatric perspectives of severe acute respiratory syndromes: Novel or just like SARS Content: Many respiratory viral infections such as influenza and measles result in severe acute respiratory symptoms and epidemics. In the spring of 2003, an epidemic of coronavirus pneumonia spread from Guangzhou to Hong Kong and subsequently to the rest of the world. The WHO coined the acronym SARS (severe acute respiratory syndrome) and subsequently the causative virus as SARS-CoV. In the summer of 2012, epidemic of pneumonia occurred again in Saudi Arabia which was subsequently found to be caused by another novel coronavirus. WHO coined the term MERS (Middle East respiratory syndrome) to denote the Middle East origin of the novel virus (MERS-CoV). In the winter of 2019, another outbreak of pneumonia occurred in Wuhan, China which rapidly spread globally. Yet another novel coronavirus was identified as the culprit and has been named SARS-CoV-2 due to its similarities with SARS-CoV, and the disease as coronavirus disease-2019. This overview aims to compare and contrast the similarities and differences of these three major episodes of coronavirus outbreak, and conclude that they are essentially the same viral respiratory syndromes caused by similar strains of coronavirus with different names. Coronaviruses have caused major epidemics and outbreaks worldwide in the last two decades. From an epidemiological perspective, they are remarkably similar in the mode of spread by droplets. Special focus is placed on the pediatric aspects, which carry less morbidity and mortality in all three entities.", "qid": 31, "docid": "49ybh6fj", "rank": 75, "score": 0.8100036978721619}, {"content": "Title: Clinical Progression of COVID-19 Patient with Extended Incubation Period, Delayed RT-PCR Time-to-positivity, and Potential Role of Chest CT-scan Content: Coronavirus Disease 2019 (COVID-19), previously called 2019-nCoV, is a novel disease caused by SARS- CoV-2 which was first identified as outbreak of unknown respiratory illness in Wuhan, China. COVID- 19 was declared as global health emergency by WHO on March 11, 2020 and quickly elevated to global pandemic on 11 March 2020. COVID-19 symptom is highly various in each patient, with fever, fatigue, shortness of breath, and cough as the main presenting symptoms. Patient with COVID-19 may shows severe symptom with severe pneumonia and ARDS, mild symptom resembling simple upper respiration tract infection, or even completely asymptomatic. Approximately 80% of cases is mild. However the number may changes as more people are getting tested. Some experts are estimating that up to 50% of all cases may be asymptomatic carrier.", "qid": 31, "docid": "3njzz1yi", "rank": 76, "score": 0.809917688369751}, {"content": "Title: Clinical Progression of COVID-19 Patient with Extended Incubation Period, Delayed RT-PCR Time-to-positivity, and Potential Role of Chest CT-scan. Content: Coronavirus Disease 2019 (COVID-19), previously called 2019-nCoV, is a novel disease caused by SARS- CoV-2 which was first identified as outbreak of unknown respiratory illness in Wuhan, China. COVID- 19 was declared as global health emergency by WHO on March 11, 2020 and quickly elevated to global pandemic on 11 March 2020. COVID-19 symptom is highly various in each patient, with fever, fatigue, shortness of breath, and cough as the main presenting symptoms. Patient with COVID-19 may shows severe symptom with severe pneumonia and ARDS, mild symptom resembling simple upper respiration tract infection, or even completely asymptomatic. Approximately 80% of cases is mild. However the number may changes as more people are getting tested. Some experts are estimating that up to 50% of all cases may be asymptomatic carrier.", "qid": 31, "docid": "e4uzvmmh", "rank": 77, "score": 0.809917688369751}, {"content": "Title: Complications of seasonal and pandemic influenza. Content: Influenza is a seasonal viral infection associated with significant morbidity and mortality. In 2009, a novel H1N1 influenza A virus emerged and has been classified as a pandemic. In contrast to seasonal influenza, severe disease from pandemic H1N1 seems concentrated in older children and young adults, with almost no cases reported in patients older than 60 yrs. Although patients with underlying cardiopulmonary disease remain at risk, most complications have occurred among previously healthy individuals, with obesity and respiratory disease as the strongest risk factors. Pulmonary complications are common. Primary influenza pneumonia occurs most commonly in adults and may progress rapidly to acute lung injury requiring mechanical ventilation. Secondary bacterial infection is more common in children. Staphylococcus aureus, including methicillin-resistant strains, is an important cause of secondary bacterial pneumonia with a high mortality rate. Treatment of pneumonia should include empirical coverage for this pathogen. Neuromuscular and cardiac complications are unusual but may occur.", "qid": 31, "docid": "0lp2aqlu", "rank": 78, "score": 0.809624195098877}, {"content": "Title: Viral respiratory infections during the 2009 influenza A(H1N1) outbreak in the West Midlands Region, UK. Content: In spring 2009 a new strain of influenza A(H1N1) emerged and caused a worldwide pandemic. This study utilized a large collection of respiratory specimens from suspected cases of influenza A(H1N1) in the UK West Midlands during the pandemic in order to investigate which other respiratory viruses were circulating and whether they played any role in the increased hospitalization rates seen during that period. Study specimens were selected from community and hospitalized patients positive and negative for influenza A(H1N1) and tested by PCR for other respiratory viruses. A number of infections diagnosed as influenza during the summer influenza outbreak were found to be due to other virus infections (most commonly rhinovirus). No statistically significant difference was found between the rates of respiratory virus co-infection with H1N1 in patients from community or hospital locations suggesting underlying factors were likely to be more significant than viral co-infections in determining severity of influenza A(H1N1) disease.", "qid": 31, "docid": "itk5axgz", "rank": 79, "score": 0.8096034526824951}, {"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": 80, "score": 0.8089841604232788}, {"content": "Title: Overview: The history and pediatric perspectives of severe acute respiratory syndromes: Novel or just like SARS Content: Many respiratory viral infections such as influenza and measles result in severe acute respiratory symptoms and epidemics. In the spring of 2003, an epidemic of coronavirus pneumonia spread from Guangzhou to Hong Kong and subsequently to the rest of the world. The WHO coined the acronym SARS (severe acute respiratory syndrome) and subsequently the causative virus as SARS\u2010CoV. In the summer of 2012, epidemic of pneumonia occurred again in Saudi Arabia which was subsequently found to be caused by another novel coronavirus. WHO coined the term MERS (Middle East respiratory syndrome) to denote the Middle East origin of the novel virus (MERS\u2010CoV). In the winter of 2019, another outbreak of pneumonia occurred in Wuhan, China which rapidly spread globally. Yet another novel coronavirus was identified as the culprit and has been named SARS\u2010CoV\u20102 due to its similarities with SARS\u2010CoV, and the disease as coronavirus disease\u20102019. This overview aims to compare and contrast the similarities and differences of these three major episodes of coronavirus outbreak, and conclude that they are essentially the same viral respiratory syndromes caused by similar strains of coronavirus with different names. Coronaviruses have caused major epidemics and outbreaks worldwide in the last two decades. From an epidemiological perspective, they are remarkably similar in the mode of spread by droplets. Special focus is placed on the pediatric aspects, which carry less morbidity and mortality in all three entities.", "qid": 31, "docid": "4oz6r7op", "rank": 81, "score": 0.8089579343795776}, {"content": "Title: Severe Acute Respiratory Syndrome Coronavirus-2 (SARS-CoV-2): An Update Content: Coronaviruses (CoVs) belong to the family of Coronaviridae, the order Nidovirales, and the genus Coronavirus. They are the largest group of viruses causing respiratory and gastrointestinal infections. Morphologically, CoVs are enveloped viruses containing a non-segmented positive-sense, single-stranded ribonucleic acid (RNA) viruses. CoVs are categorized into four important genera that include Alphacoronavirus, Betacoronavirus, Gammacoronavirus, and Deltacoronavirus. A novel member of human CoV that has recently emerged in Wuhan, China, is now formally named as SARS-CoV-2 (severe acute respiratory syndrome coronavirus 2). This is a unique strain of RNA viruses that have not been previously observed in humans. The virus has wide host adaptability and is capable of causing severe diseases in humans, masked palm civets, mice, dogs, cats, camels, pigs, chickens, and bats. The SARS-CoV-2 typically causes respiratory and gastrointestinal sickness in both humans and animals. It can be transmitted through aerosols and direct/indirect contact, as well as during medical cases and laboratory sample handling. Specific structural proteins, which might be found on the surface of the virus, play an important role in the pathogenesis and development of the complications. The disease is characterized by distinct medical signs and symptoms that include high fever, chills, cough, and shortness of breath or difficulty in breathing. The infected people may also present with other symptoms such as diarrhea, myalgia, fatigue, expectoration, and hemoptysis. It is important from the public health and economic point of view as it affects the growth of the country, which is majorly attributed to the restriction in the movement of the people and the cost associated with the control and prevention of the disease. Since there is no specific therapeutic intervention nor a vaccine available against the virus, supportive management and treatment with non-specific therapeutic agents (repurposed drugs) may provide relief to the patients. Some preventive strategies of the disease include blocking the routes of transmission of the infections, disinfection of instruments used during medical case handling, using personal protective equipment, proper and early diagnosis of the disease, avoiding contact with the sick patients, and quarantine of the infected/exposed people.", "qid": 31, "docid": "oq16de67", "rank": 82, "score": 0.8087771534919739}, {"content": "Title: Characteristics of respiratory virus infection during the outbreak of 2019 novel coronavirus in Beijing Content: Abstract Background Coronavirus disease 2019 (COVID-19) is spreading. Here, we summarized the composition of pathogens in fever clinic patients and analyzed characteristics of different respiratory virus infection. Methods Retrospectively collected patients with definite etiological results using nasal and pharyngeal swabs in fever clinic. Results Totally, 1860 patients were screened and 136 patients were enrolled. 72 (52.94%) of them were diagnosed as influenza (Flu) A virus infection. 32 (23.53%) of them were diagnosed as Flu B virus infection. 18 (13.24%) and 14 (10.29%) of them were diagnosed as COVID-19 and respiratory syncytial virus (RSV) infection respectively. COVID-19 group had a higher rate of contact with epidemic area within 14 days and clustering onset than other groups. Fever was the most common symptom in these patients. The ratio of fever and the highest temperature were higher in Flu A virus infection patients than in COVID-19 patients. COVID-19 patients had lower white blood cell count and neutrophil count than Flu A virus and RSV infection group, but higher lymphocyte count than Flu A and B virus infection groups. COVID-19 group (83.33%) had higher rate of pneumonia in chest CT scan than Flu A and B virus infection groups. Conclusions Influenza viruses accounted for a large proportion of respiratory virus infection even during the epidemic of COVID-19 in Beijing. No single symptom or laboratory finding was suggestive of specific respiratory virus, however, epidemic history was important for screening of COVID-19.", "qid": 31, "docid": "pqvlh3eg", "rank": 83, "score": 0.8087420463562012}, {"content": "Title: Influenza and COVID-19 coinfection: Report of six cases and review of the literature Content: Coronavirus disease 2019 (COVID-19) pandemic caused infection in a season when influenza is still prevalent. Both viruses have similar transmission characteristics and common clinical manifestations. Influenza has been described to cause respiratory infection with some other respiratory pathogens. However, the information of COVID-19 and influenza coinfection is limited. In this study, we reported our coinfected cases and reviewed the literature. We included all COVID-19 diagnosed patients. All patients with a presumed diagnosis of COVID-19 were routinely screened for influenza. Their thorax radiology was reviewed for COVID-19-influenza differentiation. During the study period, 1103 patients have been diagnosed with COVID-19. Among them, six patients (0.54%) were diagnosed coinfected with influenza. There have been 28 more coinfected patients reported. Laboratory-based screening studies reported more patients. Thorax radiology findings were compatible with COVID-19 in five and with influenza in one of our patients. Our cases were mild to moderate in severity. The reported cases in the literature included patients died (n = 2) and those living ventilator dependent or under mechanical ventilation. COVID-19 and influenza coinfection is rare. Screening studies report more cases, suggesting that unless screening patients with COVID-19, the coinfection remains undiagnosed and underestimated. Increasing experience in thoracic radiology may contribute to diagnose the responsible virus(es) from the clinical illness. Influenza vaccine for larger population groups can be recommended to simplify clinicians' work.", "qid": 31, "docid": "m0afd6q0", "rank": 84, "score": 0.808619499206543}, {"content": "Title: Differential diagnosis of illness in patients under investigation for the novel coronavirus (SARS-CoV-2), Italy, February 2020 Content: A novel coronavirus (SARS-CoV-2) has been identified as the causative pathogen of an ongoing outbreak of respiratory disease, now named COVID-19. Most cases and sustained transmission occurred in China, but travel-associated cases have been reported in other countries, including Europe and Italy. Since the symptoms are similar to other respiratory infections, differential diagnosis in travellers arriving from countries with wide-spread COVID-19 must include other more common infections such as influenza and other respiratory tract diseases.", "qid": 31, "docid": "err1npxf", "rank": 85, "score": 0.8085036277770996}, {"content": "Title: Spotlight on avian coronaviruses Content: Coronaviruses (CoVs) mainly cause enteric and/or respiratory signs. Mammalian CoVs including COVID-19 (now officially named SARS-CoV-2) belong to either the Alphacoronavirus or Betacoronavirus genera. In birds, the majority of the known CoVs belong to the Gammacoronavirus genus, whilst a small number are classified as Deltacoronaviruses. Gammacoronaviruses continue to be reported in an increasing number of avian species, generally by detection of viral RNA. Apart from infectious bronchitis virus in chickens, the only avian species in which CoV has been definitively associated with disease are the turkey, pheasant and guinea fowl. Whilst there is strong evidence for recombination between gammacoronaviruses of different avian species, and between betacoronaviruses in different mammals, evidence of recombination between coronaviruses of different genera is lacking. Furthermore, the recombination of an alpha or betacoronavirus with a gammacoronavirus is extremely unlikely. For recombination to happen, the two viruses would need to be present in the same cell of the same animal at the same time, a highly unlikely scenario as they cannot replicate in the same host!", "qid": 31, "docid": "y7lh4u30", "rank": 86, "score": 0.8084279894828796}, {"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": 87, "score": 0.8082442879676819}, {"content": "Title: Viral influenza-like illnesses: dynamic interrelationships during the 2015\u20132016 influenza season in hospitalized patients Content: Summary In hospitalized children and adults, the temporal relationship of viruses causing influenza-like illnesses (ILIs) and influenza has not been well described. During the 2015\u20132016 influenza season at our hospital, the dynamic interrelationships between ILI viruses (human metapneumovirus, respiratory syncytial virus, human parainfluenza viruses 3 and 4, rhinoviruses/enteroviruses, and coronaviruses) and influenza A were characterized in 768 hospitalized children and adults.", "qid": 31, "docid": "531tmdlp", "rank": 88, "score": 0.8081015348434448}, {"content": "Title: COVID 19 and Spanish flu pandemics: All it changes, nothing changes Content: The Corona Virus 19 (COVID 19) epidemic is an infectious disease which was declared as a pandemic and hit all the Countries, all over the world, from the beginning of the year 2020. There are many similarities between the COVID 19 epidemic and the Spanish flu epidemic. We considered some preventive measures which do not change in the two epidemics.", "qid": 31, "docid": "yxmtpel8", "rank": 89, "score": 0.8080441951751709}, {"content": "Title: COVID 19 and Spanish flu pandemics: All it changes, nothing changes. Content: The Corona Virus 19 (COVID 19) epidemic is an infectious disease which was declared as a pandemic and hit all the Countries, all over the world, from the beginning of the year 2020. There are many similarities between the COVID 19 epidemic and the Spanish flu epidemic. We considered some preventive measures which do not change in the two epidemics.", "qid": 31, "docid": "noaw8sba", "rank": 90, "score": 0.8080441951751709}, {"content": "Title: Coronavirus 101 Content: COVID-2019 emerged from China in late December. It follows two other coronavirus outbreaks, the SARS-CoV and the MERS-CoV. Coronaviruses usually circulate among animals but sometimes can jump to humans. These three strains have caused severe disease in humans and global transmission concerns. Symptoms of COVID-2019 include cough, fever, and shortness of breath. Related illnesses can range from mild to severe to fatal. Primary care providers must be alert to respiratory symptoms they encounter that are associated with pertinent travel history, be prepared to safely screen, examine and possibly test and/or report suspicions to the health department for further evaluation.", "qid": 31, "docid": "9zetheol", "rank": 91, "score": 0.8078590631484985}, {"content": "Title: SnapShot: COVID-19 Content: Coronavirus disease 2019 (COVID-19) is a novel respiratory illness caused by SARS-CoV-2. Viral entry is mediated through viral spike protein and host ACE2 enzyme interaction. Most cases are mild; severe disease often involves cytokine storm and organ failure. Therapeutics including antivirals, immunomodulators, and vaccines are in development. To view this SnapShot, open or download the PDF.", "qid": 31, "docid": "q3jeu45r", "rank": 92, "score": 0.8077863454818726}, {"content": "Title: Coronavirus Infections in Children Including COVID-19: An Overview of the Epidemiology, Clinical Features, Diagnosis, Treatment and Prevention Options in Children Content: Coronaviruses (CoVs) are a large family of enveloped, single-stranded, zoonotic RNA viruses. Four CoVs commonly circulate among humans: HCoV2-229E, -HKU1, -NL63 and -OC43. However, CoVs can rapidly mutate and recombine leading to novel CoVs that can spread from animals to humans. The novel CoVs severe acute respiratory syndrome coronavirus (SARS-CoV) emerged in 2002 and Middle East respiratory syndrome coronavirus (MERS-CoV) in 2012. The 2019 novel coronavirus (SARS-CoV-2) is currently causing a severe outbreak of disease (termed COVID-19) in China and multiple other countries, threatening to cause a global pandemic. In humans, CoVs mostly cause respiratory and gastrointestinal symptoms. Clinical manifestations range from a common cold to more severe disease such as bronchitis, pneumonia, severe acute respiratory distress syndrome, multi-organ failure and even death. SARS-CoV, MERS-CoV and SARS-CoV-2 seem to less commonly affect children and to cause fewer symptoms and less severe disease in this age group compared with adults, and are associated with much lower case-fatality rates. Preliminary evidence suggests children are just as likely as adults to become infected with SARS-CoV-2 but are less likely to be symptomatic or develop severe symptoms. However, the importance of children in transmitting the virus remains uncertain. Children more often have gastrointestinal symptoms compared with adults. Most children with SARS-CoV present with fever, but this is not the case for the other novel CoVs. Many children affected by MERS-CoV are asymptomatic. The majority of children infected by novel CoVs have a documented household contact, often showing symptoms before them. In contrast, adults more often have a nosocomial exposure. In this review, we summarize epidemiologic, clinical and diagnostic findings, as well as treatment and prevention options for common circulating and novel CoVs infections in humans with a focus on infections in children.", "qid": 31, "docid": "1f9x5li8", "rank": 93, "score": 0.8077098727226257}, {"content": "Title: Pandemic Human Coronavirus \u2013 Characterization and Comparison of Selected Properties of Hcov-sars and Hcov-mers Content: It: Two Coronaviruses, HCoV-229E and HCoV-OC43, causing generally mild respiratory tract infections in humans, were described in the XX c Pandemic Coronaviruses were first discovered as late as in the XXI c : SARS-HCoV in 2002 \u2013 causing severe respiratory tract infections (SARS) in China;MERS-HCoV in 2012 \u2013 circulating mostly on the Arabian Peninsula The SARS epidemic ended in 2004 resulting in morbidity of &gt;8000 and &gt;770 deaths, while the MERS epidemic is still ongoing (&gt;2000 ill, &gt;700 deaths) although its intensity decreased Both viruses are zoonotic and require at least two \u201chost jumps\u201d for the transmission of the infection to humans: for HCoV-SARS \u2013 from bat to palm civet and then to human;for HCoV-MERS \u2013 from bats to camels and subsequently to humans Primary mode of transmission is droplet in close contact (&lt;1 m), but both viruses remain active in aerosol (up to 24 h), so infection can be also spread by air (ventilation) The ability for human-to-human transmission is higher for HCoV-SARS than for HCoV-MERS (8 generations vs 4, respectively) Moreover, there are differences in genome structure and pathogenic mechanisms: different receptor, cell entry mechanism, different way of host response modulation (e g inhibition of IFN\u03b2 cascade), etc Probably, these differences influence the overall manifestation of the disease in humans Infection caused by HCoV-MERS might manifest itself as ARDS, a mild-mannered and asymptomatic disease HCoV-SARS infections seem to be associated with severe disease only In this paper, a comparison of the structure of these viruses, the mechanisms underlying their ability to cross the interspecies barrier and to multiply in the human body, including modulation of IFN\u03b2 cascade, as well as routes of infection transmission and symptoms caused, were presented", "qid": 31, "docid": "9eso10is", "rank": 94, "score": 0.8072696924209595}, {"content": "Title: Evidence of person-to-person transmission within a family cluster of novel coronavirus infections, United Kingdom, February 2013. Content: In February 2013, novel coronavirus (nCoV) infection was diagnosed in an adult male in the United Kingdom with severe respiratory illness, who had travelled to Pakistan and Saudi Arabia 10 days before symptom onset. Contact tracing identified two secondary cases among family members without recent travel: one developed severe respiratory illness and died, the other an influenza-like illness. No other severe cases were identified or nCoV detected in respiratory samples among 135 contacts followed for 10 days.", "qid": 31, "docid": "v83tcvm5", "rank": 95, "score": 0.8071414828300476}, {"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": 31, "docid": "xkzvzonj", "rank": 96, "score": 0.8070292472839355}, {"content": "Title: The newly emerged COVID-19 disease: a systemic review Content: Coronaviruses are large family-RNA viruses that belong to the order Nidovirales, family Coronaviridae, subfamily Coronavirinae. The novel COVID-19 infection, caused by a beta coronavirus called SARS-CoV-2, is a new outbreak that has been emerged in Wuhan, China in December 2019. The most common symptoms of COVID-19 are fever, cough, and dyspnea. As per the March 12, 2020, WHO report, more than 125,048 confirmed COVID-19 cases and over 4613 deaths have been identified in more than 117 countries. It is now regarded as a pandemic that seriously spread and attack the world. The primary means of transmission is person to person through droplets that occurred during coughing or sneezing, through personal contact (shaking hands), or by touching contaminated objects. So far, there is no effective therapy and vaccine available against this novel virus and therefore, only supportive care is used as the mainstay of management of patients with COVID-19. The mortality rate of COVID-19 is considerable. This work aimed to provide insight on the newly emerged COVID-19, in the hope to gain a better understanding on the general overview, epidemiology, transmission, clinical features, diagnosis, treatment, and clinical outcomes as well as the prevention and control of COVID-19.", "qid": 31, "docid": "uboe5ui7", "rank": 97, "score": 0.8069403767585754}, {"content": "Title: The causes and diagnosis of influenza-like illness. Content: BACKGROUND Influenza and other respiratory viruses circulate between spring and autumn in temperate climates and all year in tropical climates. These viruses cause symptoms often referred to as influenza-like illness (ILI), but are not generally distinguishable on clinical grounds alone. OBJECTIVE This article provides a brief review of the surveillance, viral causes and current diagnostic methods used to identify viruses causing ILI. DISCUSSION Influenza-like illness surveillance with laboratory support, conducted in most Australian stats and territories, aims to define the impact of influenza seasons in the community and provide virus strains that may be used in future vaccine formulations. Surveillance may also be useful in the early stages of an influenza pandemic. In addition to influenza, viruses known to cause ILI include respiratory syncytial virus, rhinovirus, adenovirus, parainfluenza viruses, human coronaviruses (including the virus that causes severe acute respiratory syndrome) and the recently recognised human metapneumovirus. Polymerase chain reaction assays are the most common diagnostic tests now used for the differential diagnosis of ILI.", "qid": 31, "docid": "cvv19do6", "rank": 98, "score": 0.8068011999130249}, {"content": "Title: On the global trends and spread of the COVID-19 outbreak: preliminary assessment of the potential relation between location-specific temperature and UV index Content: The novel coronavirus, since its first outbreak in December, has, up till now, affected approximately 114,542 people across 115 countries. Many international agencies are devoting efforts to enhance the understanding of the evolving COVID-19 outbreak on an international level, its influences, and preparedness. At present, COVID-19 appears to affect individuals through person-to-person means, like other commonly found cold or influenza viruses. It is widely known and acknowledged that viruses causing influenza peak during cold temperatures and gradually subside in the warmer temperature, owing to their seasonality. Thus, COVID-19, due to its regular flu-like symptoms, is also expected to show similar seasonality and subside as the global temperatures rise in the northern hemisphere with the onset of spring. Despite these speculations, however, the systematic analysis in the global perspective of the relation between COVID-19 spread and meteorological parameters is unavailable. Here, by analyzing the region- and city-specific affected global data and corresponding meteorological parameters, we show that there is an optimum range of temperature and UV index strongly affecting the spread and survival of the virus, whereas precipitation, relative humidity, cloud cover, etc. have no effect on the virus. Unavailability of pharmaceutical interventions would require greater preparedness and alert for the effective control of COVID-19. Under these conditions, the information provided here could be very helpful for the global community struggling to fight this global crisis. It is, however, important to note that the information presented here clearly lacks any physiological evidences, which may merit further investigation. Thus, any attempt for management, implementation, and evaluation strategies responding to the crisis arising due to the COVID-19 outbreak must not consider the evaluation presented here as the foremost factor.", "qid": 31, "docid": "4ry9b68l", "rank": 99, "score": 0.8067649006843567}, {"content": "Title: Comparing COVID-19 and the 1918-19 influenza pandemics in United Kingdom Content: We compare the COVID-19 pandemic and 1918-19 influenza pandemic in United Kingdom. We found that the on-going COVID-19 wave of infection matched the major wave of the 1918-19 influenza pandemic surprisingly well, both reached similar magnitude (in term of estimated weekly new infections) and spent the same duration above 5 cases per 1000 inhabitants, for the past two months. We discussed the similar characteristics between these two pandemics.", "qid": 31, "docid": "zwxk6jjo", "rank": 100, "score": 0.8067612051963806}]}
{"query": "Does SARS-CoV-2 have any subtypes, and if so what are they?", "hits": [{"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": 32, "docid": "t0cw7l2a", "rank": 1, "score": 0.8865872621536255}, {"content": "Title: Rates of Symptomatic SARS-CoV-2 Infection in Patients With Autoimmune Liver Diseases in Northern Italy: A Telemedicine Study Content: Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) is a virus responsible for a variety of clinical manifestations that, besides the lungs, can involve several other organs, leading to both mild and severe complications.1-3.", "qid": 32, "docid": "vxw349ho", "rank": 2, "score": 0.8810998201370239}, {"content": "Title: Digital Technologies-Enabled Smart Manufacturing and Industry 4.0 in the Post-COVID-19 Era: Lessons Learnt from a Pandemic Content: The \"Severe Acute Respiratory Syndrome Coronavirus Type 2\" (SARS-CoV-2) has been identified as the infectious agent responsible for the generally mild but sometimes life-threatening communicable disease known as \"Coronavirus Disease 2019\" (COVID-19) [...].", "qid": 32, "docid": "9it2g2k2", "rank": 3, "score": 0.8808560967445374}, {"content": "Title: Digital Technologies-Enabled Smart Manufacturing and Industry 4.0 in the Post-COVID-19 Era: Lessons Learnt from a Pandemic. Content: The \"Severe Acute Respiratory Syndrome Coronavirus Type 2\" (SARS-CoV-2) has been identified as the infectious agent responsible for the generally mild but sometimes life-threatening communicable disease known as \"Coronavirus Disease 2019\" (COVID-19) [...].", "qid": 32, "docid": "jch6vvty", "rank": 4, "score": 0.8808560967445374}, {"content": "Title: SARS-CoV-2 and SARS-CoV differ in their cell tropism and drug sensitivity profiles Content: SARS-CoV-2 is a novel coronavirus currently causing a pandemic. We show that the majority of amino acid positions, which differ between SARS-CoV-2 and the closely related SARS-CoV, are differentially conserved suggesting differences in biological behaviour. In agreement, novel cell culture models revealed differences between the tropism of SARS-CoV-2 and SARS-CoV. Moreover, cellular ACE2 (SARS-CoV-2 receptor) and TMPRSS2 (enables virus entry via S protein cleavage) levels did not reliably indicate cell susceptibility to SARS-CoV-2. SARS-CoV-2 and SARS-CoV further differed in their drug sensitivity profiles. Thus, only drug testing using SARS-CoV-2 reliably identifies therapy candidates. Therapeutic concentrations of the approved protease inhibitor aprotinin displayed anti-SARS-CoV-2 activity. The efficacy of aprotinin and of remdesivir (currently under clinical investigation against SARS-CoV-2) were further enhanced by therapeutic concentrations of the proton pump inhibitor omeprazole (aprotinin 2.7-fold, remdesivir 10-fold). Hence, our study has also identified anti-SARS-CoV-2 therapy candidates that can be readily tested in patients.", "qid": 32, "docid": "gpr86lxe", "rank": 5, "score": 0.8738967776298523}, {"content": "Title: Acute Kidney Injury in SARS-CoV-2 Infection: Direct Effect of Virus on Kidney Proximal Tubule Cells Content: Coronaviruses (CoVs), including Severe Acute Respiratory Syndrome (SARS), Middle East Respiratory Syndrome (MERS), and the novel coronavirus disease-2 (SARS-CoV-2) are a group of enveloped RNA viruses that cause a severe respiratory infection which is associated with a high mortality [...].", "qid": 32, "docid": "pbh1v41e", "rank": 6, "score": 0.8738825917243958}, {"content": "Title: Current Insight into the Novel Coronavirus Disease 2019 (COVID-19) Content: SARS-CoV-2 is a novel strain of coronavirus that has not been previously identified in humans. It has been declared a pandemic and has infected at least 1,844,683 individuals and caused 117,021 deaths as of 14th April 2020. Transmission among humans occurs via close contact with an infected individual that produces respiratory droplets. Patients have been shown to undergo acute respiratory distress syndrome, which is defined as cytokine storm. The diagnosis relies on detection of nucleic acid, IgG/IgM antibodies, and a chest radiograph of the suspected individuals. The genome of SARS-CoV-2 is similar to other coronaviruses that comprise of ten open reading frames (ORFs). SARS-CoV-2 spike protein exhibits higher affinity to ACE2 receptor as compared with SARS-CoV. Repurposing drugs like favipiravir, remdesivir, chloroquine, and TMPRSS2 protease inhibitors have been shown to be effective for the treatment of COVID-19. Personal protective measures should be followed to prevent SARS-CoV-2 infection. In addition, a clinical trial of SARS-CoV-2 vaccine, mRNA-1273, has been started. This chapter provides a glimpse of advancements made in the area of SARS-CoV-2 infection by proving recent clinical and research trials in the field.", "qid": 32, "docid": "zv0ysi8m", "rank": 7, "score": 0.8714717626571655}, {"content": "Title: Clinical features and outcomes of four HIV patients with COVID\u201019 in Wuhan, China Content: SARS-CoV-2 is the coronavirus that has been identified as the pathogen causing COVID-19.1 Human Immunodeficiency Virus (HIV) attacks the immune system and leads to acquired immune deficiency syndrome (AIDS) in the late stage of disease. Concerns have been raised on HIV as a risk factor for COVID-19. This article is protected by copyright. All rights reserved.", "qid": 32, "docid": "f9gmlkez", "rank": 8, "score": 0.8676684498786926}, {"content": "Title: Does bronchoscopy help the diagnosis in Covid-19 infection? Content: Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) is the agent responsible for the recent Coronavirus Disease 2019 (COVID-19) pandemic. This virus is predominantly spread through large droplets. The clinical features of COVID-19 are varied, ranging from asymptomatic to acute respiratory distress syndrome and multi-organ dysfunction [1].", "qid": 32, "docid": "y1t9emu1", "rank": 9, "score": 0.8676191568374634}, {"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": 10, "score": 0.8661032915115356}, {"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": 32, "docid": "bm0ldeue", "rank": 11, "score": 0.8641241788864136}, {"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": 32, "docid": "050fdtm8", "rank": 12, "score": 0.8639724254608154}, {"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": 32, "docid": "u3xxshqw", "rank": 13, "score": 0.8639724254608154}, {"content": "Title: The SARS-CoV-2 Coronavirus and the COVID-19 Outbreak Content: The SARS-CoV-2, a newly identified \u00df-coronavirus, is the causative agent of the third large-scale pandemic from the last two decades. The outbreak started in December 2019 in Wuhan City, Hubei province in China. The patients presented clinical symptoms of dry cough, fever, dyspnea, and bilateral lung infiltrates on imaging. By February 2020, The World Health Organization (WHO) named the disease as Coronavirus Disease 2019 (COVID-19). The Coronavirus Study Group (CSG) of the International Committee on Taxonomy of Viruses (ICTV) recognized and designated this virus as severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). The SARS-CoV-2 uses the same host receptor, angiotensin-converting enzyme 2 (ACE2), used by SARS-CoV to infect humans. One hypothesis of SARSCoV-2 origin indicates that it is likely that bats serve as reservoir hosts for SARSCoV-2, being the intermediate host not yet determined. The predominant route of transmission of SARS-CoV-2 is from human to human. As of May 10th 2020, the number of worldwide confirmed COVID-19 cases is over 4 million, while the number of global deaths is around 279.000 people. The United States of America (USA) has the highest number of COVID-19 cases with over 1.3 million cases followed by Spain, Italy, United Kingdom, Russia, France and Germany with over 223.000, 218.000, 215.000, 209.000, 176.000, and 171.000 cases, respectively.", "qid": 32, "docid": "7re3jgya", "rank": 14, "score": 0.8638932704925537}, {"content": "Title: Potential Treatments for COVID-19; a Narrative Literature Review. Content: SARS-CoV-2 is a newly emerging human infectious coronavirus that causes COVID-19, which has been recognized as a pandemic by the World Health Organization (WHO) on March 11th. There is still no vaccine or definitive treatment for this virus because its pathogenesis and proliferation pathways are still unknown. Therefore, in this article, new potential COVID-19 therapies are briefly reviewed.", "qid": 32, "docid": "yympgnfe", "rank": 15, "score": 0.8638683557510376}, {"content": "Title: The SARS-CoV-2 Coronavirus and the COVID-19 Outbreak. Content: The SARS-CoV-2, a newly identified \u03b2-coronavirus, is the causative agent of the third large-scale pandemic from the last two decades. The outbreak started in December 2019 in Wuhan City, Hubei province in China. The patients presented clinical symptoms of dry cough, fever, dyspnea, and bilateral lung infiltrates on imaging. By February 2020, The World Health Organization (WHO) named the disease as Coronavirus Disease 2019 (COVID-19). The Coronavirus Study Group (CSG) of the International Committee on Taxonomy of Viruses (ICTV) recognized and designated this virus as severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). The SARS-CoV-2 uses the same host receptor, angiotensin-converting enzyme 2 (ACE2), used by SARS-CoV to infect humans. One hypothesis of SARSCoV-2 origin indicates that it is likely that bats serve as reservoir hosts for SARSCoV-2, being the intermediate host not yet determined. The predominant route of transmission of SARS-CoV-2 is from human to human. As of May 10th 2020, the number of worldwide confirmed COVID-19 cases is over 4 million, while the number of global deaths is around 279.000 people. The United States of America (USA) has the highest number of COVID-19 cases with over 1.3 million cases followed by Spain, Italy, United Kingdom, Russia, France and Germany with over 223.000, 218.000, 215.000, 209.000, 176.000, and 171.000 cases, respectively.", "qid": 32, "docid": "1enb2vxv", "rank": 16, "score": 0.8634788393974304}, {"content": "Title: Potential Treatments for COVID-19; a Narrative Literature Review Content: SARS-CoV-2 is a newly emerging human infectious coronavirus that causes COVID-19, which has been recognized as a pandemic by the World Health Organization (WHO) on March 11(th). There is still no vaccine or definitive treatment for this virus because its pathogenesis and proliferation pathways are still unknown. Therefore, in this article, new potential COVID-19 therapies are briefly reviewed.", "qid": 32, "docid": "y29kct7v", "rank": 17, "score": 0.8630441427230835}, {"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": 32, "docid": "713ey27b", "rank": 18, "score": 0.8628448247909546}, {"content": "Title: Studies on viral pneumonia related to novel coronavirus SARS-CoV-2, SARS-CoV, and MERS-CoV: a literature review Content: Coronaviruses are a class of RNA viruses that can cause respiratory and intestinal infections in animals and humans. SARS-CoV, MERS-CoV, and a novel coronavirus (SARS-CoV-2 [2019-nCoV]) belong to the family Coronaviridae and the genus Betacoronavirus. At present, the understanding of SARS-CoV-2 is getting deeper and deeper. In order to better prevent and treat SARS-CoV-2, this article compares the infectivity, pathogenicity, and related clinical characteristics of the three human pathogenic coronaviruses, SARS-CoV-2, SARS-CoV, and MERS-CoV to help us further understand the pathogenic characteristics of novel coronaviruses.", "qid": 32, "docid": "5okp92tr", "rank": 19, "score": 0.8626710772514343}, {"content": "Title: Studies on viral pneumonia related to novel coronavirus SARS-CoV-2, SARS-CoV, and MERS-CoV: a literature review. Content: Coronaviruses are a class of RNA viruses that can cause respiratory and intestinal infections in animals and humans. SARS-CoV, MERS-CoV and a novel coronavirus (SARS-CoV-2 [2019-nCoV]) belong to the family Coronaviridae and the genus Betacoronavirus. At present, the understanding of SARS-CoV-2 is getting deeper and deeper. In order to better prevent and treat SARS-CoV-2, this article compares the infectivity, pathogenicity, and related clinical characteristics of the three human pathogenic coronaviruses, SARS-CoV-2, SARS-CoV and MERS-CoV to help us further understand the pathogenic characteristics of novel coronaviruses.", "qid": 32, "docid": "tdocssfu", "rank": 20, "score": 0.8622373342514038}, {"content": "Title: Attenuated SARS-CoV-2 variants with deletions at the S1/S2 junction Content: The emergence of SARS-CoV-2 has led to the current global coronavirus pandemic and more than one million infections since December 2019. The exact origin of SARS-CoV-2 remains elusive, but the presence of a distinct motif in the S1/S2 junction region suggests the possible acquisition of cleavage site(s) in the spike protein that promoted cross-species transmission. Through plaque purification of Vero-E6 cultured SARS-CoV-2, we found a series of variants which contain 15-30-bp deletions (Del-mut) or point mutations respectively at the S1/S2 junction. Examination of the original clinical specimen from which the isolate was derived, and 26 additional SARS-CoV-2 positive clinical specimens, failed to detect these variants. Infection of hamsters shows that one of the variants (Del-mut-1) which carries deletion of 10 amino acids (30bp) does not cause the body weight loss or more severe pathological changes in the lungs that is associated with wild type virus infection. We suggest that the unique cleavage motif promoting SARS-CoV-2 infection in humans may be under strong selective pressure, given that replication in permissive Vero-E6 cells leads to the loss of this adaptive function. It would be important to screen the prevalence of these variants in asymptomatic infected cases. The potential of the Del-mut variants as an attenuated vaccine or laboratory tool should be evaluated.", "qid": 32, "docid": "mgsaoz3j", "rank": 21, "score": 0.8614257574081421}, {"content": "Title: Identification of common deletions in the spike protein of SARS-CoV-2 Content: SARS-CoV-2 is a novel coronavirus first identified in December 2019. Notable features make SARS-CoV-2 distinct from most other previously-identified Betacoronaviruses, including the receptor binding domain of SARS-CoV-2 and a unique insertion of twelve nucleotide or four amino acids (PRRA) at the S1/S2 boundary. In this study, we identified two deletion variants of SARS-CoV-2 that either directly affect the polybasic cleavage site itself (NSPRRAR) or a flanking sequence (QTQTN). These deletions were verified by multiple sequencing methods. In vitro results showed that the deletion of NSPRRAR likely does not affect virus replication in Vero and Vero-E6 cells, however the deletion of QTQTN may restrict late phase viral replication. The deletion of QTQTN was detected in 3 of 68 clinical samples and half of 24 in vitro isolated viruses, whilst the deletion of NSPRRAR was identified in 3 in vitro isolated viruses. Our data indicate that (i) there may be distinct selection pressures on SARS-CoV-2 replication or infection in vitro and in vivo, (ii) an efficient mechanism for deleting this region from the viral genome may exist, given that the deletion variant is commonly detected after two rounds of cell passage, and (iii) the PRRA insertion, which is unique to SARS-CoV-2, is not fixed during virus replication in vitro These findings provide information to aid further investigation of SARS-CoV-2 infection mechanisms and a better understanding of the NSPRRAR deletion variant observed here.Important notes The spike protein determines the infectivity and host range of coronaviruses. SARS-CoV-2 has two unique features in its spike protein, the receptor binding domain and an insertion of twelve nucleotides at the S1/S2 boundary resulting a furin-like cleavage site. Here, we identified two deletion variants of SARS-CoV-2 that either directly affect the furin-like cleavage site itself (NSPRRAR) or a flanking sequence (QTQTN) and investigated these deletions in cell isolates and clinical samples. The absence of the polybasic cleavage site in SARS-CoV-2 did not affect virus replication in Vero or Vero-E6 cells. Our data indicate the PRRAR and its flanking sites are not fixed in vitro, thus there appears to be distinct selection pressures on SARS-CoV-2 sequences in vitro and in vivo Further investigation of the mechanism of generating these deletion variants and their infectivity in different animal models would improve our understanding of the origin and evolution of this virus.", "qid": 32, "docid": "7htfxqno", "rank": 22, "score": 0.8609164953231812}, {"content": "Title: Identification of common deletions in the spike protein of SARS-CoV-2. Content: SARS-CoV-2 is a novel coronavirus first identified in December 2019. Notable features make SARS-CoV-2 distinct from most other previously-identified Betacoronaviruses, including the receptor binding domain of SARS-CoV-2 and a unique insertion of twelve nucleotide or four amino acids (PRRA) at the S1/S2 boundary. In this study, we identified two deletion variants of SARS-CoV-2 that either directly affect the polybasic cleavage site itself (NSPRRAR) or a flanking sequence (QTQTN). These deletions were verified by multiple sequencing methods. In vitro results showed that the deletion of NSPRRAR likely does not affect virus replication in Vero and Vero-E6 cells, however the deletion of QTQTN may restrict late phase viral replication. The deletion of QTQTN was detected in 3 of 68 clinical samples and half of 24 in vitro isolated viruses, whilst the deletion of NSPRRAR was identified in 3 in vitro isolated viruses. Our data indicate that (i) there may be distinct selection pressures on SARS-CoV-2 replication or infection in vitro and in vivo, (ii) an efficient mechanism for deleting this region from the viral genome may exist, given that the deletion variant is commonly detected after two rounds of cell passage, and (iii) the PRRA insertion, which is unique to SARS-CoV-2, is not fixed during virus replication in vitro These findings provide information to aid further investigation of SARS-CoV-2 infection mechanisms and a better understanding of the NSPRRAR deletion variant observed here.Important notes The spike protein determines the infectivity and host range of coronaviruses. SARS-CoV-2 has two unique features in its spike protein, the receptor binding domain and an insertion of twelve nucleotides at the S1/S2 boundary resulting a furin-like cleavage site. Here, we identified two deletion variants of SARS-CoV-2 that either directly affect the furin-like cleavage site itself (NSPRRAR) or a flanking sequence (QTQTN) and investigated these deletions in cell isolates and clinical samples. The absence of the polybasic cleavage site in SARS-CoV-2 did not affect virus replication in Vero or Vero-E6 cells. Our data indicate the PRRAR and its flanking sites are not fixed in vitro, thus there appears to be distinct selection pressures on SARS-CoV-2 sequences in vitro and in vivo Further investigation of the mechanism of generating these deletion variants and their infectivity in different animal models would improve our understanding of the origin and evolution of this virus.", "qid": 32, "docid": "9v4uqsun", "rank": 23, "score": 0.8609164953231812}, {"content": "Title: Coronaviruses in cats and other companion animals: Where does SARS-CoV-2/COVID-19 fit? Content: \u2022 Coronaviruses are wide-ranging diseases in humans and animals. \u2022 SARS-CoV-2 is a bat-origin zoonotic coronavirus causing the COViD-19 pandemic. \u2022 SARS-CoV-2 can also infect cats and ferrets and has been detected in dogs. \u2022 The SARS-CoV-2 receptor ACE2 is highly similar between cats and humans.", "qid": 32, "docid": "dyhd8p8z", "rank": 24, "score": 0.8606356978416443}, {"content": "Title: COVID-19: The Case of Three Patients with the Same Diagnosis but Different Clinical and Laboratory Features Content: SARS-CoV-2 is an RNA virus that causes COVID-19, which has been responsible for the pandemic that was declared in early 2020. Its pathological effect is majorly in the respiratory tract, but its full pathogenicity remains a mystery. Symptoms associated with COVID-19 include fever, cough, and shortness of breath. Some patients develop other symptoms like diarrhea. However, it is possible for other organs to be affected including the central nervous system, liver, and blood cells. The purpose of this case series is to unravel other factors associated with this disease, so we report three cases of COVID-19 that were hospitalized during the pandemic.", "qid": 32, "docid": "cowt4c2c", "rank": 25, "score": 0.8603290319442749}, {"content": "Title: Taking aim at a fast-moving target: Targets to watch for SARS-CoV-2 and COVID-19 Content: Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) is characterized as a betacoronavirus and recognized as the seventh discrete coronavirus species capable of causing human disease. This new coronavirus causes febrile respiratory illness and on March 11, 2020, was characterized as a global pandemic. Investigators have accelerated the search for a vaccine to prevent infection and for agents to treat it. This article presents those drug targets that (as of March 20, 2020) are currently under active investigation for the treatment of COVID-19, the disease caused by SARS-CoV-2 infection.", "qid": 32, "docid": "ybzfhp8p", "rank": 26, "score": 0.8601239919662476}, {"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": 32, "docid": "12540n1s", "rank": 27, "score": 0.8591699004173279}, {"content": "Title: The red half\u2010moon nail sign: a novel manifestation of coronavirus infection Content: The novel Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2) is the causative agent of the coronavirus disease 2019 (COVID-19). The pandemic condition was declared by the WHO on March 11, 2020. The main clinical symptoms are fever, dry cough and dyspnea, although new symptoms are emerging, such as diarrhea, anosmia and ageusia. The virus enters cells, likely including those lining blood vessels, by binding to angiotensin converting enzyme 2 (ACE2) receptors on the cell surface. Infection can also promote blood clots, heart attacks and cardiac inflammation.", "qid": 32, "docid": "1trid65d", "rank": 28, "score": 0.8572974801063538}, {"content": "Title: The hallmarks of COVID-19 disease Content: Severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2) is a novel coronavirus that has caused a worldwide pandemic of the human respiratory illness COVID-19, resulting in a severe threat to public health and safety. Analysis of the genetic tree suggests that SARS-CoV-2 belongs to the same Betacoronavirus group as severe acute respiratory syndrome coronavirus (SARS-CoV) and Middle East respiratory syndrome coronavirus (MERS-CoV). Although the route for viral transmission remains a mystery, SARS-CoV-2 may have originated in an animal reservoir, likely that of bat. The clinical features of COVID-19, such as fever, cough, shortness of breath, and fatigue, are similar to those of many acute respiratory infections. There is currently no specific treatment for COVID-19, but antiviral therapy combined with supportive care is the main strategy. Here, we summarize recent progress in understanding the epidemiological, virological, and clinical characteristics of COVID-19 and discuss potential targets with existing drugs for the treatment of this emerging zoonotic disease.", "qid": 32, "docid": "xibub2in", "rank": 29, "score": 0.8570899963378906}, {"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": 32, "docid": "nfvbog77", "rank": 30, "score": 0.857018232345581}, {"content": "Title: COVID-19: review on latest available drugs and therapies against SARS-CoV-2. Coagulation and inflammation cross-talking Content: SARS-CoV-2 is the agent responsible for COVID-19. The infection can be dived into three phases: mild infection, the pulmonary phase and the inflammatory phase. Treatment options for the pulmonary phase include: Hydroxychloroquine, Remdesivir, Lopinavir/Ritonavir. The inflammatory phase includes therapeutic options like Tocilizumab, Anakinra, Baricitinib, Eculizumab, Emapalumab and Heparin. Human clinical trials are starting to show some results, in some cases like that of Remdesivir these are controversial. Coagulopathy is a common complication in severe cases, inflammation and coagulation are intertwined and cross-talking between these two responses is known to happen. A possible amplification of this cross-talking is suggested to be implicated in the severe cases that show both a cytokine storm and coagulopathy.", "qid": 32, "docid": "v59dpmuu", "rank": 31, "score": 0.8568934202194214}, {"content": "Title: COVID-19 and outbreak of chilblains: are they related? Content: SARS-CoV-2 is a new coronavirus that causes COVID-19, a disease associated with severe pneumonia.1 Many other clinical manifestations have been associated with the disease (diarrhoea, anosmia, dysgeusia, etc.) and patients can be healthy carriers of the virus.2 Several dermatologic manifestations associated with COVID-19 have been reported.3 Among them are numerous cases of chilblain-like lesions (CBLL) in young patients in good general condition, often not tested, or tested negative, for the SARS-CoV-2.4,5 In a recent study on 375 Spanish patients with suspected or confirmed COVID-19, these CBLL accounted for 19% of all cutaneous lesions;3 they were observed in young patients with mild systemic symptoms and seemed to appear late in the course of the disease.", "qid": 32, "docid": "yx3wxrhh", "rank": 32, "score": 0.8567517995834351}, {"content": "Title: Is COVID-19 a New Hematologic Disease? Content: SARS-CoV-2 viruses are positive single-stranded RNA viruses, whose infection can be asymptomatic or lead to the coronavirus disease 2019 (Covid-19). Covid-19 is a respiratory infection with a significant impact on the hematopoietic system and hemostasis leading to several cardiovascular complications. Hematologic consequences of this new infection allowed medical community to start new treatment approaches concerning infection going from targeted anti-inflammatory drugs to anticoagulation or stem cell therapies. A better understanding of Covid-19 pathophysiology, in particular hematological disorders, will help to choose appropriate treatment strategies.", "qid": 32, "docid": "jnspsfdp", "rank": 33, "score": 0.8563239574432373}, {"content": "Title: Seropr\u00e4valenz und SARS-CoV-2-Testung in Gesundheitsberufen./ [Seroprevalence and SARS-CoV-2 testing in healthcare occupations] Content: The SARS-CoV\u00ad2 causes a disease spectrum that includes asymptomatic and mildly symptomatic infections with subclinical manifestations but which can nevertheless still be potentially contagious. Evidence from SARS-CoV\u00ad2 infected macaque monkeys and from studies with seasonal coronaviruses suggests that the infection is likely to produce an immunity that is protective for a certain period of time. Available test methods enable a high degree of reliability, e.g. if high-quality serological methods are combined. Although individual test results have to be interpreted with caution, serosurveillance in a tertiary eye care center and large eye research institute can reduce anxiety and provide clarity regarding the actual number of (unreported) SARS-CoV\u00ad2 infections.", "qid": 32, "docid": "rlpe6tpm", "rank": 34, "score": 0.856130838394165}, {"content": "Title: COVID-19: Review on latest available drugs and therapies against SARS-CoV-2. Coagulation and inflammation cross-talking Content: SARS-CoV-2 is the agent responsible for COVID-19. The infection can be dived into three phases: mild infection, the pulmonary phase and the inflammatory phase. Treatment options for the pulmonary phase include: Hydroxychloroquine, Remdesivir, Lopinavir/Ritonavir. The inflammatory phase includes therapeutic options like Tocilizumab, Anakinra, Baricitinib, Eculizumab, Emapalumab and Heparin. Human clinical trials are starting to show some results, in some cases like that of Remdesivir and corticosteroids these are controversial. Coagulopathy is a common complication in severe cases, inflammation and coagulation are intertwined and cross-talking between these two responses is known to happen. A possible amplification of this cross-talking is suggested to be implicated in the severe cases that show both a cytokine storm and coagulopathy.", "qid": 32, "docid": "ly2ytc6t", "rank": 35, "score": 0.8560752272605896}, {"content": "Title: The SARS-CoV-2 outbreak from a one health perspective Content: The SARS-CoV-2 is a new human coronavirus candidate recently detected in China that is now reported in people on inhabited continents. The virus shares a high level of identity with some bat coronaviruses and is recognised as a potentially zoonotic virus. We are utilizing the One Health concept to understand the emergence of the virus, as well as to point to some possible control strategies that might reduce the spread of the virus across the globe; thus, containment of such virus would be possible.", "qid": 32, "docid": "dljpcwl8", "rank": 36, "score": 0.8557471632957458}, {"content": "Title: Potential Treatments for COVID-19;a Narrative Literature Review Content: SARS-CoV-2 is a newly emerging human infectious coronavirus that causes COVID-19, which has been recognized as a pandemic by the World Health Organization (WHO) on March 11(th) There is still no vaccine or definitive treatment for this virus because its pathogenesis and proliferation pathways are still unknown Therefore, in this article, new potential COVID-19 therapies are briefly reviewed", "qid": 32, "docid": "3sewe0np", "rank": 37, "score": 0.8554669618606567}, {"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": 32, "docid": "a12708qd", "rank": 38, "score": 0.8550286293029785}, {"content": "Title: A Hypothesis on the role of the human immune system in covid-19 Content: The COVID-19 pandemic has not spared any continent. The disease has affected more than 7,500,000 individuals globally and killed approximately 450,000 individuals. The disease is caused by a very small virus named severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), which is an enveloped single-stranded RNA virus with a spike-like structure on its envelope that can interact with the angiotensin-converting enzyme 2 (ACE2) receptor after cleavage. ACE2 receptors are present in the human lungs and other organs. SARS-CoV-2 is a new virus that belongs to the subgenus Sarbecovirus; viruses in this subgenus have spread widely in the previous years and caused outbreaks of severe acute respiratory syndromes.", "qid": 32, "docid": "akt4glln", "rank": 39, "score": 0.8550223112106323}, {"content": "Title: A hypothesis on the role of the human immune system in covid-19 Content: The COVID-19 pandemic has not spared any continent. The disease has affected more than 7,500,000 individuals globally and killed approximately 450,000 individuals. The disease is caused by a very small virus named severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), which is an enveloped single-stranded RNA virus with a spike-like structure on its envelope that can interact with the angiotensin-converting enzyme 2 (ACE2) receptor after cleavage. ACE2 receptors are present in the human lungs and other organs. SARS-CoV-2 is a new virus that belongs to the subgenus Sarbecovirus; viruses in this subgenus have spread widely in the previous years and caused outbreaks of severe acute respiratory syndromes.", "qid": 32, "docid": "4oe0veq9", "rank": 40, "score": 0.8550223112106323}, {"content": "Title: Is COVID-19 the first pandemic that evolves into a panzootic? Content: SARS-CoV-2 is a zoonotic virus that has achieved community spread among humans and become a pandemic. Transmission from humans to dogs, domestic cats, tigers, and lions has occurred. Pigs, cats, ferrets, and primates have been identified as good candidates for susceptibility to SARS-CoV-2. The potential implications indicate the need for One Health surveillance, intervention, and management strategies to mitigate the effects on animal populations and prevent a second preparedness failure during this health emergency.", "qid": 32, "docid": "icp9ur8k", "rank": 41, "score": 0.8549685478210449}, {"content": "Title: Brief Review on COVID-19: The 2020 Pandemic Caused by SARS-CoV-2 Content: Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) is the virus responsible for the coronavirus disease of 2019 (COVID-19). First identified in Wuhan (Hubei, China) in December of 2019, it has since been declared a pandemic by the World Health Organization in March of 2020. In this study, we will provide a brief review of viral origin, identification, symptoms, transmission, diagnosis, and potential treatment strategies for the newly identified SARS-CoV-2 strain.", "qid": 32, "docid": "v8i97mbx", "rank": 42, "score": 0.8543456196784973}, {"content": "Title: Multi-Omics and Integrated Network Approach to Unveil Evolutionary Patterns, Mutational Hotspots, Functional Crosstalk and Regulatory Interactions in SARS-CoV-2 Content: SARS-CoV-2 responsible for the pandemic of the Severe Acute Respiratory Syndrome resulting in infections and death of millions worldwide with maximum cases and mortality in USA. The current study focuses on understanding the population specific variations attributing its high rate of infections in specific geographical regions which may help in developing appropriate treatment strategies for COVID-19 pandemic. Rigorous phylogenetic network analysis of 245 complete SARS-CoV-2 genomes inferred five central clades named a (ancestral), b, c, d and e (subtype e1 & e2) showing both divergent and linear evolution types. The clade d & e2 were found exclusively comprising of USA strains with highest known mutations. Clades were distinguished by ten co-mutational combinations in proteins; Nsp3, ORF8, Nsp13, S, Nsp12, Nsp2 and Nsp6 generated by Amino Acid Variations (AAV). Our analysis revealed that only 67.46 % of SNP mutations were carried by amino acid at phenotypic level. T1103P mutation in Nsp3 was predicted to increase the protein stability in 238 strains except six strains which were marked as ancestral type; whereas com (P5731L & Y5768C) in Nsp13 were found in 64 genomes of USA highlighting its 100% co-occurrence. Docking study highlighted mutation (D7611G) caused reduction in binding of Spike proteins with ACE2, but it also showed better interaction with TMPRSS2 receptor which may contribute to its high transmissibility in USA strains. In addition, we found host proteins, MYO5A, MYO5B & MYO5C had maximum interaction with viral hub proteins (Nucleocapsid, Spike & Membrane). Thus, blocking the internalization pathway by inhibiting MYO-5 proteins which could be an effective target for COVID-19 treatment. The functional annotations of the Host-Pathogen Interaction (HPI) network were found to be highly associated with hypoxia and thrombotic conditions confirming the vulnerability and severity of infection in the patients. We also considered the presence of CpG islands in Nsp1 and N proteins which may confers the ability of SARS-CoV-2 to enter and trigger methyltransferase activity inside host cell.", "qid": 32, "docid": "m2px0pyj", "rank": 43, "score": 0.8540529608726501}, {"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": 32, "docid": "oxxrnw1r", "rank": 44, "score": 0.8536417484283447}, {"content": "Title: Lessons from dermatology about inflammatory responses in Covid-19 Content: The SARS-Cov-2 is a single-stranded RNA virus composed of 16 non-structural proteins (NSP 1-16) with specific roles in the replication of coronaviruses. NSP3 has the property to block host innate immune response and to promote cytokine expression. NSP5 can inhibit interferon (IFN) signalling and NSP16 prevents MAD5 recognition, depressing the innate immunity. Dendritic cells, monocytes, and macrophages are the first cell lineage against viruses' infections. The IFN type I is the danger signal for the human body during this clinical setting. Protective immune responses to viral infection are initiated by innate immune sensors that survey extracellular and intracellular space for foreign nucleic acids. In Covid-19 the pathogenesis is not yet fully understood, but viral and host factors seem to play a key role. Important points in severe Covid-19 are characterized by an upregulated innate immune response, hypercoagulopathy state, pulmonary tissue damage, neurological and/or gastrointestinal tract involvement, and fatal outcome in severe cases of macrophage activation syndrome, which produce a 'cytokine storm'. These systemic conditions share polymorphous cutaneous lesions where innate immune system is involved in the histopathological findings with acute respiratory distress syndrome, hypercoagulability, hyperferritinemia, increased serum levels of D-dimer, lactic dehydrogenase, reactive-C-protein and serum A amyloid. It is described that several polymorphous cutaneous lesions similar to erythema pernio, urticarial rashes, diffuse or disseminated erythema, livedo racemosa, blue toe syndrome, retiform purpura, vesicles lesions, and purpuric exanthema or exanthema with clinical aspects of symmetrical drug-related intertriginous and flexural exanthema. This review describes the complexity of Covid-19, its pathophysiological and clinical aspects.", "qid": 32, "docid": "qpblq9y8", "rank": 45, "score": 0.8529033660888672}, {"content": "Title: Lessons from dermatology about inflammatory responses in Covid-19. Content: The SARS-Cov-2 is a single-stranded RNA virus composed of 16 non-structural proteins (NSP 1-16) with specific roles in the replication of coronaviruses. NSP3 has the property to block host innate immune response and to promote cytokine expression. NSP5 can inhibit interferon (IFN) signalling and NSP16 prevents MAD5 recognition, depressing the innate immunity. Dendritic cells, monocytes, and macrophages are the first cell lineage against viruses' infections. The IFN type I is the danger signal for the human body during this clinical setting. Protective immune responses to viral infection are initiated by innate immune sensors that survey extracellular and intracellular space for foreign nucleic acids. In Covid-19 the pathogenesis is not yet fully understood, but viral and host factors seem to play a key role. Important points in severe Covid-19 are characterized by an upregulated innate immune response, hypercoagulopathy state, pulmonary tissue damage, neurological and/or gastrointestinal tract involvement, and fatal outcome in severe cases of macrophage activation syndrome, which produce a 'cytokine storm'. These systemic conditions share polymorphous cutaneous lesions where innate immune system is involved in the histopathological findings with acute respiratory distress syndrome, hypercoagulability, hyperferritinemia, increased serum levels of D-dimer, lactic dehydrogenase, reactive-C-protein and serum A amyloid. It is described that several polymorphous cutaneous lesions similar to erythema pernio, urticarial rashes, diffuse or disseminated erythema, livedo racemosa, blue toe syndrome, retiform purpura, vesicles lesions, and purpuric exanthema or exanthema with clinical aspects of symmetrical drug-related intertriginous and flexural exanthema. This review describes the complexity of Covid-19, its pathophysiological and clinical aspects.", "qid": 32, "docid": "d7q6u7vj", "rank": 46, "score": 0.8529033660888672}, {"content": "Title: Is SARS-CoV-2 a new Frankenstein monster virus? Content: Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), a novel virus of beta coronavirus genus originated in Wuhan, China in December 2019, resulted in the pandemic spread of Corona Virus Disease 2019 (COVID-19) worldwide. This genus also contains SARS-CoV (originated in China 2002-2003) and MERS-CoV (found in Saudi Arabia 2012). The nucleotide sequences of SARS-CoV-2 is closer to SARS-CoV (with approximately 80% identity) than to MERS-CoV. Despite these similarities, SARS-CoV-2 has two main features over the other coronaviruses. The first is the high contagious rate and the second is the immune response evasion. The higher transmission ability makes this virus quickly spread worldwide with a high mortality rate and more economic losses. This review will provide an overview of the current knowledge on the role of some viral and host cell factors in higher transmission and contagious spread of SARS-CoV-2.", "qid": 32, "docid": "3f9dbwd2", "rank": 47, "score": 0.8527287244796753}, {"content": "Title: Seropr\u00e4valenz und SARS-CoV-2-Testung in Gesundheitsberufen Content: The SARS-CoV\u20112 causes a disease spectrum that includes asymptomatic and mildly symptomatic infections with subclinical manifestations but which can nevertheless still be potentially contagious. Evidence from SARS-CoV\u20112 infected macaque monkeys and from studies with seasonal coronaviruses suggests that the infection is likely to produce an immunity that is protective for a certain period of time. Available test methods enable a high degree of reliability, e.g. if high-quality serological methods are combined. Although individual test results have to be interpreted with caution, serosurveillance in a tertiary eye care center and large eye research institute can reduce anxiety and provide clarity regarding the actual number of (unreported) SARS-CoV\u20112 infections.", "qid": 32, "docid": "u4sy1sjr", "rank": 48, "score": 0.8518620729446411}, {"content": "Title: Serological survey of SARS-CoV-2 for experimental, domestic, companion and wild animals excludes intermediate hosts of 35 different species of animals Content: The pandemic SARS-CoV-2 has been reported in 123 countries with more than 5,000 patients died from it. However, the original and intermediate hosts of the virus remain unknown. In this study, 1,914 serum samples from 35 animal species were used for detection of SARS-CoV-2-specific antibodies using double-antigen sandwich ELISA after validating its specificity and sensitivity. The results showed that no SARS-CoV-2-specific antibodies were detected in above samples which excluded the possibility of 35 animal species as intermediate host for SARS-CoV-2. More importantly, companion animals including pet dogs (including one dog the SARS-CoV-2 patient kept and two dogs which had close contact with it) and cats, street dogs and cats also showed serological negative to SARS-CoV-2, which relieved the public concerns for the pets as SARS-CoV-2 carriers.", "qid": 32, "docid": "fvxxy3r2", "rank": 49, "score": 0.8518502712249756}, {"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": 50, "score": 0.8517823219299316}, {"content": "Title: Coding variants in ACE2 and TMPRSS2 are not major drivers of COVID-19 severity in UK Biobank subjects. Content: There is wide individual variation in response to infection with SARS-CoV-2 and this may be influenced by ethnicity. It is plausible that coding variants in the ACE2 and TMPRSS2 genes might contribute to this variation. Exome sequence data was obtained for 49,953 UK Biobank subjects of whom 74 had tested positive for SARS-CoV-2 and could be presumed to have severe disease because mildly affected subjects were not tested in the relevant period. A weighted burden analysis was carried out using SCOREASSOC to determine whether there were differences between these cases and the other sequenced subjects in the overall burden of rare, damaging variants in ACE2 or TMPRSS2. There were no significant differences in weighted burden scores between cases and controls for either gene. There were no individual DNA sequence variants with a markedly different frequency between cases and controls. Genetic variants affecting the structure and function of the ACE2 and TMPRSS2 proteins are not a major determinant of whether infection with SARS-CoV-2 results in severe symptoms. This research has been conducted using the UK Biobank Resource.", "qid": 32, "docid": "b08rzif3", "rank": 51, "score": 0.8507115840911865}, {"content": "Title: Sex and gender differences in the outcome of patients with COVID\u201019 Content: The SARS-CoV-2 pandemic is a new wave of emerging infections that the world is struggling with. There are many unanswered questions in this regard, including Gender-specific outcome in COVID-19. Gender and age are major risk factors for SARS-CoV-2 infection. In addition to the effect of these factors on the prevalence of SARS-CoV-2, the clinical outcome varies according to both of them. This article is protected by copyright. All rights reserved.", "qid": 32, "docid": "uz2zht6u", "rank": 52, "score": 0.8501672744750977}, {"content": "Title: Analysis of RNA sequences of 3636 SARS-CoV-2 collected from 55 countries reveals selective sweep of one virus type Content: Background & objectives: SARS-CoV-2 (Severe acute respiratory syndrome coronavirus-2) is evolving with the progression of the pandemic. This study was aimed to investigate the diversity and evolution of the coronavirus SARS-CoV-2 with progression of the pandemic over time and to identify similarities and differences of viral diversity and evolution across geographical regions (countries). Methods: Publicly available data on type definitions based on whole-genome sequences of the SARS-CoV-2 sampled during December and March 2020 from 3636 infected patients spread over 55 countries were collected. Phylodynamic analyses were performed and the temporal and spatial evolution of the virus was examined. Results: It was found that (i) temporal variation in frequencies of types of the coronavirus was significant; ancestral viruses of type O were replaced by evolved viruses belonging to type A2a; (ii) spatial variation was not significant; with the spread of SARS-CoV-2, the dominant virus was the A2a type virus in every geographical region; (iii) within a geographical region, there was significant micro-level variation in the frequencies of the different viral types, and (iv) the evolved coronavirus of type A2a swept rapidly across all continents. Interpretation & conclusions: SARS-CoV-2 belonging to the A2a type possesses a non-synomymous variant (D614G) that possibly eases the entry of the virus into the lung cells of the host. This may be the reason why the A2a type has an advantage to infect and survive and as a result has rapidly swept all geographical regions. Therefore, large-scale sequencing of coronavirus genomes and, as required, of host genomes should be undertaken in India to identify regional and ethnic variation in viral composition and its interaction with host genomes. Further, careful collection of clinical and immunological data of the host can provide deep learning in relation to infection and transmission of the types of coronavirus genomes.", "qid": 32, "docid": "04bi0d50", "rank": 53, "score": 0.8490489721298218}, {"content": "Title: Mutated COVID-19 may foretell a great risk for mankind in the future Content: Coronavirus disease 2019 SARS-CoV-2 (COVID-19) is a zoonotic virus causing a variety of severe respiratory diseases. SARS-CoV-2 is closest to SARS-CoV and MERS-CoV in structure. The high prevalence of COVID-19 is a result of a lack of symptoms at onset. Our study aimed to present an overview of the virus in terms of structure, epidemiology, symptoms, treatment and prevention. Whole genome sequences and some viral proteins were investigated to determine gaps and changes in alternation of nucleotides and amino acid sequences. We evaluate 11 complete genome sequences of different coronaviruses using BAST and MAFFT software. We also selected seven types of structural proteins. We conclude that COVID-19 might produce new mutations, specifically in glycoproteins, so caution and complete preparation by health authorities is required.", "qid": 32, "docid": "qopcs6jy", "rank": 54, "score": 0.848996639251709}, {"content": "Title: COVID-19 Disease in Children: Clinical Course, Diagnosis and Treatment Overview and Literature Data Compilation Content: The novel Coronavirus is named as SARS-CoV-2 is a highly contagious infection agent compared to the previous human coronaviruses Each previous outbreak had distinctive danger The high potential of infectiousness is the primary danger of novel coronavirus While MERS-CoV infection is known to have higher mortality rate, SARS-CoV-2 has spread to many people all over the world in a concise time SARS-CoV-2 (like SARS-CoV and MERS) infects fewer children and results in milder clinical symptoms than in adults The primary pathogenesis of it is not known;the difference in children's immunities, less likelihood of exposure to the agent may be the reasons Nevertheless, along with being mostly asymptomatic, the child population is a potential source for infection spread", "qid": 32, "docid": "9ppacplo", "rank": 55, "score": 0.8489092588424683}, {"content": "Title: SARS-CoV-2 and Guillain-Barr\u00e9 syndrome: AIDP variant with favorable outcome Content: The entire world has been experiencing the outbreak of a novel infectious agent known as severe acute respiratory syndrome corona virus 2 (SARS-CoV-2), which is responsible for the coronavirus disease 19 (COVID-19)1 . Life-threatening complications described in SARS-CoV-2 infected patients include acute respiratory distress syndrome, acute kidney failure and cardiac injury2 . Nonetheless, only few neurological complications have been described so far3 .", "qid": 32, "docid": "xui1famo", "rank": 56, "score": 0.8488409519195557}, {"content": "Title: COVID-19, chronic inflammatory respiratory diseases and eosinophils - Observationsfrom reported clinical case series. Content: Currently, the world is facinga global pandemicwith a new coronavirus SARS-CoV- 2 (Severe Acute Respiratory Syndrome CoronaVirus Type 2) causing infectious disease named COVID-19 (CoronaVirus Infectious Disease 2019). Comparing the clinical presentation and epidemiological characteristics of COVID-19 with previous coronavirus-associated respiratory diseases (SARS-CoV1 and MERS) revealedsome remarkable findings and differences. Moreover, the clinical course of SARS-CoV-2 infection showed the complexity of COVID-19 profile with the variable clinical presentations.", "qid": 32, "docid": "t4ox8zar", "rank": 57, "score": 0.848800539970398}, {"content": "Title: Autoimmune and inflammatory diseases following COVID-19 Content: Emerging reports show that severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection precedes the appearance of various autoimmune and autoinflammatory diseases, including paediatric inflammatory multisystemic syndrome (PIMS) or multisystem inflammatory syndrome in children (MIS-C), thus adding to the growing mystery of this virus and raising questions about the nature of its link with autoimmune and autoinflammatory sequelae.", "qid": 32, "docid": "cgs0sui7", "rank": 58, "score": 0.8487628102302551}, {"content": "Title: Severe Acute Respiratory Syndrome Coronavirus-2 (SARS-CoV-2): An Update Content: Coronaviruses (CoVs) belong to the family of Coronaviridae, the order Nidovirales, and the genus Coronavirus. They are the largest group of viruses causing respiratory and gastrointestinal infections. Morphologically, CoVs are enveloped viruses containing a non-segmented positive-sense, single-stranded ribonucleic acid (RNA) viruses. CoVs are categorized into four important genera that include Alphacoronavirus, Betacoronavirus, Gammacoronavirus, and Deltacoronavirus. A novel member of human CoV that has recently emerged in Wuhan, China, is now formally named as SARS-CoV-2 (severe acute respiratory syndrome coronavirus 2). This is a unique strain of RNA viruses that have not been previously observed in humans. The virus has wide host adaptability and is capable of causing severe diseases in humans, masked palm civets, mice, dogs, cats, camels, pigs, chickens, and bats. The SARS-CoV-2 typically causes respiratory and gastrointestinal sickness in both humans and animals. It can be transmitted through aerosols and direct/indirect contact, as well as during medical cases and laboratory sample handling. Specific structural proteins, which might be found on the surface of the virus, play an important role in the pathogenesis and development of the complications. The disease is characterized by distinct medical signs and symptoms that include high fever, chills, cough, and shortness of breath or difficulty in breathing. The infected people may also present with other symptoms such as diarrhea, myalgia, fatigue, expectoration, and hemoptysis. It is important from the public health and economic point of view as it affects the growth of the country, which is majorly attributed to the restriction in the movement of the people and the cost associated with the control and prevention of the disease. Since there is no specific therapeutic intervention nor a vaccine available against the virus, supportive management and treatment with non-specific therapeutic agents (repurposed drugs) may provide relief to the patients. Some preventive strategies of the disease include blocking the routes of transmission of the infections, disinfection of instruments used during medical case handling, using personal protective equipment, proper and early diagnosis of the disease, avoiding contact with the sick patients, and quarantine of the infected/exposed people.", "qid": 32, "docid": "oq16de67", "rank": 59, "score": 0.848712682723999}, {"content": "Title: ACE-2 och coronavirus \u00ad en fr\u00e5ga om balans och dynamik?/ [ACE2 and coronavirus - a question of balance and dynamics?] Content: The new SARS-CoV-2 virus enters cells via angiotensin-converting enzyme 2 (ACE2). ACE2 counteracts ACE and angiotensin II in the renin-angiotensin-aldosterone system (RAAS) and has critical functions in the lung and cardiovascular system. SARS-CoV was found to down-regulate ACE2, leaving angiotensin II unbalanced in affected organs. A similar effect of SARS-CoV-2 could partly explain risk factors and symptoms, and could potentially be treatable.", "qid": 32, "docid": "wqpt073e", "rank": 60, "score": 0.8482797145843506}, {"content": "Title: [ACE2 and coronavirus - a question of balance and dynamics?] Content: The new SARS-CoV-2 virus enters cells via angiotensin-converting enzyme 2 (ACE2). ACE2 counteracts ACE and angiotensin II in the renin-angiotensin-aldosterone system (RAAS) and has critical functions in the lung and cardiovascular system. SARS-CoV was found to down-regulate ACE2, leaving angiotensin II unbalanced in affected organs. A similar effect of SARS-CoV-2 could partly explain risk factors and symptoms, and could potentially be treatable.", "qid": 32, "docid": "e97zvah8", "rank": 61, "score": 0.8482797145843506}, {"content": "Title: The different tests for the diagnosis of COVID-19 - A review in Brazil so far Content: SARS-CoV-2 is a novel virus from the coronavirus family that emerged in the end of December 2019 in Wuhan, China. The virus is now widespread and causing the current pandemic of COVID-19, a highly pathogenic viral pneumonia, commonly presented with fever and cough, which frequently lead to lower respiratory tract disease with poor clinical outcomes associated with older age and underlying health conditions. Supportive care for patients is typically the standard protocol because no specific effective antiviral therapies have been identified so far. The current outbreak is challenging governments and health authorities all over the world. In here we present a comparison among the current diagnostic tools and kits being used to test Brazilian population.", "qid": 32, "docid": "4eops3t3", "rank": 62, "score": 0.84812992811203}, {"content": "Title: The different tests for the diagnosis of COVID-19 - A review in Brazil so far. Content: SARS-CoV-2 is a novel virus from the coronavirus family that emerged in the end of December 2019 in Wuhan, China. The virus is now widespread and causing the current pandemic of COVID-19, a highly pathogenic viral pneumonia, commonly presented with fever and cough, which frequently lead to lower respiratory tract disease with poor clinical outcomes associated with older age and underlying health conditions. Supportive care for patients is typically the standard protocol because no specific effective antiviral therapies have been identified so far. The current outbreak is challenging governments and health authorities all over the world. In here we present a comparison among the current diagnostic tools and kits being used to test Brazilian population.", "qid": 32, "docid": "mxh38hwd", "rank": 63, "score": 0.84812992811203}, {"content": "Title: The useful face-protective shield \"ORIGAMI\" for gastrointestinal endoscopy during the COVID-19 pandemic Content: Severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2) related disease, called coronavirus disease 2019 (COVID-19), is mainly transmitted through droplets, aerosols, and direct contact.", "qid": 32, "docid": "uyejyhd0", "rank": 64, "score": 0.8478759527206421}, {"content": "Title: The Architecture of SARS-CoV-2 Transcriptome Content: SARS-CoV-2 is a betacoronavirus responsible for the COVID-19 pandemic. Although the SARS-CoV-2 genome was reported recently, its transcriptomic architecture is unknown. Utilizing two complementary sequencing techniques, we present a high-resolution map of the SARS-CoV-2 transcriptome and epitranscriptome. DNA nanoball sequencing shows that the transcriptome is highly complex owing to numerous discontinuous transcription events. In addition to the canonical genomic and 9 subgenomic RNAs, SARS-CoV-2 produces transcripts encoding unknown ORFs with fusion, deletion, and/or frameshift. Using nanopore direct RNA sequencing, we further find at least 41 RNA modification sites on viral transcripts, with the most frequent motif, AAGAA. Modified RNAs have shorter poly(A) tails than unmodified RNAs, suggesting a link between the modification and the 3' tail. Functional investigation of the unknown transcripts and RNA modifications discovered in this study will open new directions to our understanding of the life cycle and pathogenicity of SARS-CoV-2.", "qid": 32, "docid": "6quqydr6", "rank": 65, "score": 0.8477823734283447}, {"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": 32, "docid": "9sbrxzxu", "rank": 66, "score": 0.8476533889770508}, {"content": "Title: Analysis of RNA sequences of 3636 SARS-CoV-2 collected from 55 countries reveals selective sweep of one virus type. Content: Background & objectives SARS-CoV-2 (Severe acute respiratory syndrome coronavirus-2) is evolving with the progression of the pandemic. This study was aimed to investigate the diversity and evolution of the coronavirus SARS-CoV-2 with progression of the pandemic over time and to identify similarities and differences of viral diversity and evolution across geographical regions (countries). Methods Publicly available data on type definitions based on whole-genome sequences of the SARS-CoV-2 sampled during December and March 2020 from 3636 infected patients spread over 55 countries were collected. Phylodynamic analyses were performed and the temporal and spatial evolution of the virus was examined. Results It was found that (i) temporal variation in frequencies of types of the coronavirus was significant; ancestral viruses of type O were replaced by evolved viruses belonging to type A2a; (ii) spatial variation was not significant; with the spread of SARS-CoV-2, the dominant virus was the A2a type virus in every geographical region; (iii) within a geographical region, there was significant micro-level variation in the frequencies of the different viral types, and (iv) the evolved coronavirus of type A2a swept rapidly across all continents. Interpretation & conclusions SARS-CoV-2 belonging to the A2a type possesses a non-synomymous variant (D614G) that possibly eases the entry of the virus into the lung cells of the host. This may be the reason why the A2a type has an advantage to infect and survive and as a result has rapidly swept all geographical regions. Therefore, large-scale sequencing of coronavirus genomes and, as required, of host genomes should be undertaken in India to identify regional and ethnic variation in viral composition and its interaction with host genomes. Further, careful collection of clinical and immunological data of the host can provide deep learning in relation to infection and transmission of the types of coronavirus genomes.", "qid": 32, "docid": "b61alj5x", "rank": 67, "score": 0.847601056098938}, {"content": "Title: On the origin and continuing evolution of SARS-CoV-2 Content: The SARS-CoV-2 epidemic started in late December 2019 in Wuhan, China, and has since impacted a large portion of China and raised major global concern. Herein, we investigated the extent of molecular divergence between SARS-CoV-2 and other related coronaviruses. Although we found only 4% variability in genomic nucleotides between SARS-CoV-2 and a bat SARS-related coronavirus (SARSr-CoV; RaTG13), the difference at neutral sites was 17%, suggesting the divergence between the two viruses is much larger than previously estimated. Our results suggest that the development of new variations in functional sites in the receptor-binding domain (RBD) of the spike seen in SARS-CoV-2 and viruses from pangolin SARSr-CoVs are likely caused by mutations and natural selection besides recombination. Population genetic analyses of 103 SARS-CoV-2 genomes indicated that these viruses evolved into two major types (designated L and S), that are well defined by two different SNPs that show nearly complete linkage across the viral strains sequenced to date. Although the L type (\u223c70%) is more prevalent than the S type (\u223c30%), the S type was found to be the ancestral version. Whereas the L type was more prevalent in the early stages of the outbreak in Wuhan, the frequency of the L type decreased after early January 2020. Human intervention may have placed more severe selective pressure on the L type, which might be more aggressive and spread more quickly. On the other hand, the S type, which is evolutionarily older and less aggressive, might have increased in relative frequency due to relatively weaker selective pressure. These findings strongly support an urgent need for further immediate, comprehensive studies that combine genomic data, epidemiological data, and chart records of the clinical symptoms of patients with coronavirus disease 2019 (COVID-19).", "qid": 32, "docid": "j99cgsjt", "rank": 68, "score": 0.8473299741744995}, {"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": 32, "docid": "dtwstwbe", "rank": 69, "score": 0.8473213911056519}, {"content": "Title: A Guide to COVID-19: a global pandemic caused by the novel coronavirus SARS-CoV-2 Content: The emergence of the SARS-CoV-2 strain of the human coronavirus has thrown the world into the midst of a new pandemic. In the human body, the virus causes COVID-19, a disease characterized by shortness of breath, fever, and pneumonia, which can be fatal in vulnerable individuals. SARS-CoV-2 has characteristics of past human coronaviruses, with close genomic similarities to SARS-CoV, the virus that causes the disease SARS. Like these related coronaviruses, SARS-CoV-2 is transmitted through the inhalation of droplets and interaction with contaminated surfaces. Across the world, laboratories are developing candidate vaccines for the virus - with vaccine trials underway in the United States and the United Kingdom - and considering various drugs for possible treatments and prophylaxis. Here, we provide an overview of SARS-CoV-2 by analyzing its virology, epidemiology, and modes of transmission while examining the current progress of testing procedures and possible treatments through drugs and vaccines.", "qid": 32, "docid": "wq7ljx2f", "rank": 70, "score": 0.8472614884376526}, {"content": "Title: The impact of the SARS\u2010CoV\u20102 outbreak on the safety and availability of blood transfusions in Italy Content: Coronaviruses are enveloped single-stranded RNA viruses belonging to the family of Coronaviridae. While initial research focused on their ability to cause enzootic infections, infections which have emerged in the past two decades demonstrate their ability to cross the species barrier and infect humans [1,2]. The ensuing epidemics have included Severe Acute Respiratory Syndrome (SARS) in 2002 and the more recent Middle East Respiratory Syndrome (MERS) in 2012, and have resulted in severe disease burden, mortality and economic disruption [3]. A novel flu-like coronavirus, emerging towards the end of 2019 and subsequently named SARS-CoV-2, has been associated with an epidemic initially focused in Wuhan, China.", "qid": 32, "docid": "7imgvale", "rank": 71, "score": 0.8468772768974304}, {"content": "Title: Growth, detection, quantification, and inactivation of SARS-CoV-2 Content: Severe acute respiratory syndrome coronavirus (SARS-CoV)-2 is the agent responsible for the coronavirus disease 2019 (COVID-19) global pandemic. SARS-CoV-2 is closely related to SARS-CoV, which caused the 2003 SARS outbreak but disappeared rapidly. Although numerous reagents were developed to study SARS-CoV infections, few have been applicable to evaluating SARS-CoV-2 infection and immunity. Current limitations in studying SARS-CoV-2 include few validated assays with fully replication-competent wild-type virus. We have developed protocols to propagate, quantify, and work with infectious SARS-CoV-2. Here, we describe: (1) virus stock generation, (2) RT-qPCR quantification of SARS-CoV-2 RNA; (3) detection of SARS-CoV-2 antigen by flow cytometry, (4) quantification of infectious SARS-CoV-2 by focus-forming and plaque assays; and 5) validated protocols for virus inactivation. Collectively, these methods can be adapted to a variety of experimental designs, which should accelerate our understanding of SARS-CoV-2 biology and the development of effective countermeasures against COVID-19.", "qid": 32, "docid": "ahu7lda5", "rank": 72, "score": 0.846688985824585}, {"content": "Title: The Architecture of SARS-CoV-2 Transcriptome Content: Summary SARS-CoV-2 is a betacoronavirus responsible for the COVID-19 pandemic. Although the SARS-CoV-2 genome was reported recently, its transcriptomic architecture is unknown. Utilizing two complementary sequencing techniques, we present a high-resolution map of the SARS-CoV-2 transcriptome and epitranscriptome. DNA nanoball sequencing shows that the transcriptome is highly complex owing to numerous discontinuous transcription events. In addition to the canonical genomic and 9 subgenomic RNAs, SARS-CoV-2 produces transcripts encoding unknown ORFs with fusion, deletion, and/or frameshift. Using nanopore direct RNA sequencing, we further find at least 41 RNA modification sites on viral transcripts, with the most frequent motif, AAGAA. Modified RNAs have shorter poly(A) tails than unmodified RNAs, suggesting a link between the modification and the 3\u2032 tail. Functional investigation of the unknown transcripts and RNA modifications discovered in this study will open new directions to our understanding of the life cycle and pathogenicity of SARS-CoV-2.", "qid": 32, "docid": "ypsh3rjv", "rank": 73, "score": 0.8465226888656616}, {"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": 32, "docid": "znx5p3yp", "rank": 74, "score": 0.8462554812431335}, {"content": "Title: SARS-CoV-2\u2013A Tough Opponent for the Immune System Content: Coronaviruses recently returned with a new one, SARS-CoV-2, related to a potentially severe respiratory disease-called the coronavirus disease (COVID-19). Research shows that the SARS-CoV-2 can be clustered with the Bat SARS-like coronavirus. Bats possess an additional, innate ability for antiviral defense, and, on the other hand, the potential to go hand-in-hand with the virus to generate variability. Besides the high potential of the novel coronavirus in compromising the respiratory system, its rapid transmission and ability to engage many hosts in severe forms of infections or immunopathological complications make it a tough opponent for the immune system. The interactions between SARS-CoV2 and the host immune system result in unleashing tremendous amounts of cytokines, and these cytokines make a storm that would determine the outcome (recovery or death) of the lungs of the patient.", "qid": 32, "docid": "703febui", "rank": 75, "score": 0.8462350368499756}, {"content": "Title: SARS-CoV-2-A Tough Opponent for the Immune System Content: Coronaviruses recently returned with a new one, SARS-CoV-2, related to a potentially severe respiratory disease-called the coronavirus disease (COVID-19). Research shows that the SARS-CoV-2 can be clustered with the Bat SARS-like coronavirus. Bats possess an additional, innate ability for antiviral defense, and, on the other hand, the potential to go hand-in-hand with the virus to generate variability. Besides the high potential of the novel coronavirus in compromising the respiratory system, its rapid transmission and ability to engage many hosts in severe forms of infections or immunopathological complications make it a tough opponent for the immune system. The interactions between SARS-CoV2 and the host immune system result in unleashing tremendous amounts of cytokines, and these cytokines make a storm that would determine the outcome (recovery or death) of the lungs of the patient.", "qid": 32, "docid": "4lm663f1", "rank": 76, "score": 0.8462350368499756}, {"content": "Title: Dominant and rare SARS-Cov2 variants responsible for the COVID-19 pandemic in Athens, Greece. Content: SARS-CoV-2 (severe acute respiratory syndrome coronavirus 2) is a novel Coronavirus responsible for the Coronavirus Disease-2019 (COVID-19) pandemic. Since the beginning of the pandemic, the virus has spread in almost the entire world. Tracing and tracking virus international and local transmission has been an enormous challenge. Chains of infections starting from various countries worldwide seeded the outbreak of COVID-19 in Athens, capital city of Greece. Full-genome analysis of isolates from Athens' Hospitals and other healthcare providers revealed the variety of SARS-CoV-2 that initiated the pandemic before lock-down and passenger flight restrictions. The present work may serve as reference for resolving future lines of infection in the area and Europe especially after resumption of passenger flight connections to Athens and Greece during summer of 2020.", "qid": 32, "docid": "0qn4c5t3", "rank": 77, "score": 0.8461110591888428}, {"content": "Title: Post-donation COVID-19 identification in blood donors. Content: The coronavirus disease 19 (COVID-19) outbreak, which was characterized as a pandemic on 11 March 2020 by the WHO, started in December 2019 with the emergence of pneumonia cases of unknown cause in Wuhan, Hubei, China [1]. SARS-CoV-2, the causative agent of COVID-19, are enveloped, non-segmented, single stranded positive sense RNA viruses and are classified as a sister clade to the prototype human and bat severe acute respiratory syndrome coronaviruses (SARS-CoVs) of the species Severe acute respiratory syndrome-related coronavirus [2]. So far, no respiratory virus, including SARS-CoV and the Middle East Respiratory Syndrome (MERS)-CoV, has been confirmed as transfusion-transmissible [3,4].", "qid": 32, "docid": "82sc928x", "rank": 78, "score": 0.8460745811462402}, {"content": "Title: How did we get here? Short history of COVID-19 and other coronavirus-related epidemics Content: The COVID-19 epidemic was not the first coronavirus epidemic of this century and represents one of the increasing number of zoonoses from wildlife to impact global health. SARS CoV-2, the virus causing the COVID-19 epidemic is distinct from, but closely resembles SARS CoV-1, which was responsible for the severe acute respiratory syndrome (SARS) outbreak in 2002. SARS CoV-1 and 2 share almost 80% of genetic sequences and use the same host cell receptor to initiate viral infection. However, SARS predominantly affected individuals in close contact with infected animals and health care workers. In contrast, CoV-2 exhibits robust person to person spread, most likely by means of asymptomatic carriers, which has resulted in greater spread of disease, overall morbidity and mortality, despite its lesser virulence. We review recent coronavirus-related epidemics and distinguish clinical and molecular features of CoV-2, the causative agent for COVID-19, and review the current status of vaccine trials.", "qid": 32, "docid": "j5j3hxxw", "rank": 79, "score": 0.8460354208946228}, {"content": "Title: SARS-CoV-2: Camazotz's Curse Content: The world is currently face to face with a pandemic which is spreading rapidly across the globe caused by SARS-CoV-2, a strain of Coronaviruses (CoVs) belonging to subgenus Sarbecovirus of genus Betacoronavirus. World Health Organisation (WHO) on 11 Feb 20 named this disease caused by SARS-CoV-2 as Covid-19. This pandemic is spreading rapidly and more than 20,00,000 cases have occurred globally. The human Coronaviruses discovered in 1960s were considered potentially harmless endemic viruses with seasonal distribution before late 2002. The CoVs are found in a large number of domestic and wild animals and birds. The first pandemic caused by Coronavirus caused by SARS-CoV was recognized in the late 2002 in Guangdong Province and resulted in widespread morbidity and mortality. This was followed by MERS-CoV which began in 2012 in the Arabian peninsula with multiple outbreaks related to it in various parts of the globe. Various studies have suggested how these viruses made their entry from their natural reservoir bats via intermediate host like civets and camels in case of SARS-CoV and MERS-CoV respectively. The intermediate host of the SARS-CoV-2 still needs to be established. The SARS-CoV-2 has 96.2% similarity to the bat Severe Acute Respiratory Syndrome related-Coronavirus (SARSr-CoV RaTG13). SARS-CoV-2 has been found to be more distant in relation to SARS-CoV (79%) and MERS-CoV (50%). At the whole genome sequence level pangolin CoV and SARSr-CoV RaTG13 show 91.02% and 96.2% similarity with SARS-CoV-2 but the S1 subunit of spike protein of pangolin CoV is more closely related to SARS-CoV-2 than SARSr-CoV RaTG13. The genetic analysis of the currently circulating strains of the pandemic have shown 99.98-100% similarity in their genomes implying a recent shift to humans. The animal source of SARS-CoV-2 needs to be identified to implement control measures in the present pandemic. Also, how the virus moves interspecies will help predict and prevent future pandemics.", "qid": 32, "docid": "sbswy7el", "rank": 80, "score": 0.8460010290145874}, {"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": 32, "docid": "2skjqwis", "rank": 81, "score": 0.8459318280220032}, {"content": "Title: The Detection of SARS-CoV-2 using the Cepheid Xpert Xpress SARS-CoV-2 and Roche cobas SARS-CoV-2 Assays Content: SARS-CoV-2, a novel coronavirus responsible for a December 2019 outbreak in Wuhan, China, causes a syndrome characterized by fever, cough, and dyspnea progressing to acute respiratory distress syndrome (1). .", "qid": 32, "docid": "2lh12oda", "rank": 82, "score": 0.8459317684173584}, {"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": 32, "docid": "dd836h0r", "rank": 83, "score": 0.8459317684173584}, {"content": "Title: Pangolins Harbor SARS-CoV-2-Related Coronaviruses Content: The pandemic of coronavirus disease 2019 (COVID-19) caused by SARS-CoV-2 has posed a severe threat to global public health. Yet, the origin of SARS-CoV-2 remains mysterious. Several recent studies (e.g., Lam et al ., Xiao et al .) identified SARS-CoV-2-related viruses in pangolins, providing novel insights into the evolution and diversity of SARS-CoV-2-related viruses.", "qid": 32, "docid": "k9yus2sv", "rank": 84, "score": 0.845848560333252}, {"content": "Title: Pangolins Harbor SARS-CoV-2-Related Coronaviruses Content: The pandemic of coronavirus disease 2019 (COVID-19) caused by SARS-CoV-2 has posed a severe threat to global public health. Yet, the origin of SARS-CoV-2 remains mysterious. Several recent studies (e.g., Lam et al.,Xiao et al.) identified SARS-CoV-2-related viruses in pangolins, providing novel insights into the evolution and diversity of SARS-CoV-2-related viruses.", "qid": 32, "docid": "pfv7q4v6", "rank": 85, "score": 0.845848560333252}, {"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": 32, "docid": "ymoigqdw", "rank": 86, "score": 0.845666766166687}, {"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": 32, "docid": "vhb280gz", "rank": 87, "score": 0.8456556797027588}, {"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": 32, "docid": "35wfw3zn", "rank": 88, "score": 0.8456556797027588}, {"content": "Title: Molecular evolution and multilocus sequence typing of 145 strains of SARS-CoV Content: Abstract In this study, we have identified 876 polymorphism sites in 145 complete or partial genomes of SARS-CoV available in the NCBI GenBank. One hundred and seventy-four of these sites existed in two or more SARS-CoV genome sequences. According to the sequence polymorphism, all SARS-CoVs can be divided into three groups: (I) group 1, animal-origin viruses (such as SARS-CoV SZ1, SZ3, SZ13 and SZ16); (II) group 2, all viruses with clinical origin during first epidemic; and (III) group 3, SARS-CoV GD03T0013. According to 10 special loci, group 2 again can be divided into genotypes C and T, which can be further divided into sub-genotypes C1\u2013C4 and T1\u2013T4. Positive Darwinian selections were identified between any pair of these three groups. Genotype C gives neutral selection. Genotype T, however, shows negative selection. By comparing the death rates of SARS patients in the different regions, it was found that the death rate caused by the viruses of the genotype C was lower than that of the genotype T. SARS-CoVs might originate from an unknown ancestor.", "qid": 32, "docid": "ypgrw78s", "rank": 89, "score": 0.8456535339355469}, {"content": "Title: Emerging details about covid-19 and chronology of the pandemic in turkey/ Covid-19 hakk\u0131nda ortaya \u00e7\u0131kan bilgiler ve t\u00fcrkiye'de pandeminin kronolojisi Content: Coronaviruses are found in all mammalian and avian species. Due to its mild infection on upper respiratory tract, this virus was not considered as a serious human pathogen until the outbreaks of SARS-CoV and MERS-CoV in 2002 and 2012, respectively. Recently the third and the biggest outbreak of coronavirus \u201cCOVID-19\u201d or \u201cSARS-CoV-2\u201d has erupted and the world is now in a struggle to combat this disease. Although everything has not yet been fully clarified about this new type of virus, the data obtained from the studies conducted so far provides guidance on how to deal with SARS-CoV-2. In this context, this review provides information about pathogenesis, clinical symptoms, presence in animals, potential transmission routes of SARS-CoV-2 as well as the detection methods used in the world and Turkey.", "qid": 32, "docid": "x78iory5", "rank": 90, "score": 0.8455692529678345}, {"content": "Title: The Detection of SARS-CoV-2 using the Cepheid Xpert Xpress SARS-CoV-2 and Roche cobas SARS-CoV-2 Assays. Content: SARS-CoV-2, a novel coronavirus responsible for a December 2019 outbreak in Wuhan, China, causes a syndrome characterized by fever, cough, and dyspnea progressing to acute respiratory distress syndrome (1).\u2026.", "qid": 32, "docid": "hkxexvjb", "rank": 91, "score": 0.8454909324645996}, {"content": "Title: Angiotensin-converting enzyme 2, a SARS-CoV-2 receptor, is upregulated by interleukin-6 via STAT3 signaling in synovial tissues Content: The severe acute respiratory syndrome-coronavirus-2 (SARS-CoV-2) has spread explosively worldwide and resulted in a pandemic of a new respiratory disease called coronavirus disease 2019 (COVID-19) in 2020. Symptoms of COVID-19 include fever, malaise, cough, and in severe cases, pneumonia and acute respiratory distress syndrome (1,2).", "qid": 32, "docid": "acw2fhi8", "rank": 92, "score": 0.84511798620224}, {"content": "Title: Angiotensin-converting enzyme 2, a SARS-CoV-2 receptor, is upregulated by interleukin-6 via STAT3 signaling in synovial tissues. Content: The severe acute respiratory syndrome-coronavirus-2 (SARS-CoV-2) has spread explosively worldwide and resulted in a pandemic of a new respiratory disease called coronavirus disease 2019 (COVID-19) in 2020. Symptoms of COVID-19 include fever, malaise, cough, and in severe cases, pneumonia and acute respiratory distress syndrome (1,2).", "qid": 32, "docid": "zcjam19p", "rank": 93, "score": 0.84511798620224}, {"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": 32, "docid": "xkzvzonj", "rank": 94, "score": 0.8448309898376465}, {"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": 32, "docid": "dqour5jr", "rank": 95, "score": 0.844539999961853}, {"content": "Title: Coronavirus disease-19 and fertility: viral host entry protein expression in male and female reproductive tissues Content: OBJECTIVE: To identify cell types in the male and female reproductive systems at risk for SARS-CoV-2 infection because of the expression of host genes and proteins used by the virus for cell entry. DESIGN: Descriptive analysis of transcriptomic and proteomic data. SETTING: Academic research department and clinical diagnostic laboratory. PATIENT(S): Not applicable (focus was on previously generated gene and protein expression data). INTERVENTION(S): None. MAIN OUTCOME MEASURE(S): Identification of cell types coexpressing the key angiotensin-converting enzyme 2 (ACE2) and transmembrane serine protease 2 (TMPRSS2) genes and proteins as well as other candidates potentially involved in SARS-CoV-2 cell entry. RESULT(S): On the basis of single-cell RNA sequencing data, coexpression of ACE2 and TMPRSS2 was not detected in testicular cells, including sperm. A subpopulation of oocytes in nonhuman primate ovarian tissue was found to express ACE2 and TMPRSS2, but coexpression was not observed in ovarian somatic cells. RNA expression of TMPRSS2 in 18 samples of human cumulus cells was shown to be low or absent. There was general agreement between publicly available bulk RNA and protein datasets in terms of ACE2 and TMPRSS2 expression patterns in testis, ovary, endometrial, and placental cells. CONCLUSION(S): These analyses suggest that SARS-CoV-2 infection is unlikely to have long-term effects on male and female reproductive function. Although the results cannot be considered definitive, they imply that procedures in which oocytes are collected and fertilized in vitro are associated with very little risk of viral transmission from gametes to embryos and may indeed have the potential to minimize exposure of susceptible reproductive cell types to infection in comparison with natural conception.", "qid": 32, "docid": "3dl0tab3", "rank": 96, "score": 0.8445366024971008}, {"content": "Title: Comparative Pathogenesis Of COVID-19, MERS And SARS In A Non-Human Primate Model Content: A novel coronavirus, SARS-CoV-2, was recently identified in patients with an acute respiratory syndrome, COVID-19. To compare its pathogenesis with that of previously emerging coronaviruses, we inoculated cynomolgus macaques with SARS-CoV-2 or MERS-CoV and compared with historical SARS-CoV infections. In SARS-CoV-2-infected macaques, virus was excreted from nose and throat in absence of clinical signs, and detected in type I and II pneumocytes in foci of diffuse alveolar damage and mucous glands of the nasal cavity. In SARS-CoV-infection, lung lesions were typically more severe, while they were milder in MERS-CoV infection, where virus was detected mainly in type II pneumocytes. These data show that SARS-CoV-2 can cause a COVID-19-like disease, and suggest that the severity of SARS-CoV-2 infection is intermediate between that of SARS-CoV and MERS-CoV. One Sentence Summary SARS-CoV-2 infection in macaques results in COVID-19-like disease with prolonged virus excretion from nose and throat in absence of clinical signs.", "qid": 32, "docid": "zrbesm5b", "rank": 97, "score": 0.8443565368652344}, {"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": 32, "docid": "qm44flh4", "rank": 98, "score": 0.844237208366394}, {"content": "Title: Severe acute respiratory syndrome coronavirus 2 and coronavirus disease 2019 Content: The severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) has been confirmed as the etiological pathogen of the coronavirus disease 2019 (COVID-19) SARS-CoV-2 is the seventh member of coronavirus family that can infect humans after the emergence of the severe acute respiratory syndrome coronavirus (SARS-CoV) and the Middle East respiratory syndrome coronavirus (MERS-CoV) SARS-CoV-2 is a single-stranded, positive-sense RNA virus Due to its strong infectiousness and the lack of immunity in humans, the epidemic of the COVID-19 is still spreading On January 30, 2020 (local time), the World Health Organization (WHO) defined the epidemics of SARS-CoV-2-infected pneumonia as a Public Health Emergency of International Concern (PHEIC) This paper reviews the etiology and pathogenicity of SARS-CoV-2, and the detection and diagnosis, prevention and control, as well as the treatment of COVID-19", "qid": 32, "docid": "2mh0cuan", "rank": 99, "score": 0.8442116379737854}, {"content": "Title: Evaluation of a rapid diagnostic assay for detection of SARS CoV-2 antigen in nasopharyngeal swab. Content: Severe Acute Respiratory Syndrome coronavirus 2 (SARS-CoV-2), the virus causing causing Coronavirus disease 2019 (COVID-19) was reported for the first time in Wuhan (Hubei, China) in December 2019 (1, 2) and has become a major public health concern all over the world.\u2026.", "qid": 32, "docid": "dc9ee7qz", "rank": 100, "score": 0.8441989421844482}]}
{"query": "What vaccine candidates are being tested for Covid-19?", "hits": [{"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": 1, "score": 0.8746523857116699}, {"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": 2, "score": 0.8735573887825012}, {"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.", "qid": 33, "docid": "zn182czp", "rank": 3, "score": 0.8661897778511047}, {"content": "Title: The SARS-CoV-2 Vaccine Pipeline: an Overview Content: PURPOSE OF REVIEW: The goal of this review is to provide a timely overview on efforts to develop a vaccine for the 2019 novel coronavirus SARS-CoV-2, the causative agent of coronavirus disease (COVID-19). RECENT FINDINGS: Previous research efforts to develop a severe acute respiratory syndrome coronavirus (SARS-CoV) vaccine in the years following the 2003 pandemic have opened the door for investigators to design vaccine concepts and approaches for the COVID-19 epidemic in China. Both SARS-CoV and SARS-CoV-2 exhibit a high degree of genetic similarity and bind to the same host cell ACE2 receptor. Based on previous experience with SARS-CoV vaccines, it is expected that all COVID-19 vaccines will require careful safety evaluations for immunopotentiation that could lead to increased infectivity or eosinophilic infiltration. Besides this, a COVID-19 vaccine target product profile must address vaccinating at-risk human populations including frontline healthcare workers, individuals over the age of 60, and those with underlying and debilitating chronic conditions. Among the vaccine technologies under evaluation are whole virus vaccines, recombinant protein subunit vaccines, and nucleic acid vaccines. SUMMARY: Each current vaccine strategy has distinct advantages and disadvantages. Therefore, it is paramount that multiple strategies be advanced quickly and then evaluated for safety and efficacy. Ultimately, the safety studies to minimize undesired immunopotentiation will become the most significant bottleneck in terms of time.", "qid": 33, "docid": "rl2qxd03", "rank": 4, "score": 0.8537726402282715}, {"content": "Title: The SARS-CoV-2 Vaccine Pipeline: an Overview Content: Purpose of Review: The goal of this review is to provide a timely overview on efforts to develop a vaccine for the 2019 novel coronavirus SARS-CoV-2, the causative agent of coronavirus disease (COVID-19). Recent Findings: Previous research efforts to develop a severe acute respiratory syndrome coronavirus (SARS-CoV) vaccine in the years following the 2003 pandemic have opened the door for investigators to design vaccine concepts and approaches for the COVID-19 epidemic in China. Both SARS-CoV and SARS-CoV-2 exhibit a high degree of genetic similarity and bind to the same host cell ACE2 receptor. Based on previous experience with SARS-CoV vaccines, it is expected that all COVID-19 vaccines will require careful safety evaluations for immunopotentiation that could lead to increased infectivity or eosinophilic infiltration. Besides this, a COVID-19 vaccine target product profile must address vaccinating at-risk human populations including frontline healthcare workers, individuals over the age of 60, and those with underlying and debilitating chronic conditions. Among the vaccine technologies under evaluation are whole virus vaccines, recombinant protein subunit vaccines, and nucleic acid vaccines. Summary: Each current vaccine strategy has distinct advantages and disadvantages. Therefore, it is paramount that multiple strategies be advanced quickly and then evaluated for safety and efficacy. Ultimately, the safety studies to minimize undesired immunopotentiation will become the most significant bottleneck in terms of time.", "qid": 33, "docid": "7jsponjx", "rank": 5, "score": 0.8537725806236267}, {"content": "Title: COVIDep platform for real-time reporting of vaccine target recommendations for SARS-CoV-2: Description and connections with COVID-19 immune responses and preclinical vaccine trials Content: We introduce COVIDep (https://COVIDep.ust.hk), a web-based platform that provides immune target recommendations for guiding SARS-CoV-2 vaccine development. COVIDep implements a protocol that pools together publicly-available genetic data for SARS-CoV-2 and epitope data for SARS-CoV to identify B cell and T cell epitopes that present potential immune targets for SARS-CoV-2. Correspondences between outputs of COVIDep and immune responses recorded in COVID-19 patients and preclinical vaccine trials are also indicated. The platform is user-friendly, flexible, and based on up-to-date data. It may help guide vaccine designs and associated experimental studies for SARS-CoV-2.", "qid": 33, "docid": "90f8spxe", "rank": 6, "score": 0.8507875204086304}, {"content": "Title: Diagnosis of COVID-19: Considerations, controversies and challenges Content: Coronavirus disease 2019 (COVID-19) due to a novel virus, severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), is a global pandemic that has resulted in over 1.5 million confirmed cases and close to 100 000 deaths. In the majority of symptomatic cases, COVID-19 results in a mild disease predominantly characterised by upper respiratory tract symptoms. Reverse transcription polymerase chain reaction (RT-PCR) using a nasopharyngeal sample is the mainstay of diagnosis, but there is an ~30% false negative rate early in the disease and in patients with mild disease, and therefore repeat testing may be required. RT-PCR positivity can persist for several days after resolution of symptoms. IgM and IgG antibody responses become positive several days after the onset of symptoms, and robust antibody responses are detectable in the second week of illness. Antibody-based immunoassays have a limited role in the diagnosis of early symptomatic disease. However, their incremental benefit over RT-PCR in the first 2 weeks of illness is currently being clarified in ongoing studies. Such assays may be useful for surveillance purposes. However, their role in potentially selecting individuals who may benefit from vaccination, or as a biomarker identifying persons who could be redeployed into essential employment roles, is being investigated. Rapid antibody-based immunoassays that detect viral antigen in nasopharyngeal samples are being developed and evaluated.", "qid": 33, "docid": "chp63f69", "rank": 7, "score": 0.8502079248428345}, {"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": 8, "score": 0.8476323485374451}, {"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": 9, "score": 0.8469831943511963}, {"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": 10, "score": 0.846482515335083}, {"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": 11, "score": 0.846482515335083}, {"content": "Title: Public Willingness to Get Vaccinated Against COVID-19: How AI-Developed Vaccines Can Affect Acceptance Content: Vaccines for COVID-19 are currently under clinical trials. These vaccines are crucial for eradicating the novel coronavirus. Despite the potential, there exist conspiracies related to vaccines online, which can lead to vaccination hesitancy and, thus, a longer-standing pandemic. We used a between-subjects study design (N=572 adults in the US and UK) to understand the public willingness towards vaccination against the novel coronavirus under various circumstances. Our survey findings suggest that people are more reluctant to vaccinate their children compared to themselves. Explicitly stating the high effectiveness of the vaccine against COVID-19 led to an increase in vaccine acceptance. Interestingly, our results do not indicate any meaningful variance due to the use of artificial intelligence (AI) in developing vaccines, if these systems are described to be in use alongside human researchers. We discuss the public's expectation of local governments in assuring the safety and effectiveness of a future COVID-19 vaccine.", "qid": 33, "docid": "uhb8k967", "rank": 12, "score": 0.8462693095207214}, {"content": "Title: Diagnosis of COVID-19: Considerations, Controversies and Challenges in South Africa Content: Coronavirus disease 2019 (COVID-19) due to severe acute respiratory syndrome coronavirus 2 is a global pandemic that has resulted in over 1.5 million confirmed cases and close to 100,000 deaths. In the majority of symptomatic cases COVID-19 results in a mild disease predominantly characterised by upper respiratory tract symptoms. Reverse transcription polymerase chain reaction (RT-PCR), using a nasopharyngeal sample, is the mainstay of diagnosis, but there is an ~30% false negative rate early in the disease and in patients with mild disease. RT-PCR positivity can persist for several days after a resolution of symptoms. IgM and IgG antibody responses become positive several days after the onset of symptoms, and robust antibody responses are detectable in the second week of illness. Antibody-based immunoassays have a limited role in the diagnosis of early symptomatic disease. However, their incremental benefit over RT-PCR in the first 2 weeks of illness is currently being clarified in ongoing studies. Such assays may be useful for surveillance purposes. However, their role in potentially selecting individuals that may benefit from vaccination, or as a biomarker identifying persons that could be redeployed into essential employment roles are being investigated. Rapid antibody-based immunoassays that detect viral antigen in nasopharyngeal samples are being developed and evaluated.", "qid": 33, "docid": "eh3ztsv5", "rank": 13, "score": 0.8460483551025391}, {"content": "Title: Calling for an exponential escalation scheme in vaccine development for COVID-19 Content: PURPOSE: COVID-19 as a pandemic calls for rapid development of vaccines. METHODS: Here a proposal of a seamless, adaptive, phase 1\u20133 trial for accelerated vaccine development is described. RESULTS: Starting at 10, the number of vaccinated volunteers would exponentially increase by tenfold at an interval of 2 weeks; close surveillance of antibody responses, safety and efficacy is necessary. After only 16 weeks, general vaccination would be feasible if supply meets the demand. CONCLUSION: A COVID-19 vaccine would be rapidly available at a slightly increased risk for undetected late side effects or insufficient efficacy if compared with standard vaccine development schemes.", "qid": 33, "docid": "f2iuy9e1", "rank": 14, "score": 0.8443499207496643}, {"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": 15, "score": 0.8436825275421143}, {"content": "Title: Calling for an exponential escalation scheme in vaccine development for COVID-19 Content: PURPOSE: COVID-19 as a pandemic calls for rapid development of vaccines. METHODS: Here a proposal of a seamless, adaptive, phase 1-3 trial for accelerated vaccine development is described. RESULTS: Starting at 10, the number of vaccinated volunteers would exponentially increase by tenfold at an interval of 2 weeks; close surveillance of antibody responses, safety and efficacy is necessary. After only 16 weeks, general vaccination would be feasible if supply meets the demand. CONCLUSION: A COVID-19 vaccine would be rapidly available at a slightly increased risk for undetected late side effects or insufficient efficacy if compared with standard vaccine development schemes.", "qid": 33, "docid": "u7xfq6zo", "rank": 16, "score": 0.8429616689682007}, {"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": 33, "docid": "hotn7qha", "rank": 17, "score": 0.8423592448234558}, {"content": "Title: SARS-CoV-2 SPIKE PROTEIN: an optimal immunological target for vaccines Content: COVID-19 has rapidly spread all over the world, progressing into a pandemic. This situation has urgently impelled many companies and public research institutes to concentrate their efforts on research for effective therapeutics. Here, we outline the strategies and targets currently adopted in developing a vaccine against SARS-CoV-2. Based on previous evidence and experience with SARS and MERS, the primary focus has been the Spike protein, considered as the ideal target for COVID-19 immunotherapies.", "qid": 33, "docid": "13z63d4y", "rank": 18, "score": 0.8422915935516357}, {"content": "Title: Will the coronavirus help mRNA and DNA vaccines prove their worth? Content: Biotech companies, pharma firms, universities, and government agencies are all rushing to start clinical trials of newly created gene-based vaccines for COVID-19 Developer;Technology;Phase I clinical trial Moderna and National Institutes of Health;mRNA vaccine;Began in March 2020 CanSino Biologics;Adenoviral vector vaccine;Began in March 2020 BioNTech, Shanghai Fosun Pharmaceutical, and Pfizer;mRNA vaccine;April 2020 Inovio Pharmaceuticals and Wistar Institute;DNA vaccine;April 2020 University of Oxford;Adenoviral vector vaccine;April 2020 CureVac;mRNA vaccine;By early summer Imperial College London;mRNA vaccine;Early summer Arcturus Therapeutics and Duke-NUS Medical School;mRNA vaccine;Second half of 2020 Johnson & Johnson and Biomedical Advanced Research and Development Authority;Adenoviral vector vaccine;By September Altimmune;Adenoviral vector vaccine;Q3 2020 Translate Bio and Sanofi Pasteur;mRNA vaccine;By end of 2020 eTheRNA Immunotherapies;mRNA vaccine;2021 Karolinska Institute;DNA vaccine;2021 University of Pennsylvania and Duke Human Vaccine Institute;mRNA vaccine;Unknown", "qid": 33, "docid": "30dhqh0g", "rank": 19, "score": 0.84220290184021}, {"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": 20, "score": 0.8417681455612183}, {"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": 33, "docid": "nol2n8fo", "rank": 21, "score": 0.8416855931282043}, {"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": 33, "docid": "vl3j05bs", "rank": 22, "score": 0.8416623473167419}, {"content": "Title: Vaccination strategies to combat novel corona virus SARS-CoV-2 Content: The 2019-novel coronavirus disease (COVID-19) is caused by SARS-CoV-2 is transmitted from human to human has recently reported in China. Now COVID-19 has been spread all over the world and declared epidemics by WHO. It has caused a Public Health Emergency of International Concern. The elderly and people with underlying diseases are susceptible to infection and prone to serious outcomes, which may be associated with acute respiratory distress syndrome (ARDS) and cytokine storm. Due to the rapid increase of SARS-CoV-2 infections and unavailability of antiviral therapeutic agents, developing an effective SAR-CoV-2 vaccine is urgently required. SARS-CoV-2 which is genetically similar to SARS-CoV and Middle East respiratory syndrome coronavirus (MERS-CoV) is an enveloped, single and positive-stranded RNA virus with a genome comprising 29,891 nucleotides, which encode the 12 putative open reading frames responsible for the synthesis of viral structural and nonstructural proteins which are very similar to SARS-CoV and MERS-CoV proteins. In this review we have summarized various vaccine candidates i.e., nucleotide, subunit and vector based as well as attenuated and inactivated forms, which have already been demonstrated their prophylactic efficacy against MERS-CoV and SARS-CoV, so these candidates could be used as a potential tool for the development of a safe and effective vaccine against SARS-CoV-2.", "qid": 33, "docid": "eq2ahtlc", "rank": 23, "score": 0.8413927555084229}, {"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": 33, "docid": "7dw32xby", "rank": 24, "score": 0.8413028717041016}, {"content": "Title: [Progress and analysis on the development of 2019-nCoV vaccine]. Content: As the COVID-19 pandemic is intensifying globally, more and more people are pinning their hopes on the development of vaccines. At present, there are many research teams who have adopted different vaccine technology routes to develop 2019-nCoV vaccines. This article reviews and analyzes the current development and research status of 2019-nCoV vaccines in different routes, and explores their possible development in the future.", "qid": 33, "docid": "tfa4lixq", "rank": 25, "score": 0.8398908972740173}, {"content": "Title: On setting expectations for a SARS-CoV-2 Vaccine Content: The global coronavirus pandemic is unlike any other since 1918. A century of dramatic medical advances has produced a public expectation that the medical field will rapidly provide solutions to restore normalcy. In under 6 months, since SARS-CoV-2 was identified, the massive international effort to develop a SARS-CoV-2 vaccine has generated more than 140 vaccines in different stages of development with 9 already recruiting into clinical trials posted on clinicaltrials.gov. The long-term strategy to handle COVID-19 will almost certainly rely on vaccines. But, what type of protection can we realistically expect to achieve from vaccines and when?", "qid": 33, "docid": "7lk8h93q", "rank": 26, "score": 0.8394665718078613}, {"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": 33, "docid": "vvz5spk7", "rank": 27, "score": 0.8394127488136292}, {"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": 28, "score": 0.8391302227973938}, {"content": "Title: Emergence of Drift Variants That May Affect COVID-19 Vaccine Development and Antibody Treatment Content: New coronavirus (SARS-CoV-2) treatments and vaccines are under development to combat COVID-19. Several approaches are being used by scientists for investigation, including (1) various small molecule approaches targeting RNA polymerase, 3C-like protease, and RNA endonuclease; and (2) exploration of antibodies obtained from convalescent plasma from patients who have recovered from COVID-19. The coronavirus genome is highly prone to mutations that lead to genetic drift and escape from immune recognition; thus, it is imperative that sub-strains with different mutations are also accounted for during vaccine development. As the disease has grown to become a pandemic, B-cell and T-cell epitopes predicted from SARS coronavirus have been reported. Using the epitope information along with variants of the virus, we have found several variants which might cause drifts. Among such variants, 23403A>G variant (p.D614G) in spike protein B-cell epitope is observed frequently in European countries, such as the Netherlands, Switzerland, and France, but seldom observed in China.", "qid": 33, "docid": "mif9gf4s", "rank": 29, "score": 0.8390152454376221}, {"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": 33, "docid": "ph6pxseu", "rank": 30, "score": 0.8388866186141968}, {"content": "Title: Assay Techniques and Test Development for COVID-19 Diagnosis Content: An ongoing theme of the COVID-19 pandemic is the need for widespread availability of accurate and e\ufb03cient diagnostic testing for detection of SARS-CoV-2 and antiviral antibodies in infected individuals. This report describes various assay techniques and tests for COVID-19 diagnosis. Most tests for early detection of SARS-CoV-2 RNA rely on the reverse transcription-polymerase chain reaction, but isothermal nucleic acid ampli\ufb01cation assays, including transcription-mediated ampli\ufb01cation and CRISPR-based methodologies, are promising alternatives. Identi\ufb01cation of individuals who have developed antibodies to the SARS-CoV-2 virus requires serological tests, including enzyme-linked immunosorbent assay (ELISA) and lateral \ufb02ow immunoassay. This report also provides an overview of current development in COVID-19 diagnostic techniques and products to facilitate future improvement and innovation.", "qid": 33, "docid": "d7xq7x5g", "rank": 31, "score": 0.8383905291557312}, {"content": "Title: Bioinformatic prediction of potential T cell epitopes for SARS-Cov-2 Content: To control and prevent the current COVID-19 pandemic, the development of novel vaccines is an emergent issue. In addition, we need to develop tools that can measure/monitor T-cell and B-cell responses to know how our immune system is responding to this deleterious virus. However, little information is currently available about the immune target epitopes of novel coronavirus (SARS-CoV-2) to induce host immune responses. Through a comprehensive bioinformatic screening of potential epitopes derived from the SARS-CoV-2 sequences for HLAs commonly present in the Japanese population, we identified 2013 and 1399 possible peptide epitopes that are likely to have the high affinity (<0.5%- and 2%-rank, respectively) to HLA class I and II molecules, respectively, that may induce CD8+ and CD4+ T-cell responses. These epitopes distributed across the structural (spike, envelope, membrane, and nucleocapsid proteins) and the nonstructural proteins (proteins corresponding to six open reading frames); however, we found several regions where high-affinity epitopes were significantly enriched. By comparing the sequences of these predicted T cell epitopes to the other coronaviruses, we identified 781 HLA-class I and 418 HLA-class II epitopes that have high homologies to SARS-CoV. To further select commonly-available epitopes that would be applicable to larger populations, we calculated population coverages based on the allele frequencies of HLA molecules, and found 2 HLA-class I epitopes covering 83.8% of the Japanese population. The findings in the current study provide us valuable information to design widely-available vaccine epitopes against SARS-CoV-2 and also provide the useful information for monitoring T-cell responses.", "qid": 33, "docid": "u6l1le7e", "rank": 32, "score": 0.838089108467102}, {"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": 33, "docid": "5f95gve3", "rank": 33, "score": 0.8380668759346008}, {"content": "Title: Bioinformatic prediction of potential T cell epitopes for SARS-Cov-2 Content: To control and prevent the current COVID-19 pandemic, the development of novel vaccines is an emergent issue. In addition, we need to develop tools that can measure/monitor T-cell and B-cell responses to know how our immune system is responding to this deleterious virus. However, little information is currently available about the immune target epitopes of novel coronavirus (SARS-CoV-2) to induce host immune responses. Through a comprehensive bioinformatic screening of potential epitopes derived from the SARS-CoV-2 sequences for HLAs commonly present in the Japanese population, we identified 2013 and 1399 possible peptide epitopes that are likely to have the high affinity (<0.5%- and 2%-rank, respectively) to HLA class I and II molecules, respectively, that may induce CD8(+) and CD4(+) T-cell responses. These epitopes distributed across the structural (spike, envelope, membrane, and nucleocapsid proteins) and the nonstructural proteins (proteins corresponding to six open reading frames); however, we found several regions where high-affinity epitopes were significantly enriched. By comparing the sequences of these predicted T cell epitopes to the other coronaviruses, we identified 781 HLA-class I and 418 HLA-class II epitopes that have high homologies to SARS-CoV. To further select commonly-available epitopes that would be applicable to larger populations, we calculated population coverages based on the allele frequencies of HLA molecules, and found 2 HLA-class I epitopes covering 83.8% of the Japanese population. The findings in the current study provide us valuable information to design widely-available vaccine epitopes against SARS-CoV-2 and also provide the useful information for monitoring T-cell responses.", "qid": 33, "docid": "dew2ig0q", "rank": 34, "score": 0.8379188776016235}, {"content": "Title: Identification of IgG antibody response to SARS-CoV-2 spike protein and its receptor binding domain does not predict rapid recovery from COVID-19 Content: Diagnostic testing and evaluation of patient immunity against the novel severe acute respiratory syndrome (SARS) corona virus that emerged last year (SARS-CoV-2) are essential for health and economic crisis recovery of the world. It is suggested that potential acquired immunity against SARS-CoV-2 from prior exposure may be determined by detecting the presence of circulating IgG antibodies against viral antigens, such as the spike glycoprotein and its receptor binding domain (RBD). Testing our asymptomatic population for evidence of COVID-19 immunity would also offer valuable epidemiologic data to aid health care policies and health care management. Currently, there are over 100 antibody tests that are being used around the world without approval from the FDA or similar regulatory bodies, and they are mostly for rapid and qualitative assessment, with different degrees of error rates. ELISA-based testing for sensitive and rigorous quantitative assessment of SARS-CoV-2 antibodies can potentially offer mechanistic insights into the COVID-19 disease and aid communities uniquely challenged by limited financial resources and access to commercial testing products. Employing recombinant SARS-CoV-2 RBD and spike protein generated in the laboratory, we devised a quantitative ELISA for the detection of circulating serum antibodies. Serum from twenty SARS-CoV-2 RT-PCR confirmed COVID-19 hospitalized patients were used to detect circulating IgG titers against SARS-CoV-2 spike protein and RBD. Quantitative detection of IgG antibodies to the spike glycoprotein or the RBD in patient samples was not always associated with faster recovery, compared to patients with borderline antibody response to the RBD. One patient who did not develop antibodies to the RBD completely recovered from COVID-19. In surveying 99 healthy donor samples (procured between 2017-February 2020), we detected RBD antibodies in one donor from February 2020 collection with three others exhibiting antibodies to the spike protein but not the RBD. Collectively, our study suggests that more rigorous and quantitative analysis, employing large scale sample sets, is required to determine whether antibodies to SARS-CoV-2 spike protein or RBD is associated with protection from COVID-19 disease. It is also conceivable that humoral response to SARS-CoV-2 spike protein or RBD works in association with adaptive T cell response to determine clinical sequela and severity of COVID-19 disease.", "qid": 33, "docid": "y1afswkm", "rank": 35, "score": 0.837893009185791}, {"content": "Title: Defining Protective Epitopes for COVID\u201019 Vaccination Models Content: Recent papers in the Journal provide tangible avenues for COVID\u201019 vaccine production as immunoreactive epitopes are brought to the forefront in these and many other emerging studies.(1,2) The development of a consistent predictable animal model of COVID\u201019 infection is evidently also a welcome event for preliminary antiviral and vaccine assessments and surely brings us to another level of progression.(3) This article is protected by copyright. All rights reserved.", "qid": 33, "docid": "77mw0dws", "rank": 36, "score": 0.8378497958183289}, {"content": "Title: Validation and performance of a quantitative IgG assay for the screening of SARS-CoV-2 antibodies Content: The current COVID-19 epidemic imposed an unpreceded challenge to the scientific community in terms of treatment, epidemiology, diagnosis, social interaction, fiscal policies and many other areas. The development of accurate and reliable diagnostic tools (high specificity and sensitivity) is crucial in the current period, the near future and in the long term. These assays should provide guidance to identify immune presumptive protected persons, potential plasma, and/or B cell donors and vaccine development among others. Also, such assays will be contributory in supporting prospective and retrospective studies to identify the prevalence and incidence of COVID-19 and to characterize the dynamics of the immune response. As of today, only thirteen serological assays have received the Emergency Use Authorization (EUA) by the U.S. Federal Drug Administration (FDA). In this work we describe the development and validation of a quantitative IgG enzyme-linked immunoassay (ELISA) using the recombinant SARS-CoV-2 Spike Protein S1 domain, containing the receptor-binding domain (RBD), showing 98% sensitivity and 98.9% specificity. The assay showed to be useful to test for SARS-CoV-2 IgG antibodies in plasma samples from COVID-19-recovered subjects as potential donors for plasmapheresis. This assay is currently under review by the Federal Drug Administration for an Emergency Use Authorization request (Submission Number EUA201115).", "qid": 33, "docid": "sxfrjs58", "rank": 37, "score": 0.8373119831085205}, {"content": "Title: COVID-19: How has the scientific community risen to the challenge? Content: As the novel coronavirus SARS-CoV-2 spreads around the world, scientists have raced to develop vaccines and tests in order to curb the infection.", "qid": 33, "docid": "humoykni", "rank": 38, "score": 0.8370237946510315}, {"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": 39, "score": 0.8367393612861633}, {"content": "Title: The early landscape of coronavirus disease 2019 vaccine development in the UK and rest of the world Content: Since the first World Health Organization notification on 31 December 2019, coronavirus disease 2019 (COVID-19), the respiratory disease caused by the coronavirus severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2), has been responsible for over four million confirmed infections and almost 300 000 deaths worldwide. The pandemic has led to over half of the world's population living under lockdown conditions. To allow normal life to resume, public health interventions will be needed to prevent further waves of infections as lockdown measures are lifted. As one of the most effective countermeasures against infectious diseases, an efficacious vaccine is considered crucial to containing the COVID-19 pandemic. Following the publication of the genome sequence of SARS-CoV-2, vaccine development has accelerated at an unprecedented pace across the world. Here we review the different platforms employed to develop vaccines, the standard timelines of development and how they can be condensed in a pandemic situation. We focus on vaccine development in the UK and vaccines that have entered clinical trials around the world.", "qid": 33, "docid": "tldxsmsd", "rank": 40, "score": 0.8365482091903687}, {"content": "Title: Post-donation COVID-19 identification in blood donors. Content: The coronavirus disease 19 (COVID-19) outbreak, which was characterized as a pandemic on 11 March 2020 by the WHO, started in December 2019 with the emergence of pneumonia cases of unknown cause in Wuhan, Hubei, China [1]. SARS-CoV-2, the causative agent of COVID-19, are enveloped, non-segmented, single stranded positive sense RNA viruses and are classified as a sister clade to the prototype human and bat severe acute respiratory syndrome coronaviruses (SARS-CoVs) of the species Severe acute respiratory syndrome-related coronavirus [2]. So far, no respiratory virus, including SARS-CoV and the Middle East Respiratory Syndrome (MERS)-CoV, has been confirmed as transfusion-transmissible [3,4].", "qid": 33, "docid": "82sc928x", "rank": 41, "score": 0.8363758325576782}, {"content": "Title: Towards Precision Medicine: Inclusion of Sex and Gender Aspects in COVID-19 Clinical Studies\u2014Acting Now before It Is Too Late\u2014A Joint Call for Action Content: The COVID-19 global pandemic is accelerating investigations for effective vaccines and repurposable validated therapeutics [...].", "qid": 33, "docid": "ivpa40zg", "rank": 42, "score": 0.8363623023033142}, {"content": "Title: Towards Precision Medicine: Inclusion of Sex and Gender Aspects in COVID-19 Clinical Studies-Acting Now before It Is Too Late-A Joint Call for Action Content: The COVID-19 global pandemic is accelerating investigations for effective vaccines and repurposable validated therapeutics [...].", "qid": 33, "docid": "bfg81ha7", "rank": 43, "score": 0.8363622426986694}, {"content": "Title: A Snapshot of the Global Race for Vaccines Targeting SARS-CoV-2 and the COVID-19 Pandemic Content: A novel coronavirus SARS-CoV-2 causing Coronavirus disease 2019 (COVID-19) has entered the human population and has spread rapidly around the world in the first half of 2020 causing a global pandemic. The virus uses its spike glycoprotein receptor-binding domain to interact with host cell angiotensin-converting enzyme 2 (ACE2) sites to initiate a cascade of events that culminate in severe acute respiratory syndrome in some individuals. In efforts to curtail viral spread, authorities initiated far-reaching lockdowns that have disrupted global economies. The scientific and medical communities are mounting serious efforts to limit this pandemic and subsequent waves of viral spread by developing preventative vaccines and repurposing existing drugs as potential therapies. In this review, we focus on the latest developments in COVID-19 vaccine development, including results of the first Phase I clinical trials and describe a number of the early candidates that are emerging in the field. We seek to provide a balanced coverage of the seven main platforms used in vaccine development that will lead to a desired target product profile for the \u201cideal\u201d vaccine. Using tales of past vaccine discovery efforts that have taken many years or that have failed, we temper over exuberant enthusiasm with cautious optimism that the global medical community will reach the elusive target to treat COVID-19 and end the pandemic.", "qid": 33, "docid": "ozdwkkqn", "rank": 44, "score": 0.8362253904342651}, {"content": "Title: COVIEdb: A database for potential immune epitopes of coronaviruses Content: 2019 novel coronavirus (2019-nCoV) has caused large-scale pandemic COVID-19 all over the world. It\u2019s essential to find out which parts of the 2019-nCoV sequence are recognized by human immune system for vaccine development. And for the prevention of the potential outbreak of similar coronaviruses in the future, vaccines against immunogenic epitopes shared by different human coronaviruses are essential. Here we predict all the potential B/T-cell epitopes for SARS-CoV, MERS-CoV, 2019-nCoV and RaTG13-CoV based on the protein sequences. We found YFKYWDQTY in ORF1ab protein, VYDPLQPEL and TVYDPLQPEL in spike (S) protein might be pan-coronavirus targets for vaccine development. All the predicted results are stored in a database COVIEdb (http://biopharm.zju.edu.cn/coviedb/).", "qid": 33, "docid": "s7chie0t", "rank": 45, "score": 0.8361884355545044}, {"content": "Title: Novel SARS-CoV-2 specific antibody and neutralization assays reveal wide range of humoral immune response during COVID-19 Content: Development of antibody protection during SARS-CoV-2 (CoV-2) infection is a pressing question for public health and for vaccine development. We developed highly sensitive CoV-2-specific antibody and neutralization assays. CoV-2 Spike protein or Nucleocapsid protein specific IgG antibodies at titers more than 1:100,000 were detectable in all PCR+ subjects (n=87) and were absent in the negative controls. Other isotype antibodies (IgA, IgG1-4) were also detected. CoV-2 neutralization was determined in COVID-19 and convalescent plasma up to 10,000-fold dilution, using Spike protein pseudotyped lentiviruses, which was also blocked by neutralizing antibodies (NAbs). Hospitalized patients had up to 3000-fold higher antibody and neutralization titers compared to outpatients or convalescent plasma donors. Further, subjects who donated plasma further out from the diagnosis of COVID-19 appeared to have lower titers. Interestingly, some COVID-19 patients also contained NAbs against SARS Spike protein pseudovirus. Together these results demonstrate the high specificity and sensitivity of our assays, which may impact understanding the quality or duration of the antibody response during COVID-19 and in determining the effectiveness of potential vaccines.", "qid": 33, "docid": "y61g0hg0", "rank": 46, "score": 0.835940420627594}, {"content": "Title: Progress and Challenges in the Development of COVID-19 Vaccines and Current Understanding of SARS-CoV-2- Specific Immune Responses Content: The outbreak of coronavirus disease 2019 (COVID-19) caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) is spreading globally, and the WHO has declared this outbreak a pandemic. Vaccines are an effective way to prevent the rapid spread of COVID-19. Furthermore, the immune response against SARS-CoV-2 infection needs to be understood for the development of an efficient and safe vaccine. Here, we review the current understanding of vaccine targets and the status of vaccine development for COVID-19. We also describe host immune responses to highly pathogenic human coronaviruses in terms of innate and adaptive immunities.", "qid": 33, "docid": "pc7efh1v", "rank": 47, "score": 0.8357492089271545}, {"content": "Title: Progress and Challenges in the Development of COVID-19 Vaccines and Current Understanding of SARS-CoV-2- Specific Immune Responses. Content: The outbreak of coronavirus disease 2019 (COVID-19) caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) is spreading globally, and the WHO has declared this outbreak a pandemic. Vaccines are an effective way to prevent the rapid spread of COVID-19. Furthermore, the immune response against SARS-CoV-2 infection needs to be understood for the development of an efficient and safe vaccine. Here, we review the current understanding of vaccine targets and the status of vaccine development for COVID-19. We also describe host immune responses to highly pathogenic human coronaviruses in terms of innate and adaptive immunities.", "qid": 33, "docid": "m7yii8el", "rank": 48, "score": 0.8357492089271545}, {"content": "Title: Vaccines against Coronaviruses: The State of the Art Content: The emerging epidemic caused by the new coronavirus SARS-CoV-2 represents the most important socio-health threat of the 21st century. The high contagiousness of the virus, the strong impact on the health system of the various countries and the absence to date of treatments able to improve the prognosis of the disease make the introduction of a vaccine indispensable, even though there are currently no approved human coronavirus vaccines. The aim of the study is to carry out a review of the medical literature concerning vaccine candidates for the main coronaviruses responsible for human epidemics, including recent advances in the development of a vaccine against COVID-19. This extensive review carried out on the vaccine candidates of the main epidemic coronaviruses of the past has shown that the studies in animal models suggest a high efficacy of potential vaccines in providing protection against viral challenges. Similar human studies have not yet been carried out, as the main trials are aimed at assessing mainly vaccine safety and immunogenicity. Whereas the severe acute respiratory syndrome (SARS-CoV) epidemic ended almost two decades ago and the Middle East respiratory syndrome (MERS-CoV) epidemic is now better controlled, as it is less contagious due to the high lethality of the virus, the current SARS-CoV-2 pandemic represents a problem that is certainly more compelling, which pushes us to accelerate the studies not only for the production of vaccines but also for innovative pharmacological treatments. SARS-CoV-2 vaccines might come too late to affect the first wave of this pandemic, but they might be useful if additional subsequent waves occur or in a post-pandemic perspective in which the virus continues to circulate as a seasonal virus.", "qid": 33, "docid": "x5zvwtj7", "rank": 49, "score": 0.8356809616088867}, {"content": "Title: Vaccines against Coronaviruses: The State of the Art. Content: The emerging epidemic caused by the new coronavirus SARS-CoV-2 represents the most important socio-health threat of the 21st century. The high contagiousness of the virus, the strong impact on the health system of the various countries and the absence to date of treatments able to improve the prognosis of the disease make the introduction of a vaccine indispensable, even though there are currently no approved human coronavirus vaccines. The aim of the study is to carry out a review of the medical literature concerning vaccine candidates for the main coronaviruses responsible for human epidemics, including recent advances in the development of a vaccine against COVID-19. This extensive review carried out on the vaccine candidates of the main epidemic coronaviruses of the past has shown that the studies in animal models suggest a high efficacy of potential vaccines in providing protection against viral challenges. Similar human studies have not yet been carried out, as the main trials are aimed at assessing mainly vaccine safety and immunogenicity. Whereas the severe acute respiratory syndrome (SARS-CoV) epidemic ended almost two decades ago and the Middle East respiratory syndrome (MERS-CoV) epidemic is now better controlled, as it is less contagious due to the high lethality of the virus, the current SARS-CoV-2 pandemic represents a problem that is certainly more compelling, which pushes us to accelerate the studies not only for the production of vaccines but also for innovative pharmacological treatments. SARS-CoV-2 vaccines might come too late to affect the first wave of this pandemic, but they might be useful if additional subsequent waves occur or in a post-pandemic perspective in which the virus continues to circulate as a seasonal virus.", "qid": 33, "docid": "zi1l5883", "rank": 50, "score": 0.8356809616088867}, {"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": 33, "docid": "m88ha8ry", "rank": 51, "score": 0.8356602191925049}, {"content": "Title: Review on the global epidemiological situation and the efficacy of chloroquine and hydroxychloroquine for the treatment of COVID-19 Content: Covid-19 disease is caused by SARS-CoV-2, a virus belonging to the coronavirus family. Covid-19 is so new that there is currently no specific vaccine or treatment. Clinical trials are currently underway. In vitro tests are also being conducted to assess the efficacy of chloroquine and hydroxychloroquine for the treatment of this epidemic, which is considered a pandemic by the WHO. We note that the content of this review is dated. The information it contains is subject to change and modification as the epidemic progresses.", "qid": 33, "docid": "wbkn7yjh", "rank": 52, "score": 0.8356435298919678}, {"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": 53, "score": 0.8349260091781616}, {"content": "Title: Vaccines for SARS-CoV-2: Lessons from Other Coronavirus Strains Content: The emergence of the strain of coronavirus SARS-CoV-2 (severe acute respiratory syndrome coronavirus 2) and its impact on global health have made imperative the development of effective and safe vaccines for this lethal strain. SARS-CoV-2 now adds to the list of coronavirus diseases that have threatened global health, along with the SARS (severe acute respiratory syndrome) and MERS (Middle East respiratory syndrome) coronaviruses that emerged in 2002/2003 and 2012, respectively. As of April 2020, no vaccine is commercially available for these coronavirus strains. Nevertheless, the knowledge obtained from the vaccine development efforts for MERS and SARS can be of high value for COVID-19 (coronavirus disease 2019). Here, we review the past and ongoing vaccine development efforts for clinically relevant coronavirus strains with the intention that this information helps in the development of effective and safe vaccines for COVID-19. In addition, information from naturally exposed individuals and animal models to coronavirus strains is described for the same purpose of helping into the development of effective vaccines against COVID-19.", "qid": 33, "docid": "ri91u0f1", "rank": 54, "score": 0.8348314762115479}, {"content": "Title: Vaccines for SARS-CoV-2: Lessons from Other Coronavirus Strains. Content: The emergence of the strain of coronavirus SARS-CoV-2 (severe acute respiratory syndrome coronavirus 2) and its impact on global health have made imperative the development of effective and safe vaccines for this lethal strain. SARS-CoV-2 now adds to the list of coronavirus diseases that have threatened global health, along with the SARS (severe acute respiratory syndrome) and MERS (Middle East respiratory syndrome) coronaviruses that emerged in 2002/2003 and 2012, respectively. As of April 2020, no vaccine is commercially available for these coronavirus strains. Nevertheless, the knowledge obtained from the vaccine development efforts for MERS and SARS can be of high value for COVID-19 (coronavirus disease 2019). Here, we review the past and ongoing vaccine development efforts for clinically relevant coronavirus strains with the intention that this information helps in the development of effective and safe vaccines for COVID-19. In addition, information from naturally exposed individuals and animal models to coronavirus strains is described for the same purpose of helping into the development of effective vaccines against COVID-19.", "qid": 33, "docid": "qu7ddcw9", "rank": 55, "score": 0.8348314762115479}, {"content": "Title: Performance Characteristics of the Abbott Architect SARS-CoV-2 IgG Assay and Seroprevalence in Boise, Idaho Content: Coronavirus disease-19 (COVID19), the novel respiratory illness caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), is associated with severe morbidity and mortality. The rollout of diagnostic testing in the United States was slow, leading to numerous cases that were not tested for SARS-CoV-2 in February and March 2020, necessitating the use of serological testing to determine past infections. Here, we evaluated the Abbott SARS-CoV-2 IgG test for detection of anti-SARS-CoV-2 IgG antibodies by testing 3 distinct patient populations. We tested 1,020 serum specimens collected prior to SARS-CoV-2 circulation in the United States and found one false positive, indicating a specificity of 99.90%. We tested 125 patients who tested RT-PCR positive for SARS-CoV-2 for which 689 excess serum specimens were available and found sensitivity reached 100% at day 17 after symptom onset and day 13 after PCR positivity. Alternative index value thresholds for positivity resulted in 100% sensitivity and 100% specificity in this cohort. We tested 4,856 individuals from Boise, Idaho collected over one week in April 2020 as part of the Crush the Curve initiative and detected 87 positives for a positivity rate of 1.79%. These data demonstrate excellent analytical performance of the Abbott SARS-CoV-2 IgG test as well as the limited circulation of the virus in the western United States. We expect the availability of high-quality serological testing will be a key tool in the fight against SARS-CoV-2.", "qid": 33, "docid": "9je1v09f", "rank": 56, "score": 0.8347030282020569}, {"content": "Title: Performance Characteristics of the Abbott Architect SARS-CoV-2 IgG Assay and Seroprevalence in Boise, Idaho. Content: Coronavirus disease-19 (COVID19), the novel respiratory illness caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), is associated with severe morbidity and mortality. The rollout of diagnostic testing in the United States was slow, leading to numerous cases that were not tested for SARS-CoV-2 in February and March 2020, necessitating the use of serological testing to determine past infections. Here, we evaluated the Abbott SARS-CoV-2 IgG test for detection of anti-SARS-CoV-2 IgG antibodies by testing 3 distinct patient populations. We tested 1,020 serum specimens collected prior to SARS-CoV-2 circulation in the United States and found one false positive, indicating a specificity of 99.90%. We tested 125 patients who tested RT-PCR positive for SARS-CoV-2 for which 689 excess serum specimens were available and found sensitivity reached 100% at day 17 after symptom onset and day 13 after PCR positivity. Alternative index value thresholds for positivity resulted in 100% sensitivity and 100% specificity in this cohort. We tested 4,856 individuals from Boise, Idaho collected over one week in April 2020 as part of the Crush the Curve initiative and detected 87 positives for a positivity rate of 1.79%. These data demonstrate excellent analytical performance of the Abbott SARS-CoV-2 IgG test as well as the limited circulation of the virus in the western United States. We expect the availability of high-quality serological testing will be a key tool in the fight against SARS-CoV-2.", "qid": 33, "docid": "uyq6urw3", "rank": 57, "score": 0.8347030282020569}, {"content": "Title: Intensifying vaccine production Content: The COVID-19 pandemic has started a race to develop new vaccines. Making sure enough is made to meet demand will require manufacturing innovation. Tatum Anderson reports.", "qid": 33, "docid": "cgep9m37", "rank": 58, "score": 0.8346735835075378}, {"content": "Title: Performance Characteristics of the Abbott Architect SARS-CoV-2 IgG Assay and Seroprevalence Testing in Idaho Content: Coronavirus disease-19 (COVID19), the novel respiratory illness caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), is associated with severe morbidity and mortality. The rollout of diagnostic testing in the United States was slow, leading to numerous cases that were not tested for SARS-CoV-2 in February and March 2020, necessitating the use of serological testing to determine past infections. Here, we evaluated the Abbott SARS-CoV-2 IgG test for detection of anti-SARS-CoV-2 IgG antibodies by testing 3 distinct patient populations. We tested 1,020 serum specimens collected prior to SARS-CoV-2 circulation in the United States and found one false positive, indicating a specificity of 99.90%. We tested 125 patients who tested RT-PCR positive for SARS-CoV-2 for which 689 excess serum specimens were available and found sensitivity reached 100% at day 17 after symptom onset and day 13 after PCR positivity. Alternative index value thresholds for positivity resulted in 100% sensitivity and 100% specificity. We then tested 4,856 individuals from Boise, Idaho collected over one week in April 2020 as part of the Crush the Curve initiative and detected 87 positives for a positivity rate of 1.79%. These data demonstrate excellent analytical performance of the Abbott SARS-CoV-2 IgG test as well as the limited circulation of the virus on the West Coast. We expect the availability of high-quality serological testing will be a key tool in the fight against SARS-CoV-2.", "qid": 33, "docid": "e3e48idb", "rank": 59, "score": 0.8342418670654297}, {"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": 60, "score": 0.8336499929428101}, {"content": "Title: Currently available intravenous immunoglobulin contains antibodies reacting against severe acute respiratory syndrome coronavirus 2 antigens Content: Aim: There is a critical need for effective therapies that are immediately available to control the spread of COVID-19 disease. Material & methods: Gamunex\u00ae-C and Flebogamma\u00ae DIF (Grifols) intravenous immunoglobulin (IVIG) products were tested using ELISA techniques for antibodies against several antigens of human common betacoronaviruses that may crossreact with the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) virus. Results: Both IVIGs showed consistent reactivity to components of the tested viruses. Positive crossreactivity was seen in SARS-CoV, middle east respiratory syndrome-CoV and SARS-CoV-2. For SARS-CoV-2, positive reactivity was observed at IVIG concentrations ranging from 100 \u00b5g/ml with Gamunex-C to 1 mg/ml with Flebogamma 5% DIF. Conclusion: Gamunex-C and Flebogamma DIF contain antibodies reacting against SARS-CoV-2 antigens. Studies to confirm the utility of IVIG preparations for COVID-19 management may be warranted.", "qid": 33, "docid": "71ek9zov", "rank": 61, "score": 0.8334824442863464}, {"content": "Title: The Brighton Collaboration standardized template for collection of key information for benefit-risk assessment of protein vaccines Content: Several protein vaccine candidates are among the COVID-19 vaccines in development. The Brighton Collaboration Viral Vector Vaccines Safety Working Group (V3SWG) has prepared a standardized template to describe the key considerations for the benefit-risk assessment of protein vaccines. This will help key stakeholders to assess potential safety issues and understand the benefit-risk of such a vaccine platform. The structured and standardized assessment provided by the template would also help contribute to improved public acceptance and communication of licensed protein vaccines.", "qid": 33, "docid": "ca97b3wj", "rank": 62, "score": 0.8333415389060974}, {"content": "Title: Currently available intravenous immunoglobulin contains antibodies reacting against severe acute respiratory syndrome coronavirus 2 antigens Content: AIM: There is a critical need for effective therapies that are immediately available to control the spread of COVID-19 disease. MATERIAL & METHODS: Gamunex(\u00ae)-C and Flebogamma(\u00ae) DIF (Grifols) intravenous immunoglobulin (IVIG) products were tested using ELISA techniques for antibodies against several antigens of human common betacoronaviruses that may crossreact with the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) virus. RESULTS: Both IVIGs showed consistent reactivity to components of the tested viruses. Positive crossreactivity was seen in SARS-CoV, middle east respiratory syndrome-CoV and SARS-CoV-2. For SARS-CoV-2, positive reactivity was observed at IVIG concentrations ranging from 100 \u03bcg/ml with Gamunex-C to 1 mg/ml with Flebogamma 5% DIF. CONCLUSION: Gamunex-C and Flebogamma DIF contain antibodies reacting against SARS-CoV-2 antigens. Studies to confirm the utility of IVIG preparations for COVID-19 management may be warranted.", "qid": 33, "docid": "w8wrn9lx", "rank": 63, "score": 0.8333026170730591}, {"content": "Title: Covid-19 and drug therapy, what we learned Content: COVID-19, the disease associated in December 2019 with the novel coronavirus SARS-CoV-2, was observed for the first time in China and then spread worldwide becoming pandemic. Currently, there is still no licensed specific antiviral treatment for the human coronavirus disease and a vaccine will not be ready soon. However, based on experience from the use of other antiviral agents to treat similar virusses, some treatment options have been tried with some efficacy. Clinical trials for future therapies are still ongoing. In the meantime, prevention, control, active communication and investment in research are the only ways to overcome this challenge.", "qid": 33, "docid": "538mkxfu", "rank": 64, "score": 0.8332814574241638}, {"content": "Title: Advice regarding COVID\u201019 and use of immunomodulators, in patients with severe dermatological diseases Content: Coronavirus disease 2019 (COVID-19) is the disease caused by the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), as named by the International Committee on Taxonomy of Viruses (ICTV). There is very limited evidence base to formulate specific advice for dermatology patients on immunomodulators with regards to COVID-19. The following is based on expert opinion, taking into account known risks of influenza (a negative sense single-stranded RNA virus) and other, positive-sense single-stranded, RNA virus infections (such as SARS, MERS, and the common cold). An Australia/New Zealand consensus document is in development.", "qid": 33, "docid": "nfjxp783", "rank": 65, "score": 0.8331426382064819}, {"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": 66, "score": 0.8329173922538757}, {"content": "Title: Current Status of Epidemiology, Diagnosis, Therapeutics, and Vaccines for Novel Coronavirus Disease 2019 (COVID-19) Content: Coronavirus disease 2019 (COVID-19), which causes serious respiratory illness such as pneumonia and lung failure, was first reported in Wuhan, the capital of Hubei, China. The etiological agent of COVID-19 has been confirmed as a novel coronavirus, now known as severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), which is most likely originated from zoonotic coronaviruses, like SARS-CoV, which emerged in 2002. Within a few months of the first report, SARS-CoV-2 had spread across China and worldwide, reaching a pandemic level. As COVID-19 has triggered enormous human casualties and serious economic loss posing global threat, an understanding of the ongoing situation and the development of strategies to contain the virus's spread are urgently needed. Currently, various diagnostic kits to test for COVID-19 are available and several repurposing therapeutics for COVID-19 have shown to be clinically effective. In addition, global institutions and companies have begun to develop vaccines for the prevention of COVID-19. Here, we review the current status of epidemiology, diagnosis, treatment, and vaccine development for COVID-19.", "qid": 33, "docid": "2lxs9laj", "rank": 67, "score": 0.8328605890274048}, {"content": "Title: Current Status of Epidemiology, Diagnosis, Therapeutics, and Vaccines for Novel Coronavirus Disease 2019 (COVID-19). Content: Coronavirus disease 2019 (COVID-19), which causes serious respiratory illness such as pneumonia and lung failure, was first reported in Wuhan, the capital of Hubei, China. The etiological agent of COVID-19 has been confirmed as a novel coronavirus, now known as severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), which is most likely originated from zoonotic coronaviruses, like SARS-CoV, which emerged in 2002. Within a few months of the first report, SARS-CoV-2 had spread across China and worldwide, reaching a pandemic level. As COVID-19 has triggered enormous human casualties and serious economic loss posing global threat, an understanding of the ongoing situation and the development of strategies to contain the virus's spread are urgently needed. Currently, various diagnostic kits to test for COVID-19 are available and several repurposing therapeutics for COVID-19 have shown to be clinically effective. In addition, global institutions and companies have begun to develop vaccines for the prevention of COVID-19. Here, we review the current status of epidemiology, diagnosis, treatment, and vaccine development for COVID-19.", "qid": 33, "docid": "p3681yit", "rank": 68, "score": 0.8328605890274048}, {"content": "Title: The current update of vaccines for SARS-COV-2 Content: Late 2019 witnessed the appearance of coronavirus disease 2019 (COVID-19) outbreak triggered by a new coronavirus, Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2). SARS-CoV-2 spread across China from Wuhan and has been circulated to a broader variety of countries. Seeing that COVID-19 has caused tremendous human casualties posing a global danger, an awareness of the current situation and the strategies to curtail the spread of the virus are desperately required. As the most natural way to preserve public wellbeing, preventive and therapeutic vaccinations must have essential roles. Large organizations and companies have started implementing SARS-CoV-2 preventive vaccinations. Hence, in this study, we aimed to update the vaccine evolution for SARS-CoV-2.", "qid": 33, "docid": "ma5fr966", "rank": 69, "score": 0.8326584696769714}, {"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": 33, "docid": "yzb8pouz", "rank": 70, "score": 0.8320802450180054}, {"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": 33, "docid": "h2xn9n20", "rank": 71, "score": 0.8320802450180054}, {"content": "Title: Evaluation of the EUROIMMUN Anti-SARS-CoV-2 ELISA Assay for detection of IgA and IgG antibodies Content: As the Coronavirus 2019 (COVID-19) pandemic evolves, the development of immunoassays to help determine exposure and potentially predict immunity has become a pressing priority. In this report we present the performance of the EUROIMMUN enzyme-linked immunosorbent assay (ELISA) for semi-quantitative detection of IgA and IgG antibodies in serum and plasma samples using recombinant S1 domain of the SARS-CoV-2 spike protein as antigen. Specimens from patients, with and without COVID-19 infection, were tested at the University of Chicago Clinical Microbiology and Immunology Laboratory. Of 57 samples from COVID-19 PCR-negative patients, including 28 samples positive for common human coronavirus strains, 53 tested negative and 4 tested positive for IgA (93.0% agreement) while 56 tested negative and 1 tested positive for IgG (98.2% agreement). For COVID-19 PCR-positive patients, 29 of 30 (96.7%) samples collected \u22653 days after positive PCR were positive for IgA, and 28 of 28 samples collected \u22654 days after positive PCR were positive for IgG. The EUROIMMUN Anti-SARS-CoV-2 ELISA Assay demonstrates excellent sensitivity for detection of IgA and IgG antibodies from samples collected \u22653 days and \u22654 days, respectively, after COVID-19 diagnosis by PCR. This assay did not demonstrate cross reaction in any of the 28 samples from patients with common human coronaviruses, including types HKU1, NL63, CV229E, and OC43.", "qid": 33, "docid": "jzpwo5un", "rank": 72, "score": 0.8316317796707153}, {"content": "Title: Dengue antibodies can cross-react with SARS-CoV-2 and vice versa-Antibody detection kits can give false-positive results for both viruses in regions where both COVID-19 and Dengue co-exist Content: Five of thirteen Dengue antibody- positive serum samples, dated 2017 (pre-dating the COVID-19 outbreak) produced false-positive results in SARS-CoV-2 IgG/IgM rapid strip tests. Our results emphasize the importance of NAT and/or virus antigen tests to complement sero-surveillance for definitive diagnosis of COVID-19/Dengue in regions where both viruses are co-endemic.", "qid": 33, "docid": "orsbmfbe", "rank": 73, "score": 0.8312115669250488}, {"content": "Title: COVID-19 vaccine design: the Janus face of immune enhancement Content: Previous work on severe acute respiratory syndrome coronavirus (SARS-CoV) vaccines identified cellular immunopathology and antibody-dependent enhancement as potential safety issues. We discuss the implications of these findings for COVID-19 vaccine development and our approach to optimizing for safety and efficacy.", "qid": 33, "docid": "npzri0rh", "rank": 74, "score": 0.8311151266098022}, {"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": 75, "score": 0.8305454254150391}, {"content": "Title: Identification of potential vaccine candidates against SARS-CoV-2, A step forward to fight novel coronavirus 2019-nCoV: A Reverse Vaccinology Approach Content: The recent Coronavirus Disease 2019 (COVID-19) causes an immense health crisis to global public health. The World Health Organization (WHO) declared the COVID-19 as a pandemic. The COVID-19 is the etiologic agent of a recently arose disease caused by the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). Presently, there is no vaccine available against this emerged viral disease. Therefore, it is indeed a need of the hour to develop an effectual and safe vaccine against this decidedly pandemic disease. In the current study, we collected SARS-CoV-2 genome from Indian geographical origin against human host, further more using reverse vaccinology and immunoinformatics tools here we claim effective vaccine candidates that can be mile stone in battle against COVID19. This novel study divulged two promising antigenic peptide GVYFASTEK and NFRVQPTESIV from surface glycoproteins (protein accession no. \u2013 QIA98583.1 and QHS34546.1) of SARS-CoV-2, which were predicated to be interacted with class I and class II MHC alleles and showed up to 90% conservancy and high value of antigenicity. Subsequently, the molecular docking studies were verified molecular interaction of these prime antigenic peptides with the residues of HLA-A*11-01 allele for MHC Class I and HLA DRB1*04-01 allele for MHC class II. After vigorous analysis, these peptides were predicted to be suitable epitopes which are capable to elicit the strong cell-mediated immune response against the SARS-CoV-2. Consequences from the present study could facilitate selecting SARS-CoV-2 epitopes for vaccine production pipelines in the immediate future. This novel research will certainly pave the way for a fast, reliable and virtuous platform to provide timely countermeasure of this dangerous pandemic disease, COVID-19.", "qid": 33, "docid": "sdiwnhs0", "rank": 76, "score": 0.8301331996917725}, {"content": "Title: Antibody Tests in Detecting SARS-CoV-2 Infection: A Meta-Analysis Content: The emergence of Coronavirus disease 2019 (COVID-19) caused by SARS-CoV-2 made imperative the need for diagnostic tests that can identify the infection. Although Nucleic Acid Test (NAT) is considered to be the gold standard, serological tests based on antibodies could be very helpful. However, individual studies are usually inconclusive, thus, a comparison of different tests is needed. We performed a systematic review and meta-analysis in PubMed, medRxiv and bioRxiv. We used the bivariate method for meta-analysis of diagnostic tests pooling sensitivities and specificities. We evaluated IgM and IgG tests based on Enzyme-linked immunosorbent assay (ELISA), Chemiluminescence Enzyme Immunoassays (CLIA), Fluorescence Immunoassays (FIA), and the Lateral Flow Immunoassays (LFIA). We identified 38 studies containing data from 7848 individuals. Tests using the S antigen are more sensitive than N antigen-based tests. IgG tests perform better compared to IgM ones and show better sensitivity when the samples were taken longer after the onset of symptoms. Moreover, a combined IgG/IgM test seems to be a better choice in terms of sensitivity than measuring either antibody alone. All methods yield high specificity with some of them (ELISA and LFIA) reaching levels around 99%. ELISA- and CLIA-based methods perform better in terms of sensitivity (90%\u201394%) followed by LFIA and FIA with sensitivities ranging from 80% to 89%. ELISA tests could be a safer choice at this stage of the pandemic. LFIA tests are more attractive for large seroprevalence studies but show lower sensitivity, and this should be taken into account when designing and performing seroprevalence studies.", "qid": 33, "docid": "3aoxplp3", "rank": 77, "score": 0.8296890258789062}, {"content": "Title: Calcitriol, the active form of vitamin D, is a promising candidate for COVID-19 prophylaxis Content: COVID-19, the disease caused by SARS-CoV-2 (1), was declared a pandemic by the World Health Organization (WHO) in March 2020 (2). While awaiting a vaccine, several antivirals are being used to manage the disease with limited success (3, 4). To expand this arsenal, we screened 4 compound libraries: a United States Food and Drug Administration (FDA) approved drug library, an angiotensin converting enzyme-2 (ACE2) targeted compound library, a flavonoid compound library as well as a natural product library. Of the 121 compounds identified with activity against SARS-CoV-2, 7 were shortlisted for validation. We show for the first time that the active form of Vitamin D, calcitriol, exhibits significant potent activity against SARS-CoV-2. This finding paves the way for consideration of host-directed therapies for ring prophylaxis of contacts of SARS-CoV-2 patients.", "qid": 33, "docid": "sbon3aes", "rank": 78, "score": 0.829651951789856}, {"content": "Title: An Immunoinformatics Study to Predict Epitopes in the Envelope Protein of SARS-COV-2 Content: COVID-19 is a new viral emergent human disease caused by a novel strain of Coronavirus. This virus has caused a huge problem in the world as millions of the people are affected with this disease in the entire world. We aimed to design a peptide vaccine for COVID-19 particularly for the envelope protein using computational methods to predict epitopes inducing the immune system and can be used later to create a new peptide vaccine that could replace conventional vaccines. A total of available 370 sequences of SARS-CoV-2 were retrieved from NCBI for bioinformatics analysis using Immune Epitope Data Base (IEDB) to predict B and T cells epitopes. Then we docked the best predicted CTL epitopes with HLA alleles. CTL cell epitopes namely interacted with MHC class I alleles and we suggested them to become universal peptides based vaccine against COVID-19. Potentially continuous B cell epitopes were predicted using tools from IEDB. The Allergenicity of predicted epitopes was analyzed by AllerTOP tool and the coverage was determined throughout the worlds. We found these CTL epitopes to be T helper epitopes also. The B cell epitope, SRVKNL and T cell epitope, FLAFVVFLL were suggested to become a universal candidate for peptide-based vaccine against COVID-19. We hope to confirm our findings by adding complementary steps of both in vitro and in vivo studies to support this new universal predicted candidate.", "qid": 33, "docid": "ss6g3jkg", "rank": 79, "score": 0.8296249508857727}, {"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": 33, "docid": "xt8tld2i", "rank": 80, "score": 0.8294910192489624}, {"content": "Title: Cross-Protection Induced by Encephalitis Vaccines against COVID-19 Might be a Reason for Relatively Lower Mortality Rate in Some Countries Content: COronaVIrus Disease 2019 (COVID-19) is an on-going pandemic attributed to a novel virus named SARS-CoV-2 Comparing the statistics of incidence and death rates between nations reveals that there is discrepancy amongst countries in these regards, even between countries that share borders We herein present information from the literature indicating how cross-protection against COVID-19 conferred by the encephalitis vaccine could be the reason for lower fatality rate in the countries where immunization against encephalitis is widespread or included in national programs This may pave the way for arriving at efficient prevention strategies as well as vaccine development", "qid": 33, "docid": "rfgogqmu", "rank": 81, "score": 0.829447865486145}, {"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": 33, "docid": "t9jo76ja", "rank": 82, "score": 0.8292492628097534}, {"content": "Title: COVID-19 vaccine development and the way forward Content: The whole globe is reeling under the COVID-19 pandemic now. With the scale and severity of infection, number of deaths and lack of any definite therapeutic armamentarium, the vaccine development has been accelerated at a never-before pace. A wide variety of vaccine technologies and platforms are being attempted. Out of the over 108 efforts, 100 are in preclinical and eight in Phase 1 or 2 trial stage. While the availability of newer technologies has facilitated development, there are several challenges on the way including limited understanding of the pathophysiology, targeting humoral or mucosal immunity, lack of suitable animal model, poor success of human severe acute respiratory syndrome/Middle East Respiratory Syndrome vaccines, limited efficacy of influenza vaccines, and immune exaggeration with animal coronavirus vaccines. With the current scenario with political, funding, research, and regulatory supports, if everything sails through smoothly, the successful vaccine is expected in 12-18 months. Modestly efficacious vaccine may be also a good achievement.", "qid": 33, "docid": "8boyzwxf", "rank": 83, "score": 0.8290955424308777}, {"content": "Title: COVID-19 vaccine development and the way forward. Content: The whole globe is reeling under the COVID-19 pandemic now. With the scale and severity of infection, number of deaths and lack of any definite therapeutic armamentarium, the vaccine development has been accelerated at a never-before pace. A wide variety of vaccine technologies and platforms are being attempted. Out of the over 108 efforts, 100 are in preclinical and eight in Phase 1 or 2 trial stage. While the availability of newer technologies has facilitated development, there are several challenges on the way including limited understanding of the pathophysiology, targeting humoral or mucosal immunity, lack of suitable animal model, poor success of human severe acute respiratory syndrome/Middle East Respiratory Syndrome vaccines, limited efficacy of influenza vaccines, and immune exaggeration with animal coronavirus vaccines. With the current scenario with political, funding, research, and regulatory supports, if everything sails through smoothly, the successful vaccine is expected in 12-18 months. Modestly efficacious vaccine may be also a good achievement.", "qid": 33, "docid": "d51wognj", "rank": 84, "score": 0.8290955424308777}, {"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": 33, "docid": "bah2ege0", "rank": 85, "score": 0.8290060758590698}, {"content": "Title: Towards effective COVID-19 vaccines: Updates, perspectives and challenges (Review) Content: In the current context of the pandemic triggered by SARS-COV-2, the immunization of the population through vaccination is recognized as a public health priority. In the case of SARS-COV-2, the genetic sequencing was done quickly, in one month. Since then, worldwide research has focused on obtaining a vaccine. This has a major economic impact because new technological platforms and advanced genetic engineering procedures are required to obtain a COVID-19 vaccine. The most difficult scientific challenge for this future vaccine obtained in the laboratory is the proof of clinical safety and efficacy. The biggest challenge of manufacturing is the construction and validation of production platforms capable of making the vaccine on a large scale.", "qid": 33, "docid": "0o05oskr", "rank": 86, "score": 0.8288894295692444}, {"content": "Title: A review on Promising vaccine development progress for COVID-19 disease Content: Abstract The emergence of the strain of coronavirus SARS-CoV-2 (severe acute respiratory syndrome coronavirus 2) that causes corona virus disease 2019 (COVID-19) and its impact on in the world have made imperative progress to develop an effective and safe vaccine. Despite several measures undertaken, the spread of this virus is ongoing. So far, more than 1,560,000 cases and 1000,000 deaths occurred in the world. Efforts have been made to develop vaccines against human coronavirus (CoV) infections such as MERS and SARS. However, currently, no approved vaccine exists for these coronavirus strains. Such Previous research efforts to develop a coronavirus vaccine in the years following the 2003 pandemic have opened the door for the scientist to design a new vaccine for the COVID-19. Both SARS-CoV and SARS-CoV-2 has a high degree of genetic similarity and bind to the same host cell ACE2 receptor. By using different vaccine development platforms including whole virus vaccines, recombinant protein subunit vaccines, and nucleic acid vaccines several candidates displayed efficacy in vitro studies but few progressed to clinical trials. This review provides a brief introduction of the general features of SARS-CoV-2 and discusses the current progress of ongoing advances in designing vaccine development efforts to counter COVID-19.", "qid": 33, "docid": "gkcan78j", "rank": 87, "score": 0.8287888765335083}, {"content": "Title: SARS-CoV-2 spike glycoprotein vaccine candidate NVX-CoV2373 elicits immunogenicity in baboons and protection in mice Content: The COVID-19 pandemic continues to spread throughout the world with an urgent need for a safe and protective vaccine to effectuate herd immunity to control the spread of SARS-CoV-2. Here, we report the development of a SARS-CoV-2 subunit vaccine (NVX-CoV2373) produced from the full-length spike (S) protein, stabilized in the prefusion conformation. Purified NVX-CoV2373 S form 27.2nm nanoparticles that are thermostable and bind with high affinity to the human angiotensin-converting enzyme 2 (hACE2) receptor. In mice and baboons, low-dose NVX-CoV2373 with saponin-based Matrix-M adjuvant elicits high titer anti-S IgG that is associated with blockade of hACE2 receptor binding, virus neutralization, and protection against SARS-CoV-2 challenge in mice with no evidence of vaccine-associated enhanced respiratory disease (VAERD). NVX-CoV2373 vaccine also elicits multifunctional CD4+ and CD8+ T cells, CD4+ T follicular helper T cells (Tfh), and the generation of antigen-specific germinal center (GC) B cells in the spleen. These results support the ongoing phase 1/2 clinical evaluation of the safety and immunogenicity of NVX-CoV2327 with Matrix-M (NCT04368988).", "qid": 33, "docid": "2nruf2g7", "rank": 88, "score": 0.8286541104316711}, {"content": "Title: Evaluation of the EUROIMMUN Anti-SARS-CoV-2 ELISA Assay for detection of IgA and IgG antibodies Content: As the Coronavirus 2019 (COVID-19) pandemic evolves, the development of immunoassays to help determine exposure and potentially predict immunity has become a pressing priority. In this report we present the performance of the EUROIMMUN enzyme-linked immunosorbent assay (ELISA) for semi-quantitative detection of IgA and IgG antibodies in serum and plasma samples using recombinant S1 domain of the SARS-CoV-2 spike protein as antigen. Specimens from patients, with and without COVID-19 infection, were tested at the University of Chicago Clinical Microbiology and Immunology Laboratory. Of 86 samples from COVID-19 PCR-negative patients, including 28 samples positive for common human coronavirus strains, 76 tested negative and 10 tested positive for IgA (88.4% agreement, 95% CI: 79.9\u201393.6) while 84 tested negative and 2 tested positive for IgG (97.7% agreement, 95% CI: 91.9\u201399.6). Of 82 samples from COVID-19 PCR-positive patients, 14 tested negative and 68 tested positive for IgA (82.9% agreement, 95% CI: 73.4\u201389.5) while 27 tested negative and 55 tested positive for IgG (67.1% agreement, 95% CI: 56.3\u201376.3). Samples collected \u22654 days after positive PCR 38 of 42 (90.5% CI: 77.9\u201396.2) were positive for IgA, and 42 of 42 (100% 95% CI: 91.6\u2013100) were positive for IgG, respectively. The EUROIMMUN Anti-SARS-CoV-2 ELISA Assay demonstrates good sensitivity for detection of IgA and excellent sensitivity for detection of IgG antibodies from samples collected \u22654 days, after COVID-19 diagnosis by PCR. This assay demonstrated only borderline cross reaction in 2 of the 28 samples from patients with common human coronaviruses infection, types NL63 and OC43.", "qid": 33, "docid": "n3lrzw3o", "rank": 89, "score": 0.8285884857177734}, {"content": "Title: RT-qPCR Testing of SARS-CoV-2: A Primer Content: Testing for the presence of coronavirus is an essential diagnostic tool for monitoring and managing the current COVID-19 pandemic. The only reliable test in current use for testing acute infection targets the genome of SARS-CoV-2, and the most widely used method is quantitative fluorescence-based reverse transcription polymerase chain reaction (RT-qPCR). Despite its ubiquity, there is a significant amount of uncertainty about how this test works, potential throughput and reliability. This has resulted in widespread misrepresentation of the problems faced using this test during the current COVID-19 epidemic. This primer provides simple, straightforward and impartial information about RT-qPCR.", "qid": 33, "docid": "td2r7xm1", "rank": 90, "score": 0.828262209892273}, {"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": 91, "score": 0.828193187713623}, {"content": "Title: Intention to participate in a COVID-19 vaccine clinical trial and to get vaccinated against COVID-19 in France during the pandemic Content: Background: The world is facing the COVID-19 pandemic. Development of vaccine is challenging. Aim: To determine the proportion of people who intend to get vaccinated against COVID-19 in France or to participate in a vaccine clinical trial. Methods: We conducted an anonymous on-line survey from the 26th of March to the 20th of April 2020. Primary endpoints were the intention to get vaccinated against COVID-19 if a vaccine was available or participate in a vaccine clinical trial. Results: Three thousand two hundred and fifty nine individuals answered the survey; women accounted for 67.4 % of the responders, 670 (20.6 %) were under 30 years of age, 1,502 (46.1 %) between 30-49 years, 803 (24.6 %) between 50-64 years, 271 (8.3%) between 65-80 years, 13 (0.4%) over 80 years of age. According to their statements, 2.512 participants (77.6%, 95 % CI 76.2-79 %) will certainly or probably agree to get vaccinated against COVID-19. Older age, male gender, fear about COVID-19, being healthcare workers and individual perceived risk were associated with COVID-19 vaccine acceptance Vaccine hesitancy was associated with a decrease in COVID-19 vaccine acceptance. One thousand and five hundred and fifty responders (47.6 % 95 % CI 45.9-49.3 %) will certainly or probably agree to participate in a COVID-19 vaccine clinical trial. Conclusions and Relevance: Nearly 75 % and 48 % of the survey responders were likely to accept vaccination or participation in a clinical trial against COVID-19. Vaccine hesitancy will be the major barrier to COVID-19 vaccine uptake.", "qid": 33, "docid": "sribl7kt", "rank": 92, "score": 0.828073263168335}, {"content": "Title: Evaluation of the EUROIMMUN Anti-SARS-CoV-2 ELISA Assay for detection of IgA and IgG antibodies Content: As the Coronavirus 2019 (COVID-19) pandemic evolves, the development of immunoassays to help determine exposure and potentially predict immunity has become a pressing priority. In this report we present the performance of the EUROIMMUN enzyme-linked immunosorbent assay (ELISA) for semi-quantitative detection of IgA and IgG antibodies in serum and plasma samples using recombinant S1 domain of the SARS-CoV-2 spike protein as antigen. Specimens from patients, with and without COVID-19 infection, were tested at the University of Chicago Clinical Microbiology and Immunology Laboratory. Of 86 samples from SARS-CoV-2 PCR-negative patients, including 28 samples positive for common human coronavirus strains, 76 tested negative and 10 tested positive for IgA (88.4% agreement, 95% CI: 79.9-93.6) while 84 tested negative and 2 tested positive for IgG (97.7% agreement, 95% CI: 91.9-99.6). Of 82 samples from SARS-CoV-2 PCR-positive patients, 14 tested negative and 68 tested positive for IgA (82.9% agreement, 95% CI: 73.4-89.5) while 27 tested negative and 55 tested positive for IgG (67.1% agreement, 95% CI: 56.3-76.3). Of samples collected &#8805;4 days after positive PCR, 38 of 42 (90.5% agreement, 95% CI: 77.9-96.2) were positive for IgA, and 42 of 42 (100% agreement, 95% CI: 91.6-100) were positive for IgG, respectively. The EUROIMMUN Anti-SARS-CoV-2 ELISA Assay demonstrated good sensitivity for detection of IgA and excellent sensitivity for detection of IgG antibodies from samples collected &#8805;4 days, after COVID-19 diagnosis by PCR. This assay demonstrated good specificity for IgA and excellent specificity for IgG and demonstrated only borderline cross reaction in 2 of the 28 samples from patients with common human coronaviruses infection, types NL63 and OC43.", "qid": 33, "docid": "nbqxy846", "rank": 93, "score": 0.8278246521949768}, {"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": 94, "score": 0.8276985883712769}, {"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": 33, "docid": "82iy2prw", "rank": 95, "score": 0.827685534954071}, {"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": 33, "docid": "84yjdlab", "rank": 96, "score": 0.8276853561401367}, {"content": "Title: From SARS-CoV to SARS-CoV-2: safety and broad-spectrum are important for coronavirus vaccine development Content: The global pandemic of COVID-19 caused by SARS-CoV-2 (also known as 2019-nCoV and HCoV-19) has posed serious threats to public health and economic stability worldwide, thus calling for development of vaccines against SARS-CoV-2 and other emerging and reemerging coronaviruses. Since SARS-CoV-2 and SARS-CoV have high similarity of their genomic sequences and share the same cellular receptor (ACE2), it is essential to learn the lessons and experiences from the development of SARS-CoV vaccines for the development of SARS-CoV-2 vaccines. In this review, we summarized the current knowledge on the advantages and disadvantages of the SARS-CoV vaccine candidates and prospected the strategies for the development of safe, effective and broad-spectrum coronavirus vaccines for prevention of infection by currently circulating SARS-CoV-2 and other emerging and reemerging coronaviruses that may cause future epidemics or pandemics.", "qid": 33, "docid": "8zzi6gu9", "rank": 97, "score": 0.8275984525680542}, {"content": "Title: Countdown to a vaccine Content: More than 100 coronavirus vaccines are in development, but will any of them work?", "qid": 33, "docid": "wrgyeng3", "rank": 98, "score": 0.827548086643219}, {"content": "Title: Performance of six SARS-CoV-2 immunoassays in comparison with microneutralisation Content: There is an urgent need for reliable high-throughput serological assays for the management of the ongoing COVID-19 pandemic. Preferably, the performance of serological tests for a novel virus should be determined with clinical specimens against a gold standard, i.e. virus neutralisation. We evaluated specificity and sensitivity of six commercial immunoassays for the detection of SARS-CoV-2 IgG, IgA and IgM antibodies, including four automated assays [Abbott SARS-COV-2 IgG (CE marked), Diasorin Liaison SARS-CoV-2 S1/S2 IgG (research use only), and Euroimmun SARS-CoV-2 IgG and IgA (CE marked)], and two rapid lateral flow (immunocromatographic) tests [Acro Biotech 2019-nCoV IgG/IgM (CE marked) and Xiamen Biotime Biotechnology SARS-CoV-2 IgG/IgM (CE marked)] in comparison with a microneutralisation test (MNT). Two specimen panels from serum samples sent to Helsinki University Hospital Laboratory (HUSLAB) were compiled: the patient panel included sera from PCR confirmed COVID-19 patients, and the negative panel included sera sent for screening of autoimmune diseases and respiratory virus antibodies in 2018 and 2019. The MNT was carried out for all COVID-19 samples (70 serum samples, 62 individuals) and for 53 samples from the negative panel. Forty-one out of 62 COVID-19 patients showed neutralising antibodies with median of 11 days (range 3-51) after onset of symptoms. The specificity and sensitivity values of the commercial tests against MNT, respectively, were as follows: 95.1%/80.5% (Abbott Architect SARS-CoV-2 IgG), 94.9%/43.8% (Diasorin Liaison SARS-CoV-2 IgG), 68.3%/87.8% (Euroimmun SARS-CoV-2 IgA), 86.6%/70.7% (Euroimmun SARS-CoV-2 IgG), 74.4%/56.1% (Acro 2019-nCoV IgG), 69.5%/46.3% (Acro 2019-nCoV IgM), 97.5%/71.9% (Xiamen Biotime SARS-CoV-2 IgG), and 88.8%/81.3% (Xiamen Biotime SARS-CoV-2 IgM). This study shows variable performance values. Laboratories should carefully consider their testing process, such as a two-tier approach, in order to optimize the overall performance of SARS-CoV-2 serodiagnostics.", "qid": 33, "docid": "hb2bpyag", "rank": 99, "score": 0.8274821639060974}, {"content": "Title: COVID-19, an emerging coronavirus infection: advances and prospects in designing and developing vaccines, immunotherapeutics, and therapeutics Content: The novel coronavirus infection (COVID-19 or Coronavirus disease 2019) that emerged from Wuhan, Hubei province of China has spread to many countries worldwide. Efforts have been made to develop vaccines against human coronavirus (CoV) infections such as MERS and SARS in the past decades. However, to date, no licensed antiviral treatment or vaccine exists for MERS and SARS. Most of the efforts for developing CoV vaccines and drugs target the spike glycoprotein or S protein, the major inducer of neutralizing antibodies. Although a few candidates have shown efficacy in in vitro studies, not many have progressed to randomized animal or human trials, hence may have limited use to counter COVID-19 infection. This article highlights ongoing advances in designing vaccines and therapeutics to counter COVID-19 while also focusing on such experiences and advances as made with earlier SARS- and MERS-CoVs, which together could enable efforts to halt this emerging virus infection.", "qid": 33, "docid": "ooboeurk", "rank": 100, "score": 0.8273104429244995}]}
{"query": "What are the longer-term complications of those who recover from COVID-19?", "hits": [{"content": "Title: Long term complications and rehabilitation of COVID-19 patients Content: With the ongoing pandemic of COVID-19 having caught the world almost unaware millions of people across the globe are presently grappling to deal with its acute effects . Our previous experience with members of the same corona virus family (SARS and MERS) which have caused two major epidemics in the past albeit of much lower magnitude , has taught us that the harmful effect of such outbreaks are not limited to acute complications alone .Long term cardiopulmonary, glucometabolic and neuropsychiatric complications have been documented following these infections .In the given circumstance it is therefore imperative to keep in mind the possible complications that may occur after the acute phase of the disease subsides and to prepare the healthcare system for such challenges.", "qid": 34, "docid": "yudrouue", "rank": 1, "score": 0.8823562264442444}, {"content": "Title: Long term complications and rehabilitation of COVID-19 patients. Content: With the ongoing pandemic of COVID-19 having caught the world almost unaware millions of people across the globe are presently grappling to deal with its acute effects . Our previous experience with members of the same corona virus family (SARS and MERS) which have caused two major epidemics in the past albeit of much lower magnitude , has taught us that the harmful effect of such outbreaks are not limited to acute complications alone .Long term cardiopulmonary, glucometabolic and neuropsychiatric complications have been documented following these infections .In the given circumstance it is therefore imperative to keep in mind the possible complications that may occur after the acute phase of the disease subsides and to prepare the healthcare system for such challenges.", "qid": 34, "docid": "7s04ygm2", "rank": 2, "score": 0.8823562264442444}, {"content": "Title: La r\u00e9habilitation: indispensable pour les survivants d'un COVID-19 s\u00e9v\u00e8re./ [Rehabilitation is crucial for severe COVID-19 survivors] Content: COVID-19 survivors can have serious complications from this viral infection, particularly respiratory and cardiovascular with severe asthenia and fatigue. Several studies have already demonstrated the benefit of early rehabilitation after the acute phase, especially in patients who have been in intensive care. The authors present a rehabilitation program including interdisciplinary care with simple and reproducible clinical criteria.", "qid": 34, "docid": "6ztf2n5w", "rank": 3, "score": 0.8727734088897705}, {"content": "Title: [Rehabilitation is crucial for severe COVID-19 survivors]. Content: COVID-19 survivors can have serious complications from this viral infection, particularly respiratory and cardiovascular with severe asthenia and fatigue. Several studies have already demonstrated the benefit of early rehabilitation after the acute phase, especially in patients who have been in intensive care. The authors present a rehabilitation program including interdisciplinary care with simple and reproducible clinical criteria.", "qid": 34, "docid": "jud53dmv", "rank": 4, "score": 0.8727734088897705}, {"content": "Title: Disability through COVID-19 pandemic: Neurorehabilitation cannot wait Content: Coronavirus disease 2019 (CoViD-19) pandemic is strongly impacting all domains of our healthcare systems, including rehabilitation. In Italy, the first hit European country, medical activities were postponed to allow shifting of staff and facilities to intensive care, with neurorehabilitation limited to time-dependent diseases,1 including CoViD-19 complications.2,3 Hospital access to people with chronic neurodegenerative conditions such as multiple sclerosis, movement disorders or dementia, more at risks of serious consequences from the infection,4 has been postponed. Patients also seek less for hospital care, with over 50% reduced stroke admissions as from an Italian survey,5 possibly in fear of being infected or denied to see their families after being hospitalized. This situation can be bearable only for a short time, as any initial freezing reaction to a danger.", "qid": 34, "docid": "j52uiz01", "rank": 5, "score": 0.8591567873954773}, {"content": "Title: LONG-TERM CLINICAL OUTCOMES IN SURVIVORS OF CORONAVIRUS OUTBREAKS AFTER HOSPITALISATION OR ICU ADMISSION: A SYSTEMATIC REVIEW AND META-ANALYSIS OF FOLLOW-UP STUDIES Content: Objective: To determine the long-term clinical problems in adult survivors of coronavirus (CoV) infection [Coronavirus disease 2019 (COVID-19), Severe Acute Respiratory Syndrome (SARS) and Middle East Respiratory Syndrome (MERS)] after hospitalisation or Intensive Care Unit (ICU) admission. Design: Systematic review and meta-analysis of the literature. Data sources: Ovid MEDLINE, EMBASE, CINAHL Plus and PsycINFO were searched using the strategy: (Coronavirus OR Coronavirus Infections OR COVID OR SARS virus OR Severe acute respiratory syndrome OR MERS OR Middle east respiratory syndrome) AND (Follow-up OR Follow-up studies OR Prevalence). Original studies reporting the clinical outcomes of adult survivors of coronavirus outbreaks two months after discharge or three months after admission were included. The quality of the studies was assessed using the Oxford Centre for Evidence-Based Medicine (OCEBM) 2009 Level of Evidence Tool. Meta-analysis was conducted to derive pooled estimates of prevalence and severity for different outcomes at time points up to 6 months follow-up and beyond 6 months follow-up. Results: The search yielded 1169 studies of which 28 were included in this review. There were 15 Level 1b, 8 Level 2b, 2 Level 3b and 3 Level 4 studies by OCEBM grading. Pooled analysis of studies revealed that complications commonly observed were impaired diffusing capacity for carbon monoxide (DLCO) [prevalence of 27.26%, 95% CI 14.87 to 44.57] and reduced exercise capacity [(6-minute walking distance (6MWD) mean 461m, 95% CI 449.66 to 472.71] at 6 months with limited improvement beyond 6 months. Coronavirus survivors had considerable prevalence of psychological disorders such as post-traumatic stress disorder (PTSD) [38.80%, CI 30.93 to 47.31], depression [33.20%, CI 19.80 to 50.02] and anxiety [30.04%, CI 10.44 to 61.26) beyond 6 months. These complications were accompanied by low Short Form 36 (SF-36) scores at 6 months and beyond indicating reduced quality of life which is present long-term. Conclusions: The long term clinical problems in survivors of CoV infections (SARS and MERS) after hospitalisation or Intensive Care Unit (ICU) admission include respiratory dysfunction, reduced exercise capacity, psychological problems such as PTSD, depression and anxiety, and reduced quality of life. Critical care, rehabilitation and mental health services should anticipate a high prevalence of these problems following COVID-19 and ensure their adequate and timely management with the aim of restoring premorbid quality of life.", "qid": 34, "docid": "bzc7luwj", "rank": 6, "score": 0.8549642562866211}, {"content": "Title: Patient Follow-up after Discharge after COVID-19 Pneumonia: Considerations for Infectious Control Content: Coronavirus disease 2019 (COVID-19) represents a significant global medical issue, with a growing number of cumulative confirmed cases. However, a large number of COVID-19 patients have overcome the disease, meeting hospital discharge criteria, and are gradually returning to work and social life. Nonetheless, COVID-19 may cause further downstream issues in these patients, such as due to possible reactivation of the virus, long-term pulmonary defects, and post-traumatic stress disorder. In this study, we therefore queried relevant literature concerning SARS, MERS, and COVID-19 for reference to come to a consensus on follow-up strategies. We found that strategies such as implementation of PCR testing, imaging surveillance, and psychological assessments, starting at the time of discharge, were necessary for long-term follow-up. If close care is given to every aspect of coronavirus management, we expect that the pandemic outbreak will soon be overcome. This article is protected by copyright. All rights reserved.", "qid": 34, "docid": "x7rzvmcr", "rank": 7, "score": 0.8549342751502991}, {"content": "Title: Risk Factors Associated With Long-Term Hospitalization in Patients With COVID-19: A Single-Centered, Retrospective Study Content: Background: The coronavirus disease 19 (COVID-19) pandemic has become a global threat. Few studies have explored the risk factors for the recovery time of patients with COVID-19. This study aimed to explore risk factors associated with long-term hospitalization in patients with COVID-19. Methods: In this retrospective study, patients with laboratory-confirmed COVID-19 hospitalized in a hospital in Wuhan by March 30, 2020, were included. Demographic, clinical, laboratory, and radiological data from COVID-19 patients on hospital admission were extracted and were compared between the two groups, defined as short- and long-term hospitalization, respectively according to the median hospitalization time. Univariable and multivariable logistic regression methods were performed to identify risk factors associated with long-term hospitalization in patients with COVID-19. Results: A total of 125 discharged patients with COVID-19 were reviewed, including 123 general patients and two severe patients. The median hospitalization time was 13.0 days (IQR 10.0\u201317.0). Among them, 66 patients were discharged <14 days (short-term group) and 59 patients were discharged \u226514 days (long-term group). Compared with the short-term group, patients in the long-term group had significantly higher levels of C-reactive protein (P = 0.000), troponin I (P = 0.002), myoglobin (P = 0.037), aspartate aminotransferase (P = 0.005), lactic dehydrogenase (P = 0.000), prothrombin time (P = 0.030), fibrinogen (P = 0.000), and D-dimer (P = 0.006), but had significantly lower levels of lymphocyte count (P = 0.001), platelet count (P = 0.017), albumin (P = 0.001), and calcium (P = 0.000). Additionally, the incidences of hypocalcemia (P = 0.001), hyponatremia (P = 0.021), hypochloremia (P = 0.019), and bilateral pneumonia (P = 0.000) in the long-term group were significantly higher than those in the short-term group. Multivariable regression showed that hypocalcemia (P = 0.007, OR 3.313, 95% CI 1.392\u20137.886), hypochloremia (P = 0.029, OR 2.663, 95% CI 1.104\u20136.621), and bilateral pneumonia (P = 0.009, OR 5.907, 95% CI 1.073\u201332.521) were independent risk factors associated with long-term hospitalization in patients with COVID-19. Furthermore, a ROC curve where the area under the ROC was 0.766 for retained variables is presented. Conclusions: Hypocalcemia, hypochloremia, and bilateral pneumonia on hospital admission were independent risk factors associated with long-term hospitalization in patients with COVID-19. To the best of our knowledge, this is the first study to highlight the importance of electrolyte imbalance in predicting the hospitalization time of patients with COVID-19.", "qid": 34, "docid": "xzpqxwr2", "rank": 8, "score": 0.8548320531845093}, {"content": "Title: What if the worst consequences of COVID-19 concerned non-COVID patients? Content: We highlight in this short article the side-effects of COVID-19 pandemic on the management of non-COVID patients, with potential detrimental and irreversible complications. We thus propose adjusted strategies to deal with both COVID and non-COVID patients.", "qid": 34, "docid": "bi7hy7pk", "rank": 9, "score": 0.8535656929016113}, {"content": "Title: Thromboinflammation and the hypercoagulability of COVID-19. Content: The pathogenic coronavirus has been wreaking havoc worldwide since January. Infection with SARS-CoV-2 is problematic as no one has prior immunity, and no specific antiviral treatments are available. While many people with COVID-19 develop mild to moderate symptoms, some develop profound seemingly unchecked inflammatory responses leading to acute lung injury and hypoxemic respiratory failure, the most common cause for death.", "qid": 34, "docid": "svwkcuxf", "rank": 10, "score": 0.8533391952514648}, {"content": "Title: COVID-19 in older adults: clinical, psychosocial, and public health considerations. Content: Complications of COVID-19 have been particularly severe among older adults, who are the focus of this article. Public policy goals should prioritize pandemic preparedness in nursing homes, as well as civic and local government-based support programs for community-dwelling older adults, to ensure that risk of infection is mitigated while promoting wellness during a period of stress and uncertainty.", "qid": 34, "docid": "zg6v74l9", "rank": 11, "score": 0.8528941869735718}, {"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": 12, "score": 0.851425051689148}, {"content": "Title: SARS-CoV-2 and Guillain-Barr\u00e9 syndrome: AIDP variant with favorable outcome Content: The entire world has been experiencing the outbreak of a novel infectious agent known as severe acute respiratory syndrome corona virus 2 (SARS-CoV-2), which is responsible for the coronavirus disease 19 (COVID-19)1 . Life-threatening complications described in SARS-CoV-2 infected patients include acute respiratory distress syndrome, acute kidney failure and cardiac injury2 . Nonetheless, only few neurological complications have been described so far3 .", "qid": 34, "docid": "xui1famo", "rank": 13, "score": 0.8514209985733032}, {"content": "Title: COVID-19 and lung transplant patients Content: COVID-19 is a novel respiratory disease leading to high rates of acute respiratory failure requiring hospital admission. It is unclear if specific patient populations such as lung transplant patients are at higher risk for COVID-19. Some reports suggest that transplant patients may not be at higher risk if proper social distancing and preventive measures are employed. Efforts to ensure the safety of wait-listed patients, transplant recipients, and healthcare workers are underway. Recommendations for the care of lung transplant patients during the COVID-19 pandemic are discussed and will likely change as the pandemic evolves.", "qid": 34, "docid": "cwz7dojg", "rank": 14, "score": 0.8513411283493042}, {"content": "Title: COVID-19 and lung transplant patients. Content: COVID-19 is a novel respiratory disease leading to high rates of acute respiratory failure requiring hospital admission. It is unclear if specific patient populations such as lung transplant patients are at higher risk for COVID-19. Some reports suggest that transplant patients may not be at higher risk if proper social distancing and preventive measures are employed. Efforts to ensure the safety of wait-listed patients, transplant recipients, and healthcare workers are underway. Recommendations for the care of lung transplant patients during the COVID-19 pandemic are discussed and will likely change as the pandemic evolves.", "qid": 34, "docid": "48ouatnf", "rank": 15, "score": 0.8513411283493042}, {"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": 34, "docid": "mez1k8t0", "rank": 16, "score": 0.8512370586395264}, {"content": "Title: Rehabilitation management of patients with COVID-19. Lessons learned from the first experiences in China Content: Corona virus disease 2019 (COVID-19) is a new disease characterized by lung damage and involvement in multiple tissues and organs in the whole body. Some of the patients may have long-term impairment and dysfunctions, including pulmonary fibrosis, heart, liver, kidney, nerve and immune system. Rehabilitation has certain beneficial effect in the acute stage, and especially in the recovery stage, including improving respiratory function, exercise endurance, self-care in daily living activities, as well as psychological support, etc. Rehabilitation is not offside or absent. A reasonable rehabilitation program needs scientific research to avoid arbitrary conclusions.", "qid": 34, "docid": "i1i8ab07", "rank": 17, "score": 0.8506871461868286}, {"content": "Title: Effect and enlightenment of rehabilitation medicine in COVID-19 management. Content: Corona virus disease 2019 (COVID-19) is a new disease characterized by lung damage and involvement in multiple tissues and organs in the whole body. Some of the patients may have long-term impairment and dysfunctions, including pulmonary fibrosis, heart, liver, kidney, nerve and immune system. Rehabilitation has certain beneficial effect in the acute stage, and especially in the recovery stage, including improving respiratory function, exercise endurance, self-care in daily living activities, as well as psychological support, etc. Rehabilitation is not offside or absent. A reasonable rehabilitation program needs scientific research to avoid arbitrary conclusions.", "qid": 34, "docid": "0354z6wh", "rank": 18, "score": 0.8506871461868286}, {"content": "Title: Prognostic Factors for Adverse Outcomes in COVID-19 Infection Content: Whilst COVID-19 infection generally run a mild course in up to 80% of those affected, a number of pre-existing co-morbidities determine the severity of infection and the outcome in an individual patient. The most important of these co-morbidities that have consistently emerged in studies from across the globe, are the patients age and sex. Other important co-morbidities that adversely affect outcomes include pre-existing diabetes, obesity, hypertension, chronic lung disease and malignancy. This comprehensive review discusses the impact of these co-morbidities and the role of laboratory predictors of poor patient outcomes.", "qid": 34, "docid": "pebhhmz3", "rank": 19, "score": 0.8504400253295898}, {"content": "Title: Prognostic Factors for Adverse Outcomes in COVID-19 Infection. Content: Whilst COVID-19 infection generally run a mild course in up to 80% of those affected, a number of pre-existing co-morbidities determine the severity of infection and the outcome in an individual patient. The most important of these co-morbidities that have consistently emerged in studies from across the globe, are the patients age and sex. Other important co-morbidities that adversely affect outcomes include pre-existing diabetes, obesity, hypertension, chronic lung disease and malignancy. This comprehensive review discusses the impact of these co-morbidities and the role of laboratory predictors of poor patient outcomes.", "qid": 34, "docid": "vcoqptfx", "rank": 20, "score": 0.8504400253295898}, {"content": "Title: The War on COVID-19 Pandemic: Role of Rehabilitation Professionals and Hospitals Content: The global outbreak of coronavirus disease (COVID-19) has created an unprecedented challenge to the society. Currently, the United States stands as the most affected country, and the entire healthcare system is affected, from emergency department, intensive care unit, post-acute care, outpatient, to home care. Considering the debility, neurological, pulmonary, neuromuscular and cognitive complications, rehabilitation professionals can play an important role in the recovery process for individuals with COVID-19. Clinicians across the nation\u2019s rehabilitation system have already begun working to initiate intensive care unit-based rehabilitation care and develop programs, settings and specialized care to meet the short- and long-term needs of these individuals. We describe the anticipated rehabilitation demands, and the strategies to meet the needs of this population. The complications from COVID-19 can be reduced by (1) delivering interdisciplinary rehabilitation that is initiated early and continued throughout the acute hospital stay, (2) providing patient/family education for self-care after discharge from inpatient rehabilitation at either acute or subacute settings, and (3) continuing rehabilitation care in the outpatient setting, and at home through ongoing therapy either in-person or via telehealth.", "qid": 34, "docid": "f09fxnk9", "rank": 21, "score": 0.8503841161727905}, {"content": "Title: COVID-19 pandemic and mental health consequences: systematic review of the current evidence Content: BACKGROUND: During the COVID-19 pandemic general medical complications have received the most attention, whereas only few studies address the potential direct effect on mental health of SARS-CoV-2 and the neurotropic potential. Furthermore, the indirect effects of the pandemic on general mental health are of increasing concern, particularly since the SARS-CoV-1 epidemic (2002-2003) was associated with psychiatric complications. METHODS: We systematically searched the database Pubmed including studies measuring psychiatric symptoms or morbidities associated with COVID-19 among infected patients and among none infected groups the latter divided in psychiatric patients, health care workers and non-health care workers. RESULTS: A total of 43 studies were included. Out of these, only two studies evaluated patients with confirmed COVID-19 infection, whereas 41 evaluated the indirect effect of the pandemic (2 on patients with preexisting psychiatric disorders, 20 on medical health care workers, and 19 on the general public). 18 of the studies were case-control studies/compared to norm, while 25 of the studies had no control groups. The two studies investigating COVID-19 patients found a high level of post-traumatic stress symptoms (PTSS) (96.2%) and significantly higher level of depressive symptoms (p=0.016). Patients with preexisting psychiatric disorders reported worsening of psychiatric symptoms. Studies investigating health care workers found increased depression/depressive symptoms, anxiety, psychological distress and poor sleep quality. Studies of the general public revealed lower psychological well-being and higher scores of anxiety and depression compared to before COVID-19, while no difference when comparing these symptoms in the initial phase of the outbreak to four weeks later. A variety of factors were associated with higher risk of psychiatric symptoms and/or low psychological well-being including female gender, poor-self-related health and relatives with COVID-19. CONCLUSION: Research evaluating the direct neuropsychiatric consequences and the indirect effects on mental health is highly needed to improve treatment, mental health care planning and for preventive measures during potential subsequent pandemics.", "qid": 34, "docid": "019rcbpg", "rank": 22, "score": 0.8500274419784546}, {"content": "Title: COVID-19 pandemic and mental health consequences: Systematic review of the current evidence Content: BACKGROUND: During the COVID-19 pandemic general medical complications have received the most attention, whereas only few studies address the potential direct effect on mental health of SARS-CoV-2 and the neurotropic potential. Furthermore, the indirect effects of the pandemic on general mental health are of increasing concern, particularly since the SARS-CoV-1 epidemic (2002-2003) was associated with psychiatric complications. METHODS: We systematically searched the database Pubmed including studies measuring psychiatric symptoms or morbidities associated with COVID-19 among infected patients and among none infected groups the latter divided in psychiatric patients, health care workers and non-health care workers. RESULTS: A total of 43 studies were included. Out of these, only two studies evaluated patients with confirmed COVID-19 infection, whereas 41 evaluated the indirect effect of the pandemic (2 on patients with preexisting psychiatric disorders, 20 on medical health care workers, and 19 on the general public). 18 of the studies were case-control studies/compared to norm, while 25 of the studies had no control groups. The two studies investigating COVID-19 patients found a high level of post-traumatic stress symptoms (PTSS) (96.2%) and significantly higher level of depressive symptoms (p = 0.016). Patients with preexisting psychiatric disorders reported worsening of psychiatric symptoms. Studies investigating health care workers found increased depression/depressive symptoms, anxiety, psychological distress and poor sleep quality. Studies of the general public revealed lower psychological well-being and higher scores of anxiety and depression compared to before COVID-19, while no difference when comparing these symptoms in the initial phase of the outbreak to four weeks later. A variety of factors were associated with higher risk of psychiatric symptoms and/or low psychological well-being including female gender, poor-self-related health and relatives with COVID-19. CONCLUSION: Research evaluating the direct neuropsychiatric consequences and the indirect effects on mental health is highly needed to improve treatment, mental health care planning and for preventive measures during potential subsequent pandemics.", "qid": 34, "docid": "0jfwzfge", "rank": 23, "score": 0.8500274419784546}, {"content": "Title: Building a COVID-19 Vulnerability Index Content: COVID-19 is an acute respiratory disease that has been classified as a pandemic by the World Health Organization. Information regarding this particular disease is limited, however, it is known to have high mortality rates, particularly among individuals with preexisting medical conditions. Creating models to identify individuals who are at the greatest risk for severe complications due to COVID-19 will be useful to help for outreach campaigns in mitigating the diseases worst effects. While information specific to COVID-19 is limited, a model using complications due to other upper respiratory infections can be used as a proxy to help identify those individuals who are at the greatest risk. We present the results for three models predicting such complications, with each model having varying levels of predictive effectiveness at the expense of ease of implementation.", "qid": 34, "docid": "37dadupn", "rank": 24, "score": 0.8499612808227539}, {"content": "Title: Poor outcome and prolonged persistence of SARS-CoV-2 RNA in COVID-19 patients with haematological malignancies; King's College Hospital experience Content: Severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2), emerged at the end of 2019 and caused an infection named COVID-19 (Guan, Ni et al. 2020). Patients with compromised immune systems are at increased risk of complications but this risk is not precisely defined (Liang, Guan et al. 2020). Although age, gender, comorbidities and ethnicity are risk factors for adverse outcomes (Huang, Wang et al. 2020), various pre-existing conditions, including haematological cancers, have also been reported to correlate with poor outcomes (Aries, Davies et al. 2020, He, Chen et al. 2020, Malard, Genthon et al. 2020, Martin-Moro, Marquet et al. 2020, medRxiv 2020).", "qid": 34, "docid": "l1odoy1l", "rank": 25, "score": 0.8498795032501221}, {"content": "Title: Epidemiology of CoVID-19 and predictors of recovery in the Republic of Korea Content: Background: The recent CoVID-19 pandemic has emerged as a threat to global health. Though current evidence on the epidemiology of the disease is emerging, very little is known about the predictors of recovery. We describe the epidemiology of confirmed CoVID-19 patients in Republic of Korea and identify predictors of recovery. Materials and methods: Using publicly available data for confirmed CoVID-19 cases from the Korea Centers for Disease Control and Prevention from January 20, 2020 to April 30, 2020, we undertook descriptive analyses of cases stratified by sex, age group, place of exposure, date of confirmation and province. Correlation was tested among all predictors (sex, age group, place of exposure and province) with the Pearsons correlation coefficient. Associations between recovery from CoVID-19 and predictors were estimated using a multivariable logistic regression model. Results: Majority of the confirmed cases were females (56 percent), from 20-29 age group (24.3 percent), and primarily from three provinces Gyeongsangbuk (36.9 percent), Gyeonggi (20.5 percent) and Seoul (17.1 percent). Case fatality ratio was 2.1 percent and 41.6 percent cases recovered. Older patients, patients from certain provinces such as Daegu, Gyeonggi, Gyeongsangbuk, Jeju, Jeollabuk and Jeollanam, and those contracting the disease from healthcare settings had lower recovery. Conclusions: Our study adds to the very limited evidence base on potential predictors of recovery among confirmed CoVID-19 cases. We call additional research to explore the predictors of recovery and support development of policies to protect the vulnerable patient groups.", "qid": 34, "docid": "nmpppztq", "rank": 26, "score": 0.8498530387878418}, {"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": 34, "docid": "s6oi477q", "rank": 27, "score": 0.8493542075157166}, {"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": 34, "docid": "4n2xmx2w", "rank": 28, "score": 0.8493542075157166}, {"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": 34, "docid": "tu36aisz", "rank": 29, "score": 0.8489410877227783}, {"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": 34, "docid": "qt02t6tf", "rank": 30, "score": 0.8489410877227783}, {"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": 31, "score": 0.8487340807914734}, {"content": "Title: The Role of Data Registries in the Time of COVID-19. Content: On April 1, 2020, the confirmed global burden of COVID-19 was more than 900,000 with 46,413 deaths. Despite worldwide calls for social distancing and containment, the incidence of the disease continues to increase. COVID-19 is a respiratory tract infection caused by the novel coronavirus (SARS-CoV2). Preliminary analyses from the Chinese Center for Disease Control and Prevention indicated an overall case fatality rate (CFR) of 2.3%; however the CFR was higher in older adults (14.8% in those 80\u00b1 years) and 49% of all critical cases. Those with preexisting conditions (cardiovascular disease (CVD), diabetes, chronic respiratory disease, hypertension, and cancer) also had higher CRFs. In the United States, 116 million adults have hypertension, 26 million US adults have diabetes mellitus, 9% have preexisting CVD and may therefore be at greater risk of complications or adverse health outcomes from COVID-19 infection.", "qid": 34, "docid": "2tlbeqvb", "rank": 32, "score": 0.8484819531440735}, {"content": "Title: Neurologic complications of COVID-19 Content: BACKGROUND: Much of the focus regarding the global pandemic of coronavirus disease of 2019 (COVID-19) has been on the cardiovascular, pulmonary, and hematologic complications. However, neurologic complications have arisen as an increasingly recognized area of morbidity and mortality. OBJECTIVE: This brief report summarizes the neurologic complications associated with COVID-19 with an emphasis on the emergency medicine clinician. DISCUSSION: COVID-19 has infected over 3.5 million people and killed over 240,000 people worldwide. While pulmonary complications are profound, the neurologic system is also significantly impacted, with complications including acute cerebrovascular events, encephalitis, Guillain-Barr\u00e9 syndrome, acute necrotizing hemorrhagic encephalopathy, and hemophagocytic lymphohistiocytosis. Additionally, patients on immunosuppressive medications for pre-existing neurologic issues are at an increased risk for complications with COVID-19 infection, and many of the currently proposed COVID-19 therapies can interact with these medications. CONCLUSIONS: When caring for COVID-19 patients, emergency medicine clinicians should be aware of the neurologic complications from COVID-19.", "qid": 34, "docid": "bvm1mrdy", "rank": 33, "score": 0.8479174375534058}, {"content": "Title: Myocardial injury in patients with COVID-19 Content: In patients with COVID-19, myocardial injury is prevalent and is associated with an adverse prognosis and increased mortality, according to two retrospective cohort studies from China and the USA.", "qid": 34, "docid": "jwu0az6g", "rank": 34, "score": 0.8477717041969299}, {"content": "Title: Cardiological society of India position statement on COVID-19 and heart failure Content: The COVID 19 global pandemic has engulfed humanity with a huge impact on health systems across the world. Many patients develop myocardial injury which can lead to significant cardiovascular complications including HF. This will require aggressive management strategies which are evolving. Guideline directed drug therapy including ACEI/ARB/ARNI is to be continued in patients with pre-existing HF. Long-term cardiovascular effects of COVID-19 are yet to be ascertained. Protection of health care personnel from contracting the disease should be given high priority.", "qid": 34, "docid": "49mantab", "rank": 35, "score": 0.8475708961486816}, {"content": "Title: Coronavirus Disease 2019 in Geriatrics and Long-term Care: The ABCDs of COVID-19. Content: The pandemic of coronavirus disease of 2019 (COVID-19) has global impact unseen since the 1918 worldwide influenza epidemic. All aspects of life have changed dramatically for now. The group most susceptible to COVID-19 are older adults and those with chronic underlying chronic medical disorders. The population residing in long-term care facilities generally are those who are both old and suffering from multiple comorbidities. In this article we provide information, insights, and recommended approaches to COVID-19 in the long-term facility setting. Since the situation is fluid and changing rapidly, readers are encouraged to access the resources cited in this article frequently. This article is protected by copyright. All rights reserved.", "qid": 34, "docid": "47ltwfp8", "rank": 36, "score": 0.8473021388053894}, {"content": "Title: Radiation therapy considerations during the COVID\u201019 Pandemic: Literature review and expert opinions Content: COVID-19 is an unprecedented pandemic that has already reached over 2 million confirmed cases globally, with at least 140,000 deaths as reported by the World Health Organization (WHO) as of April 16, 2020 1 . More than 662,000 cases have been reported in the United States with more than 29,000 deaths2 . The overall crude mortality rate now stands at 6.6% (may possibly be lower due to under-testing and under-reporting of total confirmed cases), and is highly dependent on age group, comorbidities, and the locoregional resources medically1 . A report from the United States presented age-stratified COVID-19 associated hospitalization rates among 1,482 patients during March 1-28, 2020, highlighting an alarmingly high rate of 74.5% at age > 50 years with underlining medical conditions3 . Based on a data summary report provided by New York City Health, as of April 14, 2020, the shares of a total of 6839 deaths reached 0.04%, 4.5%, 23.1%, 24.6%, and 47.7% for the age groups of 0-17, 18-44, 45-64, 65-74, and 75+ years old4 . All data suggest that adults at a more advanced age group are facing higher morbidity and mortality risks.", "qid": 34, "docid": "j1j5ghl4", "rank": 37, "score": 0.8469389081001282}, {"content": "Title: COVID-19 and diabetes: Is there enough evidence? Content: The pandemic of COVID-19, a disease caused by a novel coronavirus SARS-CoV-2, is associated with significant morbidity and mortality. Recent data showed that hypertension, diabetes mellitus, cardiovascular diseases, and chronic obstructive pulmonary disease were the most prevalent comorbidities in COVID-19 patients. Additionally, data indicate that hypertension, diabetes, and cardiovascular diseases are important risk factors for progression and unfavorable outcome in COVID-19 patients. There is only limited amount of data regarding follow-up of these patients, and they provided conflicting results. The main limitation is a small number of participants and particularly those who experienced primary composite outcome (admission in intensive care unit, use of mechanical ventilation, or death). Additionally, the limited number of patients was essential obstacle for performing analysis that would include many confounding factors such as advanced age, smoking status, and obesity and potentially change conclusion. So far, there is no study that demonstrated independent predictive value of diabetes on mortality in COVID-19 patients, but there are many speculations about the association between diabetes and susceptibility to novel coronavirus, as well as its impact on progression and prognosis of COVID-19. The aim of this review article was to summarize the current knowledge about the relationship between diabetes and COVID-19 and its role in outcome in these patients.", "qid": 34, "docid": "f0pwjxfv", "rank": 38, "score": 0.8468807935714722}, {"content": "Title: SAFE ENDOUROLOGY PROCEDURE USING A C-ARM DRAPE DURING COVID-19 TIMES. Content: Healthcare providers are at the front line of the COVID-19 outbreak response and as such are exposed to hazards that put them at risk of infection. Hazards include pathogen exposure, long working hours, psychological distress, fatigue, occupational burnout, stigma, and physical and psychological violence. [1] Health care workers, particularly those involved in airway-related procedures such as endotracheal intubation are at high risk of infection.", "qid": 34, "docid": "sawa1b64", "rank": 39, "score": 0.8464685082435608}, {"content": "Title: Safe Endourology Procedure Using a C-arm Drape during Covid-19 Times Content: Healthcare providers are at the front line of the COVID-19 outbreak response and as such are exposed to hazards that put them at risk of infection. Hazards include pathogen exposure, long working hours, psychological distress, fatigue, occupational burnout, stigma, and physical and psychological violence. [1] Health care workers, particularly those involved in airway-related procedures such as endotracheal intubation are at high risk of infection.", "qid": 34, "docid": "ut9zuz8l", "rank": 40, "score": 0.8464683890342712}, {"content": "Title: Characteristics of SARS-CoV-2 positive and complicated COVID-19 patient cohorts in Israel: A comparative analysis Content: Reliably identifying patients at increased risk for COVID-19 complications could guide clinical decisions, public health policies, and preparedness efforts. The most globally accepted definitions of at-risk patients rely, primarily, on epidemiological characterization of hospitalized COVID-19 patients. However, such characterization overlooks, and fails to correct for, the prevalence of existing conditions in the wider SARS-CoV-2 positive population. Here, we use the complete medical records of 4,353 Israeli SARS-CoV-2 positive individuals, of whom 173 experienced moderate or severe symptoms of COVID-19, to identify the conditions that increase the risk of disease complications, in various age and sex strata. Our analysis suggests that cardiovascular and kidney diseases, obesity, and hypertension are significant risk factors for COVID-19 complications, as previously reported. Interestingly, it also indicates that depression (e.g., odds ratio, OR, for males 65 years or older: 2.94, 95% confidence intervals [1.55, 5.58]; P-value = 0.014) as well cognitive and neurological disorder (e.g., OR for individuals [\u2265] 65 year old: 2.65 [1.69, 4.17]; P-value < 0.001) are significant risk factors; and that smoking and background of respiratory diseases do not significantly increase the risk of complications. Adjusting existing risk definitions following these observations may improve their accuracy and impact the global pandemic containment efforts.", "qid": 34, "docid": "iaykn3yi", "rank": 41, "score": 0.8464169502258301}, {"content": "Title: Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2) and the Central Nervous System Content: Emerging evidence indicates that severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), the etiologic agent of COVID-19, can cause neurological complications. We provide a brief overview of these recent observations and discuss some of their possible implications. In particular, given the global dimension of the current pandemic, we highlight the need to consider the possible long-term impact of COVID-19, potentially including neurological and neurodegenerative disorders.", "qid": 34, "docid": "prxzcp1x", "rank": 42, "score": 0.8454856872558594}, {"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": 34, "docid": "aks5z29t", "rank": 43, "score": 0.8454722166061401}, {"content": "Title: Cardiovascular manifestations and treatment considerations in covid-19 Content: Since its recognition in December 2019, covid-19 has rapidly spread globally causing a pandemic. Pre-existing comorbidities such as hypertension, diabetes, and cardiovascular disease are associated with a greater severity and higher fatality rate of covid-19. Furthermore, covid-19 contributes to cardiovascular complications, including acute myocardial injury as a result of acute coronary syndrome, myocarditis, stress-cardiomyopathy, arrhythmias, cardiogenic shock, and cardiac arrest. The cardiovascular interactions of covid-19 have similarities to that of severe acute respiratory syndrome, Middle East respiratory syndrome and influenza. Specific cardiovascular considerations are also necessary in supportive treatment with anticoagulation, the continued use of renin-angiotensin-aldosterone system inhibitors, arrhythmia monitoring, immunosuppression or modulation, and mechanical circulatory support.", "qid": 34, "docid": "873txs85", "rank": 44, "score": 0.8453671932220459}, {"content": "Title: Follow-up studies in COVID-19 recovered patients - is it mandatory? Content: The novel Coronavirus disease 2019 (COVID-19) is an illness caused due to Severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2). The World Health Organization (WHO) has declared this outbreak a global health emergency and as on April 24, 2020, it has spread to 213 countries, with 25,91,015 confirmed cases and 742,855 cases have been recovered from COVID-19. In this dreadful situation our team has already published an article in the Science of the Total Environment, which elaborates the various aspects of the SARS-CoV-2 infection. In this situation, it is imperative to understand the possible outcome of COVID-19 recovered patients and determine if they have any other detrimental illnesses by longitudinal analysis to safeguard their life in future. It is necessary to follow-up these recovered patients and performs comprehensive assessments for detection and appropriate management towards their psychological, physical, and social realm. This urges us to suggest that it is highly important to provide counselling, moral support as well as a few recommended guidelines to the recovered patients and society to restore to normalcy. Epidemiological, clinical and immunological studies from COVID-19 recovered patients are particularly important to understand the disease and to prepare better for potential outbreaks in the future. Longitudinal studies on a larger cohort would help us to understand the in-depth prognosis as well as the pathogenesis of COVID-19. Also, follow-up studies will help us provide more information for the development of vaccines and drugs for these kinds of pandemics in the future. Hence, we recommend more studies are required to unravel the possible mechanism of COVID-19 infection and the after-effects of it to understand the characteristics of the virus and to develop the necessary precautionary measures to prevent it.", "qid": 34, "docid": "uqhaxqqh", "rank": 45, "score": 0.8451352119445801}, {"content": "Title: Preliminary Estimates of the Prevalence of Selected Underlying Health Conditions Among Patients with Coronavirus Disease 2019 \u2014 United States, February 12\u2013March 28, 2020 Content: On March 11, 2020, the World Health Organization declared Coronavirus Disease 2019 (COVID-19) a pandemic (1). As of March 28, 2020, a total of 571,678 confirmed COVID-19 cases and 26,494 deaths have been reported worldwide (2). Reports from China and Italy suggest that risk factors for severe disease include older age and the presence of at least one of several underlying health conditions (3,4). U.S. older adults, including those aged \u226565 years and particularly those aged \u226585 years, also appear to be at higher risk for severe COVID-19-associated outcomes; however, data describing underlying health conditions among U.S. COVID-19 patients have not yet been reported (5). As of March 28, 2020, U.S. states and territories have reported 122,653 U.S. COVID-19 cases to CDC, including 7,162 (5.8%) for whom data on underlying health conditions and other known risk factors for severe outcomes from respiratory infections were reported. Among these 7,162 cases, 2,692 (37.6%) patients had one or more underlying health condition or risk factor, and 4,470 (62.4%) had none of these conditions reported. The percentage of COVID-19 patients with at least one underlying health condition or risk factor was higher among those requiring intensive care unit (ICU) admission (358 of 457, 78%) and those requiring hospitalization without ICU admission (732 of 1,037, 71%) than that among those who were not hospitalized (1,388 of 5,143, 27%). The most commonly reported conditions were diabetes mellitus, chronic lung disease, and cardiovascular disease. These preliminary findings suggest that in the United States, persons with underlying health conditions or other recognized risk factors for severe outcomes from respiratory infections appear to be at a higher risk for severe disease from COVID-19 than are persons without these conditions.", "qid": 34, "docid": "4cy3er3y", "rank": 46, "score": 0.8449721336364746}, {"content": "Title: I may never see the ocean again: Loss and grief among older adults during the COVID-19 pandemic Content: The COVID-19 pandemic has disproportionately affected older adults, not only through greater risk of illness and death but also by exacerbating underlying distress related to aging and mortality. Older adults' struggles with loneliness, fear of dying, and the sequelae of untreated medical conditions are viewed through the lens of anticipatory grief, and coping and treatment strategies are offered. (PsycInfo Database Record (c) 2020 APA, all rights reserved).", "qid": 34, "docid": "2oudure1", "rank": 47, "score": 0.8448022603988647}, {"content": "Title: I may never see the ocean again: Loss and grief among older adults during the COVID-19 pandemic. Content: The COVID-19 pandemic has disproportionately affected older adults, not only through greater risk of illness and death but also by exacerbating underlying distress related to aging and mortality. Older adults' struggles with loneliness, fear of dying, and the sequelae of untreated medical conditions are viewed through the lens of anticipatory grief, and coping and treatment strategies are offered. (PsycInfo Database Record (c) 2020 APA, all rights reserved).", "qid": 34, "docid": "g0cysz78", "rank": 48, "score": 0.8448022603988647}, {"content": "Title: Effect of underlying comorbidities on the infection and severity of COVID-19 in South Korea Content: ABSTRACT Background: The coronavirus disease (COVID-19) pandemic is an emerging threat worldwide. It is still unclear how comorbidities affect the risk of infection and severity of COVID-19. Methods: A nationwide retrospective case-control study of 65,149 individuals, aged 18 years or older, whose medical cost for COVID-19 testing were claimed until April 8, 2020. The diagnosis of COVID-19 and severity of COVID-19 infection were identified from the reimbursement data using diagnosis codes and based on whether respiratory support was used, respectively. Odds ratios were estimated using multiple logistic regression, after adjusting for age, sex, region, healthcare utilization, and insurance status. Results: The COVID-19 group (5,172 of 65,149) was younger and showed higher proportion of females. 5.6% (293 of 5,172) of COVID-19 cases were severe. The severe COVID-19 group had older patients and a higher male ratio than the non-severe group. Cushing syndrome (Odds ratio range (ORR) 2.059-2.358), chronic renal disease (ORR 1.292-1.604), anemia (OR 1.132), bone marrow dysfunction (ORR 1.471-1.645), and schizophrenia (ORR 1.287-1.556) showed significant association with infection of COVID-19. In terms of severity, diabetes (OR 1.417, 95% CI 1.047-1.917), hypertension (OR 1.378, 95% CI 1.008-1.883), heart failure (ORR 1.562-1.730), chronic lower respiratory disease (ORR 1.361-1.413), non-infectious lower digestive system disease (ORR 1.361-1.418), rheumatoid arthritis (ORR 1.865-1.908), substance use (ORR 2.790-2.848), and schizophrenia (ORR 3.434-3.833) were related with severe COVID-19. Conclusions: We identified several comorbidities associated with COVID-19. Health care workers should be more careful when diagnosing and treating COVID-19 when the patient has the above-mentioned comorbidities. Keywords: COVID-19, SARS-CoV-2, Comorbidity, Risk factor, Severity", "qid": 34, "docid": "dyuw4kbm", "rank": 49, "score": 0.8447436094284058}, {"content": "Title: The need for neurologists in the care of COVID\u201019 patients Content: Coronavirus disease 2019 (COVID-19) is an infectious disease caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) resulting in severe acute respiratory syndrome in a substantial number of patients. Approximately 5% to 10% of patients need intensive care unit (ICU) admission and mechanical ventilation [1]. The primary symptoms of COVID-19 include fever, dry cough and fatigue [2]. However, a recent report from Shandong, China, disclosed that a subset of patients did not suffer from respiratory symptoms but had neurologic signs and symptoms [3]. Moreover, in a retrospective study from Wuhan, China, neurologic symptoms were observed in 36.4% of the hospitalized patients with COVID-19 infection and pertained to both the central and peripheral nervous system [4].", "qid": 34, "docid": "l21fin9q", "rank": 50, "score": 0.8447044491767883}, {"content": "Title: Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2) and the Central Nervous System Content: Emerging evidence indicates that severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), the etiologic agent of coronavirus disease 2019 (COVID-19), can cause neurological complications. We provide a brief overview of these recent observations and discuss some of their possible implications. In particular, given the global dimension of the current pandemic, we highlight the need to consider the possible long-term impact of COVID-19, potentially including neurological and neurodegenerative disorders.", "qid": 34, "docid": "f5khmuc4", "rank": 51, "score": 0.8444246649742126}, {"content": "Title: Preliminary Estimates of the Prevalence of Selected Underlying Health Conditions Among Patients with Coronavirus Disease 2019 - United States, February 12-March 28, 2020 Content: On March 11, 2020, the World Health Organization declared Coronavirus Disease 2019 (COVID-19) a pandemic (1). As of March 28, 2020, a total of 571,678 confirmed COVID-19 cases and 26,494 deaths have been reported worldwide (2). Reports from China and Italy suggest that risk factors for severe disease include older age and the presence of at least one of several underlying health conditions (3,4). U.S. older adults, including those aged &#8805;65 years and particularly those aged &#8805;85 years, also appear to be at higher risk for severe COVID-19-associated outcomes; however, data describing underlying health conditions among U.S. COVID-19 patients have not yet been reported (5). As of March 28, 2020, U.S. states and territories have reported 122,653 U.S. COVID-19 cases to CDC, including 7,162 (5.8%) for whom data on underlying health conditions and other known risk factors for severe outcomes from respiratory infections were reported. Among these 7,162 cases, 2,692 (37.6%) patients had one or more underlying health condition or risk factor, and 4,470 (62.4%) had none of these conditions reported. The percentage of COVID-19 patients with at least one underlying health condition or risk factor was higher among those requiring intensive care unit (ICU) admission (358 of 457, 78%) and those requiring hospitalization without ICU admission (732 of 1,037, 71%) than that among those who were not hospitalized (1,388 of 5,143, 27%). The most commonly reported conditions were diabetes mellitus, chronic lung disease, and cardiovascular disease. These preliminary findings suggest that in the United States, persons with underlying health conditions or other recognized risk factors for severe outcomes from respiratory infections appear to be at a higher risk for severe disease from COVID-19 than are persons without these conditions.", "qid": 34, "docid": "a4jsvdhe", "rank": 52, "score": 0.8443451523780823}, {"content": "Title: Unraveling the mystery of Covid-19 cytokine storm: From skin to organ systems Content: COVID-19 is a global pandemic that emerged from Wuhan, China. Besides pneumonia and acute respiratory distress syndrome, the disease leads to multisystem involvement in the form of myocarditis, arrhythmias, cardiac arrest, gastrointestinal symptoms, hypoxemic brain injury, acute liver, and renal function impairment. There are also reports of cutaneous lesions in form of urticarial and maculopapular rashes, chilblain like fingers and toes (covid feet), livedoid vasculopathy, and chicken-pox like or varicelliform vesicles. Clinically, many of these skin lesions are likely secondary to occlusion of small to medium blood vessels due to microthrombi formation or due to viral laden antigen-antibody immune complexes; and same explanation may hold true for possible hypoxemic injury simultaneously occurring in other vital organs like lungs, heart, brain, and kidneys. The histopathology, immunoflorescence and RT-PCR analysis of skin biopsies can provide useful insights for ascertaining the pathogenesis of this complex viral syndrome. Apparently, it is interplay of disarmed cellular immunity and over-activated humoral immunity that culminates in end-organ changes. The morbidity and mortality can be significantly reduced by upgrading the cellular immunity and downgrading the humoral response; along with prevention of hypoxemic and reperfusion injuries by using antivirals, immunomodulators, antioxidants, anti-platelets, and anticoagulants in judicious and phased manner.", "qid": 34, "docid": "zbkukpdc", "rank": 53, "score": 0.8442054986953735}, {"content": "Title: Follow-up studies in COVID-19 recovered patients - is it mandatory? Content: Abstract The novel Coronavirus disease 2019 (COVID-19) is an illness caused due to Severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2). The World Health Organization (WHO) has declared this outbreak a global health emergency and as on April 24, 2020, it has spread to 213 countries, with 25,91,015 confirmed cases and 742,855 cases have been recovered from COVID-19. In this dreadful situation our team has already published an article in the Science of the Total Environment, which elaborates the various aspects of the SARS-CoV-2 infection. In this situation, it is imperative to understand the possible outcome of COVID-19 recovered patients and determine if they have any other detrimental illnesses by longitudinal analysis to safeguard their life in future. It is necessary to follow-up these recovered patients and performs comprehensive assessments for detection and appropriate management towards their psychological, physical, and social realm. This urges us to suggest that it is highly important to provide counselling, moral support as well as a few recommended guidelines to the recovered patients and society to restore to normalcy. Epidemiological, clinical and immunological studies from COVID-19 recovered patients are particularly important to understand the disease and to prepare better for potential outbreaks in the future. Longitudinal studies on a larger cohort would help us to understand the in-depth prognosis as well as the pathogenesis of COVID-19. Also, follow-up studies will help us provide more information for the development of vaccines and drugs for these kinds of pandemics in the future. Hence, we recommend more studies are required to unravel the possible mechanism of COVID-19 infection and the after-effects of it to understand the characteristics of the virus and to develop the necessary precautionary measures to prevent it.", "qid": 34, "docid": "8p9d1c9k", "rank": 54, "score": 0.8440560102462769}, {"content": "Title: Hypertension and Diabetes Delay the Viral Clearance in COVID-19 Patients Content: Objectives: Comorbidities have significant indications for the disease outcome of COVID-19, however which underlying diseases that contribute the most to aggravate the conditions of COVID-19 patients is still largely unknown. SARS-CoV-2 viral clearance is a golden standard for defining the recovery of COVID-19 infections. To dissect the underlying diseases that could impact on viral clearance, we enrolled 106 COVID-19 patients who were hospitalized in the Zhongnan Hospital of Wuhan University, Wuhan, China between Jan 5 and Feb 25, 2020. Methodology: We comprehensively analyzed demographic, clinical and laboratory data, as well as patient treatment records. Survival analyses with Kaplan-Meier and Cox regression modelling were employed to identify factors influencing the viral clearance negatively. Results: We found that increasing age, male gender, and angiotensin-converting enzyme 2 (ACE2) associated factors (including hypertension, diabetes, and cardiovascular diseases) adversely affected the viral clearance. Furthermore, analysis by a random forest survival model pointed out hypertension, cortisone treatment, gender, and age as the four most important variables. Conclusions: We conclude that patients at old age, males, and/or having diseases associated with high expression of ACE2 will have worse prognosis during a COVID-19 infections.", "qid": 34, "docid": "whnw19pc", "rank": 55, "score": 0.8438113927841187}, {"content": "Title: Vascular skin symptoms in COVID-19: a french observational study Content: Coronavirus 19 (COVID-19) was declared as a pandemic viral infection by the World Health organization on March 11th 2020. Usual clinical manifestations of COVID-19 infection include fever, fatigue, myalgia, headache, diarrhea, dry cough, dyspnea that may lead to acute respiratory distress syndrome and death (1). Skin symptoms of COVID-19 have been poorly described but may include erythematous rash, urticaria and chicken pox like lesions (2-7). Angiotensin-converting enzyme 2 (ACE2) is a cellular receptor for COVID-19.", "qid": 34, "docid": "vp5xj8m5", "rank": 56, "score": 0.8437903523445129}, {"content": "Title: Post-COVID-19 global health strategies: the need for an interdisciplinary approach Content: For survivors of severe COVID-19 disease, having defeated the virus is just the beginning of an uncharted recovery path. What follows after the acute phase of SARS-CoV-2 infection depends on the extension and severity of viral attacks in different cell types and organs. Despite the ridiculously large number of papers that have flooded scientific journals and preprint-hosting websites, a clear clinical picture of COVID-19 aftermath is vague at best. Without larger prospective observational studies that are only now being started, clinicians can retrieve information just from case reports and or small studies. This is the time to understand how COVID-19 goes forward and what consequences survivors may expect to experience. To this aim, a multidisciplinary post-acute care service involving several specialists has been established at the Fondazione Policlinico Universitario A. Gemelli IRCSS (Rome, Italy). Although COVID-19 is an infectious disease primarily affecting the lung, its multi-organ involvement requires an interdisciplinary approach encompassing virtually all branches of internal medicine and geriatrics. In particular, during the post-acute phase, the geriatrician may serve as the case manager of a multidisciplinary team. The aim of this article is to describe the importance of the interdisciplinary approach--coordinated by geriatrician--to cope the potential post-acute care needs of recovered COVID-19 patients.", "qid": 34, "docid": "rd6cqdsf", "rank": 57, "score": 0.8437246680259705}, {"content": "Title: ANALYSIS OF CLINICAL RECOVERY-PERIOD AND RECOVERY RATE ESTIMATION OF THE FIRST 1000 COVID-19 PATIENTS IN SINGAPORE Content: COVID-19 has been declared as a global pandemic by the World Health Organization (WHO) on March 11, 2020. In this paper, we investigate various aspects of the clinical recovery of the first 1000 COVID-19 patients in Singapore, spanning from January 23 to April 01, 2020. This data consists of 245 clinically recovered patients. The first part of the paper studies the descriptive statistics and the influence of demographic parameters, namely age and gender, in the clinical recovery-period of COVID-19 patients. The second part of the paper is on identifying the distribution of the length of the recovery-period for the patients. We identify a piecewise analysis of three different periods, identified based on trends of both positive confirmation and clinical recovery of COVID-19. As expected, the overall recovery rate has reduced drastically during the exponential increase of incidences. However, our in-depth analysis shows that there is a shift in the age-group of incidences to the younger population, and the recovery-period of the younger population is considerably lower. Here, we have estimated the recovery rate to be 0.125. Overall, the prognosis of COVID-19 indicates an improvement in recovery rate owing to the government-mandated practices of restricted mobility of the older population and aggressive contact tracing.", "qid": 34, "docid": "orko04fi", "rank": 58, "score": 0.8435097336769104}, {"content": "Title: COVID-19 Cardiac Injury: Implications for Long-Term Surveillance and Outcomes in Survivors Content: Up to 20-30% of patients hospitalized with coronavirus disease (COVID-19) have evidence of myocardial involvement. Acute cardiac injury in patients hospitalized with COVID-19 is associated with higher morbidity and mortality. There are no data on how acute treatment for COVID-19 may affect convalescent phase or long-term cardiac recovery and function. Myocarditis from other viral pathogens can evolve into overt or subclinical myocardial dysfunction, and sudden death has been described in the convalescent phase of viral myocarditis. This raises concerns for patients recovering from COVID-19. Some patients will have subclinical and possibly overt cardiovascular abnormalities. Patients with ostensibly recovered cardiac function may still be at risk for cardiomyopathy and cardiac arrhythmias. Screening for residual cardiac involvement in the convalescent phase for patients recovered from COVID-19 associated cardiac injury is needed. The type of testing, and therapies for post COVID-19 myocardial dysfunction will need to be determined. Therefore, now is the time to plan for appropriate registries and clinical trials to properly assess these issues and prepare for long-term sequelae of \"post-COVID-19 Cardiac Syndrome\".", "qid": 34, "docid": "bsqpkjcj", "rank": 59, "score": 0.8435050249099731}, {"content": "Title: Survivorship after COVID-19 ICU stay Content: Prior studies of patient survivorship after an intensive care unit (ICU) stay suggest that many critically ill patients with COVID-19 will face long-lasting physical, cognitive and/or mental health impairments. This anticipated survivorship experience highlights the importance of collaboration between the fields of critical care and rehabilitation to optimize post-COVID-19 recovery.", "qid": 34, "docid": "lcqxnrge", "rank": 60, "score": 0.8431345224380493}, {"content": "Title: Post-COVID-19 global health strategies: the need for an interdisciplinary approach Content: For survivors of severe COVID-19 disease, having defeated the virus is just the beginning of an uncharted recovery path. What follows after the acute phase of SARS-CoV-2 infection depends on the extension and severity of viral attacks in different cell types and organs. Despite the ridiculously large number of papers that have flooded scientific journals and preprint-hosting websites, a clear clinical picture of COVID-19 aftermath is vague at best. Without larger prospective observational studies that are only now being started, clinicians can retrieve information just from case reports and or small studies. This is the time to understand how COVID-19 goes forward and what consequences survivors may expect to experience. To this aim, a multidisciplinary post-acute care service involving several specialists has been established at the Fondazione Policlinico Universitario A. Gemelli IRCSS (Rome, Italy). Although COVID-19 is an infectious disease primarily affecting the lung, its multi-organ involvement requires an interdisciplinary approach encompassing virtually all branches of internal medicine and geriatrics. In particular, during the post-acute phase, the geriatrician may serve as the case manager of a multidisciplinary team. The aim of this article is to describe the importance of the interdisciplinary approach\u2013\u2013coordinated by geriatrician\u2013\u2013to cope the potential post-acute care needs of recovered COVID-19 patients.", "qid": 34, "docid": "vjdwh19x", "rank": 61, "score": 0.8431215882301331}, {"content": "Title: The multifaceted long-term effects of the COVID-19 pandemic on urology Content: The COVID-19 pandemic has resulted in immediate effects on urological practice, in particular the vast reduction in elective surgeries. These changes are likely to have long-term effects for both patients and for urologists, which will persist even after the pandemic resolves. The many facets of COVID-19\u2019s effects on urology remain to be seen, but they might also offer opportunities to reassess and improve patient management in urology and beyond.", "qid": 34, "docid": "zszexapf", "rank": 62, "score": 0.8428042531013489}, {"content": "Title: COVID-19: Dados Atualizados e sua Rela\u00e7\u00e3o Com o Sistema Cardiovascular./ COVID-19: Dados Atualizados e sua Rela\u00e7\u00e3o Com o Sistema Cardiovascular./ 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": 34, "docid": "yj0png0x", "rank": 63, "score": 0.8426694869995117}, {"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": 34, "docid": "8hvv7gsm", "rank": 64, "score": 0.8426694869995117}, {"content": "Title: Coronavirus Disease 2019 in Geriatrics and Long-Term Care: The ABCDs of COVID-19 Content: The pandemic of coronavirus disease of 2019 (COVID-19) is having a global impact unseen since the 1918 worldwide influenza epidemic. All aspects of life have changed dramatically for now. The group most susceptible to COVID-19 are older adults and those with chronic underlying medical disorders. The population residing in long-term care facilities generally are those who are both old and have multiple comorbidities. In this article we provide information, insights, and recommended approaches to COVID-19 in the long-term facility setting. Because the situation is fluid and changing rapidly, readers are encouraged to access frequently the resources cited in this article. J Am Geriatr Soc 68:912-917, 2020.", "qid": 34, "docid": "9ijtwvvd", "rank": 65, "score": 0.8425941467285156}, {"content": "Title: COVID\u201019: Shedding light on racial and health inequities in the USA Content: The sudden and rapid advancement of the novel Coronavirus (COVID-19) pandemic has led to an unanticipated and unprecedented global crisis. Since its emergence in the United States, there is increasing discussion surrounding the impact of the virus among vulnerable populations. Older adults, young children, and persons with chronic medical or mental health conditions, persons with disabilities, pregnant women, immunocompromised persons and those who are institutionalized or homeless are considered most vulnerable to death and lost quality of life (World Health Organization, 2020).", "qid": 34, "docid": "4prhmi8f", "rank": 66, "score": 0.8425642848014832}, {"content": "Title: Effect of Underlying Comorbidities on the Infection and Severity of COVID-19 in Korea: a Nationwide Case-Control Study Content: BACKGROUND: The coronavirus disease 2019 (COVID-19) pandemic is an emerging threat worldwide. It remains unclear how comorbidities affect the risk of infection and severity of COVID-19. METHODS: This is a nationwide retrospective case-control study of 219,961 individuals, aged 18 years or older, whose medical costs for COVID-19 testing were claimed until May 15, 2020. COVID-19 diagnosis and infection severity were identified from reimbursement data using diagnosis codes and on the basis of respiratory support use, respectively. Odds ratios (ORs) were estimated using multiple logistic regression, after adjusting for age, sex, region, healthcare utilization, and insurance status. RESULTS: The COVID-19 group (7,341 of 219,961) was young and had a high proportion of female. Overall, 13.0% (954 of 7,341) of the cases were severe. The severe COVID-19 group had older patients and a proportion of male ratio than did the non-severe group. Diabetes (odds ratio range [ORR], 1.206-1.254), osteoporosis (ORR, 1.128-1.157), rheumatoid arthritis (ORR, 1.207-1.244), substance use (ORR, 1.321-1.381), and schizophrenia (ORR, 1.614-1.721) showed significant association with COVID-19. In terms of severity, diabetes (OR, 1.247; 95% confidential interval, 1.009-1.543), hypertension (ORR, 1.245-1.317), chronic lower respiratory disease (ORR, 1.216-1.233), chronic renal failure, and end-stage renal disease (ORR, 2.052-2.178) were associated with severe COVID-19. CONCLUSION: We identified several comorbidities associated with COVID-19. Health care workers should be more careful while diagnosing and treating COVID-19 when patients have the abovementioned comorbidities.", "qid": 34, "docid": "1exvjxwx", "rank": 67, "score": 0.8419960737228394}, {"content": "Title: How do we recover from COVID-19? Helping diabetes teams foresee and prepare for the psychological harms Content: The scale of the COVID-19 pandemic is entirely unprecedented. However, as depicted in Fig. 1, evidence from previous large-scale disasters indicates that following a first wave of admissions and deaths from COVID-19, there are likely to be subsequent waves of people with acute care needs worsened by delayed hospital treatment, and people with long-term conditions whose routine care has been disrupted [1]. People with diabetes are likely to constitute a large proportion of those with acute second- and third-wave care needs, and in many cases, management of their condition may also have been negatively affected by lockdown.", "qid": 34, "docid": "q79r4dbl", "rank": 68, "score": 0.8419857025146484}, {"content": "Title: The cognitive consequences of the COVID-19 epidemic: collateral damage? Content: Recovery from coronavirus disease 2019 (COVID-19) will be principally defined in terms of remission from respiratory symptoms, however both clinical and animal studies have shown that coronaviruses may spread to the nervous system. A systematic search on previous viral epidemics revealed that while there has been relatively little research in this area, clinical studies have commonly reported neurological disorders and cognitive difficulties. Little is known with regard to their incidence, duration or underlying neural basis. The hippocampus appears to be particularly vulnerable to coronavirus infections, thus increasing the probability of post-infection memory impairment, and acceleration of neurodegenerative disorders such as Alzheimer\u2019s disease. Future knowledge of the impact of COVID-19, from epidemiological studies and clinical practice, will be needed to develop future screening and treatment programmes to minimize the long-term cognitive consequences of COVID-19.", "qid": 34, "docid": "cb7k2zbe", "rank": 69, "score": 0.841758131980896}, {"content": "Title: Rehabilitation and respiratory management in the acute and early post-acute phase. \"Instant paper from the field\" on rehabilitation answers to the Covid-19 emergency Content: Covid-19 is a respiratory infectious disease that can cause respiratory, physical and psychological long-term dysfunctions in patients. First recommendations on respiratory management were published, but they were not based on the specific needs due to Covid-19. In this paper we share the early experiences from the clinical field in Northern Italy, where the epidemic started in February. This paper summarizes the second webinar on Covid-19 (230 live attendees, 11,600 viewers of the recorded version) organized by the Italian Society of Physical and Rehabilitation Medicine about rehabilitation and in particular respiratory management in the acute (Intensive Care Unit - ICU) and immediate post-acute phases. There is the need to prepare for the post-acute phase. ICU length of stay is relatively long, with immobilisation in prone position. Some specific problems are described, including severe muscle weakness and fatigue, joint stiffness, dysphagia, (neuro)psychological problems, impaired functioning concerning mobility, activities of daily life and work. A lot is yet unknown and patients can experience long-term consequences as we know from the literature on the post-intensive care syndrome, but Covid-19 has unique features to be investigated and understood. As one colleague stated during the Covinar: this is a marathon, not a sprint .", "qid": 34, "docid": "6bq3g51s", "rank": 70, "score": 0.8415517807006836}, {"content": "Title: Addressing male sexual and reproductive health in the wake of COVID-19 outbreak Content: PURPOSE: The COVID-19 pandemic, caused by the SARS-CoV-2, represents an unprecedented challenge for healthcare. COVID-19 features a state of hyperinflammation resulting in a \u201ccytokine storm\u201d, which leads to severe complications, such as the development of micro-thrombosis and disseminated intravascular coagulation (DIC). Despite isolation measures, the number of affected patients is growing daily: as of June 12th, over 7.5 million cases have been confirmed worldwide, with more than 420,000 global deaths. Over 3.5 million patients have recovered from COVID-19; although this number is increasing by the day, great attention should be directed towards the possible long-term outcomes of the disease. Despite being a trivial matter for patients in intensive care units (ICUs), erectile dysfunction (ED) is a likely consequence of COVID-19 for survivors, and considering the high transmissibility of the infection and the higher contagion rates among elderly men, a worrying phenomenon for a large part of affected patients. METHODS: A literature research on the possible mechanisms involved in the development of ED in COVID-19 survivors was performed. RESULTS: Endothelial dysfunction, subclinical hypogonadism, psychological distress and impaired pulmonary hemodynamics all contribute to the potential onset of ED. Additionally, COVID-19 might exacerbate cardiovascular conditions; therefore, further increasing the risk of ED. Testicular function in COVID-19 patients requires careful investigation for the unclear association with testosterone deficiency and the possible consequences for reproductive health. Treatment with phosphodiesterase-5 (PDE5) inhibitors might be beneficial for both COVID-19 and ED. CONCLUSION: COVID-19 survivors might develop sexual and reproductive health issues. Andrological assessment and tailored treatments should be considered in the follow-up.", "qid": 34, "docid": "qjfe2t9v", "rank": 71, "score": 0.8415066003799438}, {"content": "Title: Effect of Underlying Comorbidities on the Infection and Severity of COVID-19 in Korea: a Nationwide Case-Control Study Content: BACKGROUND: The coronavirus disease 2019 (COVID-19) pandemic is an emerging threat worldwide. It remains unclear how comorbidities affect the risk of infection and severity of COVID-19. METHODS: This is a nationwide retrospective case-control study of 219,961 individuals, aged 18 years or older, whose medical costs for COVID-19 testing were claimed until May 15, 2020. COVID-19 diagnosis and infection severity were identified from reimbursement data using diagnosis codes and on the basis of respiratory support use, respectively. Odds ratios (ORs) were estimated using multiple logistic regression, after adjusting for age, sex, region, healthcare utilization, and insurance status. RESULTS: The COVID-19 group (7,341 of 219,961) was young and had a high proportion of female. Overall, 13.0% (954 of 7,341) of the cases were severe. The severe COVID-19 group had older patients and a proportion of male ratio than did the non-severe group. Diabetes (odds ratio range [ORR], 1.206\u20131.254), osteoporosis (ORR, 1.128\u20131.157), rheumatoid arthritis (ORR, 1.207\u20131.244), substance use (ORR, 1.321\u20131.381), and schizophrenia (ORR, 1.614\u20131.721) showed significant association with COVID-19. In terms of severity, diabetes (OR, 1.247; 95% confidential interval, 1.009\u20131.543), hypertension (ORR, 1.245\u20131.317), chronic lower respiratory disease (ORR, 1.216\u20131.233), chronic renal failure, and end-stage renal disease (ORR, 2.052\u20132.178) were associated with severe COVID-19. CONCLUSION: We identified several comorbidities associated with COVID-19. Health care workers should be more careful while diagnosing and treating COVID-19 when patients have the abovementioned comorbidities.", "qid": 34, "docid": "n64t89pn", "rank": 72, "score": 0.8413920402526855}, {"content": "Title: Rapid Progression to Acute Respiratory Distress Syndrome: Review of Current Understanding of Critical Illness from COVID-19 Infection Content: The coronavirus disease 2019 (COVID-19) outbreak that started in Wuhan, Hubei province, China in December 2019 has now extended across the globe with &gt;100,000 cases and 3,000 deaths reported in 93 countries as of 7 March 2020 We report a case of COVID-19 infection in a 64-year-old man who developed rapidly worsening respiratory failure and acute respiratory distress syndrome (ARDS) that required intubation As the clinical spectrum of COVID-19 ranges widely from mild illness to ARDS with a high risk of mortality, there is a need for more research to identify early markers of disease severity Current evidence suggests that patients with advanced age, pre-existing comorbidities or dyspnoea should be closely monitored, especially at 1-2 weeks after symptom onset It remains to be seen if laboratory findings such as lymphopenia or elevated lactate dehydrogenase may serve as early surrogates for critical illness or markers of disease recovery Management of ARDS in COVID-19 remains supportive while we await results of drug trials More studies are needed to understand the incidence and outcomes of ARDS and critical illness from COVID-19, which will be important for critical care management and resource planning", "qid": 34, "docid": "ymt1xqo2", "rank": 73, "score": 0.8409603834152222}, {"content": "Title: The potential for COVID\u201019 to contribute to compassion fatigue in critical care nurses Content: As of April 2020, more than 2 million people worldwide had tested positive for COVID-19, and more than 200,000 deaths are attributed to this virus. It is estimated that around 15% of patients diagnosed with COVID-19 will develop severe health complications, and around 5- 10% will require intensive level care due to the seriousness of the symptoms and the high mortality risk (3-5%)( Baud et al., 2020; Murthy, Gomersall, & Fowler, 2020). At the time of writing, COVID-19 has caused the need for hospitalisation of thousands of people due to the serious pneumonia type symptoms that result in extreme breathing difficulty.", "qid": 34, "docid": "j8xu7p0w", "rank": 74, "score": 0.8409003615379333}, {"content": "Title: Unraveling the mystery of Covid-19 Cytokine storm: From skin to organ systems Content: COVID-19 is a global pandemic that emerged from Wuhan, China. Besides pneumonia and acute respiratory distress syndrome, the disease leads to multisystem involvement in the form of myocarditis, arrhythmias, cardiac arrest, gastrointestinal symptoms, hypoxemic brain injury, acute liver and renal function impairment. There are also reports of cutaneous lesions in form of urticarial and maculopapular rashes, chilblain like fingers and toes (covid feet), livedoid vasculopathy and chicken-pox like or varicelliform vesicles. Clinically, many of these skin lesions are likely secondary to occlusion of small to medium blood vessels due to microthrombi formation or due to viral laden antigen-antibody immune complexes; and same explanation may hold true for possible hypoxemic injury simultaneously occurring in other vital organs like lungs, heart, brain and kidneys. The histopathology, immunoflorescence and RT-PCR analysis of skin biopsies can provide useful insights for ascertaining the pathogenesis of this complex viral syndrome. Apparently, it is interplay of disarmed cellular immunity and over-activated humoral immunity that culminates in end-organ changes. The morbidity and mortality can be significantly reduced by upgrading the cellular immunity and downgrading the humoral response; along with prevention of hypoxemic and reperfusion injuries by using antivirals, immunomodulators, antioxidants, anti-platelets and anticoagulants in judicious and phased manner. This article is protected by copyright. All rights reserved.", "qid": 34, "docid": "ve83421h", "rank": 75, "score": 0.840824544429779}, {"content": "Title: Allergy and asthma in children and adolescents during the COVID outbreak: What we know and how we could prevent allergy and asthma flares Content: Coronavirus disease 2019 (COVID-19) pandemic is affecting people at any age with a more severe course in patients with chronic diseases or comorbidities, males and elderly patients. The Center for Disease Control and Prevention (CDC) initially proposed that patients with chronic lung diseases, including moderate-severe asthma, and allergy may have a higher risk of developing severe COVID-19 than otherwise healthy people (https://www.cdc.gov/coronavirus/2019-ncov/specific-groups/asthma.html).", "qid": 34, "docid": "9a18h2tr", "rank": 76, "score": 0.8406612873077393}, {"content": "Title: Allergy and asthma in children and adolescents during the COVID outbreak: what we know and how we could prevent allergy and asthma flares? Content: Coronavirus disease 2019 (COVID-19) pandemic is affecting people at any age with a more severe course in patients with chronic diseases or comorbidities, males and elderly patients. The Center for Disease Control and Prevention (CDC) initially proposed that patients with chronic lung diseases, including moderate-severe asthma, and allergy may have a higher risk of developing severe COVID-19 than otherwise healthy people (https://www.cdc.gov/coronavirus/2019-ncov/specific-groups/asthma.html).", "qid": 34, "docid": "3d9irptg", "rank": 77, "score": 0.8406612873077393}, {"content": "Title: COVID-19 pandemic. What should PRM specialists do? A clinician's perspective Content: BACKGROUND: COVID-19 pandemic is rapidly spreading all over the world, creating the risk for an healthcare collapse. While acute care and intensive care units are the main pillars of the early response to the disease, rehabilitative medicine should play an important part in allowing COVID-19 survivors to reduce disability and optimize the function of acute hospital setting. AIM: To share the experience and the international perspective of different rehabilitation centers, treating COVID-19 survivors. DESIGN: Not applicable. POPULATION: COVID-19 survivors. METHODS: A group of Physical Medicine & Rehabilitation specialists from eleven different countries in Europe and North America have shared their clinical experience in dealing with COVID-19 survivors and how they have managed the re-organization of rehabilitation services. RESULTS: In our experience the most important sequelae of severe and critical forms of COVID-19 are: 1) respiratory; 2) cognitive, central and peipheral nervous system; 3) deconditioning; 4) critical illness related myopathy and neuropathy; 5) dysphagia; 6) joint stiffness and pain; 7) psychiatric. CONCLUSIONS: We analyze all these consequences and propose some practical treatment options, based on current evidence and clinical experience, as well as several suggestions for management of rehabilitation services and patients with suspected or confirmed infection by SARS-CoV-2. CLINICAL REHABILITATION IMPACT: COVID-19 survivors have some specific rehabilitation needs. Experience from other centers may help colleagues in organizing their services and providing better care to their patients.", "qid": 34, "docid": "99b09xpi", "rank": 78, "score": 0.840570330619812}, {"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": 34, "docid": "u42iq0jk", "rank": 79, "score": 0.8405431509017944}, {"content": "Title: Population based estimates of comorbidities affecting risk for complications from COVID-19 in the US Content: We used 2017 Behavioral Risk Factor Surveillance System (BRFSS) data (N=444,649) to estimate the proportion of US adults who report comorbidities that suggest heightened risk of complications from COVID-19. Co-morbidities included cardiovascular disease, chronic obstructive pulmonary disease (COPD), diabetes, asthma, hypertension, and/or cancer other than skin, based on data from China. Overall 45.4% (95% CI 45.1-45.7) of adults reported any of the 6 comorbidities, increasing from 19.8% (19.1-20.4) for ages 18-29 years to 80.7% (79.5-81.8) for ages 80+ years. State rates ranged from 37.3% (36.2-38.5) in Utah to 58.7% (57.0-60.4) in West Virginia. Rates also varied by race/ethnicity, health insurance status, and employment. Excluded were residents of nursing homes or assisted living facilities. Although almost certainly an underestimate of all adults at risk due to these exclusions, these results should help in estimating healthcare needs for adults with COVID-19 complications living in the community.", "qid": 34, "docid": "a9lw6vrs", "rank": 80, "score": 0.8403722047805786}, {"content": "Title: Disability through COVID\u201019 pandemic: Neurorehabilitation cannot wait Content: Coronavirus disease 2019 (CoViD\u201019) pandemic is strongly impacting all domains of our healthcare systems, including rehabilitation. In Italy, the first hit European country, medical activities were postponed to allow shifting of staff and facilities to intensive care, with neurorehabilitation limited to time\u2010dependent diseases,(1) including CoViD\u201019 complications.(2,3) Hospital access to people with chronic neurodegenerative conditions such as multiple sclerosis, movement disorders or dementia, more at risks of serious consequences from the infection,(4) has been postponed. Patients also seek less for hospital care, with over 50% reduced stroke admissions as from an Italian survey,(5) possibly in fear of being infected or denied to see their families after being hospitalized. This situation can be bearable only for a short time, as any initial freezing reaction to a danger.", "qid": 34, "docid": "c8tgl9gy", "rank": 81, "score": 0.840137243270874}, {"content": "Title: Recommendations for the care of patients with heart failure and COVID-19. Content: The COVID-19 pandemic decreed by the World Health Organization (WHO) since March 12, 2020 is wreaking havoc globally and it is a true economic, social and health challenge. Although the clinical manifestations of COVID-19 are respiratory symptoms, some patients also have cardiological symptoms. Among patients with cardiological conditions2 they represent a group of higher risk and, in fact, they are a particularly vulnerable group, due to their higher risk of contagion and greater severity in case of acquiring the disease1 those with heart failure (HF), including heart transplant (CT) and ventricular assists, as well as patients with pulmonary arterial hypertension (PAH). HF is the main chronic cardiovascular disease and patients in this group are the most vulnerable for the development of more serious clinical symptoms after suffering the infection, and to a greater extent cases with advanced HF3. In fact, HF is one of the most frequent complications in patients with COVID-194. Likewise, transplant patients who require immunosuppressants to avoid graft rejection, constitute a population especially susceptible to infection and to develop more serious processes. This situation has made the National Association of Cardiologists of Mexico (ANCAM) and the Mexican Society of Cardiology (SMC) together with their respective chapters, have prepared the following recommendations for medical personnel, who participate in the care of this special group of patients in the different clinical settings, who suffer or not, of COVID-19.", "qid": 34, "docid": "cp23x6lp", "rank": 82, "score": 0.8400802612304688}, {"content": "Title: Rehabilitation and respiratory management in the acute and early post-acute phase. \"Instant paper from the field\" on rehabilitation answers to the Covid-19 emergency. Content: Covid-19 is a respiratory infectious disease that can cause respiratory, physical and psychological long-term dysfunctions in patients. First recommendations on respiratory management were published, but they were not based on the specific needs due to Covid-19. In this paper we share the early experiences from the clinical field in Northern Italy, where the epidemic started in February. This paper summarizes the second webinar on Covid-19 (230 live attendees, 11,600 viewers of the recorded version) organized by the Italian Society of Physical and Rehabilitation Medicine about rehabilitation and in particular respiratory management in the acute (Intensive Care Unit - ICU) and immediate post-acute phases. There is the need to prepare for the post-acute phase. ICU length of stay is relatively long, with immobilisation in prone position. Some specific problems are described, including severe muscle weakness and fatigue, joint stiffness, dysphagia, (neuro)psychological problems, impaired functioning concerning mobility, activities of daily life and work. A lot is yet unknown and patients can experience long-term consequences as we know from the literature on the post-intensive care syndrome, but Covid-19 has unique features to be investigated and understood. As one colleague stated during the Covinar: this is a marathon, not a sprint\u2026.", "qid": 34, "docid": "2exi7j6u", "rank": 83, "score": 0.8399219512939453}, {"content": "Title: Personalized therapy approach for hospitalized patients with COVID-19 Content: Hospitalized patients with COVID-19 experiencing respiratory symptoms have different complications (inflammatory, co-infection and thrombotic) that are identifiable by analytics patterns. Personalized treatment decisions decreased early mortality (OR 0.144, CI 0.03-0.686; p=0.015). Increasing age (OR 1.06; p=0.038) and therapeutic effort limitation (OR 9.684; p<0.001) were associated with higher mortality.", "qid": 34, "docid": "w4o1tfnb", "rank": 84, "score": 0.8398692607879639}, {"content": "Title: Personalized therapy approach for hospitalized patients with COVID-19. Content: Hospitalized patients with COVID-19 experiencing respiratory symptoms have different complications (inflammatory, co-infection and thrombotic) that are identifiable by analytics patterns. Personalized treatment decisions decreased early mortality (OR 0.144, CI 0.03-0.686; p=0.015). Increasing age (OR 1.06; p=0.038) and therapeutic effort limitation (OR 9.684; p<0.001) were associated with higher mortality.", "qid": 34, "docid": "j8evgl7s", "rank": 85, "score": 0.8398692607879639}, {"content": "Title: Chronic Living in a Communicable World Content: By April 2020, COVID-19 lockdowns had restricted the movements of over half the world's population. As health authorities advise people living with chronic conditions to self-isolate because they are at particular risk of serious complications and death, the epidemiological split between communicable and noncommunicable disease is tenuous. We argue that much more is at stake for people living with (multiple) medical conditions than being \"at risk\" of infection of coronavirus. We emphasize the need to attend to the long-term effects of COVID-19, but also the importance of the continued care of people living with other lifelong medical conditions.", "qid": 34, "docid": "gmcj27xz", "rank": 86, "score": 0.8398386836051941}, {"content": "Title: Chronic Living in a Communicable World. Content: By April 2020, COVID-19 lockdowns had restricted the movements of over half the world's population. As health authorities advise people living with chronic conditions to self-isolate because they are at particular risk of serious complications and death, the epidemiological split between communicable and noncommunicable disease is tenuous. We argue that much more is at stake for people living with (multiple) medical conditions than being \"at risk\" of infection of coronavirus. We emphasize the need to attend to the long-term effects of COVID-19, but also the importance of the continued care of people living with other lifelong medical conditions.", "qid": 34, "docid": "xui949ap", "rank": 87, "score": 0.8398386836051941}, {"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": 34, "docid": "r4e4tg7r", "rank": 88, "score": 0.8398265838623047}, {"content": "Title: Haddon Matrix for Kidney Transplantation during COVID-19 Pandemic: A Problem Solving Framework for Present and Future Content: Novel coronavirus disease 2019 (COVID-19) pandemic is a public health emergency with several million worldwide and a quarter of a million and soon half a million deaths including a third in the United States alone (as of May 10, 2020).1 It affects kidney transplantation and has caused mortality in waitlist dialysis and transplant patients.2,3 This inevitably raises questions about the practicality and direction of transplant surgeries during this critical period.", "qid": 34, "docid": "llhbfrax", "rank": 89, "score": 0.8393715023994446}, {"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": 34, "docid": "wkp58iov", "rank": 90, "score": 0.8392758369445801}, {"content": "Title: \u201cClinical Characteristics, Outcomes and Prognosticators in Adult Patients Hospitalized with COVID-19\u201d Content: BACKGROUND: COVID-19 is a novel disease caused by SARS-CoV-2. METHODS: We conducted a retrospective evaluation of patients admitted with COVID-19 to one site in March 2020. Patients were stratified into three groups: survivors who did not receive mechanical ventilation (MV), survivors who received MV and those who received MV and died during hospitalization. RESULTS: There were 140 hospitalizations; 22 deaths (mortality rate 15.7%), 83 (59%) survived and did not receive MV, 35 (25%) received MV and survived; 18 (12.9%) received MV and died. Thee mean age of each group was 57.8, 55.8 and 72.7 years respectively (p=.0001). Of those who received MV and died, 61% were male (p=.01). More than half the patients (n=90, 64%) were African American. First measured d-dimer >575.5 ng/mL, procalcitonin > 0.24 ng/mL, LDH > 445.6 units/L and BNP > 104.75 pg/mL had odds ratios of 10.5, 5, 4.5 and 2.9 respectively for MV (p < .05 for all). Peak BNP > 167.5 pg/mL had an odds ratio of 6.7 for inpatient mortality when mechanically ventilated (p= .02). CONCLUSIONS: Age and gender may impact outcomes in COVID-19. D-dimer, procalcitonin, LDH and BNP may serve as early indicators of disease trajectory.", "qid": 34, "docid": "rluya5ui", "rank": 91, "score": 0.8392287492752075}, {"content": "Title: \"Clinical Characteristics, Outcomes and Prognosticators in Adult Patients Hospitalized with COVID-19\" Content: BACKGROUND: COVID-19 is a novel disease caused by SARS-CoV-2. METHODS: We conducted a retrospective evaluation of patients admitted with COVID-19 to one site in March 2020. Patients were stratified into three groups: survivors who did not receive mechanical ventilation (MV), survivors who received MV and those who received MV and died during hospitalization. RESULTS: There were 140 hospitalizations; 22 deaths (mortality rate 15.7%), 83 (59%) survived and did not receive MV, 35 (25%) received MV and survived; 18 (12.9%) received MV and died. Thee mean age of each group was 57.8, 55.8 and 72.7 years respectively (p=.0001). Of those who received MV and died, 61% were male (p=.01). More than half the patients (n=90, 64%) were African American. First measured d-dimer >575.5 ng/mL, procalcitonin > 0.24 ng/mL, LDH > 445.6 units/L and BNP > 104.75 pg/mL had odds ratios of 10.5, 5, 4.5 and 2.9 respectively for MV (p < .05 for all). Peak BNP > 167.5 pg/mL had an odds ratio of 6.7 for inpatient mortality when mechanically ventilated (p= .02). CONCLUSIONS: Age and gender may impact outcomes in COVID-19. D-dimer, procalcitonin, LDH and BNP may serve as early indicators of disease trajectory.", "qid": 34, "docid": "ylzuh3t3", "rank": 92, "score": 0.8392286896705627}, {"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": 34, "docid": "0ec1cu8q", "rank": 93, "score": 0.8389699459075928}, {"content": "Title: Clinical characteristics and durations of hospitalized patients with COVID-19 in Beijing: a retrospective cohort study Content: Background: COVID-19 is still becoming an increasing global threat to public health. More detailed and specific characteristics of COVID-19 are needed to better understand this disease. Additionally, durations of COVID-19, e.g., the average time from exposure to recovery, which is of great value in understanding this disease, has not been reported so far. Aims: To give the information on clinical characteristics and different durations of COVID-19 and to identify the potential risk factors for longer hospitalization duration. Methods: In this retrospective study, we enrolled 77 patients (mean age: 52 years; 44.2% males) with laboratory-confirmed COVID-19 admitted to Beijing YouAn Hospital during 21st Jan and 8th February 2020. Epidemiological, clinical and radiological data on admission were collected; complications and outcomes were followed up until 29th February 2020. The study endpoint was the discharge within two weeks. Cox proportional-hazards regression was performed to identify risk factors for longer hospitalization duration. Results: Of 77 patients, there are 34 (44.2%) males, 24 (31.2%) with comorbidities, 22 (28.6%) lymphopenia, 20 (26.0%) categorized as severe patients, and 28 (36.4%) occurred complications. By the end of follow-up, 64 (83.1%) patients were discharged home after being tested negative for SARS-CoV-2 infections, 8 remained in hospital and 5 died. 36 (46.8%) patients were discharged within 14 days and thus reached the study endpoint, including 34 (59.6%) of 57 non-severe patients and 2 (10%) of 20 severe patients. The overall cumulative probability of the endpoint was 48.3%. Hospital length of stay and duration of exposure to discharge for 64 discharged patients were 13 (10-16.5) and 23 (18-24.5) days, respectively. Multivariable stepwise Cox regression model showed bilateral pneumonia on CT scan, shorter time from the illness onset to admission, the severity of disease and lymphopenia were independently associated with longer hospitalized duration. Conclusions: COVID-19 has significantly shorter duration of disease and hospital length of stay than SARS. Bilateral pneumonia on CT scan, shorter period of illness onset to admission, lymphopenia, the severity of disease are the risk factors for longer hospitalization duration of COVID-19.", "qid": 34, "docid": "n0uwy77g", "rank": 94, "score": 0.8389483690261841}, {"content": "Title: Cardiovascular complications in COVID-19 Content: BACKGROUND: The coronavirus disease of 2019 (COVID-19) is caused by the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). While systemic inflammation and pulmonary complications can result in significant morbidity and mortality, cardiovascular complications may also occur. OBJECTIVE: This brief report evaluates cardiovascular complications in the setting of COVID-19 infection. DISCUSSION: The current COVID-19 pandemic has resulted in over one million infected worldwide and thousands of death. The virus binds and enters through angiotensin-converting enzyme 2 (ACE2). COVID-19 can result in systemic inflammation, multiorgan dysfunction, and critical illness. The cardiovascular system is also affected, with complications including myocardial injury, myocarditis, acute myocardial infarction, heart failure, dysrhythmias, and venous thromboembolic events. Current therapies for COVID-19 may interact with cardiovascular medications. CONCLUSIONS: Emergency clinicians should be aware of these cardiovascular complications when evaluating and managing the patient with COVID-19.", "qid": 34, "docid": "hl225efn", "rank": 95, "score": 0.8388336896896362}, {"content": "Title: Profile of RT-PCR for SARS-CoV-2: a preliminary study from 56 COVID-19 patients Content: A novel coronavirus (COVID-19) pandemic threatens the world. Here, we first studied the dynamics profile of SARS-CoV-2 from 56 recovered COVID-19 patients. We found virus shedding was up to 6 weeks after onset of symptoms. Prolonged observation period is necessary for older patients.", "qid": 34, "docid": "4awl1ocd", "rank": 96, "score": 0.8388203382492065}, {"content": "Title: The potential long-term impact of the COVID-19 outbreak on patients with non-communicable diseases in Europe: consequences for healthy ageing Content: The early stages of the COVID-19 pandemic have focused on containing SARS-CoV-2 infection and identifying treatment strategies. While controlling this communicable disease is of utmost importance, the long-term effect on individuals with non-communicable diseases (NCD) is significant. Although certain NCDs appear to increase the severity of COVID-19 and mortality risk, SARS-CoV-2 infection in survivors with NCDs may also affect the progression of their pre-existing clinical conditions. Infection containment measures will have substantial short- and long-term consequences; social distancing and quarantine restrictions will reduce physical activity and increase other unhealthy lifestyles, thus increasing NCD risk factors and worsening clinical symptoms. Vitamin D levels might decrease and there might be a rise in mental health disorders. Many countries have made changes to routine management of NCD patients, e.g., cancelling non-urgent outpatient visits, which will have important implications for NCD management, diagnosis of new-onset NCDs, medication adherence, and NCD progression. We may have opportunities to learn from this unprecedented crisis on how to leverage healthcare technologies and improve procedures to optimize healthcare service provision. This article discusses how the COVID-19 outbreak and related infection control measures could hit the most frail individuals, worsening the condition of NCD patients, while further jeopardizing the sustainability of the healthcare systems. We suggest ways to define an integrated strategy that could involve both public institutional entities and the private sector to safeguard frail individuals and mitigate the impact of the outbreak.", "qid": 34, "docid": "bcd0y9c1", "rank": 97, "score": 0.8387311697006226}, {"content": "Title: SARS\u2010CoV\u20102 pandemic and the need for transplant\u2010oriented trials Content: After the first reported case of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection in Wuhan, China, in December 2019, the contagion has spread rapidly and has become a global pandemic.1 There are as of yet no published studies beyond the case series describing the incidence and clinical course of COVID-19 in transplant recipients, a population potentially at high risk due to the ongoing immunosuppression and higher risk of comorbidities.2 This pandemic has had a major impact in transplant physicians and healthcare workers as well3 and this crisis has meant reducing or even interrupting transplant program activity, with a subsequent impact on patient morbidity and mortality that is still hard to quantify.", "qid": 34, "docid": "8of2wyfd", "rank": 98, "score": 0.8385492563247681}, {"content": "Title: Potential implications of COVID\u201019 in non\u2010alcoholic fatty liver disease Content: COVID-19 burdens all areas of healthcare, and the relationship between COVID-19 and liver injury is being examined. The recently published papers by Xu et al and Xie et al nicely describe liver injury resulting from COVID-191,2 . As with many papers the focus lies on patients without pre-existing liver disease, even though it has been suggested that pre-existing conditions affect COVID-19.", "qid": 34, "docid": "easnz0u1", "rank": 99, "score": 0.8383373022079468}, {"content": "Title: COVID-19 and Multiorgan Response Content: Since the outbreak and rapid spread of COVID-19 starting late December 2019, it has been apparent that disease prognosis has largely been influenced by multiorgan involvement. Comorbidities such as cardiovascular diseases have been the most common risk factors for severity and mortality. The hyperinflammatory response of the body, coupled with the plausible direct effects of severe acute respiratory syndrome on body-wide organs via angiotensin-converting enzyme 2, has been associated with complications of the disease. Acute respiratory distress syndrome, heart failure, renal failure, liver damage, shock, and multiorgan failure have precipitated death. Acknowledging the comorbidities and potential organ injuries throughout the course of COVID-19 is therefore crucial in the clinical management of patients. This paper aims to add onto the ever-emerging landscape of medical knowledge on COVID-19, encapsulating its multiorgan impact.", "qid": 34, "docid": "fmri74v7", "rank": 100, "score": 0.8382912874221802}]}
{"query": "What new public datasets are available related to COVID-19?", "hits": [{"content": "Title: COVID-19: A Survey on Public Medical Imaging Data Resources Content: This regularly updated survey provides an overview of public resources that offer medical images and metadata of COVID-19 cases. The purpose of this survey is to simplify the access to open COVID-19 image data resources for all scientists currently working on the coronavirus crisis.", "qid": 35, "docid": "z0bkpmpk", "rank": 1, "score": 0.8721360564231873}, {"content": "Title: Comparing and Integrating US COVID-19 Daily Data from Multiple Sources: A County-Level Dataset with Local Characteristics Content: Over the past several months, the outbreak of COVID-19 has been expanding over the world. A reliable and accurate dataset of the cases is vital for scientists to conduct related research and for policy-makers to make better decisions. We collect the COVID-19 daily reported data from four open sources: the New York Times, the COVID-19 Data Repository by Johns Hopkins University, the COVID Tracking Project at the Atlantic, and the USAFacts, and compare the similarities and differences among them. In addition, we examine the following problems which occur frequently: (1) the order dependencies violation, (2) the delay-reported issue on weekends and/or holidays, and (3) abnormal data point or data period. We also integrate the COVID-19 reported cases with the county-level auxiliary information of the local features from official sources, such as health infrastructure, demographic, socioeconomic, and environment information, which are important for understanding the spread of the virus.", "qid": 35, "docid": "yfuq8na6", "rank": 2, "score": 0.8584218621253967}, {"content": "Title: A New Resource for Genomics and Precision Health Information and Publications on the Investigation and Control of COVID-19 and other Coronaviruses Content: Summary We developed a new online database that contains the most updated published scientific literature, online news and reports, CDC and National Institutes of Health (NIH) resources. The tool captures emerging discoveries and applications of genomics, molecular, and other precision medicine and precision public health tools in the investigation and control of coronavirus diseases, including COVID-19, MERS-CoV, and SARS. Availability Coronavirus Disease Portal (CDP) can be freely accessed via https://phgkb.cdc.gov/PHGKB/coVInfoStartPage.action. Contact wyu@cdc.gov", "qid": 35, "docid": "1s0hhx71", "rank": 3, "score": 0.8581339120864868}, {"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": 4, "score": 0.8510706424713135}, {"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": 5, "score": 0.8489500880241394}, {"content": "Title: An Interactive Online Dashboard for Tracking COVID-19 in U.S. Counties, Cities, and States in Real Time Content: OBJECTIVE: To create an online resource that informs the public of COVID-19 outbreaks in their area. MATERIALS AND METHODS: This R Shiny application aggregates data from multiple resources that track COVID-19 and visualizes them through an interactive, online dashboard. RESULTS: The web resource, called the COVID-19 Watcher, can be accessed at https://covid19watcher.research.cchmc.org/. It displays COVID-19 data from every county and 188 metropolitan areas in the U.S. Features include rankings of the worst affected areas and auto-generating plots that depict temporal changes in testing capacity, cases, and deaths. DISCUSSION: The Centers for Disease Control and Prevention (CDC) do not publish COVID-19 data for local municipalities, so it is critical that academic resources fill this void so the public can stay informed. The data used have limitations and likely underestimate the scale of the outbreak. CONCLUSIONS: The COVID-19 Watcher can provide the public with real-time updates of outbreaks in their area.", "qid": 35, "docid": "9kb1tt5d", "rank": 6, "score": 0.8443915843963623}, {"content": "Title: Preserva\u00e7\u00e3o da privacidade no enfrentamento da COVID-19: dados pessoais e a pandemia global./ Preserva\u00e7\u00e3o da privacidade no enfrentamento da COVID-19: dados pessoais e a pandemia global./ Personal data usage and privacy considerations in the COVID-19 global pandemic Content: Data has become increasingly important and valuable for both scientists and health authorities searching for answers to the COVID-19 crisis. Due to difficulties in diagnosing this infection in populations around the world, initiatives supported by digital technologies are being developed by governments and private companies to enable the tracking of the public's symptoms, contacts and movements. Considering the current scenario, initiatives designed to support infection surveillance and monitoring are essential and necessary. Nonetheless, ethical, legal and technical questions abound regarding the amount and types of personal data being collected, processed, shared and used in the name of public health, as well as the concomitant or posterior use of this data. These challenges demonstrate the need for new models of responsible and transparent data and technology governance in efforts to control SARS-COV2, as well as in future public health emergencies.", "qid": 35, "docid": "d0f7qux9", "rank": 7, "score": 0.8431444764137268}, {"content": "Title: Personal data usage and privacy considerations in the COVID-19 global pandemic. Content: Data has become increasingly important and valuable for both scientists and health authorities searching for answers to the COVID-19 crisis. Due to difficulties in diagnosing this infection in populations around the world, initiatives supported by digital technologies are being developed by governments and private companies to enable the tracking of the public's symptoms, contacts and movements. Considering the current scenario, initiatives designed to support infection surveillance and monitoring are essential and necessary. Nonetheless, ethical, legal and technical questions abound regarding the amount and types of personal data being collected, processed, shared and used in the name of public health, as well as the concomitant or posterior use of this data. These challenges demonstrate the need for new models of responsible and transparent data and technology governance in efforts to control SARS-COV2, as well as in future public health emergencies.", "qid": 35, "docid": "03nh2f1g", "rank": 8, "score": 0.8431444764137268}, {"content": "Title: COVID-19: Open-data resources for monitoring, modeling, and forecasting the epidemic Content: We provide an insight into the open-data resources pertinent to the study of the spread of the Covid-19 pandemic and its control. We identify the variables required to analyze fundamental aspects like seasonal behavior, regional mortality rates, and effectiveness of government measures. Open-data resources, along with data-driven methodologies, provide many opportunities to improve the response of the different administrations to the virus. We describe the present limitations and difficulties encountered in most of the open-data resources. To facilitate the access to the main open-data portals and resources, we identify the most relevant institutions, on a global scale, providing Covid-19 information and/or auxiliary variables (demographics, mobility, etc.). We also describe several open resources to access Covid-19 datasets at a country-wide level (i.e., China, Italy, Spain, France, Germany, US, etc.). To facilitate the rapid response to the study of the seasonal behavior of Covid-19, we enumerate the main open resources in terms of weather and climate variables. We also assess the reusability of some representative open-data sources.", "qid": 35, "docid": "iukudcbo", "rank": 9, "score": 0.8425186276435852}, {"content": "Title: Dataset for country profile and mobility analysis in the assessment of COVID-19 pandemic Content: Understanding the COVID-19 pandemic is a multidisciplinary effort that requires a significant number of variables. This dataset comprises (i) sociodemographic characteristics, compiled from 35 datasets obtained at UN Data; (ii) mobility metrics that can assist the analysis of social distancing, from Google Community Mobility Reports and; (iii) daily counts of cases and deaths by COVID-19, from the European Centre for Disease Prevention and Control and the Johns Hopkins University Center for Systems Science and Engineering. This unified dataset ranges from February 15, 2020 to April 26, 2020, a total of 72 days, and is provided as a collection of time series for 131 countries with 192 variables. The pipeline to preprocess and generate the dataset, along with the dataset itself, are versioned with the Data Version Control tool (DVC) and are thus easily reproducible.", "qid": 35, "docid": "2llnlr8a", "rank": 10, "score": 0.842412531375885}, {"content": "Title: A real-time policy dashboard can aid global transparency in the response to coronavirus disease 2019 Content: There has been great provision of open data across the coronavirus disease 2019 (COVID-19) pandemic response, with, for example, dashboards presenting real-time descriptions of new daily cases and risk factors. Transparency has been an important discussion point and there have been concerns and criticisms of governments for not publishing the evidence base that is informing their decision-making. A 'policy dashboard' could act as a hub to show the localised reasoning behind COVID-19 policy decisions and allow the global health community to provide further support to governments and international stakeholders.", "qid": 35, "docid": "z2hobz7x", "rank": 11, "score": 0.840157151222229}, {"content": "Title: A real-time policy dashboard can aid global transparency in the response to coronavirus disease 2019. Content: There has been great provision of open data across the coronavirus disease 2019 (COVID-19) pandemic response, with, for example, dashboards presenting real-time descriptions of new daily cases and risk factors. Transparency has been an important discussion point and there have been concerns and criticisms of governments for not publishing the evidence base that is informing their decision-making. A 'policy dashboard' could act as a hub to show the localised reasoning behind COVID-19 policy decisions and allow the global health community to provide further support to governments and international stakeholders.", "qid": 35, "docid": "n9ux7gqm", "rank": 12, "score": 0.840157151222229}, {"content": "Title: COVID-19 Government Response Event Dataset (CoronaNet v.1.0) Content: Governments worldwide have implemented countless policies in response to the COVID-19 pandemic. We present an initial public release of a large hand-coded dataset of over 13,000 such policy announcements across more than 195 countries. The dataset is updated daily, with a 5-day lag for validity checking. We document policies across numerous dimensions, including the type of policy, national versus subnational enforcement, the specific human group and geographical region targeted by the policy, and the time frame within which each policy is implemented. We further analyse the dataset using a Bayesian measurement model, which shows the quick acceleration of the adoption of costly policies across countries beginning in mid-March 2020 through 24 May 2020. We believe that these data will be instrumental for helping policymakers and researchers assess, among other objectives, how effective different policies are in addressing the spread and health outcomes of COVID-19.", "qid": 35, "docid": "x7v4iwts", "rank": 13, "score": 0.8394107222557068}, {"content": "Title: COVID-19 Government Response Event Dataset (CoronaNet v.1.0). Content: Governments worldwide have implemented countless policies in response to the COVID-19 pandemic. We present an initial public release of a large hand-coded dataset of over 13,000 such policy announcements across more than 195 countries. The dataset is updated daily, with a 5-day lag for validity checking. We document policies across numerous dimensions, including the type of policy, national versus subnational enforcement, the specific human group and geographical region targeted by the policy, and the time frame within which each policy is implemented. We further analyse the dataset using a Bayesian measurement model, which shows the quick acceleration of the adoption of costly policies across countries beginning in mid-March 2020 through 24 May 2020. We believe that these data will be instrumental for helping policymakers and researchers assess, among other objectives, how effective different policies are in addressing the spread and health outcomes of COVID-19.", "qid": 35, "docid": "4dgvuaxr", "rank": 14, "score": 0.8394107222557068}, {"content": "Title: Data-driven Analytical Models of COVID-2019 for Epidemic Prediction, Clinical Diagnosis, Policy Effectiveness and Contact Tracing: A Survey Content: The widely spread CoronaVirus Disease (COVID)-19 is one of the worst infectious disease outbreaks in history and has become an emergency of primary international concern. As the pandemic evolves, academic communities have been actively involved in various capacities, including accurate epidemic estimation, fast clinical diagnosis, policy effectiveness evaluation and development of contract tracing technologies. There are more than 23,000 academic papers on the COVID-19 outbreak, and this number is doubling every 20 days while the pandemic is still on-going [1]. The literature, however, at its early stage, lacks a comprehensive survey from a data analytics perspective. In this paper, we review the latest models for analyzing COVID19 related data, conduct post-publication model evaluations and cross-model comparisons, and collect data sources from different projects.", "qid": 35, "docid": "xe0dhx4o", "rank": 15, "score": 0.838948130607605}, {"content": "Title: A Joint Dataset of Official COVID-19 Reports and the Governance, Trade and Competitiveness Indicators of World Bank Group Platforms Content: The presented cross-sectional dataset can be employed to analyze the governmental, trade, and competitiveness relationships of official COVID-19 reports. It contains 18 COVID-19 variables generated based on the official reports of 138 countries [1,2], as well as an additional 2203 governance, trade, and competitiveness indicators from the World Bank Group GovData360[3] and TCdata360[4] platforms. From these platforms, only annual indicators from 2015 and later were collected, and their missing values were replaced with previous annual values, in descending order by year, until 2015. During preprocessing, indicators (columns) were filtered out when the ratio of missing values exceeded 50%. Then, the same filtration was applied for the ratio of missing values above 25% in the case of countries (rows). Finally, duplicated variables were removed from the dataset. As a result of these steps, the missing value rate of the employed indicators was reduced to 4.25% on average. In addition to the database, the Kendall rank correlation matrix is provided to facilitate subsequent analysis. The dataset and the correlation matrix can be updated and customized with an R Notebook file, which is also available publicly in Mendeley Data [5].", "qid": 35, "docid": "6vmgqamd", "rank": 16, "score": 0.8380496501922607}, {"content": "Title: CORD-19: The Covid-19 Open Research Dataset. Content: The Covid-19 Open Research Dataset (CORD-19) is a growing resource of scientific papers on Covid-19 and related historical coronavirus research. CORD-19 is designed to facilitate the development of text mining and information retrieval systems over its rich collection of metadata and structured full text papers. Since its release, CORD-19 has been downloaded over 75K times and has served as the basis of many Covid-19 text mining and discovery systems. In this article, we describe the mechanics of dataset construction, highlighting challenges and key design decisions, provide an overview of how CORD-19 has been used, and preview tools and upcoming shared tasks built around the dataset. We hope this resource will continue to bring together the computing community, biomedical experts, and policy makers in the search for effective treatments and management policies for Covid-19.", "qid": 35, "docid": "pt8nh7wx", "rank": 17, "score": 0.8368048071861267}, {"content": "Title: Open Data Resources for Fighting COVID-19 Content: We provide an insight into the open data resources pertinent to the study of the spread of Covid-19 pandemic and its control. We identify the variables required to analyze fundamental aspects like seasonal behaviour, regional mortality rates, and effectiveness of government measures. Open data resources, along with data-driven methodologies, provide many opportunities to improve the response of the different administrations to the virus. We describe the present limitations and difficulties encountered in most of the open-data resources. To facilitate the access to the main open-data portals and resources, we identify the most relevant institutions, at a world scale, providing Covid-19 information and/or auxiliary variables (demographics, mobility, etc.). We also describe several open resources to access Covid-19 data-sets at a country-wide level (i.e. China, Italy, Spain, France, Germany, U.S., etc.). In an attempt to facilitate the rapid response to the study of the seasonal behaviour of Covid-19, we enumerate the main open resources in terms of weather and climate variables. CONCO-Team: The authors of this paper belong to the CONtrol COvid-19 Team, which is composed of different researches from universities of Spain, Italy, France, Germany, United Kingdom and Argentina. The main goal of CONCO-Team is to develop data-driven methods for the better understanding and control of the pandemic.", "qid": 35, "docid": "lysvg3vw", "rank": 18, "score": 0.836802065372467}, {"content": "Title: Common Pitfalls in the Interpretation of COVID-19 Data and Statistics Content: Policymakers, experts and the general public heavily rely on the data that are being reported in the context of the coronavirus pandemic. Daily data releases on confirmed COVID-19 cases and deaths provide information on the course of the pandemic.", "qid": 35, "docid": "zbjig3pt", "rank": 19, "score": 0.8365341424942017}, {"content": "Title: CovidCounties - an interactive, real-time tracker of the COVID-19 pandemic at the level of US counties Content: Management of the COVID-19 pandemic has proven to be a significant challenge to policy makers. This is in large part due to uneven reporting and the absence of open-access visualization tools to present local trends and infer healthcare needs. Here we report the development of CovidCounties.org, an interactive web application that depicts daily disease trends at the level of US counties using time series plots and maps. This application is accompanied by a manually curated dataset that catalogs all major public policy actions made at the state-level, as well as technical validation of the primary data. Finally, the underlying code for the site is also provided as open source, enabling others to validate and learn from this work.", "qid": 35, "docid": "07v9qign", "rank": 20, "score": 0.8359733819961548}, {"content": "Title: Autopsy registry can facilitate COVID-19 research Content: The WHO declared the global outbreak of SARS-CoV-2 a pandemic on March 11, 2020, and \"call(ed) on all countries to exchange country experiences and practices in a transparent and timely way\" (http://www.euro.who.int/en/health-topics/health-emergencies/pages/news/news/2020/03/who-announces-covid-19-outbreak-a-pandemic). To date, many medical societies have announced their intention to collect and analyze data from COVID-19 patients and some large-scale prospective data collections are already running, such as the LEOSS registry (Lean European Open Survey on SARS-CoV-2 Infected Patients) or the CAPACITYCOVID registry (registry of patients with COVID-19 including cardiovascular risk and complications). The necessity to mobilize and harmonize basic and applied research worldwide is of utmost importance (Sansonetti, 2020).", "qid": 35, "docid": "oll9usqd", "rank": 21, "score": 0.8351745009422302}, {"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": 22, "score": 0.8351445198059082}, {"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": 35, "docid": "r0gr0bhl", "rank": 23, "score": 0.8348759412765503}, {"content": "Title: A review of mathematical modeling, artificial intelligence and datasets used in the study, prediction and management of COVID-19 Content: In the past few months, several works were published in regards to the dynamics and early detection of COVID-19 via mathematical modeling and Artificial intelligence (AI). The aim of this work is to provide the research community with comprehensive overview of the methods used in these studies as well as a compendium of available open source datasets in regards to COVID-19. In all, 61 journal articles, reports, fact sheets, and websites dealing with COVID-19 were studied and reviewed. It was found that most mathematical modeling done were based on the Susceptible-Exposed-Infected-Removed (SEIR) and Susceptible-infected-recovered (SIR) models while most of the AI implementations were Convolutional Neural Network (CNN) on X-ray and CT images. In terms of available datasets, they include aggregated case reports, medical images, management strategies, healthcare workforce, demography, and mobility during the outbreak. Both Mathematical modeling and AI have both shown to be reliable tools in the fight against this pandemic. Several datasets concerning the COVID-19 have also been collected and shared open source. However, much work is needed to be done in the diversification of the datasets. Other AI and modeling applications in healthcare should be explored in regards to this COVID-19.", "qid": 35, "docid": "3wfnnrvo", "rank": 24, "score": 0.8334224820137024}, {"content": "Title: Use of Available Data To Inform The COVID-19 Outbreak in South Africa: A Case Study Content: The coronavirus disease (COVID-19), caused by the SARS-CoV-2 virus, was declared a pandemic by the World Health Organization (WHO) in February 2020. Currently, there are no vaccines or treatments that have been approved after clinical trials. Social distancing measures, including travel bans, school closure, and quarantine applied to countries or regions are being used to limit the spread of the disease and the demand on the healthcare infrastructure. The seclusion of groups and individuals has led to limited access to accurate information. To update the public, especially in South Africa, announcements are made by the minister of health daily. These announcements narrate the confirmed COVID-19 cases and include the age, gender, and travel history of people who have tested positive for the disease. Additionally, the South African National Institute for Communicable Diseases updates a daily infographic summarising the number of tests performed, confirmed cases, mortality rate, and the regions affected. However, the age of the patient and other nuanced data regarding the transmission is only shared in the daily announcements and not on the updated infographic. To disseminate this information, the Data Science for Social Impact research group at the University of Pretoria, South Africa, has worked on curating and applying publicly available data in a way that is computer-readable so that information can be shared to the public - using both a data repository and a dashboard. Through collaborative practices, a variety of challenges related to publicly available data in South Africa came to the fore. These include shortcomings in the accessibility, integrity, and data management practices between governmental departments and the South African public. In this paper, solutions to these problems will be shared by using a publicly available data repository and dashboard as a case study.", "qid": 35, "docid": "op4z052p", "rank": 25, "score": 0.8333686590194702}, {"content": "Title: CovidNet: To Bring Data Transparency in the Era of COVID-19 Content: Timely, creditable, and fine-granular case information is vital for local communities and individual citizens to make rational and data-driven responses to the COVID-19 pandemic. This paper presents CovidNet, a COVID-19 tracking project associated with a large scale epidemic dataset, which was initiated by 1Point3Acres. To the best of our knowledge, the project is the only platform providing real-time global case information of more than 4,124 sub-divisions from over 27 countries worldwide with multi-language supports. The platform also offers interactive visualization tools to analyze the full historical case curves in each region. Initially launched as a voluntary project to bridge the data transparency gap in North America in January 2020, this project by far has become one of the major independent sources worldwide and has been consumed by many other tracking platforms. The accuracy and freshness of the dataset is a result of the painstaking efforts from our voluntary teamwork, crowd-sourcing channels, and automated data pipelines. As of May 18, 2020, the project website has been visited more than 200 million times and the CovidNet dataset has empowered over 522 institutions and organizations worldwide in policy-making and academic researches. All datasets are openly accessible for non-commercial purposes at https://coronavirus.1point3acres.com via a formal request through our APIs.", "qid": 35, "docid": "zxvim4t8", "rank": 26, "score": 0.8329139947891235}, {"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": 35, "docid": "950x4b9a", "rank": 27, "score": 0.8325753211975098}, {"content": "Title: Epidemiological data from the COVID-19 outbreak, real-time case information Content: Cases of a novel coronavirus were first reported in Wuhan, Hubei province, China, in December 2019 and have since spread across the world. Epidemiological studies have indicated human-to-human transmission in China and elsewhere. To aid the analysis and tracking of the COVID-19 epidemic we collected and curated individual-level data from national, provincial, and municipal health reports, as well as additional information from online reports. All data are geo-coded and, where available, include symptoms, key dates (date of onset, admission, and confirmation), and travel history. The generation of detailed, real-time, and robust data for emerging disease outbreaks is important and can help to generate robust evidence that will support and inform public health decision making.", "qid": 35, "docid": "irt0wmt2", "rank": 28, "score": 0.8318343162536621}, {"content": "Title: Targeting SARS-CoV-2 with AI- and HPC-enabled Lead Generation: A First Data Release Content: Researchers across the globe are seeking to rapidly repurpose existing drugs or discover new drugs to counter the the novel coronavirus disease (COVID-19) caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). One promising approach is to train machine learning (ML) and artificial intelligence (AI) tools to screen large numbers of small molecules. As a contribution to that effort, we are aggregating numerous small molecules from a variety of sources, using high-performance computing (HPC) to computer diverse properties of those molecules, using the computed properties to train ML/AI models, and then using the resulting models for screening. In this first data release, we make available 23 datasets collected from community sources representing over 4.2 B molecules enriched with pre-computed: 1) molecular fingerprints to aid similarity searches, 2) 2D images of molecules to enable exploration and application of image-based deep learning methods, and 3) 2D and 3D molecular descriptors to speed development of machine learning models. This data release encompasses structural information on the 4.2 B molecules and 60 TB of pre-computed data. Future releases will expand the data to include more detailed molecular simulations, computed models, and other products.", "qid": 35, "docid": "h23w89h2", "rank": 29, "score": 0.831585705280304}, {"content": "Title: OpenSAFELY: factors associated with COVID-19 death in 17 million patients. Content: COVID-19 has rapidly affected mortality worldwide1. There is unprecedented urgency to understand who is most at risk of severe outcomes, requiring new approaches for timely analysis of large datasets. Working on behalf of NHS England, here we created OpenSAFELY: a secure health analytics platform covering 40% of all patients in England, holding patient data within the existing data centre of a major primary care electronic health records vendor. Primary care records of 17,278,392 adults were pseudonymously linked to 10,926 COVID-19-related deaths. COVID-19-related death was associated with: being male (hazard ratio (HR) 1.59, 95% confidence interval (CI) 1.53-1.65); older age and deprivation (both with a strong gradient); diabetes; severe asthma; and various other medical conditions. Compared with people with white ethnicity, Black and South Asian people were at higher risk even after adjustment for other factors (HR 1.48, 1.30-1.69 and 1.44, 1.32-1.58, respectively). We have quantified a range of clinical risk factors for COVID-19-related death in the largest cohort study conducted by any country to date. OpenSAFELY is rapidly adding further patients' records; we will update and extend results regularly.", "qid": 35, "docid": "cs2mgj70", "rank": 30, "score": 0.8307795524597168}, {"content": "Title: OpenSAFELY: factors associated with COVID-19 death in 17 million patients Content: COVID-19 has rapidly affected mortality worldwide1. There is unprecedented urgency to understand who is most at risk of severe outcomes, requiring new approaches for timely analysis of large datasets. Working on behalf of NHS England, here we created OpenSAFELY: a secure health analytics platform covering 40% of all patients in England, holding patient data within the existing data centre of a major primary care electronic health records vendor. Primary care records of 17,278,392 adults were pseudonymously linked to 10,926 COVID-19-related deaths. COVID-19-related death was associated with: being male (hazard ratio (HR) 1.59, 95% confidence interval (CI) 1.53-1.65); older age and deprivation (both with a strong gradient); diabetes; severe asthma; and various other medical conditions. Compared with people with white ethnicity, Black and South Asian people were at higher risk even after adjustment for other factors (HR 1.48, 1.30-1.69 and 1.44, 1.32-1.58, respectively). We have quantified a range of clinical risk factors for COVID-19-related death in the largest cohort study conducted by any country to date. OpenSAFELY is rapidly adding further patients' records; we will update and extend results regularly.", "qid": 35, "docid": "4nmw69co", "rank": 31, "score": 0.830779492855072}, {"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": 35, "docid": "5fg87lvu", "rank": 32, "score": 0.8304250836372375}, {"content": "Title: Tracing open data in emergencies: the case of the COVID-19 pandemic Content: BACKGROUND: The COVID-19 pandemic constitutes an ongoing, burning Public Health Emergency of International Concern (PHEIC). In 2015, the World Health Organization (WHO) adopted an open-data policy recommendation in such situations. OBJECTIVES: The present cross-sectional meta-research study aimed to assess the availability of open data and metrics and of articles pertaining to the COVID-19 outbreak in five high-impact journals. METHODS: All articles regarding the SARS-CoV-2, published in five high impact journals (Ann Intern Med, BMJ, JAMA, NEJM and Lancet) until March 14, 2020 were retrieved. Meta-data (namely the type of article, number of authors, number of patients, citations, errata, news and social media mentions) were extracted for each article in each journal in a systematic way. Google Scholar and Scopus were used for citations and author metrics respectively, and Altmetrics and PlumX were used for news and social media mentions retrieval. The degree of adherence to the PHEIC open data call was also evaluated. RESULTS: A total of 140 articles were published until March 14, 2020, mostly opinion papers. Sixteen errata followed these publications. The number of authors in each article ranged from 1 to 63, whereas the number of patients with a laboratory-confirmed SARS-CoV-2 infection reached 2,645. The impact of these publications reached a total of 4,210 cumulative crude citations and 342,790 news and social media mentions. Only one publication (0.7%) provided complete open data, while 32 (22.9%) included patient data. CONCLUSIONS: Even though a large number of manuscripts was produced since the pandemic, availability of open data remains restricted.", "qid": 35, "docid": "vhx430l3", "rank": 33, "score": 0.8302587270736694}, {"content": "Title: CORD-19: The COVID-19 Open Research Dataset Content: The COVID-19 Open Research Dataset (CORD-19) is a growing resource of scientific papers on COVID-19 and related historical coronavirus research. CORD-19 is designed to facilitate the development of text mining and information retrieval systems over its rich collection of metadata and structured full text papers. Since its release, CORD-19 has been downloaded over 200K times and has served as the basis of many COVID-19 text mining and discovery systems. In this article, we describe the mechanics of dataset construction, highlighting challenges and key design decisions, provide an overview of how CORD-19 has been used, and describe several shared tasks built around the dataset. We hope this resource will continue to bring together the computing community, biomedical experts, and policy makers in the search for effective treatments and management policies for COVID-19.", "qid": 35, "docid": "4n6v5kfv", "rank": 34, "score": 0.8302316665649414}, {"content": "Title: The first few cases and fatalities of Corona Virus Disease 2019 (COVID-19) in the Eastern Mediterranean Region of the World Health Organization: A rapid review Content: In December 2019, a cluster of atypical Pneumonia cases in Wuhan, China were reported to the World Health Organization (WHO). Later, those cases were attributed to a novel respiratory virus currently known as COVID-19. The infection is affecting every continent. It was characterized by WHO as a global pandemic on 11 March 2020. Countries worldwide are implementing various preventive measures to contain the spread of the infection such as travel and trade restrictions, closure of educational institutions and shops, and some took more strict measures such as imposing curfew. WHO is emphasizing the importance of early detection of cases, contact tracing, risk communications, implementing multisectoral approach in order to combat COVID-19 infection. Countries should provide the public with accurate, transparent information about the local and global situation of this escalating infection. Much uncertainty still surrounds this viral infection, its modes of transmission and dynamics. Epidemiological investigations particularly for the first few cases of COVID-19 infection are critical to expand our knowledge about this evolving pandemic. In this review we summarized the data available about the first few cases and fatalities of COVID-19 infection up to 18 March 2020 across Eastern Mediterranean Region of the World Health Organization. such data were only available in websites of ministries of health of the targeted countries, WHO situational reports, online newspapers, and other media channels and this gave us an idea about the amount and type of data available for the public regarding this evolving infection.", "qid": 35, "docid": "481uktzz", "rank": 35, "score": 0.8302006125450134}, {"content": "Title: How to Best Predict the Daily Number of New Infections of Covid-19 Content: Knowledge about the daily number of new infections of Covid-19 is important because it is the basis for political decisions resulting in lockdowns and urgent health care measures. We use Germany as an example to illustrate shortcomings of official numbers, which are, at least in Germany, disclosed only with several days of delay and severely underreported on weekends (more than 40%). These shortcomings outline an urgent need for alternative data sources. The other widely cited source provided by the Center for Systems Science and Engineering at Johns Hopkins University (JHU) also deviates for Germany on average by 79% from the official numbers. We argue that Google Search and Twitter data should complement official numbers. They predict even better than the original values from Johns Hopkins University and do so several days ahead. These two data sources could also be used in parts of the world where official numbers do not exist or are perceived to be unreliable.", "qid": 35, "docid": "ojhc7peo", "rank": 36, "score": 0.830093502998352}, {"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": 35, "docid": "7hw4nzwp", "rank": 37, "score": 0.8296961784362793}, {"content": "Title: An OpenData portal to share COVID-19 drug repurposing data in real time Content: The National Center for Advancing Translational Sciences (NCATS) has developed an online open science data portal for its COVID-19 drug repurposing campaign \u2013 named OpenData \u2013 with the goal of making data across a range of SARS-CoV-2 related assays available in real-time. The assays developed cover a wide spectrum of the SARS-CoV-2 life cycle, including both viral and human (host) targets. In total, over 10,000 compounds are being tested in full concentration-response ranges from across multiple annotated small molecule libraries, including approved drug, repurposing candidates and experimental therapeutics designed to modulate a wide range of cellular targets. The goal is to support research scientists, clinical investigators and public health officials through open data sharing and analysis tools to expedite the development of SARS-CoV-2 interventions, and to prioritize promising compounds and repurposed drugs for further development in treating COVID-19.", "qid": 35, "docid": "uh8w5nuj", "rank": 38, "score": 0.8293249011039734}, {"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": 39, "score": 0.828826904296875}, {"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": 40, "score": 0.828826904296875}, {"content": "Title: What Are People Asking About COVID-19? A Question Classification Dataset Content: We present COVID-Q, a set of 1,690 questions about COVID-19 from 13 sources, which we annotate into 15 question categories and 207 question classes. The most common questions in our dataset asked about transmission, prevention, and societal effects of COVID, and we found that many questions that appeared in multiple sources were not answered by any FAQ websites of reputable organizations such as the CDC and FDA. We post our dataset publicly at https://github.com/JerryWei03/COVID-Q . For classifying questions into 15 categories, a BERT baseline scored 58.1% accuracy when trained on 20 examples per class, and for classifying questions into 89 question classes, the baseline achieved 54.6% accuracy. We hope COVID-Q can be helpful either for direct use in developing applied systems or as a domain-specific resource for model evaluation.", "qid": 35, "docid": "bm99zrxz", "rank": 41, "score": 0.8283356428146362}, {"content": "Title: COVID-KOP: Integrating Emerging COVID-19 Data with the ROBOKOP Database. Content: In response to the COVID-19 pandemic, we established COVID-KOP, a new knowledgebase integrating the existing ROBOKOP biomedical knowledge graph with information from recent biomedical literature on COVID-19 annotated in the CORD-19 collection. COVID-KOP can be used effectively to test new hypotheses concerning repurposing of known drugs and clinical drug candidates against COVID-19. COVID-KOP is freely accessible at https://covidkop.renci.org/. For code and instructions for the original ROBOKOP, see: https://github.com/NCATS-Gamma/robokop.", "qid": 35, "docid": "dz2qftyv", "rank": 42, "score": 0.8280329704284668}, {"content": "Title: COVID-KOP: Integrating Emerging COVID-19 Data with the ROBOKOP Database Content: In response to the COVID-19 pandemic, we established COVID-KOP, a new knowledgebase integrating the existing ROBOKOP biomedical knowledge graph with information from recent biomedical literature on COVID-19 annotated in the CORD-19 collection. COVID-KOP can be used effectively to test new hypotheses concerning repurposing of known drugs and clinical drug candidates against COVID-19. COVID-KOP is freely accessible at https://covidkop.renci.org/. For code and instructions for the original ROBOKOP, see: https://github.com/NCATS-Gamma/robokop.", "qid": 35, "docid": "6txh7jgc", "rank": 43, "score": 0.8280328512191772}, {"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": 44, "score": 0.8278964161872864}, {"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": 0.8278964161872864}, {"content": "Title: Analyzing the epidemiological outbreak of COVID-19: A visual exploratory data analysis approach Content: There is an obvious concern globally regarding the fact about the emerging coronavirus 2019 novel coronavirus (2019-nCoV) as a worldwide public health threat. As the outbreak of COVID-19 causes by the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) progresses within China and beyond, rapidly available epidemiological data are needed to guide strategies for situational awareness and intervention. The recent outbreak of pneumonia in Wuhan, China, caused by the SARS-CoV-2 emphasizes the importance of analyzing the epidemiological data of this novel virus and predicting their risks of infecting people all around the globe. In this study, we present an effort to compile and analyze epidemiological outbreak information on COVID-19 based on the several open datasets on 2019-nCoV provided by the Johns Hopkins University, World Health Organization, Chinese Center for Disease Control and Prevention, National Health Commission, and DXY. An exploratory data analysis with visualizations has been made to understand the number of different cases reported (confirmed, death, and recovered) in different provinces of China and outside of China. Overall, at the outset of an outbreak like this, it is highly important to readily provide information to begin the evaluation necessary to understand the risks and begin containment activities.", "qid": 35, "docid": "kfy7v56x", "rank": 46, "score": 0.8274056911468506}, {"content": "Title: COVID-19 Datasets: A Survey and Future Challenges Content: In December 2019, a novel virus named as COVID-19 emerged in the city of Wuhan, China. In early 2020, the COVID-19 virus spread in all continents of the world except Antarctica causing widespread infections and deaths due to its contagious characteristics and no medically proven treatment. The COVID-19 pandemic has been termed as most consequential global crisis after the World Wars. The first line of defense against the COVID-19 spread are the non-pharmaceutical measures like social distancing and personal hygiene. On the other hand, the medical service providers are the first responders for infected persons with severe symptoms of COVID-19. The great pandemic affecting billions of lives economically and socially has motivated the scientific community to come up with solutions based on computer-aided digital technologies for diagnosis, prevention, and estimation of COVID-19. Some of these efforts focus on statistical and Artificial Intelligence-based analysis of the available data concerning COVID-19. All of these scientific efforts necessitate that the data brought to service for the analysis should be open-source to promote the extension, validation, and collaboration of the work in the fight against the global pandemic. Our survey is motivated by the open-source efforts that can be mainly categorized as: (a) COVID-19 diagnosis from CT scans and X-ray images, (b) COVID-19 case reporting, transmission estimation, and prognosis from epidemiological, demographic, and mobility data, (c) COVID-19 emotional and sentiment analysis from social media, and (d) knowledge-based discovery and semantic analysis from the collection of scholarly articles covering COVID-19. We review and critically analyze works in these directions that are accompanied by open-source data and code. We hope that the article will provide the scientific community with an initiative to start open-source extensible and transparent research in the collective fight against COVID-19.", "qid": 35, "docid": "f9eqbaj5", "rank": 47, "score": 0.8268247842788696}, {"content": "Title: Online Information Search During COVID-19 Content: Public information search data from sources such as Google Trends affords researchers a perspective on what society does not know, or what society wants to find out prompted by, or in response to, developments in societal communication and news media events. In times of crisis, online public information search thus offers a window into the most urgent concerns of, and demands by society. By extension, such data offers a window into upcoming, and currently pressing demands on businesses, policymakers and researchers. This research note aims to illustrate some of these themes with a visual-based overview of the current COVID-19 / Coronavirus crisis.", "qid": 35, "docid": "as74qa0l", "rank": 48, "score": 0.8264503479003906}, {"content": "Title: Negative Nasopharyngeal and Oropharyngeal Swabs Do Not Rule Out COVID-19 Content: Coronavirus Disease 19 (COVID-19), has become the Public Health Emergency of International Concern.\u2026.", "qid": 35, "docid": "tnzzr0cl", "rank": 49, "score": 0.8264224529266357}, {"content": "Title: Scientific solidarity in the face of the COVID-19 pandemic: researchers, publishers, and medical associations Content: In the face of COVID-19, the scientific community has rapidly come together to address this outbreak in an open and collaborative manner to support the global response to this outbreak by rapidly sharing and highlighting research data and relevant findings COVID-19 research is being published at a furious pace Over 6,000 articles have been published as of 20 April 2020, and at least 15 online resource centers/websites for COVID-19 have been created by publishers to enable fast and free access to the latest research, evidence, and data available Moreover, many evidence-based guidelines for COVID-19 have been issued based on academic articles and summaries of the experiences of frontline medical personnel Various academic medical associations are also actively sharing information and providing technical support As an example, 93 guides/proposals/responses to COVID-19 have been issued so far by 50 medical associations in Japan However, few publications and national situation reports have provided information on the number of infected healthcare workers (HCWs) More publications and national situation reports are urgently needed to provide scientific information to devise specific infection prevention and control measures in order to protect HCWs from infection", "qid": 35, "docid": "wkzv1dkd", "rank": 50, "score": 0.8260558843612671}, {"content": "Title: Tracing open data in emergencies: the case of the COVID\u201019 pandemic Content: BACKGROUND: The COVID\u201019 pandemic constitutes an ongoing, burning Public Health Emergency of International Concern (PHEIC). In 2015, the World Health Organization (WHO) adopted an open\u2010data policy recommendation in such situations. OBJECTIVES: The present cross\u2010sectional meta\u2010research study aimed to assess the availability of open data and metrics and of articles pertaining to the COVID\u201019 outbreak in five high\u2010impact journals. METHODS: All articles regarding the SARS\u2010CoV\u20102, published in five high impact journals (Ann Intern Med, BMJ, JAMA, NEJM and Lancet) until March 14, 2020 were retrieved. Meta\u2010data (namely the type of article, number of authors, number of patients, citations, errata, news and social media mentions) were extracted for each article in each journal in a systematic way. Google Scholar and Scopus were used for citations and author metrics respectively, and Altmetrics and PlumX were used for news and social media mentions retrieval. The degree of adherence to the PHEIC open data call was also evaluated. RESULTS: A total of 140 articles were published until March 14, 2020, mostly opinion papers. Sixteen errata followed these publications. The number of authors in each article ranged from 1 to 63, whereas the number of patients with a laboratory\u2010confirmed SARS\u2010CoV\u20102 infection reached 2,645. The impact of these publications reached a total of 4,210 cumulative crude citations and 342,790 news and social media mentions. Only one publication (0.7%) provided complete open data, while 32 (22.9%) included patient data. CONCLUSIONS: Even though a large number of manuscripts was produced since the pandemic, availability of open data remains restricted.", "qid": 35, "docid": "4h2ma00j", "rank": 51, "score": 0.8250656723976135}, {"content": "Title: OUTBREAK: A user-friendly georeferencing online tool for disease surveillance Content: The current COVID-19 pandemic has already claimed more than 100,000 victims and it will cause more deaths in the coming months. Tools that can track the number and locations of cases are critical for surveillance and can help in making policy decisions for controlling the outbreak. The current surveillance web-based dashboards run on proprietary platforms, which are often expensive and require specific computational knowledge. We present a new tool (OUTBREAK) for studying and visualizing epidemiological data. It permits even non-specialist users to input data most conveniently and track outbreaks in real-time. This tool has the potential to guide and help health authorities to intervene and minimize the effects of the outbreaks. It is freely available at http://outbreak.sysbio.tools/.", "qid": 35, "docid": "7m55c6u0", "rank": 52, "score": 0.8238532543182373}, {"content": "Title: Predictive Analysis of COVID-19 Time-series Data from Johns Hopkins University Content: We provide a predictive analysis of the spread of COVID-19, also known as SARS-CoV-2, using the dataset made publicly available online by the Johns Hopkins University. Our main objective is to provide predictions of the number of infected people for different countries in the next 14 days. The predictive analysis is done using time-series data transformed on a logarithmic scale. We use two well-known methods for prediction: polynomial regression and neural network. As the number of training data for each country is limited, we use a single-layer neural network called the extreme learning machine (ELM) to avoid over-fitting. Due to the non-stationary nature of the time-series, a sliding window approach is used to provide a more accurate prediction.", "qid": 35, "docid": "c8xit4tf", "rank": 53, "score": 0.8238407373428345}, {"content": "Title: Mental health groups providing support, education in wake of COVID\u201019 Content: As news and updates continue to spread regarding the new coronavirus (COVID\u201019), the deadly virus that causes respiratory illness and pneumonia, mental health groups and organizations have issued information to consumers, providers and the mental health community at large about ways of addressing the virus and seeking information from public health sources.", "qid": 35, "docid": "54t8xg3a", "rank": 54, "score": 0.8234394788742065}, {"content": "Title: Povidone\u2010iodine gargle as a prophylactic intervention to interrupt the transmission of SARS\u2010CoV\u20102 Content: Coronavirus disease 2019 (COVID-19), caused by a novel coronavirus, SARS-COV-2 was declared a Public Health Emergency of International Concern (PHEIC) by the World Health Organization (WHO) in January 2020. Human-to-Human transmission occurs through close contact with an infected person or surfaces that are contaminated with droplets or secretions.", "qid": 35, "docid": "pd78369r", "rank": 55, "score": 0.8233054876327515}, {"content": "Title: Repurposing current therapeutics for treating COVID-19: A vital role of prescription records data mining Content: Since its outbreak in late 2019, the SARS-Cov-2 pandemic already infected over 3.7 million people and claimed more than 250,000 lives globally. At least 1 year may take for an approved vaccine to be in place, and meanwhile millions more could be infected, some with fatal outcome. Over thousand clinical trials with COVID-19 patients are already listed in ClinicalTrials.com, some of them for assessing the utility of therapeutics approved for other conditions. However, clinical trials take many months, and are typically done with small cohorts. A much faster and by far more efficient method for rapidly identifying approved therapeutics that can be repurposed for treating COVID-19 patients is data mining their past and current electronic health and prescription records for identifying drugs that may protect infected individuals from severe COVID-19 symptoms. Examples are discussed for applying health and prescription records for assessing the potential repurposing (repositioning) of angiotensin receptor blockers, estradiol, or antiandrogens for reducing COVID-19 morbidity and fatalities. Data mining of prescription records of COVID-19 patients will not cancel the need for conducting controlled clinical trials, but could substantially assist in trial design, drug choice, inclusion and exclusion criteria, and prioritization. This approach requires a strong commitment of health provides for open collaboration with the biomedical research community, as health provides are typically the sole owners of retrospective drug prescription records.", "qid": 35, "docid": "2hkcfbiq", "rank": 56, "score": 0.822754442691803}, {"content": "Title: Open-source analytics tools for studying the COVID-19 coronavirus outbreak Content: To provide convenient access to epidemiological data on the coronavirus outbreak, we developed an R package, nCov2019 (https://github.com/GuangchuangYu/nCov2019). Besides detailed real-time statistics, it offers access to three data sources with detailed daily statistics from December 1, 2019, for 43 countries and more than 500 Chinese cities. We also developed a web app (http://www.bcloud.org/e/) with interactive plots and simple time-series forecasts. These analytics tools could be useful in informing the public and studying how this and similar viruses spread in populous countries.", "qid": 35, "docid": "qtrquuvv", "rank": 57, "score": 0.8227283358573914}, {"content": "Title: Rapid implementation of mobile technology for real-time epidemiology of COVID-19 Content: The rapid pace of the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) pandemic (COVID-19) presents challenges to the robust collection of population-scale data to address this global health crisis. We established the COronavirus Pandemic Epidemiology (COPE) consortium to bring together scientists with expertise in big data research and epidemiology to develop a COVID-19 Symptom Tracker mobile application that we launched in the UK on March 24, 2020 and the US on March 29, 2020 garnering more than 2.8 million users as of May 2, 2020. This mobile application offers data on risk factors, herald symptoms, clinical outcomes, and geographical hot spots. This initiative offers critical proof-of-concept for the repurposing of existing approaches to enable rapidly scalable epidemiologic data collection and analysis which is critical for a data-driven response to this public health challenge.", "qid": 35, "docid": "wfgmvy9i", "rank": 58, "score": 0.822502613067627}, {"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": 35, "docid": "55dihml5", "rank": 59, "score": 0.8222377896308899}, {"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": 35, "docid": "kdsbw4ji", "rank": 60, "score": 0.8222237825393677}, {"content": "Title: Keeping Journal Club Relevant in a Pandemic: The 'Rapid Fire' 5-Minute Format Content: There has been an explosion of data published in a short period of time about COVID-19. It can be difficult for learners to stay on top of the latest information while also critically appraising each new piece of information. As a result, there can be a lack of local consensus on how to best manage these patients as new data continually becomes available.", "qid": 35, "docid": "2ixv9zfi", "rank": 61, "score": 0.8222166299819946}, {"content": "Title: Keeping Journal Club Relevant in a Pandemic: The 'Rapid Fire' 5-Minute Format. Content: There has been an explosion of data published in a short period of time about COVID-19. It can be difficult for learners to stay on top of the latest information while also critically appraising each new piece of information. As a result, there can be a lack of local consensus on how to best manage these patients as new data continually becomes available.", "qid": 35, "docid": "8n7cyrry", "rank": 62, "score": 0.8222166299819946}, {"content": "Title: COVID-19 Image Data Collection Content: This paper describes the initial COVID-19 open image data collection. It was created by assembling medical images from websites and publications and currently contains 123 frontal view X-rays.", "qid": 35, "docid": "53aq480d", "rank": 63, "score": 0.8220767378807068}, {"content": "Title: Mega-COV: A Billion-Scale Dataset of 65 Languages For COVID-19 Content: We describe Mega-COV, a billion-scale dataset from Twitter for studying COVID-19. The dataset is diverse (covers 234 countries), longitudinal (goes as back as 2007), multilingual (comes in 65 languages), and has a significant number of location-tagged tweets (~32M tweets). We release tweet IDs from the dataset, hoping it will be useful for studying various phenomena related to the ongoing pandemic and accelerating viable solutions to associated problems.", "qid": 35, "docid": "lk13v7j6", "rank": 64, "score": 0.8219773769378662}, {"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": 35, "docid": "im5lqh6d", "rank": 65, "score": 0.821632981300354}, {"content": "Title: Genomic surveillance of SARS-CoV-2 in Thailand reveals mixed imported populations, a local lineage expansion and a virus with truncated ORF7a Content: Coronavirus Disease 2019 (COVID-19) is a global public health threat. Genomic surveillance of SARS-CoV-2 was implemented during March 2020 at a major diagnostic hub in Bangkok, Thailand. Several virus lineages supposedly originated in many countries were found, and a Thai-specific lineage, designated A/Thai-1, has expanded to be predominant in Thailand. A virus sample in the SARS-CoV-2 A/Thai-1 lineage contains a frame-shift deletion at ORF7a, encoding a putative host antagonizing factor of the virus.", "qid": 35, "docid": "ok4ah1r7", "rank": 66, "score": 0.8212605714797974}, {"content": "Title: Rapid implementation of mobile technology for real-time epidemiology of COVID-19 Content: The rapid pace of the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) pandemic (COVID-19) presents challenges to the robust collection of population-scale data to address this global health crisis. We established the COronavirus Pandemic Epidemiology (COPE) consortium to bring together scientists with expertise in big data research and epidemiology to develop a COVID-19 Symptom Tracker mobile application that we launched in the UK on March 24, 2020 and the US on March 29, 2020 garnering more than 2.25 million users to date. This mobile application offers data on risk factors, herald symptoms, clinical outcomes, and geographical hot spots. This initiative offers critical proof-of-concept for the repurposing of existing approaches to enable rapidly scalable epidemiologic data collection and analysis which is critical for a data-driven response to this public health challenge.", "qid": 35, "docid": "mmcszoxb", "rank": 67, "score": 0.8210391998291016}, {"content": "Title: Time Course of COVID-19 Cases in Austria Content: COVID-19 is an infectious disease caused by a novel coronavirus, which first appeared in China in late 2019, and reached pandemic distribution in early 2020. The first major outbreak in Europe occurred in Northern Italy where it spread to neighboring countries, notably to Austria, where skiing resorts served as a main transmission hub. Soon, the Austrian government introduced strict measures to curb the spread of the virus. Using publicly available data, we assessed the efficiency of the governmental measures. We assumed an average incubation period of one week and an average duration of infectivity of 10 days. One week after the introduction of strict measures, the increase in daily new cases was reversed, and the reproduction number dropped. The crude estimates tended to overestimate the reproduction rate in the early phase. Publicly available data provide a first estimate about the effectiveness of public health measures. However, more data are needed for an unbiased assessment.", "qid": 35, "docid": "cfk25vpu", "rank": 68, "score": 0.8209478259086609}, {"content": "Title: Monitoring the Covid-19 epidemics in Italy from mortality data Content: The mortality data can be used as an alternative source to monitor the status of Covid-19. We have studied a dataset including deaths up to the fourth week of April. There is a large excess, more pronounced at the beginning of the pandemic, showing a difference in age and gender compared to the Covid-19-confirmed cases. The study indicates that mortality information can be used to provide a less biased time profile of the pandemic.", "qid": 35, "docid": "ftbnmwet", "rank": 69, "score": 0.8209171295166016}, {"content": "Title: Should SARS-CoV-2 influence immunosuppressive therapy for autoimmune blistering diseases? Content: In this dramatic period where the whole world is affected by the outbreak of coronavirus disease 19 (COVID-19), scientific data relating to the causative virus SARS-CoV-2 as well as the subsequent therapeutic repercussions on the management of other diseases should be divulged in order to share as much information as possible among experts in a timely manner.", "qid": 35, "docid": "cleximpf", "rank": 70, "score": 0.8206799030303955}, {"content": "Title: Genetic diversity and evolution of SARS-CoV-2 Content: COVID-19 is a viral respiratory illness caused by a new coronavirus called SARS-CoV-2. The World Health Organization declared the SARS-CoV-2 outbreak a global public health emergency. We performed genetic analyses of eighty-six complete or near-complete genomes of SARS-CoV-2 and revealed many mutations and deletions on coding and non-coding regions. These observations provided evidence of the genetic diversity and rapid evolution of this novel coronavirus.", "qid": 35, "docid": "can1e8ro", "rank": 71, "score": 0.8205307722091675}, {"content": "Title: What country, university or research institute, performed the best on COVID-19? Bibliometric analysis of scientific literature Content: In this article, we conduct data mining to discover the countries, universities and companies, produced or collaborated the most research on Covid-19 since the pandemic started. We present some interesting findings, but despite analysing all available records on COVID-19 from the Web of Science Core Collection, we failed to reach any significant conclusions on how the world responded to the COVID-19 pandemic. Therefore, we increased our analysis to include all available data records on pandemics and epidemics from 1900 to 2020. We discover some interesting results on countries, universities and companies, that produced collaborated most the most in research on pandemic and epidemics. Then we compared the results with the analysing on COVID-19 data records. This has created some interesting findings that are explained and graphically visualised in the article.", "qid": 35, "docid": "5mnmh84s", "rank": 72, "score": 0.8200651407241821}, {"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": 73, "score": 0.8200564980506897}, {"content": "Title: COVID-19, Australia: Epidemiology Report 3 (Reporting week ending 19:00 AEDT 15 February 2020) Content: This is the third epidemiological report for coronavirus disease 2019 (COVID-19), previously known as novel coronavirus (2019-nCoV), from the virus now known as SARS-CoV-2, reported in Australia as at 19:00 Australian Eastern Daylight Time [AEDT] 15 February 2020. It includes data on the COVID-19 Australian cases, the international situation and current information on the severity, transmission and spread.", "qid": 35, "docid": "yelsc9cc", "rank": 74, "score": 0.8199871182441711}, {"content": "Title: COVID-19, Australia: Epidemiology Report 3 (Reporting week ending 19:00 AEDT 15 February 2020). Content: This is the third epidemiological report for coronavirus disease 2019 (COVID-19), previously known as novel coronavirus (2019-nCoV), from the virus now known as SARS-CoV-2, reported in Australia as at 19:00 Australian Eastern Daylight Time [AEDT] 15 February 2020. It includes data on the COVID-19 Australian cases, the international situation and current information on the severity, transmission and spread.", "qid": 35, "docid": "5bdoz5am", "rank": 75, "score": 0.8199871182441711}, {"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": 76, "score": 0.8198971152305603}, {"content": "Title: Artificial Intelligence-Powered Search Tools and Resources in the Fight Against COVID-19. Content: Emerging technologies are set to play an important role in our response to the COVID-19 pandemic. This paper explores three prominent initiatives: COVID-19 focused datasets (e.g., CORD-19); Artificial intelligence-powered search tools (e.g., WellAI, SciSight); and contact tracing based on mobile communication technology. We believe that increasing awareness of these tools will be important in future research into the disease, COVID-19, and the virus, SARS-CoV-2.", "qid": 35, "docid": "0p6al1j4", "rank": 77, "score": 0.8196452260017395}, {"content": "Title: Artificial Intelligence-Powered Search Tools and Resources in the Fight Against COVID-19 Content: Emerging technologies are set to play an important role in our response to the COVID-19 pandemic. This paper explores three prominent initiatives: COVID-19 focused datasets (e.g., CORD-19); Artificial intelligence-powered search tools (e.g., WellAI, SciSight); and contact tracing based on mobile communication technology. We believe that increasing awareness of these tools will be important in future research into the disease, COVID-19, and the virus, SARS-CoV-2.", "qid": 35, "docid": "uxhme6r1", "rank": 78, "score": 0.8196452260017395}, {"content": "Title: COVID-19 publications: Database coverage, citations, readers, tweets, news, Facebook walls, Reddit posts Content: The COVID-19 pandemic requires a fast response from researchers to help address biological, medical and public health issues to minimize its impact. In this rapidly evolving context, scholars, professionals and the public may need to quickly identify important new studies. In response, this paper assesses the coverage of scholarly databases and impact indicators during 21 March to 18 April 2020. The results confirm a rapid increase in the volume of research, which particularly accessible through Google Scholar and Dimensions, and less through Scopus, the Web of Science, PubMed. A few COVID-19 papers from the 21,395 in Dimensions were already highly cited, with substantial news and social media attention. For this topic, in contrast to previous studies, there seems to be a high degree of convergence between articles shared in the social web and citation counts, at least in the short term. In particular, articles that are extensively tweeted on the day first indexed are likely to be highly read and relatively highly cited three weeks later. Researchers needing wide scope literature searches (rather than health focused PubMed or medRxiv searches) should start with Google Scholar or Dimensions and can use tweet and Mendeley reader counts as indicators of likely importance.", "qid": 35, "docid": "6n8ozd36", "rank": 79, "score": 0.8194403052330017}, {"content": "Title: Point-of-Care RNA-Based Diagnostic Device for COVID-19 Content: At the end of 2019, the novel coronavirus disease (COVID-19), a fast-spreading respiratory disease caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), was reported in Wuhan, China and has now affected over 123 countries globally [...].", "qid": 35, "docid": "k6j7ukmq", "rank": 80, "score": 0.8190732002258301}, {"content": "Title: COVID-19 und die Niere Content: The drastic consequences that emerging infectious diseases can have for people and society are currently being demonstrated by coronavirus disease 2019 (COVID-19). Since its initial description in December 2019 severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) has dominated current scientific and public interest.", "qid": 35, "docid": "scdrs93u", "rank": 81, "score": 0.8190712928771973}, {"content": "Title: Tests, surgical masks, hospital beds, and ventilators: add big data to the list of tools to fight the coronavirus that are in short supply Content: Big data could help identify potential clues about the immediate (and future) impact of coronavirus disease 2019, but it is in short supply.", "qid": 35, "docid": "5f29q0kk", "rank": 82, "score": 0.8188443183898926}, {"content": "Title: Tests, surgical masks, hospital beds, and ventilators: add big data to the list of tools to fight the coronavirus that are in short supply. Content: Big data could help identify potential clues about the immediate (and future) impact of coronavirus disease 2019, but it is in short supply.", "qid": 35, "docid": "q9nfnzph", "rank": 83, "score": 0.8188443183898926}, {"content": "Title: Evaluation of a rapid diagnostic assay for detection of SARS CoV-2 antigen in nasopharyngeal swab Content: Severe Acute Respiratory Syndrome coronavirus 2 (SARS-CoV-2), the virus causing causing Coronavirus disease 2019 (COVID-19) was reported for the first time in Wuhan (Hubei, China) in December 2019 (1, 2) and has become a major public health concern all over the world. .", "qid": 35, "docid": "06ee5i8t", "rank": 84, "score": 0.8188125491142273}, {"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": 85, "score": 0.8186971545219421}, {"content": "Title: An Interactive Tool to Forecast US Hospital Needs in the Coronavirus 2019 Pandemic Content: Hospital enterprises are currently faced with anticipating the spread of COVID-19 and the effects it will have on visits, admissions, bed needs, and crucial supplies. While many studies have focused on understanding the basic epidemiology of the disease, few open source tools have been made available to aid hospitals in their planning. We developed a web-based application for US states and territories that allows users to choose from a suite of models already employed in characterizing the spread of COVID-19. Users can obtain forecasts for hospital visits and admissions as well as anticipated needs for ICU and non-ICU beds, ventilators, and personal protective equipment supplies. Users can also customize a large set of inputs, view the variability in forecasts over time, and download forecast data. We describe our web application and its models in detail and provide recommendations and caveats for its use. Our application is primarily designed for hospital leaders, healthcare workers, and government official who may lack specialized knowledge in epidemiology and modeling. However, specialists can also use our open source code as a platform for modification and deeper study. As the dynamics of COVID-19 within the US change, our application will also change to meet emerging needs and questions of the healthcare community.", "qid": 35, "docid": "fzs99kku", "rank": 86, "score": 0.8186060786247253}, {"content": "Title: Evaluation of a rapid diagnostic assay for detection of SARS CoV-2 antigen in nasopharyngeal swab. Content: Severe Acute Respiratory Syndrome coronavirus 2 (SARS-CoV-2), the virus causing causing Coronavirus disease 2019 (COVID-19) was reported for the first time in Wuhan (Hubei, China) in December 2019 (1, 2) and has become a major public health concern all over the world.\u2026.", "qid": 35, "docid": "dc9ee7qz", "rank": 87, "score": 0.8185442090034485}, {"content": "Title: Concerns and Fears of Indian Dentists on Professional Practice During the Coronavirus Disease-2019 (COVID-19) Pandemic Content: The Coronavirus disease-2019 (COVID-19) pandemic, due to the Severe Acute Respiratory Syndrome Virus 2 (SARS-CoV-2) was declared a public health emergency of international concern by the World Health Organization on 30th of January 2020 (World Health Organization, 2020). The first case of COVID-19 was reported in India on the same day, and at the time of writing, on 20th May 2020, India has reported over 106,000 patients, with over 3,300 related deaths. The country is under a state of lockdown since 25th March, 2020, and over 600 health care providers have been infected.", "qid": 35, "docid": "0xo3zkaq", "rank": 88, "score": 0.8184285163879395}, {"content": "Title: How Big Data and Artificial Intelligence Can Help Better Manage the COVID-19 Pandemic Content: SARS-CoV2 is a novel coronavirus, responsible for the COVID-19 pandemic declared by the World Health Organization. Thanks to the latest advancements in the field of molecular and computational techniques and information and communication technologies (ICTs), artificial intelligence (AI) and Big Data can help in handling the huge, unprecedented amount of data derived from public health surveillance, real-time epidemic outbreaks monitoring, trend now-casting/forecasting, regular situation briefing and updating from governmental institutions and organisms, and health facility utilization information. The present review is aimed at overviewing the potential applications of AI and Big Data in the global effort to manage the pandemic.", "qid": 35, "docid": "lnp8ic9y", "rank": 89, "score": 0.8183777332305908}, {"content": "Title: Global Preparedness Against COVID-19: We Must Leverage the Power of Digital Health Content: The coronavirus disease (COVID-19) pandemic has revealed many areas of public health preparedness that are lacking, especially in lower- and middle-income countries. Digital interventions provide many opportunities for strengthening health systems and could be vital resources in the current public health emergency. We provide several use cases for infection control, home-based diagnosis and screening, empowerment through information, public health surveillance and epidemiology, and leveraging crowd-sourced data. A thoughtful, concerted effort\u2014leveraging existing experience and robust enterprise-grade technologies\u2014can have a substantive impact on the immediate and distal consequences of COVID-19.", "qid": 35, "docid": "ssy2bbrn", "rank": 90, "score": 0.8183442950248718}, {"content": "Title: Go local: The key to controlling the COVID-19 pandemic in the post lockdown era Content: The UK government announced its first wave of lockdown easing on 10 May 2020, two months after the non-pharmaceutical measures to reduce the spread of COVID-19 were first introduced on 23 March 2020. Analysis of reported case rate data from Public Health England and aggregated and anonymised crowd level mobility data shows variability across local authorities in the UK. A locality-based approach to lockdown easing is needed, enabling local public health and associated health and social care services to rapidly respond to emerging hotspots of infection. National level data will hide an increasing heterogeneity of COVID-19 infections and mobility, and new ways of real-time data presentation to the public are required. Data sources (including mobile) allow for faster visualisation than more traditional data sources, and are part of a wider trend towards near real-time analysis of outbreaks needed for timely, targeted local public health interventions. Real time data visualisation may give early warnings of unusual levels of activity which warrant further investigation by local public health authorities.", "qid": 35, "docid": "okq83dp1", "rank": 91, "score": 0.8182315826416016}, {"content": "Title: Challenges and opportunities brought by COVID-19: Understanding and prevention of COVID-19 Content: The ongoing outbreak of coronavirus disease 2019 (COVID-19) caused by severe acute respiratory syndrome (SARS) coronavirus 2 was first reported in Wuhan, Hubei Province at the end of December 2019. The number of confirmed cases is increasing every day, causing more deaths than the SARS outbreak in China from 2002 to 2003. COVID-19 has become a public health emergency of global concern, and all governments and medical institutions are on high alert. Therefore, we summarize the genomics, epidemiology, clinical manifestations, diagnosis, treatment, and other aspects of COVID-19 based on the currently available data.", "qid": 35, "docid": "aiel1i0u", "rank": 92, "score": 0.818027138710022}, {"content": "Title: COVID-19: air pollution remains low as people stay at home Content: Coronavirus diseases 2019 (COVID-19) is transmitted worldwide in over a very short time, as it was originated in late 2019 from Wuhan city, China. To reduce the possible effects due to COVID-19, some sort of lockdown activities have been applied in many countries. In this regard, the outcomes reported bonus benefits to the natural environment showing a significant decrease in air pollution worldwide due to COVID-19. The National Aeronautics and Space Administration (NASA) and European Space Agency (ESA) released air pollution data for Asian and European countries to assess the significant changes in air quality. The main objective of the study is to compare the air quality data released by international agencies before and after the novel coronavirus pandemic.", "qid": 35, "docid": "pbj819vk", "rank": 93, "score": 0.8180034756660461}, {"content": "Title: The geographic spread of COVID-19 correlates with structure of social networks as measured by Facebook Content: We use anonymized and aggregated data from Facebook to show that areas with stronger social ties to two early COVID-19\"hotspots\"(Westchester County, NY, in the U.S. and Lodi province in Italy) generally have more confirmed COVID-19 cases as of March 30, 2020. These relationships hold after controlling for geographic distance to the hotspots as well as for the income and population density of the regions. These results suggest that data from online social networks may prove useful to epidemiologists and others hoping to forecast the spread of communicable diseases such as COVID-19.", "qid": 35, "docid": "ij6ciglx", "rank": 94, "score": 0.8179666996002197}, {"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": 95, "score": 0.8177173137664795}, {"content": "Title: Infodemiological Study Using Google Trends on Coronavirus Epidemic in Wuhan, China Content: The recent emergence of a new coronavirus (COVID-19) has gained a high cover in public media and worldwide news. The virus has caused a viral pneumonia in tens of thousands of people in Wuhan, a central city of China. This short paper gives a brief introduction on how the demand for information on this new epidemic is reported through Google Trends. The reported period is 31 December 2020 to 20 March 2020. The authors draw conclusions on current infodemiological data on COVID-19 using three main search keywords: coronavirus, SARS and MERS. Two approaches are set. First is the worldwide perspective, second - the Chinese one, which reveals that in China this disease in the first days was more often referred to SARS then to general coronaviruses, whereas worldwide, since the beginning, it is more often referred to coronaviruses.", "qid": 35, "docid": "fa5r7axh", "rank": 96, "score": 0.8177054524421692}, {"content": "Title: Coinfection with SARS-CoV-2 and other respiratory pathogens in COVID-19 patients in Guangzhou, China Content: The emergence of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2; previously provisionally named 2019 novel coronavirus or 2019-nCoV) disease (COVID-19) in China at the end of 2019 has caused a global pandemic and remains as a major public health issue This article is protected by copyright. All rights reserved.", "qid": 35, "docid": "28nl6jzx", "rank": 97, "score": 0.8174172639846802}, {"content": "Title: Where we are in fighting against COVID-19 Content: On March 11, 2020, the World Health Organization announced the novel coronavirus disease (COVID-19) as a pandemic. Despite an increasing number of international attempts using maps to present and communicate COVID-19-related information in different organizations, most map products have only used the presentation function of maps. Against this backdrop, we offer an automatically daily-updated, color-blind-friendly, Tableau-based interactive dashboard to demonstrate where and how different countries are fighting against COVID-19. The dashboard allows users to specify countries they want to compare and aggregate relevant data on a daily, weekly, or monthly basis.", "qid": 35, "docid": "cs3dpp20", "rank": 98, "score": 0.8174148201942444}, {"content": "Title: First-principles machine learning modelling of COVID-19 Content: The coronavirus disease 2019 (COVID-19) has changed the world since the World Health Organization declared its outbreak on 30th January 2020, recognizing the outbreak as a pandemic on 11th March 2020. As often said by politicians and scientific advisors, the objective is\"to flatten the curve\", or\"push the peak down\", or similar wording, of the virus spreading. Central to the official advice are mathematical models and data, which provide estimates on the evolution of the number of infected, recovered and deaths. The accuracy of the models is improved day by day by inferring the contact, recovery, and death rates from data (confirmed cases). A data-driven model trained with {\\it both} data {\\it and} first principles is proposed. The model can quickly be re-trained any time that new data becomes available. The method can be applied to more detailed epidemic models with virtually no conceptual modification.", "qid": 35, "docid": "tw0qyjq2", "rank": 99, "score": 0.8172931671142578}, {"content": "Title: Public Concern and the Financial Markets during the COVID-19 outbreak Content: We measure the public concern during the outbreak of COVID-19 disease using three data sources from Google Trends (YouTube, Google News, and Google Search). Our findings are three-fold. First, the public concern in Italy is found to be a driver of the concerns in other countries. Second, we document that Google Trends data for Italy better explains the stock index returns of France, Germany, Great Britain, the United States, and Spain with respect to their country-based indicators. Finally, we perform a time-varying analysis and identify that the most severe impacts in the financial markets occur at each step of the Italian lock-down process.", "qid": 35, "docid": "8fasz5ht", "rank": 100, "score": 0.8171151876449585}]}
{"query": "What is the protein structure of the SARS-CoV-2 spike?", "hits": [{"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": 1, "score": 0.8993358612060547}, {"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": 2, "score": 0.8989759683609009}, {"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": 3, "score": 0.8986637592315674}, {"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": 4, "score": 0.8981500267982483}, {"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": 36, "docid": "ccau1qwc", "rank": 5, "score": 0.896369218826294}, {"content": "Title: In situ structural analysis of SARS-CoV-2 spike reveals flexibility mediated by three hinges Content: The spike (S) protein of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) is required for cell entry and is the major focus for vaccine development. We combine cryo electron tomography, subtomogram averaging and molecular dynamics simulations to structurally analyze S in situ. Compared to recombinant S, the viral S is more heavily glycosylated and occurs predominantly in a closed pre-fusion conformation. We show that the stalk domain of S contains three hinges that give the globular domain unexpected orientational freedom. We propose that the hinges allow S to scan the host cell surface, shielded from antibodies by an extensive glycan coat. The structure of native S contributes to our understanding of SARS-CoV-2 infection and the development of safe vaccines. The large scale tomography data set of SARS-CoV-2 used for this study is therefore sufficient to resolve structural features to below 5 \u00c5ngstrom, and is publicly available at EMPIAR-10453.", "qid": 36, "docid": "otovxksn", "rank": 6, "score": 0.8959255218505859}, {"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": 7, "score": 0.8957822322845459}, {"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": 8, "score": 0.8957822322845459}, {"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": 36, "docid": "9qneslip", "rank": 9, "score": 0.8957056999206543}, {"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": 10, "score": 0.8945306539535522}, {"content": "Title: Blocking Coronavirus 19 Infection via the SARS-CoV-2 Spike Protein: Initial Steps Content: [Image: see text] Recent crystal structure data for protein\u2013protein interactions featuring the SARS-CoV-2 spike protein will inevitably trigger a new wave of research in this area that was not possible before. This Viewpoint outlines a few of the ways that it is already happening.", "qid": 36, "docid": "908d8bax", "rank": 11, "score": 0.8942185640335083}, {"content": "Title: The biological characteristics of SARS-CoV-2 spike protein Pro330-Leu650 Content: SARS-CoV-2 is the cause of the worldwide outbreak of COVID-19 that has been characterized as a pandemic by the WHO. Since the first report of COVID-19 on December 31, 2019, 179,111 cases were confirmed in 160 countries/regions with 7426 deaths as of March 17, 2020. However, there have been no vaccines approved in the world to date. In this study, we analyzed the biological characteristics of the SARS-CoV-2 Spike protein, Pro330-Leu650 (SARS-CoV-2-SPL), using biostatistical methods. SARS-CoV-2-SPL possesses a receptor-binding region (RBD) and important B (Ser438-Gln506, Thr553-Glu583, Gly404-Aps427, Thr345-Ala352, and Lys529-Lys535) and T (9 CD4 and 11 CD8 T cell antigenic determinants) cell epitopes. High homology in this region between SARS-CoV-2 and SARS-CoV amounted to 87.7%, after taking the biological similarity of the amino acids into account and eliminating the receptor-binding motif (RBM). The overall topology indicated that the complete structure of SARS-CoV-2-SPL was with RBM as the head, and RBD as the trunk and the tail region. SARS-CoV-2-SPL was found to have the potential to elicit effective B and T cell responses. Our findings may provide meaningful guidance for SARS-CoV-2 vaccine design.", "qid": 36, "docid": "ufmzv9f4", "rank": 12, "score": 0.8935631513595581}, {"content": "Title: The biological characteristics of SARS-CoV-2 Spike protein Pro330-Leu650 Content: SARS-CoV-2 is the cause of the worldwide outbreak of COVID-19 that has been characterized as a pandemic by the WHO. Since the first report of COVID-19 on December 31, 2019, 179,111 cases were confirmed in 160 countries/regions with 7,426 deaths as of March 17, 2020. However, there have been no vaccines approved in the world to date. In this study, we analyzed the biological characteristics of the SARS-CoV-2 Spike protein, Pro330-Leu650 (SARS-CoV-2-SPL), using biostatistical methods. SARS-CoV-2-SPL possesses a receptor-binding region (RBD) and important B (Ser438-Gln506, Thr553-Glu583, Gly404-Aps427, Thr345-Ala352, and Lys529-Lys535) and T (9 CD4 and 11 CD8 T cell antigenic determinants) cell epitopes. High homology in this region between SARS-CoV-2 and SARS-CoV amounted to 87.7%, after taking the biological similarity of the amino acids into account and eliminating the receptor-binding motif (RBM). The overall topology indicated that the complete structure of SARS-CoV-2-SPL was with RBM as the head, and RBD as the trunk and the tail region. SARS-CoV-2-SPL was found to have the potential to elicit effective B and T cell responses. Our findings may provide meaningful guidance for SARS-CoV-2 vaccine design.", "qid": 36, "docid": "vhl5adaw", "rank": 13, "score": 0.8932759761810303}, {"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": 14, "score": 0.8911041021347046}, {"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": 15, "score": 0.8910260200500488}, {"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": 16, "score": 0.8893595933914185}, {"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": 17, "score": 0.8893546462059021}, {"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": 18, "score": 0.8893546462059021}, {"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": 19, "score": 0.8893438577651978}, {"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": 20, "score": 0.8888850212097168}, {"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": 21, "score": 0.8884174823760986}, {"content": "Title: Characterization of the 3a Protein of SARS-associated Coronavirus in Infected Vero E6 Cells and SARS Patients Content: Abstract Proteomics was used to identify a protein encoded by ORF 3a in a SARS-associated coronavirus (SARS-CoV). Immuno-blotting revealed that interchain disulfide bonds might be formed between this protein and the spike protein. ELISA indicated that sera from SARS patients have significant positive reactions with synthesized peptides derived from the 3a protein. These results are concordant with that of a spike protein-derived peptide. A tendency exists for co-mutation between the 3a protein and the spike protein of SARS-CoV isolates, suggesting that the function of the 3a protein correlates with the spike protein. Taken together, the 3a protein might be tightly correlated to the spike protein in the SARS-CoV functions. The 3a protein may serve as a new clinical marker or drug target for SARS treatment.", "qid": 36, "docid": "me5ff1pb", "rank": 22, "score": 0.8877623677253723}, {"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": 0.8860626220703125}, {"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": 24, "score": 0.8860626220703125}, {"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": 25, "score": 0.8860107064247131}, {"content": "Title: A thermostable, closed, SARS-CoV-2 spike protein trimer Content: The spike (S) protein of SARS-CoV-2 mediates receptor binding and cell entry and is the dominant target of the immune system. S exhibits substantial conformational flexibility. It transitions from closed to open conformations to expose its receptor binding site, and subsequently from prefusion to postfusion conformations to mediate fusion of viral and cellular membranes. S protein derivatives are components of vaccine candidates and diagnostic assays, as well as tools for research into the biology and immunology of SARS-CoV-2. Here we have designed mutations in S which allow production of thermostable, crosslinked, S protein trimers that are trapped in the closed, pre-fusion, state. We have determined the structures of crosslinked and non-crosslinked proteins, identifying two distinct closed conformations of the S trimer. We demonstrate that the designed, thermostable, closed S trimer can be used in serological assays. This protein has potential applications as a reagent for serology, virology and as an immunogen.", "qid": 36, "docid": "oqixb26h", "rank": 26, "score": 0.8855443596839905}, {"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": 27, "score": 0.8850152492523193}, {"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": 28, "score": 0.8847877979278564}, {"content": "Title: Immunological, structural, and preliminary X-ray diffraction characterizations of the fusion core of the SARS-coronavirus spike protein Content: Abstract The SARS-CoV spike protein, a glycoprotein essential for viral entry, is a primary target for vaccine and drug development. Two peptides denoted HR-N(SN50) and HR-C(SC40), corresponding to the Leu/Ile/Val-rich heptad-repeat regions from the N-terminal and C-terminal segments of the SARS-CoV spike S2 sequence, respectively, were synthesized and predicted to form trimeric assembly of hairpin-like structures. The polyclonal antibodies produced by recombinant S2 protein were tested for antigenicity of the two heptad repeats. We report here the first crystallographic study of the SARS spike HR-N/HR-C complex. The crystal belongs to the triclinic space group P1 and the data-set collected to 2.98\u00c5 resolution showed noncrystallographic pseudo-222 and 3-fold symmetries. Based on these data, comparative modeling of the SARS-CoV fusion core was performed. The immunological and structural information presented herein may provide a more detailed understanding of the viral fusion mechanism as well as the development of effective therapy against SARS-CoV infection.", "qid": 36, "docid": "19h2i631", "rank": 29, "score": 0.8846395015716553}, {"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": 30, "score": 0.8845213651657104}, {"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": 31, "score": 0.8840042352676392}, {"content": "Title: Structure of SARS coronavirus spike receptor-binding domain complexed with receptor. Content: The spike protein (S) of SARS coronavirus (SARS-CoV) attaches the virus to its cellular receptor, angiotensin-converting enzyme 2 (ACE2). A defined receptor-binding domain (RBD) on S mediates this interaction. The crystal structure at 2.9 angstrom resolution of the RBD bound with the peptidase domain of human ACE2 shows that the RBD presents a gently concave surface, which cradles the N-terminal lobe of the peptidase. The atomic details at the interface between the two proteins clarify the importance of residue changes that facilitate efficient cross-species infection and human-to-human transmission. The structure of the RBD suggests ways to make truncated disulfide-stabilized RBD variants for use in the design of coronavirus vaccines.", "qid": 36, "docid": "hmswnrgg", "rank": 32, "score": 0.8818022012710571}, {"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": 33, "score": 0.8815969228744507}, {"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": 34, "score": 0.8801792860031128}, {"content": "Title: COVID-19 Coronavirus spike protein analysis for synthetic vaccines, a peptidomimetic antagonist, and therapeutic drugs, and analysis of a proposed achilles' heel conserved region to minimize probability of escape mutations and drug resistance Content: This paper continues a recent study of the spike protein sequence of the COVID-19 virus (SARS-CoV-2). It is also in part an introductory review to relevant computational techniques for tackling viral threats, using COVID-19 as an example. Q-UEL tools for facilitating access to knowledge and bioinformatics tools were again used for efficiency, but the focus in this paper is even more on the virus. Subsequence KRSFIEDLLFNKV of the S2' spike glycoprotein proteolytic cleavage site continues to appear important. Here it is shown to be recognizable in the common cold coronaviruses, avian coronaviruses and possibly as traces in the nidoviruses of reptiles and fish. Its function or functions thus seem important to the coronaviruses. It might represent SARS-CoV-2 Achilles' heel, less likely to acquire resistance by mutation, as has happened in some early SARS vaccine studies discussed in the previous paper. Preliminary conformational analysis of the receptor (ACE2) binding site of the spike protein is carried out suggesting that while it is somewhat conserved, it appears to be more variable than KRSFIEDLLFNKV. However compounds like emodin that inhibit SARS entry, apparently by binding ACE2, might also have functions at several different human protein binding sites. The enzyme 11\u00df-hydroxysteroid dehydrogenase type 1 is again argued to be a convenient model pharmacophore perhaps representing an ensemble of targets, and it is noted that it occurs both in lung and alimentary tract. Perhaps it benefits the virus to block an inflammatory response by inhibiting the dehydrogenase, but a fairly complex web involves several possible targets.", "qid": 36, "docid": "8y4j510s", "rank": 35, "score": 0.8792097568511963}, {"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": 36, "docid": "iihgc5nr", "rank": 36, "score": 0.8787471055984497}, {"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": 37, "score": 0.8785825967788696}, {"content": "Title: Site-specific glycan analysis of the SARS-CoV-2 spike Content: The emergence of the betacoronavirus, SARS-CoV-2, the causative agent of COVID-19, represents a significant threat to global human health. Vaccine development is focused on the principal target of the humoral immune response, the spike (S) glycoprotein, which mediates cell entry and membrane fusion. SARS-CoV-2 S gene encodes 22 N-linked glycan sequons per protomer, which likely play a role in protein folding and immune evasion. Here, using a site-specific mass spectrometric approach, we reveal the glycan structures on a recombinant SARS-CoV-2 S immunogen. This analysis enables mapping of the glycan-processing states across the trimeric viral spike. We show how SARS-CoV-2 S glycans differ from typical host glycan processing, which may have implications in viral pathobiology and vaccine design.", "qid": 36, "docid": "kfnq4tv6", "rank": 38, "score": 0.8782926797866821}, {"content": "Title: Conserved High Free Energy Sites in Human Coronavirus Spike Glycoprotein Backbones Content: Methods previously developed by the author are applied to uncover several sites of interest in the spike glycoproteins of all known human coronaviruses (hCoVs), including SARS-CoV-2 that causes COVID-19. The sites comprise three-dimensional neighborhoods of peptides characterized by four key properties: (1) they pinpoint regions of high free energy in the backbone whose obstruction might interrupt function; (2) by their very definition, they occur rarely in the universe of all gene-encoded proteins that could obviate host response to compounds designed for their interference; (3) they are common to all known hCoV spikes, possibly retaining activity in light of inevitable viral mutation; and (4) they are exposed in the molecular surface of the glycoprotein. These peptides in SARS-CoV-2 are given by the triples of residues (131, 117, 134), (203, 227, 228), and (1058, 730, 731) in its spike.", "qid": 36, "docid": "8ha8qv5o", "rank": 39, "score": 0.8779271841049194}, {"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": 40, "score": 0.8775243759155273}, {"content": "Title: [A preliminary study of the structure prediction and expression of SARS-CoV spike protein]. Content: In this study, the encoding sequences of SARS-CoV spike protein were analyzed by bioinformatics methods, the structural characteristics and functions were forecasted based on available data. It suggests that the fragment of spike glycoprotein (S401-659) may be crucial for viral attachment and may be a major immunodominant epitope. Then the fragment was amplified and subcloned into expression vector pET28a(+) and pPIC9K. These two plasmids pET28a(+)-S and pPIC9K-S were transformed to E.coli strain BL21(DE3)-star and Pichia pastoris, respectively. SDS-PAGE and Western blot analysis showed that the recombinant protein was successfully expressed. The denatured inclusion bodies were purified with Ni-NTA chelate agarose and its purity can reach 90%.", "qid": 36, "docid": "x55bdcy5", "rank": 41, "score": 0.8773643374443054}, {"content": "Title: Conserved High Free Energy Sites in Human Coronavirus Spike Glycoprotein Backbones. Content: Methods previously developed by the author are applied to uncover several sites of interest in the spike glycoproteins of all known human coronaviruses (hCoVs), including SARS-CoV-2 that causes COVID-19. The sites comprise three-dimensional neighborhoods of peptides characterized by four key properties: (1) they pinpoint regions of high free energy in the backbone whose obstruction might interrupt function; (2) by their very definition, they occur rarely in the universe of all gene-encoded proteins that could obviate host response to compounds designed for their interference; (3) they are common to all seven hCoV spikes, possibly retaining activity in light of inevitable viral mutation; and (4) they are exposed in the molecular surface of the glycoprotein. These peptides in SARS-CoV-2 are given by the triples of residues (131, 117, 134), (203, 227, 228), and (1058, 730, 731) in its spike.", "qid": 36, "docid": "y42lzirq", "rank": 42, "score": 0.8770769834518433}, {"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": 43, "score": 0.8770217895507812}, {"content": "Title: The spike protein of severe acute respiratory syndrome (SARS) is cleaved in virus infected Vero-E6 cells Content: Spike protein is one of the major structural proteins of severe acute respiratory syndrome-coronavirus. It is essential for the interaction of the virons with host cell receptors and subsequent fusion of the viral envelop with host cell membrane to allow infection. Some spike proteins of coronavirus, such as MHV, HCoV-OC43, AIBV and BcoV, are proteolytically cleaved into two subunits, S1 and S2. In contrast, TGV, FIPV and HCoV-229E are not. Many studies have shown that the cleavage of spike protein seriously affects its function. In order to investigate the maturation and proteolytic processing of the S protein of SARS CoV, we generated S1 and S2 subunit specific antibodies (Abs) as well as N, E and 3CL protein-specific Abs. Our results showed that the antibodies could efficiently and specifically bind to their corresponding proteins from E.coli expressed or lysate of SARS-CoV infected Vero-E6 cells by Western blot analysis. Furthermore, the anti-S1 and S2 Abs were proved to be capable of binding to SARS CoV under electron microscope observation. When S2 Ab was used to perform immune precipitation with lysate of SARS-CoV infected cells, a cleaved S2 fragment was detected with S2-specific mAb by Western blot analysis. The data demonstrated that the cleavage of S protein was observed in the lysate, indicating that proteolytic processing of S protein is present in host cells.", "qid": 36, "docid": "fy1lqk00", "rank": 44, "score": 0.8766942024230957}, {"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": 36, "docid": "vf32wxkx", "rank": 45, "score": 0.8762879967689514}, {"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": 46, "score": 0.8760083913803101}, {"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": 47, "score": 0.8758757710456848}, {"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": 48, "score": 0.8758198022842407}, {"content": "Title: COVID-19 Coronavirus spike protein analysis for synthetic vaccines, a peptidomimetic antagonist, and therapeutic drugs, and analysis of a proposed achilles\u2019 heel conserved region to minimize probability of escape mutations and drug resistance Content: Abstract This paper continues a recent study of the spike protein sequence of the COVID-19 virus (SARS-CoV-2). It is also in part an introductory review to relevant computational techniques for tackling viral threats, using COVID-19 as an example. Q-UEL tools for facilitating access to knowledge and bioinformatics tools were again used for efficiency, but the focus in this paper is even more on the virus. Subsequence KRSFIEDLLFNKV of the S2\u2032 spike glycoprotein proteolytic cleavage site continues to appear important. Here it is shown to be recognizable in the common cold coronaviruses, avian coronaviruses and possibly as traces in the nidoviruses of reptiles and fish. Its function or functions thus seem important to the coronaviruses. It might represent SARS-CoV-2 Achilles\u2019 Heel, less likely to acquire resistance by mutation, as has happened in some early SARS vaccine studies discussed in the previous paper. Preliminary conformational analysis of the receptor (ACE2) binding site of the spike protein is carried suggesting that while it is somewhat conserved, it appears to be more variable than KRSFIEDLLFNKV. However compounds like emodin that inhibit SARS entry, apparently by binding ACE2, might also have functions at several different human protein binding studies. The enzyme 11\u03b2-hydroxysteroid dehydrogenase type 1 is again argued to be a convenient model pharmacophore perhaps representing an ensemble of targets, and it is noted that it occurs both in lung and alimentary tract. Perhaps it benefits the virus to block an inflammatory response by inhibiting the dehydrogenase, but a fairly complex web involves several possible targets.", "qid": 36, "docid": "xvfl7ycj", "rank": 49, "score": 0.8757327795028687}, {"content": "Title: Comprehensive annotations of the mutational spectra of SARS-CoV-2 spike protein: a fast and accurate pipeline Content: In order to explore nonsynonymous mutations and deletions in the spike (S) protein of SARS-CoV-2, we comprehensively analyzed 35,750 complete S protein gene sequences from across six continents and five climate zones around the world, as documented in the GISAID database as of June 24th, 2020. Through a custom Python-based pipeline for analyzing mutations, we identified 27,801 (77.77 % of spike sequences) mutated strains compared to Wuhan-Hu-1 strain. 84.40% of these strains had only single amino-acid (aa) substitution mutations, but an outlier strain from Bosnia and Herzegovina (EPI_ISL_463893) was found to possess six aa substitutions. The D614G variant of the major G clade was found to be predominant across circulating strains in all climates. We also identified 988 unique aa substitution mutations distributed across 660 positions within the spike protein, with eleven sites showing high variability \u2013 these sites had four types of aa variations at each position. Besides, 17 in-frame deletions at four major regions (three in N-terminal domain and one just downstream of the RBD) may have possible impact on attenuation. Moreover, the mutational frequency differed significantly (p= 0.003, Kruskal\u2013Wallis test) among the SARS-CoV-2 strains worldwide. This study presents a fast and accurate pipeline for identifying nonsynonymous mutations and deletions from large dataset for any particular protein coding sequence and presents this S protein data as representative analysis. By using separate multi-sequence alignment with MAFFT, removing ambiguous sequences and in-frame stop codons, and utilizing pairwise alignment, this method can derive nonsynonymus mutations (Reference:Position:Strain). We believe this will aid in the surveillance of any proteins encoded by SARS-CoV-2, and will prove to be crucial in tracking the ever-increasing variation of many other divergent RNA viruses in the future.", "qid": 36, "docid": "1iqg0efn", "rank": 50, "score": 0.875593900680542}, {"content": "Title: The Structural Characterization and Antigenicity of the S Protein of SARS-CoV Content: The corona-like spikes or peplomers on the surface of the virion under electronic microscope are the most striking features of coronaviruses. The S (spike) protein is the largest structural protein, with 1,255 amino acids, in the viral genome. Its structure can be divided into three regions: a long N-terminal region in the exterior, a characteristic transmembrane (TM) region, and a short C-terminus in the interior of a virion. We detected fifteen substitutions of nucleotides by comparisons with the seventeen published SARS-CoV genome sequences, eight (53.3%) of which are non-synonymous mutations leading to amino acid alternations with predicted physiochemical changes. The possible antigenic determinants of the S protein are predicted, and the result is confirmed by ELISA (enzyme-linked immunosorbent assay) with synthesized peptides. Another profound finding is that three disulfide bonds are defined at the C-terminus with the N-terminus of the E (envelope) protein, based on the typical sequence and positions, thus establishing the structural connection with these two important structural proteins, if confirmed. Phylogenetic analysis reveals several conserved regions that might be potent drug targets.", "qid": 36, "docid": "hc0ma2cq", "rank": 51, "score": 0.8753912448883057}, {"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": 52, "score": 0.8751431703567505}, {"content": "Title: The SARS-CoV S glycoprotein Content: The severe acute respiratory syndrome-coronavirus (SARS-CoV) spike (S) glycoprotein alone can mediate the membrane fusion required for virus entry and cell fusion. It is also a major immunogen and a target for entry inhibitors. Recent rapid advances in our knowledge of the structure and function of this protein have lead to the development of a number of candidate vaccine immunogens and SARS-CoV entry inhibitors.", "qid": 36, "docid": "2o8u4eny", "rank": 53, "score": 0.8750770092010498}, {"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": 54, "score": 0.8748220205307007}, {"content": "Title: Comparing the Binding Interactions in the Receptor Binding Domains of SARS-CoV-2 and SARS-CoV Content: [Image: see text] SARS-CoV-2, since emerging in Wuhan, China, has been a major concern because of its high infection rate and has left more than six million infected people around the world. Many studies endeavored to reveal the structure of the SARS-CoV-2 compared to the SARS-CoV, in order to find solutions to suppress this high infection rate. Some of these studies showed that the mutations in the SARS-CoV spike (S) 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 S proteins of SARS-CoV and SARS-CoV-2 to the ACE2. Our results show that the protein surface of the ACE2 at the receptor binding domain (RBD) exhibits negative electrostatic potential, while a positive potential is observed for the S proteins of SARS-CoV/SARS-CoV-2. In addition, the binding energies at the interface are slightly higher for SARS-CoV-2 because of enhanced electrostatic interactions. The major contributions to the electrostatic binding energies result from the salt bridges forming between R426 and ACE-2-E329 in the case of SARS-CoV and K417 and ACE2-D30 in the SARS-CoV-2. In addition, our results indicate that the enhancement in the binding energy is not due to a single mutant but rather because of the sophisticated structural changes induced by all these mutations together. This finding suggests that it is implausible for the SARS-CoV-2 to be a lab-engineered virus.", "qid": 36, "docid": "1iq1j47x", "rank": 55, "score": 0.8746649622917175}, {"content": "Title: Making sense of mutation: what D614G means for the COVID-19 pandemic remains unclear Content: Abstract Korber et al. (2020) found that a SARS-CoV-2 variant in the spike protein, D614G, rapidly became dominant around the world. While clinical and in vitro data suggest that D614G changes the virus phenotype, the impact of the mutation on transmission, disease, and vaccine and therapeutic development are largely unknown.", "qid": 36, "docid": "rwxhdg8r", "rank": 56, "score": 0.8745365738868713}, {"content": "Title: Structural similarity between HIV-1 gp41 and SARS-CoV S2 proteins suggests an analogous membrane fusion mechanism Content: Abstract SARS-associated coronavirus (SARS-CoV) has been identified as the causal agent of a new emerging disease: severe acute respiratory syndrome (SARS). Its spike protein S2 is responsible for mediating fusion of viral and cellular membrane. In this study, we modeled the 3D structure of S2 subunit and compared this model with the core structure of gp41 from HIV-1. We found that SARS-CoV S2 and gp41 share the same two \u03b1 helices, suggesting that the two viruses could follow an analogous membrane fusion mechanism. Further ligand-binding analysis showed that two inhibitors GGL and D-peptide from HIV-1 gp41 may serve as inhibitors for SARS-CoV entry.", "qid": 36, "docid": "38d140wp", "rank": 57, "score": 0.8743163347244263}, {"content": "Title: Comparing the Binding Interactions in the Receptor Binding Domains of SARS-CoV-2 and SARS-CoV Content: SARS-CoV-2, since emerging in Wuhan, China, has been a major concern because of its high infection rate and has left more than six million infected people around the world. Many studies endeavored to reveal the structure of the SARS-CoV-2 compared to the SARS-CoV, in order to find solutions to suppress this high infection rate. Some of these studies showed that the mutations in the SARS-CoV spike (S) 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 S proteins of SARS-CoV and SARS-CoV-2 to the ACE2. Our results show that the protein surface of the ACE2 at the receptor binding domain (RBD) exhibits negative electrostatic potential, while a positive potential is observed for the S proteins of SARS-CoV/SARS-CoV-2. In addition, the binding energies at the interface are slightly higher for SARS-CoV-2 because of enhanced electrostatic interactions. The major contributions to the electrostatic binding energies result from the salt bridges forming between R426 and ACE-2-E329 in the case of SARS-CoV and K417 and ACE2-D30 in the SARS-CoV-2. In addition, our results indicate that the enhancement in the binding energy is not due to a single mutant but rather because of the sophisticated structural changes induced by all these mutations together. This finding suggests that it is implausible for the SARS-CoV-2 to be a lab-engineered virus.", "qid": 36, "docid": "ai7q035z", "rank": 58, "score": 0.8743104338645935}, {"content": "Title: Site-specific analysis of the SARS-CoV-2 glycan shield Content: The emergence of the betacoronavirus, SARS-CoV-2 that causes COVID-19, represents a significant threat to global human health. Vaccine development is focused on the principal target of the humoral immune response, the spike (S) glycoprotein, that mediates cell entry and membrane fusion. SARS-CoV-2 S gene encodes 22 N-linked glycan sequons per protomer, which likely play a role in immune evasion and occluding immunogenic protein epitopes. Here, using a site-specific mass spectrometric approach, we reveal the glycan structures on a recombinant SARS-CoV-2 S immunogen. This analysis enables mapping of the glycan-processing states across the trimeric viral spike. We show how SARS-CoV-2 S glycans differ from typical host glycan processing, which may have implications in viral pathobiology and vaccine design.", "qid": 36, "docid": "63j4qc7d", "rank": 59, "score": 0.8730490207672119}, {"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": 60, "score": 0.8724219799041748}, {"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": 61, "score": 0.8719428777694702}, {"content": "Title: A spike with which to beat COVID-19? Content: This month\u2019s Under the Lens discusses how structural studies of the SARS-CoV-2 spike glycoprotein might guide a path towards a vaccine.", "qid": 36, "docid": "f5g2r4n9", "rank": 62, "score": 0.8717434406280518}, {"content": "Title: Analyses of spike protein from first deposited sequences of SARS-CoV2 from West Bengal, India Content: India has recently started sequencing SARS-CoV2 genome from clinical isolates. Currently only few sequences are available from three states in India. Kerala was the first state to deposit complete sequence from two isolates followed by one from Gujarat. On April 27, 2020, the first five sequences from the state of West Bengal (Eastern India) were deposited on GISAID, a global initiative for sharing avian flu data. In this study, we have analysed the spike protein sequences from all five isolates and also compared their similarities or differences with other sequences reported in India and with isolates of Wuhan origin. We report one unique mutation at position 723 and another at 1124 in the S2 domain of spike protein of the isolates from West Bengal only. There was one mutation downstream of the receptor binding domain at position 614 in S1 domain which was common with the sequence from Gujarat (a state of western India). Mutation in the S2 domain showed changes in the secondary structure of the spike protein at region of the mutation. We also studied molecular dynamics using normal mode analyses and found that this mutation decreases the flexibility of S2 domain. Since both S1 and S2 are important in receptor binding followed by entry in the host cells, such mutations may define the affinity or avidity of receptor binding.", "qid": 36, "docid": "gi5ajeic", "rank": 63, "score": 0.8717095851898193}, {"content": "Title: Exploring Conformational Transition of 2019 Novel Coronavirus Spike Glycoprotein Between Its Closed and Open States Using Molecular Dynamics Simulations Content: Since its first recorded appearance in December 2019, a novel coronavirus (SARS-CoV-2) causing the disease COVID-19 has resulted in more than 2,000,000 infections and 128,000 deaths. Currently there is no proven treatment for COVID-19 and there is an urgent need for the development of vaccines and therapeutics. Coronavirus spike glycoproteins play a critical role in coronavirus entry into the host cells, as they provide host cell recognition and membrane fusion between virus and host cell. Thus, they emerged as popular and promising drug targets. Crystal structures of spike protein in its closed and open states were resolved very recently in March 2020. These structures comprise 77% of the sequence and provide almost the complete protein structure. Based on down and up positions of receptor binding domain (RBD), spike protein can be in a receptor inaccessible closed or receptor accessible open state, respectively. Starting from closed and open state crystal structures, and also 16 intermediate conformations, an extensive set of all-atom molecular dynamics (MD) simulations in the presence of explicit water and ions were performed. Simulations show that in its down position, RBD has significantly lower mobility compared to its up position; probably caused by the 6 interdomain salt bridges of RBD in down position compared to 3 in up position. Free energy landscapes based on MD simulations revealed a semi-open state located between closed and open states. Minimum energy pathway between down and up positions comprised a gradual salt bridge switching mechanism. Furthermore, although significantly lower than open state, ACE2 binding surface of RBD contained a partial solvent accessibility in its closed state.", "qid": 36, "docid": "o14tj8fi", "rank": 64, "score": 0.8704002499580383}, {"content": "Title: Stabilizing the Closed SARS-CoV-2 Spike Trimer Content: The trimeric spike (S) protein of SARS-CoV-2 is the primary focus of most vaccine design and development efforts. Due to intrinsic instability typical of class I fusion proteins, S tends to prematurely refold to the post-fusion conformation, compromising immunogenic properties and prefusion trimer yields. To support ongoing vaccine development efforts, we report the structure-based design of soluble S trimers, with increased yields and stabilities, based on introduction of single point mutations and disulfide-bridges. We identify two regions in the S-protein critical for the protein\u2019s stability: the heptad repeat region 1 of the S2 subunit and subunit domain 1 at the interface with S2. We combined a minimal selection of mostly interprotomeric mutations to create a stable S-closed variant with a 6.4-fold higher expression than the parental construct while no longer containing a heterologous trimerization domain. The cryo-EM structure reveals a correctly folded, predominantly closed pre-fusion conformation. Highly stable and well producing S protein and the increased understanding of S protein structure will support vaccine development and serological diagnostics.", "qid": 36, "docid": "h90c721k", "rank": 65, "score": 0.8701980113983154}, {"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": 66, "score": 0.8700700998306274}, {"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": 67, "score": 0.8700670003890991}, {"content": "Title: Biochemical evidence of furin specificity and potential for phospho-regulation at Spike protein S1/S2 cleavage site in SARS-CoV2 but not in SARS-CoV1 or MERS-CoV Content: The Spike protein of the novel coronavirus SARS-CoV2 contains an insertion 680SPRRAR\u2193SV687 forming a cleavage motif RxxR for furin-like enzymes at the boundary of S1/S2 subunits. Cleavage at S1/S2 is important for efficient viral entry into target cells. The insertion is absent in other CoV-s of the same clade, including SARS-CoV1 that caused the 2003 outbreak. However, an analogous insertion was present in the Spike protein of the more distant Middle East Respiratory Syndrome coronavirus MERS-CoV. We show that a crucial third arginine at the left middle position, comprising a motif RRxR is required for furin recognition in vitro, while the general motif RxxR in common with MERS-CoV is not sufficient for cleavage. Further, we describe a surprising finding that the two serines at the edges of the insert SPRRAR\u2193SV can be efficiently phosphorylated by proline-directed and basophilic protein kinases. Both phosphorylations switch off furin\u2019s ability to cleave the site. Although phosphoregulation of secreted proteins is still poorly understood, further studies, supported by a recent report of ten in vivo phosphorylated sites in the Spike protein of SARS-CoV2, could potentially uncover important novel regulatory mechanisms for SARS-CoV2.", "qid": 36, "docid": "vhiccw18", "rank": 68, "score": 0.870036244392395}, {"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": 69, "score": 0.8699989318847656}, {"content": "Title: SARS-CoV-2 growth, furin-cleavage-site adaptation and neutralization using serum from acutely infected, hospitalized COVID-19 patients Content: SARS-CoV-2, the causative agent of COVID-19, emerged at the end of 2019 and by mid-June 2020, the virus has spread to at least 215 countries, caused more than 8,000,000 confirmed infections and over 450,000 deaths, and overwhelmed healthcare systems worldwide. Like SARS-CoV, which emerged in 2002 and caused a similar disease, SARS-CoV-2 is a betacoronavirus. Both viruses use human angiotensin-converting enzyme 2 (hACE2) as a receptor to enter cells. However, the SARS-CoV-2 spike (S) glycoprotein has a novel insertion that generates a putative furin cleavage signal and this has been postulated to expand the host range. Two low passage (P) strains of SARS-CoV-2 (Wash1: P4 and Munich: P1) were cultured twice in Vero-E6 cells and characterized virologically. Sanger and MinION sequencing demonstrated significant deletions in the furin cleavage signal of Wash1: P6 and minor variants in the Munich: P3 strain. Cleavage of the S glycoprotein in SARS-CoV-2-infected Vero-E6 cell lysates was inefficient even when an intact furin cleavage signal was present. Indirect immunofluorescence demonstrated the S glycoprotein reached the cell surface. Since the S protein is a major antigenic target for the development of neutralizing antibodies we investigated the development of neutralizing antibody titers in serial serum samples obtained from COVID-19 human patients. These were comparable regardless of the presence of an intact or deleted furin cleavage signal. These studies illustrate the need to characterize virus stocks meticulously prior to performing either in vitro or in vivo pathogenesis studies.", "qid": 36, "docid": "6dijw282", "rank": 70, "score": 0.8698864579200745}, {"content": "Title: Characterization of the SARS-CoV-2 Spike in an Early Prefusion Conformation Content: Pandemic coronavirus disease 2019 (COVID-19) is caused by the emerging severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), for which there are no efficacious vaccines or therapeutics that are urgently needed. We expressed three versions of spike (S) proteins\u2014receptor binding domain (RBD), S1 subunit and S ectodomain\u2014in insect cells. RBD appears monomer in solutions, whereas S1 and S associate into homotrimer with substantial glycosylation. The three proteins confer excellent antigenicity with six convalescent COVID-19 patient sera. Cryo-electron microscopy (cryo-EM) analyses indicate that the SARS-CoV-2 S trimer dominate in a unique conformation distinguished from the classic prefusion conformation of coronaviruses by the upper S1 region at lower position ~15 \u00c5 proximal to viral membrane. Such conformation is proposed as an early prefusion state for the SARS-CoV-2 spike that may broaden the knowledge of coronavirus and facilitate vaccine development.", "qid": 36, "docid": "i9r77o70", "rank": 71, "score": 0.869045615196228}, {"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": 72, "score": 0.8688721656799316}, {"content": "Title: An exploration of the SARS-CoV-2 spike receptor binding domain (RBD) \u2013 a complex palette of evolutionary and structural features Content: SARS-CoV-2 spike protein (S) is associated with the entry of virus inside the host cell by recruiting its loop dominant receptor binding domain (RBD) and interacting with the host ACE2 receptor. Our study deploying a two-tier approach encompassing evolutionary and structural analysis provides a comprehensive picture of the RBD, which could be of potential use for better understanding the RBD and address its druggability issues. Resorting to an ensemble of sequence space exploratory tools including co-evolutionary analysis and deep mutational scans we provide a quantitative insight into the evolutionarily constrained subspace of the RBD sequence space. Guided by structure network analysis and Monte Carlo simulation we highlight regions inside the RBD, which are critical for providing structural integrity and conformational flexibility of the binding cleft. We further deployed fuzzy C-means clustering by plugging the evolutionary and structural features of discrete structure blocks of RBD to understand which structure blocks share maximum overlap based on their evolutionary and structural features. Deploying this multi-tier interlinked approach, which essentially distilled the evolutionary and structural features of RBD, we highlight discrete region, which could be a potential druggable pocket thereby destabilizing the structure and addressing evolutionary routes.", "qid": 36, "docid": "fa96qw24", "rank": 73, "score": 0.8688554763793945}, {"content": "Title: Expression, crystallization and preliminary crystallographic study of the C-terminal half of nsp2 from SARS coronavirus Content: SARS coronavirus (SARS-CoV) is the aetiological agent of the highly infectious severe acute respiratory syndrome (SARS). To gain a better understanding of SARS-CoV replication and transcription proteins, a preliminary X-ray crystallo\u00adgraphic study of the C-terminal domain of SARS-CoV nonstructural protein 2 (nsp2) is reported here. The C-\u00adterminal domain of SARS-CoV nsp2 was cloned, overexpressed, purified and crystallized using polyethylene glycol 5000 monomethyl ether as the precipitant; the crystals diffracted to 2.5 \u00c5 resolution. The crystals belonged to space group P6(5), with unit-cell parameters a = b = 112.8, c = 91.1 \u00c5, \u03b1 = \u03b2 = 90, \u03b3 = 120\u00b0. One molecule is assumed to be present per asymmetric unit, which gives a Matthews coefficient of 2.89 \u00c5(3) Da(\u22121) and a solvent content of 56.2%.", "qid": 36, "docid": "myr48meo", "rank": 74, "score": 0.8688087463378906}, {"content": "Title: Dual nature of human ACE2 glycosylation in binding to SARS-CoV-2 spike Content: Binding of the spike protein of SARS-CoV-2 to the human angiotensin converting enzyme 2 (ACE2) receptor triggers translocation of the virus into cells. Both the ACE2 receptor and the spike protein are heavily glycosylated, including at sites near their binding interface. We built fully glycosylated models of the ACE2 receptor bound to the receptor binding domain (RBD) of the SARS-CoV-2 spike protein. Using atomistic molecular dynamics (MD) simulations, we found that the glycosylation of the human ACE2 receptor contributes substantially to the binding of the virus. Interestingly, the glycans at two glycosylation sites, N90 and N322, have opposite effects on spike protein binding. The glycan at the N90 site partly covers the binding interface of the spike RBD. Therefore, this glycan can interfere with the binding of the spike protein and protect against docking of the virus to the cell. By contrast, the glycan at the N322 site interacts tightly with the RBD of the ACE2-bound spike protein and strengthens the complex. Remarkably, the N322 glycan binds into a conserved region of the spike protein identified previously as a cryptic epitope for a neutralizing antibody. By mapping the glycan binding sites, our MD simulations aid in the targeted development of neutralizing antibodies and SARS-CoV-2 fusion inhibitors.", "qid": 36, "docid": "cvqgtpbw", "rank": 75, "score": 0.868184506893158}, {"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": 76, "score": 0.8681787252426147}, {"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": 36, "docid": "023h20vk", "rank": 77, "score": 0.8679543137550354}, {"content": "Title: Distant sequence similarity between hepcidin and the novel coronavirus spike glycoprotein: a potential hint at the possibility of local iron dysregulation in COVID-19 Content: The spike glycoprotein of the SARS-CoV-2 virus, which causes COVID-19, has attracted attention for its vaccine potential and binding capacity to host cell surface receptors. Much of this research focus has centered on the ectodomain of the spike protein. The ectodomain is anchored to a transmembrane region, followed by a cytoplasmic tail. Here we report a distant sequence similarity between the cysteine-rich cytoplasmic tail of the coronavirus spike protein and the hepcidin protein that is found in humans and other vertebrates. Hepcidin is thought to be the key regulator of iron metabolism in humans. An implication of this preliminary observation is to suggest a potential route of investigation in the coronavirus research field making use of an already-established literature on the interplay of local and systemic iron regulation, cytokine-mediated inflammatory processes, respiratory infections and the hepcidin protein. The question of possible homology and an evolutionary connection between the viral spike protein and hepcidin is not assessed in this report, but some scenarios for its study are discussed.", "qid": 36, "docid": "gdcui1zb", "rank": 78, "score": 0.8678683042526245}, {"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": 79, "score": 0.8678501844406128}, {"content": "Title: SARS\u2010CoV\u20102 immunogenicity at the crossroads Content: The outbreak of coronavirus disease 2019 (COVID-19) caused by the novel coronavirus severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) poses a global health emergency and became a worldwide pandemic. We summarize the recent findings with respect to the function, structure and immunogenicity of the spike (S) protein, arising mutations, and implications on vaccine development and therapeutics.", "qid": 36, "docid": "se70hzdt", "rank": 80, "score": 0.8677846789360046}, {"content": "Title: Molecular Basis for ADP-ribose Binding to the Macro-X Domain of SARS-CoV-2 Nsp3 Content: The virus that causes COVID-19, SARS-CoV-2, has a large RNA genome that encodes numerous proteins that might be targets for antiviral drugs. Some of these proteins, such as the RNA-dependent RNA polymers, helicase and main protease, are well conserved between SARS-CoV-2 and the original SARS virus, but several others are not. This study examines one of the proteins encoded by SARS-CoV-2 that is most different, a macrodomain of nonstructural protein 3 (nsp3). Although 26% of the amino acids in this SARS-CoV-2 macrodomain differ from those seen in other coronaviruses, biochemical and structural data reveal that the protein retains the ability to bind ADP-ribose, which is an important characteristic of beta coronaviruses, and potential therapeutic target.", "qid": 36, "docid": "02q9y011", "rank": 81, "score": 0.8677470684051514}, {"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": 82, "score": 0.8674153089523315}, {"content": "Title: Proteolytic Cleavage of the SARS-CoV-2 Spike Protein and the Role of the Novel S1/S2 Site Content: Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), the causative agent of coronavirus disease 19 (COVID-19) has rapidly spread to the entire world within a few months. The origin of SARS-CoV-2 has been related to the lineage B Betacoronavirus SARS-CoV and SARS-related coronaviruses found in bats. Early characterizations of the SARS-CoV-2 genome revealed the existence of a distinct four amino acid insert within the spike (S) protein (underlined, SPRRAR&#8595;S), at the S1/S2 site located at the interface between the S1 receptor binding subunit and the S2 fusion subunit. Notably, this insert appears to be a distinguishing feature among SARS-related sequences and introduces a potential cleavage site for the protease furin. Here, we investigate the potential role of this novel S1/S2 cleavage site and present direct biochemical evidence for proteolytic processing by a variety of proteases. We discuss these findings in the context of the origin of SARS-CoV-2, viral stability, and transmission.", "qid": 36, "docid": "tsq26r7u", "rank": 83, "score": 0.8671960830688477}, {"content": "Title: A virus that has gone viral: amino acid mutation in S protein of Indian isolate of Coronavirus COVID-19 might impact receptor binding, and thus, infectivity Content: Since 2002, \u03b2 coronaviruses (CoVs) have caused three zoonotic outbreaks, SARS-CoV in 2002, MERS-CoV in 2012, and the recent outbreak of SARS-CoV-2 late in 2019 (also named as COVID-19 or novel coronavirus 2019 or nCoV2019). Spike (S) protein, one of the structural proteins of this virus plays key role in receptor (ACE2) binding and thus virus entry. Thus, this protein has attracted scientists for detailed study and therapeutic targeting. As the nCoV2019 takes its course throughout the world, more and more sequence analyses are being done and genome sequences are being deposited in various databases. From India, two clinical isolates have been sequenced and the full genome has been deposited in GenBank. We have performed sequence analyses of the Spike protein of the Indian isolates and compared with that of the Wuhan, China (where the outbreak was first reported). While all the sequences of Wuhan isolates are identical, we found point mutations in the Indian isolates. Out of the two isolates, one was found to harbor a mutation in its receptor-binding domain (RBD) at position 407. At this site, arginine (a positively charged amino acid) was replaced by isoleucine (a hydrophobic amino acid that is also a C-\u03b2 branched amino acid). This mutation has been seen to change the secondary structure of the protein at that region and this can potentially alter receptor binding of the virus. Although this finding needs further validation and more sequencing, the information might be useful in rational drug designing and vaccine engineering.", "qid": 36, "docid": "o3nfoqgs", "rank": 84, "score": 0.8671538829803467}, {"content": "Title: Identification of 22 N-glycosites on spike glycoprotein of SARS-CoV-2 and accessible surface glycopeptide motifs: implications for vaccination and antibody therapeutics Content: Coronaviruses hijack human enzymes to assemble the sugar coat on their spike glycoproteins. The mechanisms by which human antibodies may recognize the antigenic viral peptide epitopes hidden by the sugar coat are unknown. Glycosylation by insect cells differs from the native form produced in human cells, but insect cell-derived influenza vaccines have been approved by the US Food and Drug Administration. In this study, we analyzed recombinant severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) spike protein secreted from BTI-Tn-5B1-4 insect cells, by trypsin and chymotrypsin digestion followed by mass spectrometry analysis. We acquired tandem mass spectrometry (MS/MS) spectrums for glycopeptides of all 22 predicted N-glycosylated sites. We further analyzed the surface accessibility of spike proteins according to cryogenic electron microscopy and homolog-modeled structures, and available antibodies that bind to SARS-CoV-1. All 22 N-glycosylated sites of SARS-CoV-2 are modified by high-mannose N-glycans. MS/MS fragmentation clearly established the glycopeptide identities. Electron densities of glycans cover most of the spike receptor-binding domain of SARS-CoV-2, except YQAGSTPCNGVEGFNCYFPLQSYGFQPTNGVGYQ, similar to a region FSPDGKPCTPPALNCYWPLNDYGFYTTTGIGYQ in SARS-CoV-1. Other surface-exposed domains include those located on central helix, connecting region, heptad repeats, and N-terminal domain. Because the majority of antibody paratopes bind to the peptide portion with or without sugar modification, we propose a snake-catching model for predicted paratopes: a minimal length of peptide is first clamped by a paratope, and sugar modifications close to the peptide either strengthen or do not hinder the binding.", "qid": 36, "docid": "0i5dcbzz", "rank": 85, "score": 0.8669876456260681}, {"content": "Title: Whole-genome sequence analysis and homology modelling of the main protease and non-structural protein 3 of SARS-CoV-2 reveal an aza-peptide and a lead inhibitor with possible antiviral properties Content: Viruses belonging to the family Coronaviridae consist of virulent pathogens that have a zoonotic property. Severe acute respiratory syndrome coronaviruses (SARS-CoVs) and Middle East respiratory syndrome coronaviruses (MERS-CoVs) of this family have emerged before and SARS-CoV-2 has emerged now globally. The characterization of spike glycoproteins, polyproteins and other viral proteins from viruses is important for antiviral drug development. Homology modelling of these proteins with known templates offers the opportunity to discover ligand-binding sites and explore the possible antiviral properties of these protein-ligand complexes. In this study, we performed a complete bioinformatic analysis, sequence alignment, comparison of multiple sequences and modelling of the SARS-CoV-2 whole-genome sequences, the spike protein and the polyproteins for homology with known proteins. We also analysed binding sites in these models for possible binding with ligands that exhibit antiviral properties. Our results indicated that the sequence of the polyprotein isolate SARS-CoV-2_HKU-SZ-001_2020 showed 98.94 percent identity to SARS-coronavirus NSP12 bound to NSP7 and NSP8 co-factors. The results also indicated that a part of the viral genome (residues 3268-3573 in Frame 2 with 306 amino acids) of the SARS-CoV-2 isolate Wuhan-Hu-1 (GenBank Accession Number MN908947.3) when modelled with templateof the PDB database showed 96 percent identity to a 3C-like peptidase of SARS-CoVs, which has the ability to bind with an aza-peptide epoxide (APE) known for the irreversible inhibition of SARS-CoV main peptidase. A docking profile with 9 different conformations of the ligand with the protein model using Autodock Vina showed an affinity of \u22127.1 kcal mol\u22121. This region was conserved in 831 genomes of SARS-CoV-2. The part of the genome (residues 1568-1882 in Frame 2 with 315 amino acids) when modelled with template of the PDB database showed 82 percent identity to a papain-like protease/deubiquitinase, which when complexed with ligand GRL0617 acts as an inhibitor and can block SARS-CoV replication. A docking profile with 9 different conformations of the ligand with the protein model using Autodock Vina showed an affinity of \u22127.9 kcal mol\u22121. This region was conserved in 831 genomes of SARS-CoV-2. It is possible that these ligands can be used as antivirals of SARS-CoV-2.", "qid": 36, "docid": "pp5h06eo", "rank": 86, "score": 0.8669635057449341}, {"content": "Title: Molecular modelling of S1 and S2 subunits of SARS coronavirus spike glycoprotein Content: Abstract The S1 and S2 subunits of the spike glycoprotein of the coronavirus which is responsible for the severe acute respiratory syndrome (SARS) have been modelled, even though the corresponding amino acid sequences were not suitable for tertiary structure predictions with conventional homology and/or threading procedures. An indirect search for a protein structure to be used as a template for 3D modelling has been performed on the basis of the genomic organisation similarity generally exhibited by coronaviruses. The crystal structure of Clostridium botulinum neurotoxin B appeared to be structurally adaptable to human and canine coronavirus spike protein sequences and it was successfully used to model the two subunits of SARS coronavirus spike glycoprotein. The overall shape and the surface hydrophobicity of the two subunits in the obtained models suggest the localisation of the most relevant regions for their activity.", "qid": 36, "docid": "imyfo83x", "rank": 87, "score": 0.8668667078018188}, {"content": "Title: Identification of an antigenic determinant on the S2 domain of the severe acute respiratory syndrome coronavirus spike glycoprotein capable of inducing neutralizing antibodies. Content: Severe acute respiratory syndrome (SARS) is a life-threatening disease caused by a newly identified coronavirus (CoV), SARS-CoV. The spike (S) glycoprotein of CoV is the major structural protein responsible for induction of host immune response and virus neutralization by antibodies. Hence, knowledge of neutralization determinants on the S protein is helpful for designing protective vaccines. To analyze the antigenic structure of the SARS-CoV S2 domain, the carboxyl-terminal half of the S protein, we first used sera from convalescent SARS patients to test the antigenicity of 12 overlapping fragments spanning the entire S2 and identified two antigenic determinants (Leu 803 to Ala 828 and Pro 1061 to Ser 1093). To determine whether neutralizing antibodies can be elicited by these two determinants, we immunized animals and found that both of them could induce the S2-specific antisera. In some animals, however, only one determinant (Leu 803 to Ala 828) was able to induce the antisera with the binding ability to the native S protein and the neutralizing activity to the SARS-CoV pseudovirus. This determinant is highly conserved across different SARS-CoV isolates. Identification of a conserved antigenic determinant on the S2 domain of the SARS-CoV S protein, which has the potential for inducing neutralizing antibodies, has implications in the development of effective vaccines against SARS-CoV.", "qid": 36, "docid": "azn75kqd", "rank": 88, "score": 0.8668560981750488}, {"content": "Title: Update on the target structures of SARS-CoV-2: A systematic review Content: Knowledge of structural details is very much essential from the drug-design perspective. In the systematic review, we systematically reviewed the structural basis of different target proteins of SARS-corona virus (CoV2) from a viral life cycle and from drug design perspective. We searched four literature (PubMed, EMBASE, NATURE, and Willey online library) databases and one structural database (RCSB.org) with appropriate keywords till April 18, and finally, 26 articles were included in the systematic review. The published literature mainly centered upon the structural details of \"spike protein,\" \"main protease/M Pro/3CL pro,\" \"RNA-dependent RNA polymerase,\" and \"nonstructural protein 15 Endoribonuclease\" of SARS-CoV-2. However, inhibitor bound structures were very less. We need better structures elucidating the interactions between different targets and their inhibitors which will help us in understanding the atomic level importance of different amino acid residues in the functionality of the target structures. To summarize, we need structures with fine resolution, co-crystallized structures with biologically validated inhibitors, and functional characterization of different target proteins. Some other routes of entry of SARS-CoV-2 are also mentioned (e.g., CD147); however, these findings are not structurally validated. This review may pave way for better understanding of SARS-CoV-2 life cycle from structural biology perspective.", "qid": 36, "docid": "wak7ie3q", "rank": 89, "score": 0.866797924041748}, {"content": "Title: Computational Electrostatics Predict Variations in SARS-CoV-2 Spike and Human ACE2 Interactions Content: SARS-CoV-2 is a novel virus that is presumed to have emerged from bats to crossover into humans in late 2019. As the global pandemic ensues, scientist are working to evaluate the virus and develop a vaccine to counteract the deadly disease that has impacted lives across the entire globe. We perform computational electrostatic simulations on multiple variants of SARS-CoV-2 spike protein s1 in complex with human angiotensin-converting enzyme 2 (ACE2) variants to examine differences in electrostatic interactions across the various complexes. Calculations are performed across the physiological pH range to also examine the impact of pH on these interactions. Two of six spike protein s1 variations having greater electric forces at pH levels consistent with nasal secretions and significant variations in force across all five variants of ACE2. Five out of six spike protein s1 variations have relatively consistent forces at pH levels of the lung, and one spike protein s1 variant that has low potential across a wide range of pH. These predictions indicate that variants of SARS-CoV-2 spike proteins and human ACE2 in certain combinations could potentially play a role in increased binding efficacy of SARS-CoV-2 in vivo.", "qid": 36, "docid": "rj3wkpk3", "rank": 90, "score": 0.86666339635849}, {"content": "Title: Analyses of spike protein from first deposited sequences of SARS-CoV2 from West Bengal, India Content: India has recently started sequencing SARS-CoV2 genome from clinical isolates. Currently only few sequences are available from three states in India. Kerala was the first state to deposit complete sequence from two isolates followed by one from Gujarat. On April 27, 2020, the first five sequences from the state of West Bengal (Eastern India) were deposited on \u2018a global initiative on sharing avian flu data\u2019 (GISAID) platform. In this paper we have analysed the spike protein sequences from all these five isolates and also compared for their similarities or differences with other sequences reported in India and with isolates of Wuhan origin. We report one unique mutation at position 723 and the other at 1124 in the S2 domain of spike protein of the isolates from West Bengal only and one mutation downstream of the receptor binding domain at position 614 in S1 domain which was common with the sequence from Gujarat (a state of western part of India). Mutation in the S2 domain showed changes in the secondary structure of the spike protein at region of mutation. We also studied molecular dynamics using normal mode analyses and found that this mutation decreases the flexibility of S2 domain. Since both S1 and S2 are important in receptor binding followed by entry in the host cells, such mutations may define the affinity or avidity of receptor binding.", "qid": 36, "docid": "wdgbno9p", "rank": 91, "score": 0.8665719032287598}, {"content": "Title: Severe acute respiratory syndrome coronavirus entry into host cells: Opportunities for therapeutic intervention Content: A novel human coronavirus (CoV) has been identified as the etiological agent that caused the severe acute respiratory syndrome (SARS) outbreak in 2003. The spike (S) protein of this virus is a type I surface glycoprotein that mediates binding of the virus to the host receptor and the subsequent fusion between the viral and host membranes. Because of its critical role in viral entry, the S protein is an important target for the development of anti\u2010SARS CoV therapeutics and prophylactics. This article reviews the structure and function of the SARS CoV S protein in the context of its role in virus entry. Topics that are discussed include: the interaction between the S1 domain of the SARS spike protein and the cellular receptor, angiotensin converting enzyme 2 (ACE2), and the structural features of the ectodomain of ACE2; the antigenic determinants presented by the S protein and the nature of neutralizing monoclonal antibodies that are elicited in vivo; the structure of the 4,3\u2010hydrophobic heptad repeats HR1 and HR2 of the S2 domain and their interaction to form a six\u2010helical bundle during the final stages of fusion. Opportunities for the design and development of anti\u2010SARS agents based on the inhibition of receptor binding, the therapeutic uses of S\u2010directed monoclonal antibodies and inhibitors of HR1\u2013HR2 complex formation are presented. \u00a9 2006 Wiley Periodicals, Inc. Med Res Rev, 26, No. 4, 414\u2013433, 2006", "qid": 36, "docid": "mt8aqu8j", "rank": 92, "score": 0.866468071937561}, {"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": 93, "score": 0.8664675354957581}, {"content": "Title: Unfractionated heparin potently inhibits the binding of SARS-CoV-2 spike protein to a human cell line Content: The SARS-CoV-2 spike protein is known to bind to the receptor, ACE2, on the surface of target cells. The spike protein is processed by membrane proteases, including TMPRSS2, and is either internalised or fuses directly with the cell, leading to infection. We identified a human cell line that expresses both ACE2 and TMPRSS2, the RT4 urinary bladder transitional carcinoma, and used it to develop a proxy assay for viral interactions with host cells. A tagged recombinant form of the spike protein, containing both the S1 and S2 domains, binds strongly to RT4 cells as determined by flow cytometry. Binding is temperature dependent and increases sharply at 37\u00b0C, suggesting that processing of the spike protein is likely to be important in the interaction. As the spike protein has previously been shown to bind heparin, a soluble glycosaminoglycan, we used a flow cytometry assay to determine the effect of heparin on spike protein binding to RT4 cells. Unfractionated heparin inhibited spike protein binding with an IC50 value of <0.05U/ml whereas two low molecular weight heparins were much less effective. This suggests that heparin, particularly unfractionated forms, could be considered to reduce clinical manifestations of COVID-19 by inhibiting continuing viral infection. Despite the sensitivity to heparin, we found no evidence that host cell glycosaminoglycans such as heparan and chondroitin sulphates play a major role in spike protein attachment.", "qid": 36, "docid": "3w5fvbts", "rank": 94, "score": 0.86623215675354}, {"content": "Title: The insert sequence in SARS-CoV-2 enhances spike protein cleavage by TMPRSS Content: At the end of 2019, the SARS-CoV-2 induces an ongoing outbreak of pneumonia in China1, even more spread than SARS-CoV infection2. The entry of SARS-CoV into host cells mainly depends on the cell receptor (ACE2) recognition and spike protein cleavage-induced cell membrane fusion3,4. The spike protein of SARS-CoV-2 also binds to ACE2 with a similar affinity, whereas its spike protein cleavage remains unclear5,6. Here we show that an insertion sequence in the spike protein of SARS-CoV-2 enhances the cleavage efficiency, and besides pulmonary alveoli, intestinal and esophagus epithelium were also the target tissues of SARS-CoV-2. Compared with SARS-CoV, we found a SPRR insertion in the S1/S2 protease cleavage sites of SARS-CoV-2 spike protein increasing the cleavage efficiency by the protein sequence aligment and furin score calculation. Additionally, the insertion sequence facilitates the formation of an extended loop which was more suitable for protease recognition by the homology modeling and molicular docking. Furthermore, the single-cell transcriptomes identified that ACE2 and TMPRSSs are highly coexpressed in AT2 cells of lung, along with esophageal upper epithelial cells and absorptive enterocytes. Our results provide the bioinformatics evidence for the increased spike protein cleavage of SARS-CoV-2 and indicate its potential target cells.", "qid": 36, "docid": "pm8usc55", "rank": 95, "score": 0.8661544322967529}, {"content": "Title: Molecular Basis for ADP-Ribose Binding to the Mac1 Domain of SARS-CoV-2 nsp3 Content: The virus that causes COVID-19, SARS-CoV-2, has a large RNA genome that encodes numerous proteins that might be targets for antiviral drugs. Some of these proteins, such as the RNA-dependent RNA polymerase, helicase, and main protease, are well conserved between SARS-CoV-2 and the original SARS virus, but several others are not. This study examines one of the proteins encoded by SARS-CoV-2 that is most different, a macrodomain of nonstructural protein 3 (nsp3). Although 26% of the amino acids in this SARS-CoV-2 macrodomain differ from those observed in other coronaviruses, biochemical and structural data reveal that the protein retains the ability to bind ADP-ribose, which is an important characteristic of beta coronaviruses and a potential therapeutic target.", "qid": 36, "docid": "e8dvhlf3", "rank": 96, "score": 0.8659853339195251}, {"content": "Title: Identification of 22 N-glycosites on spike glycoprotein of SARS-CoV-2 and accessible surface glycopeptide motifs: implications for vaccination and antibody therapeutics Content: Coronaviruses hijack human enzymes to assemble the sugar coat on their spike glycoproteins. The mechanisms by which human antibodies may recognize the antigenic viral peptide epitopes hidden by the sugar coat are unknown. Glycosylation by insect cells differs from the native form produced in human cells, but insect cell\u2013derived influenza vaccines have been approved by the US Food and Drug Administration. In this study, we analyzed recombinant severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) spike protein secreted from BTI-Tn-5B1\u20134 insect cells, by trypsin and chymotrypsin digestion followed by mass spectrometry analysis. We acquired tandem mass spectrometry (MS/MS) spectrums for glycopeptides of all 22 predicted N-glycosylated sites. We further analyzed the surface accessibility of spike proteins according to cryogenic electron microscopy and homolog-modeled structures, and available antibodies that bind to SARS-CoV-1. All 22 N-glycosylated sites of SARS-CoV-2 are modified by high-mannose N-glycans. MS/MS fragmentation clearly established the glycopeptide identities. Electron densities of glycans cover most of the spike receptor-binding domain of SARS-CoV-2, except YQAGSTPCNGVEGFNCYFPLQSYGFQPTNGVGYQ, similar to a region FSPDGKPCTPPALNCYWPLNDYGFYTTTGIGYQ in SARS-CoV-1. Other surface-exposed domains include those located on central helix, connecting region, heptad repeats, and N-terminal domain. Because the majority of antibody paratopes bind to the peptide portion with or without sugar modification, we propose a snake-catching model for predicted paratopes: a minimal length of peptide is first clamped by a paratope, and sugar modifications close to the peptide either strengthen or do not hinder the binding.", "qid": 36, "docid": "elhz77ek", "rank": 97, "score": 0.8658817410469055}, {"content": "Title: A Cryptic Site of Vulnerability on the Receptor Binding Domain of the SARS-CoV-2 Spike Glycoprotein Content: SARS-CoV-2 is a zoonotic virus that has caused a pandemic of severe respiratory disease\u2014COVID-19\u2014 within several months of its initial identification. Comparable to the first SARS-CoV, this novel coronavirus\u2019s surface Spike (S) glycoprotein mediates cell entry via the human ACE-2 receptor, and, thus, is the principal target for the development of vaccines and immunotherapeutics. Molecular information on the SARS-CoV-2 S glycoprotein remains limited. Here we report the crystal structure of the SARS-CoV-2 S receptor-binding-domain (RBD) at a the highest resolution to date, of 1.95 \u00c5. We identified a set of SARS-reactive monoclonal antibodies with cross-reactivity to SARS-CoV-2 RBD and other betacoronavirus S glycoproteins. One of these antibodies, CR3022, was previously shown to synergize with antibodies that target the ACE-2 binding site on the SARS-CoV RBD and reduce viral escape capacity. We determined the structure of CR3022, in complex with the SARS-CoV-2 RBD, and defined a broadly reactive epitope that is highly conserved across betacoronaviruses. This epitope is inaccessible in the \u201cclosed\u201d prefusion S structure, but is accessible in \u201copen\u201d conformations. This first-ever resolution of a human antibody in complex with SARS-CoV-2 and the broad reactivity of this set of antibodies to a conserved betacoronavirus epitope will allow antigenic assessment of vaccine candidates, and provide a framework for accelerated vaccine, immunotherapeutic and diagnostic strategies against SARS-CoV-2 and related betacoronaviruses. HIGHLIGHTS High resolution structure of the SARS-CoV-2 Receptor-Binding-Domain (RBD). Recognition of the SARS-CoV-2 RBD by SARS-CoV antibodies. Structure of the SARS-COV-2 RBD in complex with antibody CR3022. Identification of a cryptic site of vulnerability on the SARS-CoV-2 Spike.", "qid": 36, "docid": "ebbzx8yr", "rank": 98, "score": 0.8658447265625}, {"content": "Title: Truncated human angiotensin converting enzyme 2; a potential inhibitor of SARS-CoV-2 spike glycoprotein and potent COVID-19 therapeutic agent Content: The current pandemic of Covid-19 caused by SARS-CoV-2 is continued to spread globally and no potential drug or vaccine against it is available. Spike (S) glycoprotein is the structural protein of SARS-CoV-2 located on the envelope surface, involve in interaction with angiotensin converting enzyme 2 (ACE2), a cell surface receptor, followed by entry into the host cell. Thereby, blocking the S glycoprotein through potential inhibitor may interfere its interaction with ACE2 and impede its entry into the host cell. Here, we present a truncated version of human ACE2 (tACE2), comprising the N terminus region of the intact ACE2 from amino acid position 21-119, involved in binding with receptor binding domain (RBD) of SARS-CoV-2. We analyzed the in-silico potential of tACE2 to compete with intact ACE2 for binding with RBD. The protein-protein docking and molecular dynamic simulation showed that tACE2 has higher binding affinity for RBD and form more stabilized complex with RBD than the intact ACE2. Furthermore, prediction of tACE2 soluble expression in E. coli makes it a suitable candidate to be targeted for Covid-19 therapeutics. This is the first MD simulation based findings to provide a high affinity protein inhibitor for SARS-CoV-2 S glycoprotein, an important target for drug designing against this unprecedented challenge.Communicated by Ramaswamy H. Sarma.", "qid": 36, "docid": "gf4o3n3z", "rank": 99, "score": 0.8656879663467407}, {"content": "Title: ACE2 fragment as a decoy for novel SARS-Cov-2 virus Content: Novel SARS-Cov-2 enters human cells via interaction between the surface spike (S) glycoprotein and the cellular membrane receptor angiotensin-converting enzyme 2 (ACE2). Using a combination of comparative structural analyses of the binding surface of the S protein to ACE2, docking experiments, and molecular dynamics simulations we computationally identified a minimal, stable fragment of ACE2. This fragment binds to the S protein, is soluble, and appears not to bind to the physiological ligand angiotensinII. These results suggest a possible use of the ACE2 fragment as a decoy that could interfere with viral binding by competition.", "qid": 36, "docid": "77ku0164", "rank": 100, "score": 0.8655585646629333}]}
{"query": "What is the result of phylogenetic analysis of SARS-CoV-2 genome sequence?", "hits": [{"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": 37, "docid": "t0cw7l2a", "rank": 1, "score": 0.8896482586860657}, {"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": 37, "docid": "msggi1p2", "rank": 2, "score": 0.8857278823852539}, {"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": 3, "score": 0.8839442729949951}, {"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": 4, "score": 0.8817408680915833}, {"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": 37, "docid": "bsypo08l", "rank": 5, "score": 0.8808194994926453}, {"content": "Title: Whole genome sequencing of SARS-CoV-2 isolated in Guangdong Province and factors influencing the sequencing/ \u5e7f\u4e1c\u7701\u65b0\u578b\u51a0\u72b6\u75c5\u6bd2\u5168\u57fa\u56e0\u7ec4\u5e8f\u5217\u6d4b\u5b9a\u53ca\u5176\u5f71\u54cd\u56e0\u7d20\u5206\u6790 Content: Objective: To obtain the genome sequences of SARS-CoV-2 in respiratory specimens in Guangdong Province with next-generation sequencing (NGS) and analyze the factors influencing sequencing. Methods: Eight upper and lower respiratory tract specimens were collected from patients with SARS-CoV-2 infection in Guangdong Province in January 2020. RNA library construction was used to obtain the genome sequences of SARS-CoV-2. A bio-informatics software package (CLC Genomics Workbench 12.0) was used to analyze and compare the genomic sequences. Results: Five SARS-CoV-2 genome sequences were obtained from the eight specimens and two were obtained from lower respiratory tract specimens. The nucleotide homology to SARS-CoV-2 was 97.74%-99.90%. The Ct values were lower, while the sequencing depth, coverage, relative abundance and genome integrity were higher in sequencing the SARS-CoV-2 in lower respiratory tract specimens. Conclusions: The low Ct value of SARS-CoV-2 in the samples was good for sequencing.", "qid": 37, "docid": "2k7gckj2", "rank": 6, "score": 0.8789186477661133}, {"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": 7, "score": 0.8782950639724731}, {"content": "Title: The Architecture of SARS-CoV-2 Transcriptome Content: SARS-CoV-2 is a betacoronavirus responsible for the COVID-19 pandemic. Although the SARS-CoV-2 genome was reported recently, its transcriptomic architecture is unknown. Utilizing two complementary sequencing techniques, we present a high-resolution map of the SARS-CoV-2 transcriptome and epitranscriptome. DNA nanoball sequencing shows that the transcriptome is highly complex owing to numerous discontinuous transcription events. In addition to the canonical genomic and 9 subgenomic RNAs, SARS-CoV-2 produces transcripts encoding unknown ORFs with fusion, deletion, and/or frameshift. Using nanopore direct RNA sequencing, we further find at least 41 RNA modification sites on viral transcripts, with the most frequent motif, AAGAA. Modified RNAs have shorter poly(A) tails than unmodified RNAs, suggesting a link between the modification and the 3' tail. Functional investigation of the unknown transcripts and RNA modifications discovered in this study will open new directions to our understanding of the life cycle and pathogenicity of SARS-CoV-2.", "qid": 37, "docid": "6quqydr6", "rank": 8, "score": 0.876044511795044}, {"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": 9, "score": 0.8747723698616028}, {"content": "Title: The Architecture of SARS-CoV-2 Transcriptome Content: Summary SARS-CoV-2 is a betacoronavirus responsible for the COVID-19 pandemic. Although the SARS-CoV-2 genome was reported recently, its transcriptomic architecture is unknown. Utilizing two complementary sequencing techniques, we present a high-resolution map of the SARS-CoV-2 transcriptome and epitranscriptome. DNA nanoball sequencing shows that the transcriptome is highly complex owing to numerous discontinuous transcription events. In addition to the canonical genomic and 9 subgenomic RNAs, SARS-CoV-2 produces transcripts encoding unknown ORFs with fusion, deletion, and/or frameshift. Using nanopore direct RNA sequencing, we further find at least 41 RNA modification sites on viral transcripts, with the most frequent motif, AAGAA. Modified RNAs have shorter poly(A) tails than unmodified RNAs, suggesting a link between the modification and the 3\u2032 tail. Functional investigation of the unknown transcripts and RNA modifications discovered in this study will open new directions to our understanding of the life cycle and pathogenicity of SARS-CoV-2.", "qid": 37, "docid": "ypsh3rjv", "rank": 10, "score": 0.8747469186782837}, {"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": 37, "docid": "aqkpnz0o", "rank": 11, "score": 0.8731463551521301}, {"content": "Title: The architecture of SARS-CoV-2 transcriptome Content: SARS-CoV-2 is a betacoronavirus that is responsible for the COVID-19 pandemic. The genome of SARS-CoV-2 was reported recently, but its transcriptomic architecture is unknown. Utilizing two complementary sequencing techniques, we here present a high-resolution map of the SARS-CoV-2 transcriptome and epitranscriptome. DNA nanoball sequencing shows that the transcriptome is highly complex owing to numerous recombination events, both canonical and noncanonical. In addition to the genomic RNA and subgenomic RNAs common in all coronaviruses, SARS-CoV-2 produces a large number of transcripts encoding unknown ORFs with fusion, deletion, and/or frameshift. Using nanopore direct RNA sequencing, we further find at least 41 RNA modification sites on viral transcripts, with the most frequent motif being AAGAA. Modified RNAs have shorter poly(A) tails than unmodified RNAs, suggesting a link between the internal modification and the 3\u2032 tail. Functional investigation of the unknown ORFs and RNA modifications discovered in this study will open new directions to our understanding of the life cycle and pathogenicity of SARS-CoV-2. Highlights We provide a high-resolution map of SARS-CoV-2 transcriptome and epitranscriptome using nanopore direct RNA sequencing and DNA nanoball sequencing. The transcriptome is highly complex owing to numerous recombination events, both canonical and noncanonical. In addition to the genomic and subgenomic RNAs common in all coronaviruses, SARS-CoV-2 produces transcripts encoding unknown ORFs. We discover at least 41 potential RNA modification sites with an AAGAA motif.", "qid": 37, "docid": "wt4pxu08", "rank": 12, "score": 0.8730342388153076}, {"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": 13, "score": 0.8728665709495544}, {"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": 14, "score": 0.872321605682373}, {"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": 15, "score": 0.8716583251953125}, {"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": 16, "score": 0.8715517520904541}, {"content": "Title: Unfolding SARS-CoV-2 viral genome to understand its gene expression regulation Content: SARS-CoV-2 is a new virus responsible for an outbreak of respiratory illness known as COVID-19, which has spread to several countries around the world and a global effort is being undertaken to characterize the molecular features and evolutionary origins of this virus. In silico analysis of the transcription start sites, promoter regions, transcription factors and their binding sites, gene ontology, CpG islands for SARS-CoV-2 viral genome are a first step to understand the regulation mechanisms of gene expression and association with genetic variations in the genomes. For this purpose, we first computationally surveyed all SARS-CoV-2 virus genes with the open reading frames from NCBI database and found eleven sequences to accomplish the mentioned features by using bioinformatics tools. Our analysis revealed that all (100%) of the SARS-CoV-2 virus genes have more than one TSS. By taking all TSSs with the highest predictive score we determined promoter regions and identified five common candidate motifs (MVI, MVII, MVIII, MVIV and MVV) of which MVI was found to be shared by all promoter regions of SARS-CoV-2 virus genes with the least E-value (3.8e-056, statistically highly significant). In our further analysis of MVI we showed MVI serve as binding sites for a single transcription factor (TF) family, EXPREG, involved in the regulatory mode of these genes. From EXPREG family four TFs that belongs to Cyclic AMP (cAMP) receptor protein (CRP) and Catabolite control protein A (CcpA) group mostly serve as transcriptional activator whereas two TFs that belong to LexA group always serve as transcriptional repressor in different kinds of cellular processes and molecular functions. Therefore, we unfolded SARS-CoV-2 viral genome to shed light on its gene expression regulation that could help to design and evaluate diagnostic tests, to track and trace the ongoing outbreak and to identify potential intervention options.", "qid": 37, "docid": "imwa033f", "rank": 17, "score": 0.8706095218658447}, {"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": 18, "score": 0.8696070909500122}, {"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": 19, "score": 0.8692467212677002}, {"content": "Title: Unfolding SARS-CoV-2 viral genome to understand its gene expression regulation Content: SARS-CoV-2 is a new virus responsible for an outbreak of respiratory illness known as COVID-19, which has spread to several countries around the world and a global effort is being undertaken to characterize the molecular features and evolutionary origins of this virus. In silico analysis of the transcription start sites, promoter regions, transcription factors and their binding sites, gene ontology, CpG islands for SARS-CoV-2 viral genome are a first step to understand the regulation mechanisms of gene expression and its association with genetic variations in the genomes. For this purpose, we first computationally surveyed all SARS-CoV-2 virus genes with the open reading frames from NCBI database and found eleven sequences to accomplish the mentioned features by using bioinformatics tools. Our analysis revealed that all (100%) of the SARS-CoV-2 virus genes have more than one TSS. By taking all TSSs with the highest predictive score we determined promoter regions and identified five common candidate motifs (MVI, MVII, MVIII, MVIV and MVV) of which MVI was found to be shared by all promoter regions of SARS-CoV-2 virus genes with the least E-value (3.8e-056, statistically highly significant). In our further analysis of MVI we showed MVI serve as binding sites for a single transcription factor (TF) family, EXPREG, involved in the regulatory mode of these genes. From EXPREG family four TFs that belongs to Cyclic AMP (cAMP) receptor protein (CRP) and Catabolite control protein A (CcpA) group mostly serve as transcriptional activator whereas two TFs that belong to LexA group always serve as transcriptional repressor in different kinds of cellular processes and molecular functions. Therefore, we unfolded SARS-CoV-2 viral genome to shed light on its gene expression regulation that could help to design and evaluate diagnostic tests, to track and trace the ongoing outbreak and to identify potential intervention options.", "qid": 37, "docid": "jlrk8fg0", "rank": 20, "score": 0.868956446647644}, {"content": "Title: Bioinformatics analysis of SARS coronavirus genome polymorphism Content: BACKGROUND: We have compared 38 isolates of the SARS-CoV complete genome. The main goal was twofold: first, to analyze and compare nucleotide sequences and to identify positions of single nucleotide polymorphism (SNP), insertions and deletions, and second, to group them according to sequence similarity, eventually pointing to phylogeny of SARS-CoV isolates. The comparison is based on genome polymorphism such as insertions or deletions and the number and positions of SNPs. RESULTS: The nucleotide structure of all 38 isolates is presented. Based on insertions and deletions and dissimilarity due to SNPs, the dataset of all the isolates has been qualitatively classified into three groups each having their own subgroups. These are the A-group with \"regular\" isolates (no insertions / deletions except for 5' and 3' ends), the B-group of isolates with \"long insertions\", and the C-group of isolates with \"many individual\" insertions and deletions. The isolate with the smallest average number of SNPs, compared to other isolates, has been identified (TWH). The density distribution of SNPs, insertions and deletions for each group or subgroup, as well as cumulatively for all the isolates is also presented, along with the gene map for TWH. Since individual SNPs may have occurred at random, positions corresponding to multiple SNPs (occurring in two or more isolates) are identified and presented. This result revises some previous results of a similar type. Amino acid changes caused by multiple SNPs are also identified (for the annotated sequences, as well as presupposed amino acid changes for non-annotated ones). Exact SNP positions for the isolates in each group or subgroup are presented. Finally, a phylogenetic tree for the SARS-CoV isolates has been produced using the CLUSTALW program, showing high compatibility with former qualitative classification. CONCLUSIONS: The comparative study of SARS-CoV isolates provides essential information for genome polymorphism, indication of strain differences and variants evolution. It may help with the development of effective treatment.", "qid": 37, "docid": "wt8zfqk0", "rank": 21, "score": 0.8681008815765381}, {"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": 22, "score": 0.868018627166748}, {"content": "Title: [Genomic characterization of SARS coronavirus: a novel member of coronavirus]. Content: In March 2003, SARS-CoV, a novel coronavirus which has been proved to be a pathogen causing Severe Acute Respiratory Syndrome (SARS). The complete genome of SARS-CoV has been sequenced by international collaboration including China. In the present study, the genome sequences were collected from NCBI and genomic characterization was analyzed. SARS-CoV has a genome of 28-30 kb including 11 ORFs (Open Reading Frames), which is consistent with that of coronavirus family, and its genome organization is similar to those of other coronaviruses as well. SARS-CoV evolutionally closes to other coronavirus in their corresponding proteins, such as spike protein, small membrane protein and nucleocapsid protein. In some regions of the genome, the genomic sequence of SARS-CoV was significantly different from that of other coronavirus, and has a self-conservative genomic sequence. Moreover, its encoding protein sequences were greatly different from those of other coronavirus. The analysis indicated that SARS-CoV has lower redundancy, that is, it has a high variation possibility. It may not be a variant of other coronaviruses but a novel coronavirus, which existed independently in nature and was not recognized by human being before, although SARS-CoV is morphologically similar to other coronavirus and belongs to coronavirus family. The sequences of its genes and encoding proteins are substantially different from those of other coronavirus.", "qid": 37, "docid": "7972ps41", "rank": 23, "score": 0.8676058053970337}, {"content": "Title: Comprehensive evolution and molecular characteristics of a large number of SARS-CoV-2 genomes revealed its epidemic trend and possible origins Content: Objectives To reveal epidemic trend and possible origins of SARS-CoV-2 by exploring its evolution and molecular characteristics based on a large number of genomes since it has infected millions of people and spread quickly all over the world. Methods Various evolution analysis methods were employed. Results The estimated Ka/Ks ratio of SARS-CoV-2 is 1.008 or 1.094 based on 622 or 3624 SARS-CoV-2 genomes, and the time to the most recent common ancestor (tMRCA) was inferred in late September 2019. Further 9 key specific sites of highly linkage and four major haplotypes H1, H2, H3 and H4 were found. The Ka/Ks, detected population size and development trends of each major haplotype showed H3 and H4 subgroups were going through a purify evolution and almost disappeared after detection, indicating H3 and H4 might have existed for a long time, while H1 and H2 subgroups were going through a near neutral or neutral evolution and globally increased with time. Notably the frequency of H1 was generally high in Europe and correlated to death rate (r>0.37). Conclusions In this study, the evolution and molecular characteristics of more than 16000 genomic sequences provided a new perspective for revealing epidemiology of SARS-CoV-2.", "qid": 37, "docid": "npcu4wq1", "rank": 24, "score": 0.8671313524246216}, {"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": 25, "score": 0.8665838837623596}, {"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": 37, "docid": "su5tlg3l", "rank": 26, "score": 0.8664194941520691}, {"content": "Title: SARS-CoV2 envelope protein: Non-synonymous mutations and its consequences Content: In the NCBI database, as on June 6, 2020, total number of available complete genome sequences of SARS-CoV2 across the world is 3617. The envelope protein of SARS-CoV2 possesses several non-synonymous mutations over the transmembrane domain and (C)-terminus in 15 (0.414%) genomes among 3617 available SARS-CoV2 genomes. More precisely, it is to be mentioned that 10(0.386%) out of 2588 genomes from the USA, 3(0.806%) from Asia, 1 (0.348%) from Europe and 1 (0.274%) from Oceania contain the missense mutations over the envelope proteins of SARS-CoV2 genomes. The C-terminus motif DLLV has been changed to DFLV and YLLV in the proteins QJR88103 (Australia: Victoria) and QKI36831 (China: Guangzhou) respectively, which might affect the binding of this motif with the host protein PALS1.", "qid": 37, "docid": "phl6ibbv", "rank": 27, "score": 0.8659507036209106}, {"content": "Title: Genomic Analysis and Comparative Multiple Sequence of SARS-CoV2. Content: BACKGROUND China announced an outbreak of new coronavirus in the city of Wuhan on December 31, 2019; lash to now, the virus transmission has become pandemic worldwide. Severe cases from Huanan Seafood Wholesale market in Wuhan were confirmed pneumonia with a novel coronavirus. (2019-nCoV). Understanding the molecular mechanisms of genome selection and packaging is critical for developing antiviral strategies. Thus, we defined the correlation in ten SARS-CoV2 sequences from different countries to analyze the genomic patterns of disease origin and evolution aiming for development new control pandemic processes. METHODS We apply genomic analysis to observe SARS-Co-V2 sequences from GenBank (http:// www.ncbi.nim.nih.gov/genebank/): MN 908947 China, C1), MN985325 (USA:WA, UW), MN996527 (China, C2), MT007544 (Australia:Victoria, A1), MT027064 (USA:CA, UC), MT039890 (South Korea, K1), MT066175 (Taiwan,T1), MT066176 (Taiwan, T2), LC528232 (Japan, J1), and LC528233 (Japan, J2) for genomic sequence alignment an analysis. Multiple Sequence Alignment by Clustalw (https://www.genome.jp/tools-bin/clustalw) web is applied as our alignment tool. RESULTS We analyze ten sequences from NCBI database by genome alignment and find no difference in amino acid sequences within M and N proteins. There are two amino acid variances in Spike protein region. One mutation found from south Korea sequence is verified. Two possible \"L\" and \"S\" SNP found in ORF1ab and ORF8 regions are detected CONCLUSION:: We perform genomic analysis and comparative multiple sequence of SARS-CoV-2. Studies about the biological symptoms of SARS-CoV-2 in clinic animal and humans will manipulate an understanding the origin of pandemic crisis.", "qid": 37, "docid": "zzi2xv3p", "rank": 28, "score": 0.8656255006790161}, {"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": 29, "score": 0.8653615713119507}, {"content": "Title: On spatial molecular arrangements of SARS-CoV2 genomes of Indian patients Content: A pandemic caused by the SARS-CoV2 is being experienced by the whole world since December, 2019. A thorough understanding beyond just sequential similarities among the protein coding genes of SARS-CoV2 is important in order to differentiate or relate to the other known CoVs of the same genus. In this study, we compare three genomes namely MT012098 (India-Kerala), MT050493 (India-Kerala), MT358637 (India-Gujrat) from India with NC_045512 (China-Wuhan) to view the spatial as well as molecular arrangements of nucleotide bases of all the genes embedded in these four genomes. Based on different features extracted for each gene embedded in these genomes, corresponding phylogenetic relationships have been built up. Differences in phylogenetic tree arrangement with individual gene suggest that three genomes of Indian origin have come from three different origins or the evolution of viral genome is very fast process. This study would also help to understand the virulence factors, disease pathogenicity, origin and transmission of the SARS-CoV2.", "qid": 37, "docid": "k2juhyex", "rank": 30, "score": 0.8652483224868774}, {"content": "Title: Characterization of a novel coronavirus associated with severe acute respiratory syndrome. Content: In March 2003, a novel coronavirus (SARS-CoV) was discovered in association with cases of severe acute respiratory syndrome (SARS). The sequence of the complete genome of SARS-CoV was determined, and the initial characterization of the viral genome is presented in this report. The genome of SARS-CoV is 29,727 nucleotides in length and has 11 open reading frames, and its genome organization is similar to that of other coronaviruses. Phylogenetic analyses and sequence comparisons showed that SARS-CoV is not closely related to any of the previously characterized coronaviruses.", "qid": 37, "docid": "7fvuyim8", "rank": 31, "score": 0.865084171295166}, {"content": "Title: Emergence of multiple variants of SARS-CoV-2 with signature structural changes Content: This study explores the divergence pattern of SARS-CoV-2 using whole genome sequences of the isolates from various COVID-19 affected countries. The phylogenomic analysis indicates the presence of at least four distinct groups of the SARS-CoV-2 genomes. The emergent groups have been found to be associated with signature structural changes in specific proteins. Also, this study reveals the differential levels of divergence patterns for the protein coding regions. Moreover, we have predicted the impact of structural changes on a couple of important viral proteins via structural modelling techniques. This study further advocates for more viral genetic studies with associated clinical outcomes and hosts\u2019 response for better understanding of SARS-CoV-2 pathogenesis enabling better mitigation of this pandemic situation.", "qid": 37, "docid": "bu1bc2bi", "rank": 32, "score": 0.8645071983337402}, {"content": "Title: Analysis of the Hosts and Transmission Paths of SARS-CoV-2 in the COVID-19 Outbreak Content: The severe respiratory disease COVID-19 was initially reported in Wuhan, China, in December 2019, and spread into many provinces from Wuhan. The corresponding pathogen was soon identified as a novel coronavirus named SARS-CoV-2 (formerly, 2019-nCoV). As of 2 May, 2020, over 3 million COVID-19 cases had been confirmed, and 235,290 deaths had been reported globally, and the numbers are still increasing. It is important to understand the phylogenetic relationship between SARS-CoV-2 and known coronaviruses, and to identify its hosts for preventing the next round of emergency outbreak. In this study, we employ an effective alignment-free approach, the Natural Vector method, to analyze the phylogeny and classify the coronaviruses based on genomic and protein data. Our results show that SARS-CoV-2 is closely related to, but distinct from the SARS-CoV branch. By analyzing the genetic distances from the SARS-CoV-2 strain to the coronaviruses residing in animal hosts, we establish that the most possible transmission path originates from bats to pangolins to humans.", "qid": 37, "docid": "i14gkdw0", "rank": 33, "score": 0.8644210696220398}, {"content": "Title: Molecular phylogeny of coronaviruses including human SARS-CoV Content: Phylogenetic tree of coronaviruses (CoVs) including the human SARS-associated virus is reconstructed from complete genomes by using our newly developed K-string composition approach. The relation of the human SARS-CoV to other coronaviruses, i.e. the rooting of the tree is suggested by choosing an appropriate outgroup. SARS-CoV makes a separate group closer but still distant from G2 (CoVs in mammalian host). The relation between different isolates of the human SARS virus is inferred by first constructing an ultrametric distance matrix from counting sequence variations in the genomes. The resulting tree is consistent with clinic relations between the SARS-CoV isolates. In addition to a larger variety of coronavirus genomes these results provide phylogenetic knowledge based on independent novel methodology as compared to recent phylogenetic studies on SARS-CoV.", "qid": 37, "docid": "iowyb7xs", "rank": 34, "score": 0.8640809059143066}, {"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": 35, "score": 0.8639901876449585}, {"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": 36, "score": 0.8636864423751831}, {"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": 37, "docid": "6dsx7pey", "rank": 37, "score": 0.8636150360107422}, {"content": "Title: Complete Genome Sequence of a 2019 Novel Coronavirus (SARS-CoV-2) Strain Isolated in Nepal Content: A complete genome sequence was obtained for a severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) strain isolated from an oropharyngeal swab specimen of a Nepalese patient with coronavirus disease 2019 (COVID-19), who had returned to Nepal after traveling to Wuhan, China.", "qid": 37, "docid": "uk8rfroj", "rank": 38, "score": 0.8621850609779358}, {"content": "Title: SARS-CoV2 envelope protein: Non-synonymous mutations and its consequences Content: Abstract In the NCBI database, as on June 6, 2020, total number of available complete genome sequences of SARS-CoV2 across the world is 3617. The envelope protein of SARS-CoV2 possesses several non-synonymous mutations over the transmembrane domain and (C)-terminus in 15 (0.414%) genomes among 3617 available SARS-CoV2 genomes. More precisely, it is to be mentioned that 10(0.386%) out of 2588 genomes from the USA, 3(0.806%) from Asia, 1 (0.348%) from Europe and 1 (0.274%) from Oceania contain the missense mutations over the envelope proteins of SARS-CoV2 genomes. The C-terminus motif DLLV has been changed to DFLV and YLLV in the proteins QJR88103 (Australia: Victoria) and QKI36831 (China: Guangzhou) respectively, which might affect the binding of this motif with the host protein PALS1.", "qid": 37, "docid": "gnrnsxej", "rank": 39, "score": 0.8621730804443359}, {"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": 40, "score": 0.8621580600738525}, {"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": 37, "docid": "16lkzgtq", "rank": 41, "score": 0.8620946407318115}, {"content": "Title: SARS-CoV-2 orf1b Gene Sequence in the NTNG1 Gene on Human Chromosome 1 Content: Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) is a positive-sense single-stranded RNA virus. It is contagious in humans and is the cause of the coronavirus disease 2019 (COVID-19) pandemic. In the current analysis, we searched for SARS-CoV-2 sequences within the human genome. To compare the SARS-CoV-2 genome to the human genome, we used the blast-like alignment tool (BLAT) of the University of California, Santa Cruz Genome Browser. BLAT can align a user sequence of 25 bases or more to the genome. BLAT search results revealed a 117-base pair SARS-CoV-2 sequence in the human genome with 94.6% identity. The sequence was in chromosome 1p within an intronic region of the netrin G1 (NTNG1) gene. The sequence matched a sequence in the SARS-CoV-2 orf1b (open reading frames) gene. The SARS-CoV-2 human sequence lies within non-structural proteins 14 and 15 (NSP14 and NSP15), and is quite close to the viral spike sequence, separated only by NSP16, a 904-base pair sequence. The mechanism for SARS-CoV-2 infection is the binding of the virus spike protein to the membrane-bound form of angiotensin-converting enzyme 2 and internalization of the complex by the host cell. It is probably no accident that a sequence from the SARS-CoV-2 orf1b gene is found in the human NTNG1 gene, implicated in schizophrenia, and that haloperidol, used to treat schizophrenia, may also be a treatment for COVID-19. We suggest, therefore, that it is important to investigate other haloperidol analogs. Among them are benperidol, bromperidol, bromperidol decanoate, droperidol, seperidol hydrochloride, and trifluperidol. These analogs might be valuable in the treatment of COVID-19 and other coronavirus infections.", "qid": 37, "docid": "mzsrg0sn", "rank": 42, "score": 0.8620153665542603}, {"content": "Title: SARS-CoV-2 orf1b Gene Sequence in the NTNG1 Gene on Human Chromosome 1. Content: Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) is a positive-sense single-stranded RNA virus. It is contagious in humans and is the cause of the coronavirus disease 2019 (COVID-19) pandemic. In the current analysis, we searched for SARS-CoV-2 sequences within the human genome. To compare the SARS-CoV-2 genome to the human genome, we used the blast-like alignment tool (BLAT) of the University of California, Santa Cruz Genome Browser. BLAT can align a user sequence of 25 bases or more to the genome. BLAT search results revealed a 117-base pair SARS-CoV-2 sequence in the human genome with 94.6% identity. The sequence was in chromosome 1p within an intronic region of the netrin G1 (NTNG1) gene. The sequence matched a sequence in the SARS-CoV-2 orf1b (open reading frames) gene. The SARS-CoV-2 human sequence lies within non-structural proteins 14 and 15 (NSP14 and NSP15), and is quite close to the viral spike sequence, separated only by NSP16, a 904-base pair sequence. The mechanism for SARS-CoV-2 infection is the binding of the virus spike protein to the membrane-bound form of angiotensin-converting enzyme 2 and internalization of the complex by the host cell. It is probably no accident that a sequence from the SARS-CoV-2 orf1b gene is found in the human NTNG1 gene, implicated in schizophrenia, and that haloperidol, used to treat schizophrenia, may also be a treatment for COVID-19. We suggest, therefore, that it is important to investigate other haloperidol analogs. Among them are benperidol, bromperidol, bromperidol decanoate, droperidol, seperidol hydrochloride, and trifluperidol. These analogs might be valuable in the treatment of COVID-19 and other coronavirus infections.", "qid": 37, "docid": "w9ld7jpx", "rank": 43, "score": 0.8620153665542603}, {"content": "Title: Investigating the genomic landscape of novel coronavirus (2019-nCoV) to identify non-synonymous mutations for use in diagnosis and drug design Content: This study presents a comprehensive phylogenetic analysis of SARS-CoV2 isolates to understand discrete mutations that are occurring between patient samples. The analysis unravel various amino acid mutations in the viral proteins which may provide an explanation for varying treatment efficacies of different inhibitory drugs and a future direction towards a combinatorial treatment therapies based on the kind of mutation in the viral genome.", "qid": 37, "docid": "ttte21up", "rank": 44, "score": 0.8619418740272522}, {"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": 45, "score": 0.8618590235710144}, {"content": "Title: Noncanonical junctions in subgenomic RNAs of SARS-CoV-2 lead to variant open reading frames Content: SARS-CoV-2, a positive-sense RNA virus in the family Coronaviridae, has caused the current worldwide pandemic, known as coronavirus disease 2019 or COVID-19. The definition of SARS-CoV-2 open reading frames is a key step in delineating targets for vaccination and treatment for COVID-19. Here, we report an integrative analysis of three independent direct RNA sequencing datasets of the SARS-CoV-2 transcriptome. We find strong evidence for variant open reading frames (ORFs) encoded by SARS-CoV-2 RNA. A variant transcript for the matrix protein (M) lacking its N-terminal transmembrane domain, initiated by a TTG start codon, is produced by a strong transcriptional regulatory sequence (TRS)-mediated junction within the M ORF and represents up to 19% of all M ORFs. Sporadic non-canonical junctions in the spike (S) ORF lead to N-terminal truncations that remove the N-terminal and receptor-binding domains from up to 25% of S ORFs. Surprisingly, nearly all ORFs from ORF1a identified in these transcriptome sequences were variant. These ORFs contain the first 200-800 amino acids of ORF1a and may represent a mechanism to regulate the relative abundance of ORF1a nonstructural proteins. We show there is strong transcriptome and junctional support for variant ORF1a ORFs in independent direct RNA sequencing and short-read RNA sequencing datasets, and further show that up to 1/3 of these ORFs are expected to have C-terminal fusions with downstream genes. Finally, we show that currently unannotated ORFs are abundant in the SARS-CoV-2 transcriptome. Together, these analyses help to elucidate the diverse coding potential of SARS-CoV-2.", "qid": 37, "docid": "8y9gaoqb", "rank": 46, "score": 0.8618317246437073}, {"content": "Title: Identification of a common deletion in the spike protein of SARS-CoV-2 Content: Two notable features have been identified in the SARS-CoV-2 genome: (1) the receptor binding domain of SARS-CoV-2; (2) a unique insertion of twelve nucleotide or four amino acids (PRRA) at the S1 and S2 boundary. For the first feature, the similar RBD identified in SARs-like virus from pangolin suggests the RBD in SARS-CoV-2 may already exist in animal host(s) before it transmitted into human. The left puzzle is the history and function of the insertion at S1/S2 boundary, which is uniquely identified in SARS-CoV-2. In this study, we identified two variants from the first Guangdong SARS-CoV-2 cell strain, with deletion mutations on polybasic cleavage site (PRRAR) and its flank sites. More extensive screening indicates the deletion at the flank sites of PRRAR could be detected in 3 of 68 clinical samples and half of 22 in vitro isolated viral strains. These data indicate (1) the deletion of QTQTN, at the flank of polybasic cleavage site, is likely benefit the SARS-CoV-2 replication or infection in vitro but under strong purification selection in vivo since it is rarely identified in clinical samples; (2) there could be a very efficient mechanism for deleting this region from viral genome as the variants losing 23585-23599 is commonly detected after two rounds of cell passage. The mechanistic explanation for this in vitro adaptation and in vivo purification processes (or reverse) that led to such genomic changes in SARS-CoV-2 requires further work. Nonetheless, this study has provided valuable clues to aid further investigation of spike protein function and virus evolution. The deletion mutation identified in vitro isolation should be also noted for current vaccine development.", "qid": 37, "docid": "5oisrm5s", "rank": 47, "score": 0.8616998195648193}, {"content": "Title: Global genetic diversity patterns and transmissions of SARS-CoV-2 Content: Background: Since it was firstly discovered in China, the SARS-CoV-2 epidemic has caused a substantial health emergency and economic stress in the world. However, the global genetic diversity and transmissions are still unclear. Methods: 3050 SARS-CoV-2 genome sequences were retrieved from GIASID database. After aligned by MAFFT, the mutation patterns were identified by phylogenetic tree analysis. Results: We detected 17 high frequency (>6%) mutations in the 3050 sequences. Based on these mutations, we classed the SARS-CoV-2 into four main groups and 10 subgroups. We found that group A was mainly presented in Asia, group B was primarily detected in North America, group C was prevailingly appeared in Asia and Oceania and group D was principally emerged in Europe and Africa. Additionally, the distribution of these groups was different in age, but was similar in gender. Group A, group B1 and group C2 were declined over time, inversely, group B2, group C3 and group D were rising. At last, we found two apparent expansion stages (late Jan-2020 and late Feb-2020 to early Mar-2020, respectively). Notably, most of groups are quickly expanding, especially group D. Conclusions: We classed the SARS-CoV-2 into four main groups and 10 subgroups based on different mutation patterns at first time. The distribution of the 10 subgroups was different in geography, time and age, but not in gender. Most of groups are rapidly expanding, especially group D. Therefore, we should attach importance to these genetic diversity patterns of SARS-CoV-2 and take more targeted measures to constrain its spread.", "qid": 37, "docid": "r3t4bd78", "rank": 48, "score": 0.8616958856582642}, {"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": 37, "docid": "3n37dlt4", "rank": 49, "score": 0.8616607189178467}, {"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": 50, "score": 0.8615323305130005}, {"content": "Title: Molecular Characterization and Amino Acid Homology of Nucleocapsid (N) Protein in SARS-CoV-1, SARS-CoV-2, MERS-CoV, and Bat Coronavirus Content: Coronavirus disease - 2019 (COVID-19) pandemic, due to severe acute respiratory syndrome-coronavirus-2 (SARS-CoV-2), is posing a severe bio threat to the entire world Nucleocapsids of SARS-CoV-2 and the related viruses were studied for gene and amino acid sequence homologies In this study, we established similarities and differences in nucleocapsids in SARS-CoV-2, severe acute respiratory syndrome - coronavirus-1 (SARS-CoV-1), bat coronavirus (bat-CoV) and Middle East respiratory syndrome - coronavirus (MERS-CoV) We conducted a detailed analysis of the nucleocapsid protein amino acid and gene sequence encoding it, found in various coronavirus strains After thoroughly screening the different nucleocapsids, we observed a close molecular homology between SARS-CoV-1 and SARS-CoV-2 More than 95% sequence similarity was observed between the two SARS-CoV strains Bat-CoV and SARS-CoV-2 showed 92% sequence similarity MERS-CoV and SARS-CoV-2 nucleocapsid analysis indicated only 65% identity Molecular characterization of nucleocapsids from various coronaviruses revealed that SARS-CoV 2 is more related to SARS-CoV 1 and bat-CoV SARS-CoV 2 exhibited less resemblance with MERS-CoV SARS-CoV 2 showed less similarity to MERS-CoV Thus, either SARS-CoV-1 or bat-CoV may be the source of SARS-CoV-2 evolution Moreover, the existing differences in nucleocapsid molecular structures in SARS-CoV-2 make this virus more virulent and highly infectious, which means that the non-identical SARS-CoV-2 genes (which are absent in SARS-CoV-1 and bat-CoV) are responsible for COVID-19 severity We observed that SARS-CoV-2 nucleocapsid from different locations varied in amino acid sequences This revealed that there are many SARS-CoV-2 subtypes/subsets currently circulating globally This study will help to develop antiviral vaccine and drugs, study viral replication and immunopathogenesis, and synthesize monoclonal antibodies that can be used for precise COVID-19 diagnosis, without false-positive/false-negative results", "qid": 37, "docid": "m505x8qo", "rank": 51, "score": 0.8615072965621948}, {"content": "Title: Dominant and rare SARS-Cov2 variants responsible for the COVID-19 pandemic in Athens, Greece. Content: SARS-CoV-2 (severe acute respiratory syndrome coronavirus 2) is a novel Coronavirus responsible for the Coronavirus Disease-2019 (COVID-19) pandemic. Since the beginning of the pandemic, the virus has spread in almost the entire world. Tracing and tracking virus international and local transmission has been an enormous challenge. Chains of infections starting from various countries worldwide seeded the outbreak of COVID-19 in Athens, capital city of Greece. Full-genome analysis of isolates from Athens' Hospitals and other healthcare providers revealed the variety of SARS-CoV-2 that initiated the pandemic before lock-down and passenger flight restrictions. The present work may serve as reference for resolving future lines of infection in the area and Europe especially after resumption of passenger flight connections to Athens and Greece during summer of 2020.", "qid": 37, "docid": "0qn4c5t3", "rank": 52, "score": 0.8611702919006348}, {"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": 37, "docid": "fujejfwb", "rank": 53, "score": 0.8611192107200623}, {"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": 37, "docid": "a12708qd", "rank": 54, "score": 0.8609921932220459}, {"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": 55, "score": 0.8609664440155029}, {"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": 56, "score": 0.8609664440155029}, {"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": 37, "docid": "tjmx6msm", "rank": 57, "score": 0.8605560064315796}, {"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": 37, "docid": "ow2aijmj", "rank": 58, "score": 0.8602855205535889}, {"content": "Title: Positive selection of ORF3a and ORF8 genes drives the evolution of SARS-CoV-2 during the 2020 COVID-19 pandemic Content: In this study, we analyzed full-length SARS-CoV-2 genomes from multiple countries to determine early trends in the evolutionary dynamics of the novel COVID-19 pandemic. Results indicated SARS-CoV-2 evolved early into at least three phylogenetic groups, characterized by positive selection at specific residues of the accessory proteins OFR3a and ORF8a. We also report evidence of epistatic interactions among sites in the genome that may be important in the generation of variants adapted to humans. These observations might impact not only public health, but also suggest more studies are needed to understand the genetic mechanisms that may affect the development of therapeutic and preventive tools, like antivirals and vaccines.", "qid": 37, "docid": "z7yzg325", "rank": 59, "score": 0.8598400950431824}, {"content": "Title: Comparative genomic signature representations of the emerging COVID-19 coronavirus and other coronaviruses: High identity and possible recombination between Bat and Pangolin coronaviruses Content: Coronaviruses are responsible on respiratory diseases in animal and human. The combination of numerical encoding techniques and digital signal processing methods are becoming increasingly important in handling large genomic data. In this paper, we propose to analyze the SARS-CoV-2 genomic signature using the combination of different nucleotide representations and signal processing tools in the aim to identify its genetic origin. The sequence of SARS-CoV-2 was compared with 21 relevant sequences including bat, yak and pangolin coronavirus sequences. In addition, we developed a new algorithm to locate the nucleotide modifications. The results show that the Bat and Pangolin coronaviruses were the most related to SARS-CoV-2 with 96% and 86% of identity all along the genome. Within the S gene sequence, the Pangolin sequence presents local highest nucleotide identity. Those findings suggest genesis of SARS-Cov-2 through evolution from bat and pangolin strains. This study offers new ways to automatically characterize viruses.", "qid": 37, "docid": "6ydswv0a", "rank": 60, "score": 0.8597931861877441}, {"content": "Title: Multi-Omics and Integrated Network Approach to Unveil Evolutionary Patterns, Mutational Hotspots, Functional Crosstalk and Regulatory Interactions in SARS-CoV-2 Content: SARS-CoV-2 responsible for the pandemic of the Severe Acute Respiratory Syndrome resulting in infections and death of millions worldwide with maximum cases and mortality in USA. The current study focuses on understanding the population specific variations attributing its high rate of infections in specific geographical regions which may help in developing appropriate treatment strategies for COVID-19 pandemic. Rigorous phylogenetic network analysis of 245 complete SARS-CoV-2 genomes inferred five central clades named a (ancestral), b, c, d and e (subtype e1 & e2) showing both divergent and linear evolution types. The clade d & e2 were found exclusively comprising of USA strains with highest known mutations. Clades were distinguished by ten co-mutational combinations in proteins; Nsp3, ORF8, Nsp13, S, Nsp12, Nsp2 and Nsp6 generated by Amino Acid Variations (AAV). Our analysis revealed that only 67.46 % of SNP mutations were carried by amino acid at phenotypic level. T1103P mutation in Nsp3 was predicted to increase the protein stability in 238 strains except six strains which were marked as ancestral type; whereas com (P5731L & Y5768C) in Nsp13 were found in 64 genomes of USA highlighting its 100% co-occurrence. Docking study highlighted mutation (D7611G) caused reduction in binding of Spike proteins with ACE2, but it also showed better interaction with TMPRSS2 receptor which may contribute to its high transmissibility in USA strains. In addition, we found host proteins, MYO5A, MYO5B & MYO5C had maximum interaction with viral hub proteins (Nucleocapsid, Spike & Membrane). Thus, blocking the internalization pathway by inhibiting MYO-5 proteins which could be an effective target for COVID-19 treatment. The functional annotations of the Host-Pathogen Interaction (HPI) network were found to be highly associated with hypoxia and thrombotic conditions confirming the vulnerability and severity of infection in the patients. We also considered the presence of CpG islands in Nsp1 and N proteins which may confers the ability of SARS-CoV-2 to enter and trigger methyltransferase activity inside host cell.", "qid": 37, "docid": "m2px0pyj", "rank": 61, "score": 0.8592383861541748}, {"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": 37, "docid": "fw4pmaoc", "rank": 62, "score": 0.8592067956924438}, {"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": 37, "docid": "tldg8c94", "rank": 63, "score": 0.8589959144592285}, {"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": 64, "score": 0.8589638471603394}, {"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": 37, "docid": "iihgc5nr", "rank": 65, "score": 0.8588995933532715}, {"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": 66, "score": 0.8588769435882568}, {"content": "Title: Emerging genetic diversity among clinical isolates of SARS-CoV-2: Lessons for today Content: Considering the current pandemic of COVID-19, it is imperative to gauge the role of molecular divergence in SARS-CoV-2 with time, due to clinical and epidemiological concerns. Our analyses involving molecular phylogenetics is a step toward understanding the transmission clusters that can be correlated to pathophysiology of the disease to gain insight into virulence mechanism. As the infections are increasing rapidly, more divergence is expected followed possibly by viral adaptation. We could identify mutational hotspots which appear to be major drivers of diversity among strains, with RBD of spike protein emerging as the key region involved in interaction with ACE2 and consequently a major determinant of infection outcome. We believe that such molecular analyses correlated with clinical characteristics and host predisposition need to be evaluated at the earliest to understand viral adaptability, disease prognosis, and transmission dynamics.", "qid": 37, "docid": "bz6xy94r", "rank": 67, "score": 0.8588212728500366}, {"content": "Title: Complete Genome Sequence of a Novel Coronavirus (SARS-CoV-2) Isolate from Bangladesh Content: The complete genome sequence of a novel coronavirus (severe acute respiratory syndrome coronavirus 2 [SARS-CoV-2]) isolate obtained from a nasopharyngeal swab from a patient with COVID-19 in Bangladesh is reported.", "qid": 37, "docid": "o1ky8tyv", "rank": 68, "score": 0.8587709665298462}, {"content": "Title: Genomic analysis and comparative multiple sequences of SARS-CoV2 Content: BACKGROUND: China announced an outbreak of new coronavirus in the city of Wuhan on December 31, 2019; lash to now, the virus transmission has become pandemic worldwide. Severe cases from the Huanan Seafood Wholesale market in Wuhan were confirmed pneumonia with a novel coronavirus (2019-nCoV). Understanding the molecular mechanisms of genome selection and packaging is critical for developing antiviral strategies. Thus, we defined the correlation in 10 severe acute respiratory syndrome coronavirus (SARS-CoV2) sequences from different countries to analyze the genomic patterns of disease origin and evolution aiming for developing new control pandemic processes. METHODS: We apply genomic analysis to observe SARS-CoV2 sequences from GenBank (http://www.ncbi.nim.nih.gov/genebank/): MN 908947 (China, C1), MN985325 (USA: WA, UW), MN996527 (China, C2), MT007544 (Australia: Victoria, A1), MT027064 (USA: CA, UC), MT039890 (South Korea, K1), MT066175 (Taiwan, T1), MT066176 (Taiwan, T2), LC528232 (Japan, J1), and LC528233 (Japan, J2) for genomic sequence alignment analysis. Multiple Sequence Alignment by Clustalw (https://www.genome.jp/tools-bin/clustalw) web service is applied as our alignment tool. RESULTS: We analyzed 10 sequences from the National Center for Biotechnology Information (NCBI) database by genome alignment and found no difference in amino acid sequences within M and N proteins. There are two amino acid variances in the spike (S) protein region. One mutation found from the South Korea sequence is verified. Two possible \"L\" and \"S\" SNPs found in ORF1ab and ORF8 regions are detected. CONCLUSION: We performed genomic analysis and comparative multiple sequences of SARS-CoV2. Studies about the biological symptoms of SARS-CoV2 in clinic animals and humans will manipulate an understanding on the origin of pandemic crisis.", "qid": 37, "docid": "x1evu4w9", "rank": 69, "score": 0.8584901094436646}, {"content": "Title: Extended ORF8 Gene Region Is Valuable in the Epidemiological Investigation of Severe Acute Respiratory Syndrome-Similar Coronavirus Content: Severe acute respiratory syndrome coronavirus (SARS-CoV) was discovered as a novel pathogen in the 2002-2003 SARS epidemic. The emergence and disappearance of this pathogen have brought questions regarding its source and evolution. Within the genome sequences of 281 SARS-CoVs, severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), and SARS-related CoVs (SARSr-CoVs), a ~430 bp genomic region (from 27 701 bp to 28 131 bp in AY390556.1) with regular variations was investigated. This ~430 bp region overlaps with the ORF8 gene and is prone to deletions and nucleotide substitutions. Its complexity suggested the need for a new genotyping method for coronaviruses related to SARS-similar coronaviruses (SARS-CoV, SARSr-CoV, and SARS-CoV-2). Bat SARSr-CoV presented 3 genotypes, of which type 0 is only seen in bat SARSr-CoV, type I is present in SARS in the early phase, and type II is found in all SARS-CoV-2. This genotyping also shows potential usage in distinguishing the SARS-similar coronaviruses from different hosts and geographic areas. This genomic region has important implications for predicting the epidemic trend and studying the evolution of coronavirus.", "qid": 37, "docid": "sl560i2a", "rank": 70, "score": 0.8584855198860168}, {"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": 37, "docid": "t8q99tlq", "rank": 71, "score": 0.8580631613731384}, {"content": "Title: The divergence between SARS-CoV-2 and RaTG13 might be overestimated due to the extensive RNA modification Content: Aim: Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) has spread throughout the world. There is urgent need to understand the phylogeny, divergence and origin of SARS-CoV-2. Materials & methods: A recent study claimed that there was 17% divergence between SARS-CoV-2 and RaTG13 (a SARS-related coronaviruses) on synonymous sites by using sequence alignment. We re-analyzed the sequences of the two coronaviruses with the same methodology. Results: We found that 87% of the synonymous substitutions between the two coronaviruses could be potentially explained by the RNA modification system in hosts, with 65% contributed by deamination on cytidines (C-T mismatches) and 22% contributed by deamination on adenosines (A-G mismatches). Conclusion: Our results demonstrate that the divergence between SARS-CoV-2 and RaTG13 has been overestimated.", "qid": 37, "docid": "cns5rnj8", "rank": 72, "score": 0.858031153678894}, {"content": "Title: Extended ORF8 Gene Region Is Valuable in the Epidemiological Investigation of Severe Acute Respiratory Syndrome\u2013Similar Coronavirus Content: Severe acute respiratory syndrome coronavirus (SARS-CoV) was discovered as a novel pathogen in the 2002\u20132003 SARS epidemic. The emergence and disappearance of this pathogen have brought questions regarding its source and evolution. Within the genome sequences of 281 SARS-CoVs, severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), and SARS-related CoVs (SARSr-CoVs), a ~430 bp genomic region (from 27 701 bp to 28 131 bp in AY390556.1) with regular variations was investigated. This ~430 bp region overlaps with the ORF8 gene and is prone to deletions and nucleotide substitutions. Its complexity suggested the need for a new genotyping method for coronaviruses related to SARS-similar coronaviruses (SARS-CoV, SARSr-CoV, and SARS-CoV-2). Bat SARSr-CoV presented 3 genotypes, of which type 0 is only seen in bat SARSr-CoV, type I is present in SARS in the early phase, and type II is found in all SARS-CoV-2. This genotyping also shows potential usage in distinguishing the SARS-similar coronaviruses from different hosts and geographic areas. This genomic region has important implications for predicting the epidemic trend and studying the evolution of coronavirus.", "qid": 37, "docid": "lttavvly", "rank": 73, "score": 0.8579674959182739}, {"content": "Title: Coding-Complete Genome Sequence of SARS-CoV-2 Isolate from Bangladesh by Sanger Sequencing. Content: A coding-complete genome sequence of a severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) isolate was revealed. The sample for the virus was isolated from a female patient from Dhaka, Bangladesh, suffering from coronavirus disease-2019 (COVID-19).", "qid": 37, "docid": "kc8j8h5e", "rank": 74, "score": 0.8579291701316833}, {"content": "Title: Emerging genetic diversity among clinical isolates of SARS-CoV-2: Lessons for today Content: Abstract Considering the current pandemic of COVID-19, it is imperative to gauge the role of molecular divergence in SARS-CoV-2 with time, due to clinical and epidemiological concerns. Our analyses involving molecular phylogenetics is a step toward understanding the transmission clusters that can be correlated to pathophysiology of the disease to gain insight into virulence mechanism. As the infections are increasing rapidly, more divergence is expected followed possibly by viral adaptation. We could identify mutational hotspots which appear to be major drivers of diversity among strains, with RBD of spike protein emerging as the key region involved in interaction with ACE2 and consequently a major determinant of infection outcome. We believe that such molecular analyses correlated with clinical characteristics and host predisposition need to be evaluated at the earliest to understand viral adaptability, disease prognosis, and transmission dynamics.", "qid": 37, "docid": "sw34iotp", "rank": 75, "score": 0.8577145934104919}, {"content": "Title: Variant analysis of SARS-CoV-2 strains in Middle Eastern countries Content: Background SARS-CoV-2 is diverging from the initial Wuhan serotype, and different variants of the virus are reported. Mapping the variant strains and studying their pattern of evolution will provide better insights into the pandemic spread Methods Data on different SARS-CoV2 for WHO EMRO countries were obtained from the Chinese National Genomics Data Center (NGDC), Genbank and the Global Initiative on Sharing All Influenza Data (GISAID). Multiple sequence alignments (MSA) was performed to study the evolutionary relationship between the genomes. Variant calling, genome and variant alignment were performed to track the strains in each country. Evolutionary and phylogenetic analysis is used to explore the evolutionary hypothesis. Findings Of the total 50 samples, 4 samples did not contain any variants. Variant calling identified 379 variants. Earliest strains are found in Iranian samples. Variant alignment indicates Iran samples have a low variant frequency. Saudi Arabia has formed an outgroup. Saudi Arabia, Qatar and Kuwait were the most evolved genomes and are the countries with the highest number of cases per million. Interpretation Iran was exposed to the virus earlier than other countries in the Eastern Mediterranean Region. Funding None", "qid": 37, "docid": "cyp9fbw0", "rank": 76, "score": 0.8571639060974121}, {"content": "Title: GENOMIC CHARACTERISATION AND PHYLOGENETIC ANALYSIS OF SARS-COV-2 IN ITALY Content: This report describes the isolation, the molecular characterization and the phylogenetic analysis of the first three complete genomes of SARS-CoV-2 isolated from three patients involved in the first outbreak of COVID-19 in Lombardy, Italy. Early molecular epidemiological tracing suggests that SARS-CoV-2 was present in Italy weeks before the first reported cases of infection.", "qid": 37, "docid": "t5ar9pp0", "rank": 77, "score": 0.8570973873138428}, {"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": 37, "docid": "59492sjb", "rank": 78, "score": 0.8567861318588257}, {"content": "Title: COVID-19 in Latin America: Contrasting phylodynamic inference with epidemiological surveillance. Content: Introduction: SARS-CoV-2 infection has represented the one of the largest challenges for humanity. This virus was first detected in Latin America and the Caribbean (LAC) in Brazil in February 26, 2020 and it has revealed important gaps in infectious disease surveillance that must be covered. Phylodynamic analysis is a tool that can help to monitor and adapt traditional surveillance measures in order to cover those. Therefore, this work aims to contrast data driven from epidemiologic surveillance in LAC with parameters inferred from phylodynamic analysis of reported genomes of SARS-CoV-2 across different LAC countries Methods: We obtained epidemiological data from daily reports provided by European Centre for Disease Prevention and Control up to 13th May, 2020. We estimated Effective Reproductive Number (Re) and calculated epidemic curves with exponential growth (EG) and maximum likelihood (ML) methods. SARS-CoV-2 phylodynamic in Latin-American was analyzed using sequences reported in GISAID for Central and South America up to May 13th 2020. Sequences were aligned, and ML phylogeny was constructed. Coalescent model Birth Death SIR (serial) was run, and SIR trajectories from the birth-death SIR model were plotted. Results: A total of 404,448 cases were reported up to 13th May 2020. Overall reproduction number for Latin America, estimated through the EG and ML methods, were 1.424 (IC95% 1.422 to 1.426) and 1.305 (IC95% 1.299 to 1.311) respectively. Phylodynamic analysis for Latin America showed an overall Re of 1.27 (IC95% 1.07 to 1.49). We did not find statistically significant differences between epidemiological and phylodynamic data at the cut-off time, except for Brazil. Discussion: Our results support that epidemiological and genomic surveillance are two complementary approaches. Evidence suggests that even with a low number of sequences proper estimations of Re could be performed. We suggest that countries, especially developing countries, should consider to add genomic surveillance to their systems for monitoring and adapting epidemiological surveillance of SARS-CoV-2.", "qid": 37, "docid": "pfu6q0v1", "rank": 79, "score": 0.8567401766777039}, {"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": 37, "docid": "vahud6o5", "rank": 80, "score": 0.8567111492156982}, {"content": "Title: Comparative genomic signature representations of the emerging COVID-19 coronavirus and other coronaviruses: High identity and possible recombination between Bat and Pangolin coronaviruses Content: Abstract Coronaviruses are responsible on respiratory diseases in animal and human. The combination of numerical encoding techniques and digital signal processing methods are becoming increasingly important in handling large genomic data. In this paper, we propose to analyze the SARS-CoV-2 genomic signature using the combination of different nucleotide representations and signal processing tools in the aim to identify its genetic origin. The sequence of SARS-CoV-2 was compared with 21 relevant sequences including bat, yak and pangolin coronavirus sequences. In addition, we developed a new algorithm to locate the nucleotide modifications. The results show that the Bat and Pangolin coronaviruses were the most related to SARS-CoV-2 with 96% and 86% of identity all along the genome. Within the S gene sequence, the Pangolin sequence presents local highest nucleotide identity. Those findings suggest genesis of SARS-Cov-2 through evolution from bat and pangolin strains. This study offers new ways to automatically characterize viruses.", "qid": 37, "docid": "13ir7swr", "rank": 81, "score": 0.8565682768821716}, {"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": 37, "docid": "bawgldfi", "rank": 82, "score": 0.8565573692321777}, {"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": 37, "docid": "lvqwszsf", "rank": 83, "score": 0.8565495610237122}, {"content": "Title: The SARS-CoV-2 Coronavirus and the COVID-19 Outbreak. Content: The SARS-CoV-2, a newly identified \u03b2-coronavirus, is the causative agent of the third large-scale pandemic from the last two decades. The outbreak started in December 2019 in Wuhan City, Hubei province in China. The patients presented clinical symptoms of dry cough, fever, dyspnea, and bilateral lung infiltrates on imaging. By February 2020, The World Health Organization (WHO) named the disease as Coronavirus Disease 2019 (COVID-19). The Coronavirus Study Group (CSG) of the International Committee on Taxonomy of Viruses (ICTV) recognized and designated this virus as severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). The SARS-CoV-2 uses the same host receptor, angiotensin-converting enzyme 2 (ACE2), used by SARS-CoV to infect humans. One hypothesis of SARSCoV-2 origin indicates that it is likely that bats serve as reservoir hosts for SARSCoV-2, being the intermediate host not yet determined. The predominant route of transmission of SARS-CoV-2 is from human to human. As of May 10th 2020, the number of worldwide confirmed COVID-19 cases is over 4 million, while the number of global deaths is around 279.000 people. The United States of America (USA) has the highest number of COVID-19 cases with over 1.3 million cases followed by Spain, Italy, United Kingdom, Russia, France and Germany with over 223.000, 218.000, 215.000, 209.000, 176.000, and 171.000 cases, respectively.", "qid": 37, "docid": "1enb2vxv", "rank": 84, "score": 0.8565318584442139}, {"content": "Title: Genomic characterization and phylogenetic analysis of SARS-COV-2 in Italy Content: This report describes the isolation, molecular characterization, and phylogenetic analysis of the first three complete genomes of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) isolated from three patients involved in the first outbreak of COVID-19 in Lombardy, Italy. Early molecular epidemiological tracing suggests that SARS-CoV-2 was present in Italy weeks before the first reported cases of infection.", "qid": 37, "docid": "1mbn5cc5", "rank": 85, "score": 0.8564198017120361}, {"content": "Title: The SARS-CoV-2 Coronavirus and the COVID-19 Outbreak Content: The SARS-CoV-2, a newly identified \u00df-coronavirus, is the causative agent of the third large-scale pandemic from the last two decades. The outbreak started in December 2019 in Wuhan City, Hubei province in China. The patients presented clinical symptoms of dry cough, fever, dyspnea, and bilateral lung infiltrates on imaging. By February 2020, The World Health Organization (WHO) named the disease as Coronavirus Disease 2019 (COVID-19). The Coronavirus Study Group (CSG) of the International Committee on Taxonomy of Viruses (ICTV) recognized and designated this virus as severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). The SARS-CoV-2 uses the same host receptor, angiotensin-converting enzyme 2 (ACE2), used by SARS-CoV to infect humans. One hypothesis of SARSCoV-2 origin indicates that it is likely that bats serve as reservoir hosts for SARSCoV-2, being the intermediate host not yet determined. The predominant route of transmission of SARS-CoV-2 is from human to human. As of May 10th 2020, the number of worldwide confirmed COVID-19 cases is over 4 million, while the number of global deaths is around 279.000 people. The United States of America (USA) has the highest number of COVID-19 cases with over 1.3 million cases followed by Spain, Italy, United Kingdom, Russia, France and Germany with over 223.000, 218.000, 215.000, 209.000, 176.000, and 171.000 cases, respectively.", "qid": 37, "docid": "7re3jgya", "rank": 86, "score": 0.8563681840896606}, {"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": 87, "score": 0.8563663959503174}, {"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": 88, "score": 0.8563336730003357}, {"content": "Title: CovProfile: profiling the viral genome and gene expressions of SARS-COV-2 Content: The SARS-CoV-2 virus has infected more than one million people worldwide to date. Knowing its genome and gene expressions is essential to understand the virus\u2019 mechanism. Here, we propose a computational tool CovProfile to detect the viral genomic variations as well as viral gene expressions from the sequences obtained from Nanopore devices. We applied CovProfile to 11 samples, each from a terminally ill patient, and discovered that all the patients are infected by multiple viral strains, which might affect the reliability of phylogenetic analysis. Moreover, the expression of viral genes ORF1ab gene, S gene, M gene, and N gene are high among most of the samples. While performing the tests, we noticed a consistent abundance of transcript segments of MUC5B, presumably from the host, across all the samples.", "qid": 37, "docid": "o045bvn7", "rank": 89, "score": 0.8559985160827637}, {"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": 37, "docid": "nqfo3qtb", "rank": 90, "score": 0.855839729309082}, {"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": 37, "docid": "86byq11c", "rank": 91, "score": 0.8557378053665161}, {"content": "Title: Polymorphism of SARS-CoV Genomes Content: Abstract In this work, severe acute respiratory syndrome associated coronavirus (SARS-CoV) genome BJ202 (AY864806) was completely sequenced. The genome was directly accessed from the stool sample of a patient in Beijing. Comparative genomics methods were used to analyze the sequence variations of 116 SARS-CoV genomes (including BJ202) available in the NCBI Gen-Bank. With the genome sequence of GZ02 as the reference, there were 41 polymorphic sites identified in BJ202 and a total of 278 polymorphic sites present in at least two of the 116 genomes. The distribution of the polymorphic sites was biased over the whole genome. Nearly half of the variations (50.4%, 140/278) clustered in the one third of the whole genome at the 3\u2032 end (19.0 kb-29.7 kb). Regions encoding Orf10\u201311, Orf3/4, E, M and S protein had the highest mutation rates. A total of 15 PCR products (about 6.0 kb of the genome) including 11 fragments containing 12 known polymorphic sites and 4 fragments without identified polymorphic sites were cloned and sequenced. Results showed that 3 unique polymorphic sites of BJ202 (positions 13 804, 15 031 and 20 792) along with 3 other polymorphic sites (26 428, 26 477 and 27 243) all contained 2 kinds of nucleotides. It is interesting to find that position 18379 which has not been identified to be polymorphic in any of the other 115 published SARS-CoV genomes is actually a polymorphic site. The nucleotide composition of this site is A (8) to G (6). Among 116 SARS-CoV genomes, 18 types of deletions and 2 insertions were identified. Most of them were related to a 300 bp region (27 700\u201328 000) which encodes parts of the putative ORF9 and ORF10\u201311. A phylogenetic tree illustrating the divergence of whole BJ202 genome from 115 other completely sequenced SARS-CoVs was also constructed. BJ202 was phylogeneticly closer to BJ01 and LLJ-2004.", "qid": 37, "docid": "6vw88jib", "rank": 92, "score": 0.8557027578353882}, {"content": "Title: Tracking the genomic footprints of SARS-CoV-2 transmission Content: Abstract There is considerable public and scientific interest on the origin, spread and evolution of SARS-CoV-2. A recent study by Lu et al. [1], conducted genomic sequencing and analysis of SARS-CoV-2 in Guangdong, revealing its early transmission out of Hubei and shedding light on the effectiveness of controlling local transmission chains.", "qid": 37, "docid": "o004ggon", "rank": 93, "score": 0.8555407524108887}, {"content": "Title: Unsupervised cluster analysis of SARS-CoV-2 genomes indicates that recent (June 2020) cases in Beijing are from a genetic subgroup that consists of mostly European and South(east) Asian samples, of which the latter are the most recent Content: Research efforts of the ongoing SARS-CoV-2 pandemic have focused on viral genome sequence analysis to understand how the virus spread across the globe. Here, we assess three recently identified SARS-CoV-2 genomes in Beijing from June 2020 and attempt to determine the origin of these genomes, made available in the GISAID database. The database contains fully or partially sequenced SARS-CoV-2 samples from laboratories around the world. Including the three new samples and excluding samples with missing annotations, we analyzed 7, 643 SARS-CoV-2 genomes. Using principal component analysis computed on a similarity matrix that compares all pairs of the SARS-CoV-2 nucleotide sequences at all loci simultaneously, using the Jaccard index, we find that the newly discovered virus genomes from Beijing are in a genetic cluster that consists mostly of cases from Europe and South(east) Asia. The sequences of the new cases are most related to virus genomes from a small number of cases from China (March 2020), cases from Europe (February to early May 2020), and cases from South(east) Asia (May to June 2020). These findings could suggest that the original cases of this genetic cluster originated from China in March 2020 and were re-introduced to China by transmissions from samples from South(east) Asia between April and June 2020.", "qid": 37, "docid": "4oa0gsos", "rank": 94, "score": 0.855499267578125}, {"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": 95, "score": 0.8553009033203125}, {"content": "Title: Ancestral origin, antigenic resemblance and epidemiological insights of novel coronavirus (SARS-CoV-2): Global burden and Bangladesh perspective Content: SARS-CoV-2, a new coronavirus strain responsible for COVID-19 has emerged in Wuhan City, China and still continuing its worldwide pandemic nature. Considering the severity of the disease, a number of studies are underway, and full genomic sequences have already been released in the last few weeks to enable the understanding of the evolutionary origin and molecular characteristics of this virus. Bioinformatics analysis, satellite derived imaging data and epidemiological attributes were employed to investigate origin, immunogenic resemblance and global threat of newly pandemic SARS-CoV-2 including Bangladesh perspective. Based on currently available genomic information, a phylogeny study was employed focusing four types of representative viral proteins (spike, membrane, envelope and nucleoprotein) of SARS-CoV-2, HCoV-229E, HCoV-OC43, SARS-CoV, HCoV-NL63, HKU1, MERS-CoV, HKU4, HKU5 and BufCoV-HKU26. The findings clearly demonstrated that SARS-CoV-2 exhibited evolutionary convergent relation with previously reported SARS-CoV. It was also found that SARS-CoV-2 proteins were highly similar and identical to SARS-CoV proteins, though proteins from other coronaviruses showed lower level of similarity and identical patterns. The cross-checked conservancy analysis of SARS-CoV-2 antigenic epitopes showed significant conservancy with antigenic epitopes derived from SARS-CoV. The study also prioritized the temperature comparison through satellite imaging alongside compiling and analyzing the epidemiological outbreak information on the 2019 novel coronavirus based on several open datasets on COVID-19 (SARS-CoV-2) and discussed possible threats to Bangladesh.", "qid": 37, "docid": "a4jn6gpk", "rank": 96, "score": 0.855286717414856}, {"content": "Title: Comparative genomics suggests limited variability and similar evolutionary patterns between major clades of SARS-CoV-2 Content: Phylogenomic analysis of SARS-CoV-2 as available from publicly available repositories suggests the presence of 3 prevalent groups of viral episomes (super-clades), which are mostly associated with outbreaks in distinct geographic locations (China, USA and Europe). While levels of genomic variability between SARS-CoV-2 isolates are limited, to our knowledge, it is not clear whether the observed patterns of variability in viral super-clades reflect ongoing adaptation of SARS-CoV-2, or merely genetic drift and founder effects. Here, we analyze more than 1100 complete, high quality SARS-CoV-2 genome sequences, and provide evidence for the absence of distinct evolutionary patterns/signatures in the genomes of the currently known major clades of SARS-CoV-2. Our analyses suggest that the presence of distinct viral episomes at different geographic locations are consistent with founder effects, coupled with the rapid spread of this novel virus. We observe that while cross species adaptation of the virus is associated with hypervariability of specific protein coding regions (including the RDB domain of the spike protein), the more variable genomic regions between extant SARS-CoV-2 episomes correspond with the 3\u2019 and 5\u2019 UTRs, suggesting that at present viral protein coding genes should not be subjected to different adaptive evolutionary pressures in different viral strains. Although this study can not be conclusive, we believe that the evidence presented here is strongly consistent with the notion that the biased geographic distribution of SARS-CoV-2 isolates should not be associated with adaptive evolution of this novel pathogen.", "qid": 37, "docid": "uubndgio", "rank": 97, "score": 0.8551486730575562}, {"content": "Title: SARS-CoV-2 sequence typing, evolution and signatures of selection using CoVa, a Python-based command-line utility Content: The current global pandemic COVID-19, caused by SARS-CoV-2, has resulted in millions of infections worldwide in a few months. Global efforts to tackle this situation have produced a tremendous body of genomic data, which can be used for tracing transmission routes, characterization of isolates, and monitoring variants with potential for unusual virulence. Several groups have analyzed these genomes using different approaches. However, as new data become available, the research community needs a pipeline to perform a set of routine analyses, that can quickly incorporate new genome sequences and update the analysis reports. We developed a programmatic tool, CoVa, with this objective. It is a fast, accurate and user-friendly utility to perform a variety of genome analyses on hundreds of SARS-CoV-2 sequences. Using CoVa, we define a modified sequence typing nomenclature and identify sites under positive selection. Further analysis identified some peptides and sites showing geographical patterns of selection. Specifically, we show differences in sequence type distribution between sequences from India and those from the rest of the world. We also show that several sites show signatures of positive selection uniquely in sequences from India. Preliminary evolutionary analysis, using features that will be incorporated into CoVa in the near future, show a mutation rate of 7.4 \u00d7 10\u22124 substitutions/site/year, confirm a temporal signal with a November 2019 origin of SARS-CoV-2, and a heterogeneity in the geographical distribution of Indian samples.", "qid": 37, "docid": "w8vs7s28", "rank": 98, "score": 0.8551092743873596}, {"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": 99, "score": 0.854902982711792}, {"content": "Title: Decoding the evolution and transmissions of the novel pneumonia coronavirus (SARS-CoV-2 / HCoV-19) using whole genomic data Content: The outbreak of COVID-19 started in mid-December 2019 in Wuhan, China. Up to 29 February 2020, SARS-CoV-2 (HCoV-19 / 2019-nCoV) had infected more than 85 000 people in the world. In this study, we used 93 complete genomes of SARS-CoV-2 from the GISAID EpiFlu TM database to investigate the evolution and human-to-human transmissions of SARS-CoV-2 in the first two months of the outbreak. We constructed haplotypes of the SARS-CoV-2 genomes, performed phylogenomic analyses and estimated the potential population size changes of the virus. The date of population expansion was calculated based on the expansion parameter tau ( &#964;) using the formula t= &#964;/2 u. A total of 120 substitution sites with 119 codons, including 79 non-synonymous and 40 synonymous substitutions, were found in eight coding-regions in the SARS-CoV-2 genomes. Forty non-synonymous substitutions are potentially associated with virus adaptation. No combinations were detected. The 58 haplotypes (31 found in samples from China and 31 from outside China) were identified in 93 viral genomes under study and could be classified into five groups. By applying the reported bat coronavirus genome (bat-RaTG13-CoV) as the outgroup, we found that haplotypes H13 and H38 might be considered as ancestral haplotypes, and later H1 was derived from the intermediate haplotype H3. The population size of the SARS-CoV-2 was estimated to have undergone a recent expansion on 06 January 2020, and an early expansion on 08 December 2019. Furthermore, phyloepidemiologic approaches have recovered specific directions of human-to-human transmissions and the potential sources for international infected cases.", "qid": 37, "docid": "gy78e87y", "rank": 100, "score": 0.8548685312271118}]}
{"query": "What is the mechanism of inflammatory response and pathogenesis of COVID-19 cases?", "hits": [{"content": "Title: COVID-19: risk for cytokine targeting in chronic inflammatory diseases? Content: COVID-19, caused by the SARS-CoV-2 virus, has become pandemic. With sharply rising infection rates, patient groups characterized by an enhanced infection risk will be challenged by the virus. In this context, patients with chronic immune-mediated inflammatory diseases are of particular interest, as these diseases are characterized by an intrinsic immune dysfunction leading to inflammation that may enhance risk for severe infection.", "qid": 38, "docid": "440j2zoi", "rank": 1, "score": 0.8936541080474854}, {"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": 2, "score": 0.8896219730377197}, {"content": "Title: New intriguing possibility for prevention of coronavirus pneumonitis: Natural purified polyphenols Content: COVID-19 is an infectious disease characterized by several important systemic problems such as severe pneumonia. One of mechanisms responsible of these systemic problems is the release of pro-inflammatory cytokines, such as interleukin (IL)-1beta and IL-6(Conti et al., 2020). The binding of virus to TRL (Toll Like Receptor) can determine the release of pro-IL-1beta with successive activation and production of active mature IL-1beta, responsible of lung inflammation, fever and fibrosis(Conti et al., 2020). The interstitial pneumonia is linked to an over-production of IL-6. Based on this principle, several researchers started the use of an anti-arthritis drug, tocilizumab, for its anti-IL-6 action.", "qid": 38, "docid": "z9c9r3xw", "rank": 3, "score": 0.8894654512405396}, {"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": 4, "score": 0.8889748454093933}, {"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": 5, "score": 0.888192892074585}, {"content": "Title: Innate Immune Signaling and Proteolytic Pathways in the Resolution or Exacerbation of SARS-CoV-2 in Covid-19: Key Therapeutic Targets? Content: COVID-19 is caused by the Severe Acute Respiratory Syndrome (SARS) coronavirus (Cov)-2, an enveloped virus with a positive-polarity, single-stranded RNA genome. The initial outbreak of the pandemic began in December 2019, and it is affecting the human health of the global community. In common with previous pandemics (Influenza H1N1 and SARS-CoV) and the epidemics of Middle east respiratory syndrome (MERS)-CoV, CoVs target bronchial and alveolar epithelial cells. Virus protein ligands (e.g., haemagglutinin or trimeric spike glycoprotein for Influenza and CoV, respectively) interact with cellular receptors, such as (depending on the virus) either sialic acids, Dipeptidyl peptidase 4 (DPP4), or angiotensin-converting enzyme 2 (ACE2). Host proteases, e.g., cathepsins, furin, or members of the type II transmembrane serine proteases (TTSP) family, such as Transmembrane protease serine 2 (TMPRSS2), are involved in virus entry by proteolytically activating virus ligands. Also involved are Toll Like Receptor (TLR) family members, which upregulate anti-viral and pro-inflammatory mediators [interleukin (IL)-6 and IL-8 and type I and type III Interferons among others], through the activation of Nuclear Factor (NF)-kB. When these events (virus cellular entry and innate immune responses) are uncontrolled, a deleterious systemic response is sometimes encountered in infected patients, leading to the well-described \"cytokine storm\" and an ensuing multiple organ failure promoted by a downregulation of dendritic cell, macrophage, and T-cell function. We aim to describe how the lung and systemic host innate immune responses affect survival either positively, through downregulating initial viral load, or negatively, by triggering uncontrolled inflammation. An emphasis will be put on host cellular signaling pathways and proteases involved with a view on tackling these therapeutically.", "qid": 38, "docid": "ls88uo78", "rank": 6, "score": 0.881967306137085}, {"content": "Title: Innate Immune Signaling and Proteolytic Pathways in the Resolution or Exacerbation of SARS-CoV-2 in Covid-19: Key Therapeutic Targets? Content: COVID-19 is caused by the Severe Acute Respiratory Syndrome (SARS) coronavirus (Cov)-2, an enveloped virus with a positive-polarity, single-stranded RNA genome. The initial outbreak of the pandemic began in December 2019, and it is affecting the human health of the global community. In common with previous pandemics (Influenza H1N1 and SARS-CoV) and the epidemics of Middle east respiratory syndrome (MERS)-CoV, CoVs target bronchial and alveolar epithelial cells. Virus protein ligands (e.g., haemagglutinin or trimeric spike glycoprotein for Influenza and CoV, respectively) interact with cellular receptors, such as (depending on the virus) either sialic acids, Dipeptidyl peptidase 4 (DPP4), or angiotensin-converting enzyme 2 (ACE2). Host proteases, e.g., cathepsins, furin, or members of the type II transmembrane serine proteases (TTSP) family, such as Transmembrane protease serine 2 (TMPRSS2), are involved in virus entry by proteolytically activating virus ligands. Also involved are Toll Like Receptor (TLR) family members, which upregulate anti-viral and pro-inflammatory mediators [interleukin (IL)-6 and IL-8 and type I and type III Interferons among others], through the activation of Nuclear Factor (NF)-kB. When these events (virus cellular entry and innate immune responses) are uncontrolled, a deleterious systemic response is sometimes encountered in infected patients, leading to the well-described \u201ccytokine storm\u201d and an ensuing multiple organ failure promoted by a downregulation of dendritic cell, macrophage, and T-cell function. We aim to describe how the lung and systemic host innate immune responses affect survival either positively, through downregulating initial viral load, or negatively, by triggering uncontrolled inflammation. An emphasis will be put on host cellular signaling pathways and proteases involved with a view on tackling these therapeutically.", "qid": 38, "docid": "5gz2dotn", "rank": 7, "score": 0.8815674781799316}, {"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": 8, "score": 0.8795638084411621}, {"content": "Title: Distinct infection process of SARS-CoV-2 in human bronchial epithelial cells line Content: COVID-19, caused by SARS-CoV-2, leads to a series of clinical symptoms of respiratory and pulmonary inflammatory reactions via unknown pathologic mechanisms related to the viral infection process in tracheal or bronchial epithelial cells. Investigation of this viral infection in the human bronchial epithelial cell line (16HBE) suggests that SARS-CoV-2 can enter these cells through interaction between its membrane-localized S protein with the ACE2 molecule on the host cell membrane. Further observation indicates distinct viral replication with a dynamic and moderate increase, whereby viral replication does not lead to a specific cytopathic effect but maintains a continuous release of progeny virions from infected cells. Although mRNA expression of various innate immune signaling molecules is altered in the cells, transcription of IFN&#945;, IFN\u00df and IFN\u00ce\u00b3 is unchanged. Furthermore, expression of some interleukins related to inflammatory reactions, such as IL-6, IL-2 and IL-8, is maintained at low levels, whereas that of interleukins involved in immune regulation is upregulated. Interestingly, IL-22, an interleukin that functions mainly in tissue repair, shows very high expression. Collectively, these data suggest a distinct infection process for this virus in respiratory epithelial cells, which may be linked to its clinicopathological mechanism. This article is protected by copyright. All rights reserved.", "qid": 38, "docid": "k4lfow9h", "rank": 9, "score": 0.8792843222618103}, {"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": 10, "score": 0.8789453506469727}, {"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": 11, "score": 0.8789453506469727}, {"content": "Title: Type 3 hypersensitivity in COVID-19 vasculitis Content: Coronavirus Disease 2019 (COVID-19) is an ongoing public health emergency and new knowledge about its immunopathogenic mechanisms is deemed necessary in the attempt to reduce the death burden, globally. For the first time in worldwide literature, we provide scientific evidence that in COVID-19 vasculitis a life-threatening escalation from type 2 T-helper immune response (humoral immunity) to type 3 hypersensitivity (immune complex disease) takes place. The subsequent deposition of immune complexes inside the vascular walls is supposed to induce a severe inflammatory state and a cytokine release syndrome, whose interleukin-6 is the key myokine, from the smooth muscle cells of blood vessels.", "qid": 38, "docid": "tcq50bst", "rank": 12, "score": 0.8780895471572876}, {"content": "Title: Type 3 hypersensitivity in COVID-19 vasculitis Content: Coronavirus Disease 2019 (COVID-19) is an ongoing public health emergency and new knowledge about its immunopathogenic mechanisms is deemed necessary in the attempt to reduce the death burden around the world. For the first time in worldwide literature, we provide scientific evidence that in COVID-19 vasculitis a life-threatening escalation from type 2 T-helper immune response (humoral immunity) to type 3 hypersensitivity (immune complex disease) takes place. The subsequent deposition of immune complexes inside the vascular walls is supposed to induce a severe inflammatory state and a cytokine release syndrome, whose interleukin-6 is the key myokine, from the smooth muscle cells of blood vessels.", "qid": 38, "docid": "nj7prvvj", "rank": 13, "score": 0.8776142597198486}, {"content": "Title: COVID-19 revisiting inflammatory pathways of arthritis Content: Coronavirus disease 2019 (COVID-19) is an infectious disease, caused by severe acute respiratory syndrome coronavirus 2, which predominantly affects the lungs and, under certain circumstances, leads to an excessive or uncontrolled immune activation and cytokine response in alveolar structures. The pattern of pro-inflammatory cytokines induced in COVID-19 has similarities to those targeted in the treatment of rheumatoid arthritis. Several clinical studies are underway that test the effects of inhibiting IL-6, IL-1\u00df or TNF or targeting cytokine signalling via Janus kinase inhibition in the treatment of COVID-19. Despite these similarities, COVID-19 and other zoonotic coronavirus-mediated diseases do not induce clinical arthritis, suggesting that a local inflammatory niche develops in alveolar structures and drives the disease process. COVID-19 constitutes a challenge for patients with inflammatory arthritis for several reasons, in particular, the safety of immune interventions during the pandemic. Preliminary data, however, do not suggest that patients with inflammatory arthritis are at increased risk of COVID-19.", "qid": 38, "docid": "xcnqsbkd", "rank": 14, "score": 0.8770256042480469}, {"content": "Title: Induction of pro-inflammatory cytokines (IL-1 and IL-6) and lung inflammation by COVID-19: anti-inflammatory strategies Content: COVID-19 (coronavirus disease-19) involves humans as well as animals and may cause serious damage to the respiratory tract including the lung This pathogenic virus has been identified in swabs performed on the throat and nose of patients who suffer from or are suspected of the disease When COVID-19 infect the upper and lower respiratory tract it can cause mild or highly acute respiratory syndrome with consequent release of pro-inflammatory cytokines, including interleukin (IL)-1b and IL-6 The binding of COVID-19 to the Toll Like Receptor (TLR) causes the release of pro-IL-1b which is cleaved by caspase-1, followed by inflammasome activation and production of active mature IL-1b which is a mediator of lung inflammation, fever and fibrosis Suppression of pro-inflammatory IL-1 family members and IL-6 have been shown to have a therapeutic effect in many inflammatory diseases, including viral infections Cytokine IL-37 has the ability to suppress innate and acquired immune response and also has the capacity to inhibit inflammation by acting on IL-18Ra receptor IL-37 performs its immunosuppressive activity by acting on mTOR and increasing the adenosine monophosphate (AMP) kinase This cytokine inhibits class II histocompatibility complex (MHC) molecules and inflammation in inflammatory diseases by suppressing MyD88 and subsequently IL-1\u03b2, IL-6, TNF and CCL2 The suppression of IL-1b by IL-37 in inflammatory state induced by COVID-19 can have a new therapeutic effect previously unknown Another inhibitory cytokine is IL-38, the newest cytokine of the IL-1 family members, produced by several immune cells including B cells and macrophages IL-38 is also a suppressor cytokine which inhibits IL-1b and other pro-inflammatory IL-family members IL-38 is a potential therapeutic cytokine which inhibits inflammation in viral infections including that caused by COVID-19, providing a new relevant strategy", "qid": 38, "docid": "4gze6w35", "rank": 15, "score": 0.8770093321800232}, {"content": "Title: COVID-19 revisiting inflammatory pathways of arthritis Content: Coronavirus disease 2019 (COVID-19) is an infectious disease, caused by severe acute respiratory syndrome coronavirus 2, which predominantly affects the lungs and, under certain circumstances, leads to an excessive or uncontrolled immune activation and cytokine response in alveolar structures. The pattern of pro-inflammatory cytokines induced in COVID-19 has similarities to those targeted in the treatment of rheumatoid arthritis. Several clinical studies are underway that test the effects of inhibiting IL-6, IL-1\u03b2 or TNF or targeting cytokine signalling via Janus kinase inhibition in the treatment of COVID-19. Despite these similarities, COVID-19 and other zoonotic coronavirus-mediated diseases do not induce clinical arthritis, suggesting that a local inflammatory niche develops in alveolar structures and drives the disease process. COVID-19 constitutes a challenge for patients with inflammatory arthritis for several reasons, in particular, the safety of immune interventions during the pandemic. Preliminary data, however, do not suggest that patients with inflammatory arthritis are at increased risk of COVID-19.", "qid": 38, "docid": "ao0jesnj", "rank": 16, "score": 0.8766605257987976}, {"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": 17, "score": 0.876398503780365}, {"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": 18, "score": 0.8740419149398804}, {"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": 38, "docid": "3fp46sov", "rank": 19, "score": 0.87347412109375}, {"content": "Title: Complex Immune Dysregulation in Covid-19 Patients with Severe Respiratory Failure Content: Proper management of COVID-19 mandates better understanding of disease pathogenesis The sudden clinical deterioration 7-8 days after initial symptom onset suggests that severe respiratory failure (SRF) in COVID-19 is driven by a unique pattern of immune dysfunction We studied immune responses of 54 COVID-19 patients, 28 of whom had SRF All SRF patients displayed either macrophage activation syndrome (MAS) or very low human leukocyte antigen (HLA)-DR expression accompanied by profound depletion of CD4-lymphocytes, CD19- lymphocytes and natural killer cells TNF\u03b1 and IL-6 production by circulating monocytes was sustained, a pattern distinct from bacterial sepsis or influenza SARS-CoV-2 patient plasma inhibited HLA-DR expression, and this was partially restored by the IL-6 blocker Tocilizumab;off-label Tocilizumab treatment of patients was accompanied by increase in circulating lymphocytes Thus, the unique pattern of immune dysregulation in severe COVID-19 is characterized by IL-6-mediated low HLA-DR expression and lymphopenia, associated with sustained cytokine production and hyper-inflammation", "qid": 38, "docid": "wunfrt1v", "rank": 20, "score": 0.8729464411735535}, {"content": "Title: A contemporary review on pathogenesis and immunity of COVID-19 infection Content: Emerging of the COVID-19 pandemic has raised interests in the field of biology and pathogenesis of coronaviruses; including interactions between host immune reactions specific, and viral factors. Deep knowledge about the interaction between coronaviruses and the host factors could be useful to provide a better support for the disease sufferers and be advantageous for managing and treatment of the lung infection caused by the virus. At this study, we reviewed the updated information on the pathogenesis of the COVID-19 and the immune responses toward it, with a special focus on structure, genetics, and viral accessory proteins, viral replication, viral receptors, the human immune reactions, cytopathic effects, and host-related factors.", "qid": 38, "docid": "owby50fr", "rank": 21, "score": 0.8721900582313538}, {"content": "Title: SARS-CoV2 may evade innate immune response, causing uncontrolled neutrophil extracellular traps formation and multi-organ failure Content: We demonstrate that the general clinical conditions, risk factors and numerous pathological and biological features of COVID-19 are analogous with various disorders caused by the uncontrolled formation of neutrophil extracellular traps and their by-products. Given the rapid evolution of this disease's symptoms and its lethality, we hypothesize that SARS-CoV2 evades innate immune response causing COVID-19 progresses under just such an amplifier loop, leading to a massive, uncontrolled inflammation process. This work allows us to propose new strategies for treating the pandemic.", "qid": 38, "docid": "faz6icy3", "rank": 22, "score": 0.8719335794448853}, {"content": "Title: SARS-CoV2 may evade innate immune response, causing uncontrolled neutrophil extracellular traps formation and multi-organ failure. Content: We demonstrate that the general clinical conditions, risk factors and numerous pathological and biological features of COVID-19 are analogous with various disorders caused by the uncontrolled formation of neutrophil extracellular traps and their by-products. Given the rapid evolution of this disease's symptoms and its lethality, we hypothesize that SARS-CoV2 evades innate immune response causing COVID-19 progresses under just such an amplifier loop, leading to a massive, uncontrolled inflammation process. This work allows us to propose new strategies for treating the pandemic.", "qid": 38, "docid": "va8kg3kb", "rank": 23, "score": 0.8719335794448853}, {"content": "Title: COVID-19 : physiopathologie d'une maladie \u00e0 plusieurs visages./ [COVID-19: Pathogenesis of a multi-faceted disease] Content: SARS-CoV-2 infection, named COVID-19, can lead to a dysregulated immune response and abnormal coagulation responsible for a viral sepsis. In this review, we specify physiopathological mechanisms of each phase of COVID-19 - viral, immune and pro-thrombotic - notably because they involve different treatment. Finally, we specify the physiopathological mechanisms of organ injury.", "qid": 38, "docid": "goordy3i", "rank": 24, "score": 0.8692011833190918}, {"content": "Title: Lessons from dermatology about inflammatory responses in Covid-19 Content: The SARS-Cov-2 is a single-stranded RNA virus composed of 16 non-structural proteins (NSP 1-16) with specific roles in the replication of coronaviruses. NSP3 has the property to block host innate immune response and to promote cytokine expression. NSP5 can inhibit interferon (IFN) signalling and NSP16 prevents MAD5 recognition, depressing the innate immunity. Dendritic cells, monocytes, and macrophages are the first cell lineage against viruses' infections. The IFN type I is the danger signal for the human body during this clinical setting. Protective immune responses to viral infection are initiated by innate immune sensors that survey extracellular and intracellular space for foreign nucleic acids. In Covid-19 the pathogenesis is not yet fully understood, but viral and host factors seem to play a key role. Important points in severe Covid-19 are characterized by an upregulated innate immune response, hypercoagulopathy state, pulmonary tissue damage, neurological and/or gastrointestinal tract involvement, and fatal outcome in severe cases of macrophage activation syndrome, which produce a 'cytokine storm'. These systemic conditions share polymorphous cutaneous lesions where innate immune system is involved in the histopathological findings with acute respiratory distress syndrome, hypercoagulability, hyperferritinemia, increased serum levels of D-dimer, lactic dehydrogenase, reactive-C-protein and serum A amyloid. It is described that several polymorphous cutaneous lesions similar to erythema pernio, urticarial rashes, diffuse or disseminated erythema, livedo racemosa, blue toe syndrome, retiform purpura, vesicles lesions, and purpuric exanthema or exanthema with clinical aspects of symmetrical drug-related intertriginous and flexural exanthema. This review describes the complexity of Covid-19, its pathophysiological and clinical aspects.", "qid": 38, "docid": "qpblq9y8", "rank": 25, "score": 0.8689826130867004}, {"content": "Title: Lessons from dermatology about inflammatory responses in Covid-19. Content: The SARS-Cov-2 is a single-stranded RNA virus composed of 16 non-structural proteins (NSP 1-16) with specific roles in the replication of coronaviruses. NSP3 has the property to block host innate immune response and to promote cytokine expression. NSP5 can inhibit interferon (IFN) signalling and NSP16 prevents MAD5 recognition, depressing the innate immunity. Dendritic cells, monocytes, and macrophages are the first cell lineage against viruses' infections. The IFN type I is the danger signal for the human body during this clinical setting. Protective immune responses to viral infection are initiated by innate immune sensors that survey extracellular and intracellular space for foreign nucleic acids. In Covid-19 the pathogenesis is not yet fully understood, but viral and host factors seem to play a key role. Important points in severe Covid-19 are characterized by an upregulated innate immune response, hypercoagulopathy state, pulmonary tissue damage, neurological and/or gastrointestinal tract involvement, and fatal outcome in severe cases of macrophage activation syndrome, which produce a 'cytokine storm'. These systemic conditions share polymorphous cutaneous lesions where innate immune system is involved in the histopathological findings with acute respiratory distress syndrome, hypercoagulability, hyperferritinemia, increased serum levels of D-dimer, lactic dehydrogenase, reactive-C-protein and serum A amyloid. It is described that several polymorphous cutaneous lesions similar to erythema pernio, urticarial rashes, diffuse or disseminated erythema, livedo racemosa, blue toe syndrome, retiform purpura, vesicles lesions, and purpuric exanthema or exanthema with clinical aspects of symmetrical drug-related intertriginous and flexural exanthema. This review describes the complexity of Covid-19, its pathophysiological and clinical aspects.", "qid": 38, "docid": "d7q6u7vj", "rank": 26, "score": 0.8689826130867004}, {"content": "Title: COVID-19: laboratory diagnosis for clinicians. An updating article Content: COVID-19 (coronavirus disease 2019) is an infectious disease caused by the new coronavirus associated with severe acute respiratory syndrome 2 (SARS-CoV-2) Coronaviridae comprises a large family, of which at least seven members are known to cause respiratory diseases in humans Coronaviruses have the ability to infect virtually all major groups of animals and, eventually, can infect humans SARS-CoV-2 is the third coronavirus to cross the species barrier and infect humans This virus was identified in an outbreak of pneumonia cases in Wuhan city, Hubei province, China, in December 2019 Its entire genome is inscribed on a single strand of ribonucleic acid Some proteins present on the surface of the virus act as facilitators for its entry into host cells, while others, apparently, are related to its pathogenesis Coronaviruses are responsible for respiratory infections in humans and some animals The infection is often mild to moderate in intensity, but some coronaviruses may cause serious illnesses, such as severe acute respiratory syndrome (SARS), which occurred in 2002, and the Middle East respiratory syndrome (MERS) Coronaviruses can activate an excessive and unregulated immune response, which may promote SARS development Although the lungs are one of the target organs, the hypoxia mechanism is systemic and other organs begin to suffer both through lack of oxygen and through deregulation of inflammation control mechanisms", "qid": 38, "docid": "8685l1n9", "rank": 27, "score": 0.8689075112342834}, {"content": "Title: Early Insights into Immune Responses during COVID-19 Content: Coronavirus disease-2019 (COVID-19) is caused by the newly emerged virus severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) and was recently declared as a pandemic by the World Health Organization. In its severe form, the disease is characterized by acute respiratory distress syndrome, and there are no targeted intervention strategies to treat or prevent it. The immune response is thought to both contribute to the pathogenesis of disease and provide protection during its resolution. Thus, understanding the immune response to SARS-CoV-2 is of the utmost importance for developing and testing vaccines and therapeutics. In this review, we discuss the earliest knowledge and hypotheses of the mechanisms of immune pathology in the lung during acute infection as well at the later stages of disease resolution, recovery, and immune memory formation.", "qid": 38, "docid": "pp71jaau", "rank": 28, "score": 0.868660569190979}, {"content": "Title: Early Insights into Immune Responses during COVID-19. Content: Coronavirus disease-2019 (COVID-19) is caused by the newly emerged virus severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) and was recently declared as a pandemic by the World Health Organization. In its severe form, the disease is characterized by acute respiratory distress syndrome, and there are no targeted intervention strategies to treat or prevent it. The immune response is thought to both contribute to the pathogenesis of disease and provide protection during its resolution. Thus, understanding the immune response to SARS-CoV-2 is of the utmost importance for developing and testing vaccines and therapeutics. In this review, we discuss the earliest knowledge and hypotheses of the mechanisms of immune pathology in the lung during acute infection as well at the later stages of disease resolution, recovery, and immune memory formation.", "qid": 38, "docid": "1mhxy9hh", "rank": 29, "score": 0.868660569190979}, {"content": "Title: Predicting COVID-19 distribution in Mexico through a discrete and time-dependent Markov chain and an SIR-like model Content: COVID-19 is an emergent viral infection which rose in December 2019 in a city in the Chinese province of Hubei, Wuhan; the viral aetiology of this infection is now known as COVID-19 virus, which belongs to the Betacoronavirus genus. This virus produces the syndrome of acute respiratory stress that h as been witnessed in other coronaviruses, such as that MERS-CoV in Middle East countries or SARS-CoV which was seen in 2002 and 2003 in China. This virus mediates its entry through its spike (S) proteins interacting with ACE2 receptors in lung epithelial cells, and may promote an inflammatory response by means of inflammasome NLRP3 activation and unfolded protein response (these are possibly consequence of the envelope E protein of COVID-19 virus). Efforts have been made worldwide to prevent further spread of the disease, but in March 2020 the WHO declared it a pandemic emergency and Mexico started to report its first cases. In this paper we attempt to summarize the biological features of the virus and the possible pathophysiological mechanisms of its disease, as well as a stochastic model characterizing the probability distribution of cases in Mexico by states and the estimated number of cases in Mexico through a differential equation model (modified SIR model), thus will we be able to characterize the disease and its course in Mexico in order to display more preparedness and promote more logical actions by both the policy makers as well as the general population.", "qid": 38, "docid": "jlv5llys", "rank": 30, "score": 0.8681272268295288}, {"content": "Title: Complex Immune Dysregulation in COVID-19 Patients with Severe Respiratory Failure Content: Summary Proper management of COVID-19 mandates better understanding of disease pathogenesis. The sudden clinical deterioration 7\u20138 days after initial symptom onset suggests that severe respiratory failure (SRF) in COVID-19 is driven by a unique pattern of immune dysfunction. We studied immune responses of 54 COVID-19 patients, 28 of whom had SRF. All patients with SRF displayed either macrophage activation syndrome (MAS) or very low human leukocyte antigen D related (HLA-DR) expression accompanied by profound depletion of CD4 lymphocytes, CD19 lymphocytes, and natural killer (NK) cells. Tumor necrosis factor-\u03b1 (TNF-\u03b1) and interleukin-6 (IL-6) production by circulating monocytes was sustained, a pattern distinct from bacterial sepsis or influenza. SARS-CoV-2 patient plasma inhibited HLA-DR expression, and this was partially restored by the IL-6 blocker Tocilizumab; off-label Tocilizumab treatment of patients was accompanied by increase in circulating lymphocytes. Thus, the unique pattern of immune dysregulation in severe COVID-19 is characterized by IL-6-mediated low HLA-DR expression and lymphopenia, associated with sustained cytokine production and hyper-inflammation.", "qid": 38, "docid": "e9mepqvn", "rank": 31, "score": 0.8680431842803955}, {"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": 38, "docid": "a290vxor", "rank": 32, "score": 0.8666748404502869}, {"content": "Title: Cytokine Storm in COVID19: A Neural Hypothesis Content: Cytokine storm in COVID-19 is characterized by an excessive inflammatory response to SARS-CoV-2 that is caused by a dysregulated immune system of the host. We are proposing a new hypothesis that SARS-CoV-2 mediated inflammation of nucleus tractus solitarius (NTS) may be responsible for the cytokine storm in COVID 19. The inflamed NTS may result in a dysregulated cholinergic anti-inflammatory pathway and hypothalamic-pituitary-adrenal axis.", "qid": 38, "docid": "ynrvowoc", "rank": 33, "score": 0.866668701171875}, {"content": "Title: Cytokine Storm in COVID19: A Neural Hypothesis. Content: Cytokine storm in COVID-19 is characterized by an excessive inflammatory response to SARS-CoV-2 that is caused by a dysregulated immune system of the host. We are proposing a new hypothesis that SARS-CoV-2 mediated inflammation of nucleus tractus solitarius (NTS) may be responsible for the cytokine storm in COVID 19. The inflamed NTS may result in a dysregulated cholinergic anti-inflammatory pathway and hypothalamic-pituitary-adrenal axis.", "qid": 38, "docid": "e58nciq3", "rank": 34, "score": 0.866668701171875}, {"content": "Title: Severe COVID-19, Another Piece in the Puzzle of the Hyperferritinemic Syndrome. An Immunomodulatory Perspective to Alleviate the Storm Content: The coronavirus disease 2019 (COVID-19), an acute respiratory disease caused by severe acute respiratory syndrome-coronavirus-2 (SARS-CoV-2), has been declared as a worldwide public health emergency. Interestingly, severe COVID-19 is characterized by fever, hyperferritinemia, and a hyper-inflammatory process with a massive release of pro-inflammatory cytokines, which may be responsible for the high rate of mortality. These findings may advocate for a similarity between severe COVID-19 and some challenging rheumatic diseases, such as adult onset Still's disease, secondary hemophagocytic lymphohistiocytosis, and catastrophic anti-phospholipid syndrome, which have been included in the \"hyperferritinemic syndrome\" category. Furthermore, as performed in these hyper-inflammatory states, severe COVID-19 may benefit from immunomodulatory therapies.", "qid": 38, "docid": "zdau7xd1", "rank": 35, "score": 0.8665235638618469}, {"content": "Title: SnapShot: COVID-19 Content: Abstract Coronavirus disease 2019 (COVID-19) is a novel respiratory illness caused by SARS-CoV-2. Viral entry is mediated through viral spike protein and host ACE2 enzyme interaction. Most cases are mild; severe disease often involves cytokine storm and organ failure. Therapeutics including antivirals, immunomodulators, and vaccines are in development. To view this SnapShot, open or download the PDF.", "qid": 38, "docid": "c3rbmysh", "rank": 36, "score": 0.8662891387939453}, {"content": "Title: What would S\u00e9rgio Ferreira say to your physician in this war against COVID-19: How about kallikrein/kinin system? Content: Coronavirus disease 2019 (COVID-19) is an infectious disease with fast spreading all over the world caused by the SARS-CoV-2 virus which can culminate in a severe acute respiratory syndrome by the injury caused in the lungs. However, other organs can be also damaged. SARS-CoV-2 enter into the host cells using the angiotensin-converting enzyme 2 (ACE2) as receptor, like its ancestor SARS-CoV. ACE2 is then downregulated in lung tissues with augmented serum levels of ACE2 in SARS-CoV-2 patients. Interestingly, ACE2+ organs reveal the symptomatic repercussions, which are signals of the infection such as dry cough, shortness of breath, heart failure, liver and kidney damage, anosmia or hyposmia, and diarrhea. ACE2 exerts a chief role in the renin-angiotensin system (RAS) by converting angiotensin II to angiotensin-(1-7) that activates Mas receptor, inhibits ACE1, and modulates bradykinin (BK) receptor sensitivity, especially the BK type 2 receptor (BKB2R). ACE2 also hydrolizes des-Arg9-bradykinin (DABK), an active BK metabolite, agonist at BK type 1 receptors (BKB1R), which is upregulated by inflammation. In this opinion article, we conjecture a dialogue by the figure of S\u00e9rgio Ferreira which brought together basic science of classical pharmacology and clinical repercussions in COVID-19, then we propose that in the course of SARS-CoV-2 infection: i) downregulation of ACE2 impairs the angiotensin II and DABK inactivation; ii) BK and its metabolite DABK seems to be in elevated levels in tissues by interferences in kallikrein/kinin system; iii) BK1 receptor contributes to the outbreak and maintenance of the inflammatory response; iv) kallikrein/kinin system crosstalks to RAS and coagulation system, linking inflammation to thrombosis and organ injury. We hypothesize that targeting the kallikrein/kinin system and BKB1R pathway may be beneficial in SARS-CoV-2 infection, especially on early stages. This route of inference should be experimentally verified by SARS-CoV-2 infected mice.", "qid": 38, "docid": "8es3ibcs", "rank": 37, "score": 0.866218090057373}, {"content": "Title: What would s\u00e9rgio ferreira say to your physician in this war against COVID-19: How about kallikrein/kinin system? Content: Coronavirus disease 2019 (COVID-19) is an infectious disease with fast spreading all over the world caused by the SARS-CoV-2 virus which can culminate in a severe acute respiratory syndrome by the injury caused in the lungs. However, other organs can be also damaged. SARS-CoV-2 enter into the host cells using the angiotensin-converting enzyme 2 (ACE2) as receptor, like its ancestor SARS-CoV. ACE2 is then downregulated in lung tissues with augmented serum levels of ACE2 in SARS-CoV-2 patients. Interestingly, ACE2(+) organs reveal the symptomatic repercussions, which are signals of the infection such as dry cough, shortness of breath, heart failure, liver and kidney damage, anosmia or hyposmia, and diarrhea. ACE2 exerts a chief role in the renin-angiotensin system (RAS) by converting angiotensin II to angiotensin-(1-7) that activates Mas receptor, inhibits ACE1, and modulates bradykinin (BK) receptor sensitivity, especially the BK type 2 receptor (BKB2R). ACE2 also hydrolizes des-Arg(9)-bradykinin (DABK), an active BK metabolite, agonist at BK type 1 receptors (BKB1R), which is upregulated by inflammation. In this opinion article, we conjecture a dialogue by the figure of S\u00e9rgio Ferreira which brought together basic science of classical pharmacology and clinical repercussions in COVID-19, then we propose that in the course of SARS-CoV-2 infection: i) downregulation of ACE2 impairs the angiotensin II and DABK inactivation; ii) BK and its metabolite DABK seems to be in elevated levels in tissues by interferences in kallikrein/kinin system; iii) BK1 receptor contributes to the outbreak and maintenance of the inflammatory response; iv) kallikrein/kinin system crosstalks to RAS and coagulation system, linking inflammation to thrombosis and organ injury. We hypothesize that targeting the kallikrein/kinin system and BKB1R pathway may be beneficial in SARS-CoV-2 infection, especially on early stages. This route of inference should be experimentally verified by SARS-CoV-2 infected mice.", "qid": 38, "docid": "c9qkcnvv", "rank": 38, "score": 0.8660093545913696}, {"content": "Title: SnapShot: COVID-19 Content: Coronavirus disease 2019 (COVID-19) is a novel respiratory illness caused by SARS-CoV-2. Viral entry is mediated through viral spike protein and host ACE2 enzyme interaction. Most cases are mild; severe disease often involves cytokine storm and organ failure. Therapeutics including antivirals, immunomodulators, and vaccines are in development. To view this SnapShot, open or download the PDF.", "qid": 38, "docid": "q3jeu45r", "rank": 39, "score": 0.8658151030540466}, {"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": 38, "docid": "cuv5xxoj", "rank": 40, "score": 0.8654636740684509}, {"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": 38, "docid": "qpwu24e8", "rank": 41, "score": 0.864895224571228}, {"content": "Title: IL-6 blockade treatment for severe COVID-19 in two patients with multiple myeloma. Content: Coronavirus disease 2019 (COVID-19) presents with a broad clinical spectrum, varying from asymptomatic infection to severe pneumonitis, leading to acute respiratory distress syndrome (ARDS) and death(Guan, et al 2020). Accumulating evidence suggests that in severe COVID-19, an acute hyperinflammatory syndrome characterised by fever, hypoxia and increased serum inflammatory markers, occurring 5-10 days from the first symptoms, is the major driver of morbidity and death(Zhou, et al 2020b). Hyperinflammation is not specific to COVID-19. Similar syndromes were previously described in respiratory disease associated with other coronaviruses, including the severe acute respiratory syndrome-coronavirus (SARS-CoV) in 2003 and Middle East respiratory syndrome-coronavirus (MERS-CoV) in 2012(Castilletti, et al 2005, Tseng, et al 2005).", "qid": 38, "docid": "pwq1ar61", "rank": 42, "score": 0.8644624352455139}, {"content": "Title: Induction of pro-inflammatory cytokines (IL-1 and IL-6) and lung inflammation by Coronavirus-19 (COVI-19 or SARS-CoV-2): anti-inflammatory strategies Content: Coronavirus-19 (COVI-19) involves humans as well as animals and may cause serious damage to the respiratory tract, including the lung: coronavirus disease (COVID-19). This pathogenic virus has been identified in swabs performed on the throat and nose of patients who suffer from or are suspected of the disease. When COVI-19 infect the upper and lower respiratory tract it can cause mild or highly acute respiratory syndrome with consequent release of pro-inflammatory cytokines, including interleukin (IL)-1\u00df and IL-6. The binding of COVI-19 to the Toll Like Receptor (TLR) causes the release of pro-IL-1\u00df which is cleaved by caspase-1, followed by inflammasome activation and production of active mature IL-1\u00df which is a mediator of lung inflammation, fever and fibrosis. Suppression of pro-inflammatory IL-1 family members and IL-6 have been shown to have a therapeutic effect in many inflammatory diseases, including viral infections. Cytokine IL-37 has the ability to suppress innate and acquired immune response and also has the capacity to inhibit inflammation by acting on IL-18R&#945; receptor. IL-37 performs its immunosuppressive activity by acting on mTOR and increasing the adenosine monophosphate (AMP) kinase. This cytokine inhibits class II histocompatibility complex (MHC) molecules and inflammation in inflammatory diseases by suppressing MyD88 and subsequently IL-1\u00df, IL-6, TNF and CCL2. The suppression of IL-1\u00df by IL-37 in inflammatory state induced by coronavirus-19 can have a new therapeutic effect previously unknown. Another inhibitory cytokine is IL-38, the newest cytokine of the IL-1 family members, produced by several immune cells including B cells and macrophages. IL-38 is also a suppressor cytokine which inhibits IL-1\u00df and other pro-inflammatory IL-family members. IL-38 is a potential therapeutic cytokine which inhibits inflammation in viral infections including that caused by coronavirus-19, providing a new relevant strategy.", "qid": 38, "docid": "sw4t9yaw", "rank": 43, "score": 0.8643734455108643}, {"content": "Title: Severe COVID-19, Another Piece in the Puzzle of the Hyperferritinemic Syndrome. An Immunomodulatory Perspective to Alleviate the Storm Content: The coronavirus disease 2019 (COVID-19), an acute respiratory disease caused by severe acute respiratory syndrome-coronavirus-2 (SARS-CoV-2), has been declared as a worldwide public health emergency. Interestingly, severe COVID-19 is characterized by fever, hyperferritinemia, and a hyper-inflammatory process with a massive release of pro-inflammatory cytokines, which may be responsible for the high rate of mortality. These findings may advocate for a similarity between severe COVID-19 and some challenging rheumatic diseases, such as adult onset Still's disease, secondary hemophagocytic lymphohistiocytosis, and catastrophic anti-phospholipid syndrome, which have been included in the \u201chyperferritinemic syndrome\u201d category. Furthermore, as performed in these hyper-inflammatory states, severe COVID-19 may benefit from immunomodulatory therapies.", "qid": 38, "docid": "1s6wtj25", "rank": 44, "score": 0.8641871213912964}, {"content": "Title: Mechanisms of Myocardial Injury in Coronavirus Disease 2019 Content: Coronavirus disease 2019 (COVID-19) predominantly presents with symptoms of fever, fatigue, cough and respiratory failure. However, it appears to have a unique interplay with cardiovascular disease (CVD); patients with pre-existing CVD are at highest risk for mortality from COVID-19, along with the elderly. COVID-19 contributes to cardiovascular complications including arrhythmias, myocardial dysfunction and myocardial inflammation. Although the exact mechanism of myocardial inflammation in patients with COVID-19 is not known, several plausible mechanisms have been proposed based on early observational reports. In this article, the authors summarise the available literature on mechanisms of myocardial injury in COVID-19.", "qid": 38, "docid": "h2xmxwd1", "rank": 45, "score": 0.8638216257095337}, {"content": "Title: Potential pathophysiological mechanisms leading to increased COVID-19 susceptibility and severity in obesity Content: As we are facing worldwide pandemic of COVID-19, we aimed to identify potential pathophysiological mechanisms leading to increased COVID-19 susceptibility and severity in obesity. Special emphasis will be given on increased susceptibility to infections due to obesity-related low-grade chronic inflammation, higher expression of angiotensin converting enzyme-2 and pathway-associated components, as well as decreased vitamin D bioavailability, since all of them provide easier ways for the virus to enter into host cells, replicate and stunt adequate immune responses.", "qid": 38, "docid": "h7xf1kxa", "rank": 46, "score": 0.863375186920166}, {"content": "Title: Unraveling the mystery of Covid-19 cytokine storm: From skin to organ systems Content: COVID-19 is a global pandemic that emerged from Wuhan, China. Besides pneumonia and acute respiratory distress syndrome, the disease leads to multisystem involvement in the form of myocarditis, arrhythmias, cardiac arrest, gastrointestinal symptoms, hypoxemic brain injury, acute liver, and renal function impairment. There are also reports of cutaneous lesions in form of urticarial and maculopapular rashes, chilblain like fingers and toes (covid feet), livedoid vasculopathy, and chicken-pox like or varicelliform vesicles. Clinically, many of these skin lesions are likely secondary to occlusion of small to medium blood vessels due to microthrombi formation or due to viral laden antigen-antibody immune complexes; and same explanation may hold true for possible hypoxemic injury simultaneously occurring in other vital organs like lungs, heart, brain, and kidneys. The histopathology, immunoflorescence and RT-PCR analysis of skin biopsies can provide useful insights for ascertaining the pathogenesis of this complex viral syndrome. Apparently, it is interplay of disarmed cellular immunity and over-activated humoral immunity that culminates in end-organ changes. The morbidity and mortality can be significantly reduced by upgrading the cellular immunity and downgrading the humoral response; along with prevention of hypoxemic and reperfusion injuries by using antivirals, immunomodulators, antioxidants, anti-platelets, and anticoagulants in judicious and phased manner.", "qid": 38, "docid": "zbkukpdc", "rank": 47, "score": 0.8632287979125977}, {"content": "Title: SARS-CoV-2 infection pathogenesis is related to oxidative stress as a response to aggression Content: Since the WHO declared COVID-19 a pandemic, a great effort has been made to understand this serious disease. Thousands of studies are being devoted to understanding its epidemiology, its molecular characteristics, its mechanisms, and the clinical evolution of this viral infection. However, little has been published on its pathogenesis and the host response mechanisms in the progress of the disease. Therefore, we propose a hypothesis based on strong scientific documentation, associating oxidative stress with changes found in patients with COVID-19, such as its participation in the amplification and perpetuation of the cytokine storm, coagulopathy, and cell hypoxia. Finally, we suggest a therapeutic strategy to reduce oxidative stress using antioxidants, NFkB inhibitors, Nrf2 activators, and iron complexing agents. We believe that this hypothesis can guide new studies and therapeutic strategies on this topic.", "qid": 38, "docid": "lkhmgfnc", "rank": 48, "score": 0.8629605770111084}, {"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": 38, "docid": "p6h7k7ty", "rank": 49, "score": 0.8624007701873779}, {"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": 38, "docid": "r7ahl9gd", "rank": 50, "score": 0.8623263239860535}, {"content": "Title: Inflammatory markers in Covid-19 Patients: a systematic review and meta-analysis. Content: Introduction Diagnosis of COVID-19 is based on clinical manifestation, history of exposure, positive findings on chest CT and laboratory tests. It has been shown that inflammation plays a role in pathogenesis of COVID-19. Method We used the necessary transformations to convert the median and IQR to mean and SD Random-effect model using Der Simonian, and Laird methods was used if heterogeneity between studies was significant, the homogeneity among studies was assessed with I2 Statistic, values above 50%, and for the chi-square test, P-values <0.1 was supposed statistically significant Results Twelve studies were included in the analysis that all of which were conducted in China in the year 2020. The result of combining 12 articles with 772 participants showed that the pooled estimate of the mean of lymphocyte with 95% CI was (Mean: 1.01; 95% CI (0.76-1.26); p-value<0.001). About WBC the pooled result of 9 studies with 402 participants was (Mean: 5.11; 95% CI (3.90-6.32); p-value<0.001) Also the pooled mean estimate of 9 studies with 513 patients for the ratio of Neutrophil/lymphocyte was (Mean: 3.62; 95% CI (1.48-5.77); p-value=0.001). The pooled mean from the combination of 7 studies with 521 patients on CRP was (Mean: 28.75; 95% CI (8.04-49.46). Conclusion Inflammatory Markers increase in patients with Covid-19, which can be a good indicator to find patients.", "qid": 38, "docid": "9db9dpvd", "rank": 51, "score": 0.8622186183929443}, {"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": 38, "docid": "s82qv18v", "rank": 52, "score": 0.8619575500488281}, {"content": "Title: p38 MAPK inhibition: A promising therapeutic approach for COVID-19 Content: COVID-19, caused by the SARS-CoV-2 virus, is a major source of morbidity and mortality due to its inflammatory effects in the lungs and heart. The p38 MAPK pathway plays a crucial role in the release of pro-inflammatory cytokines such as IL-6 and has been implicated in acute lung injury and myocardial dysfunction. The overwhelming inflammatory response in COVID-19 infection may be caused by disproportionately upregulated p38 activity, explained by two mechanisms. First, angiotensin-converting enzyme 2 (ACE2) activity is lost during SARS-CoV-2 viral entry. ACE2 is highly expressed in the lungs and heart and converts Angiotensin II into Angiotensin 1\u20137. Angiotensin II signals proinflammatory, pro-vasoconstrictive, pro-thrombotic activity through p38 MAPK activation, which is countered by Angiotensin 1\u20137 downregulation of p38 activity. Loss of ACE2 upon viral entry may tip the balance towards destructive p38 signaling through Angiotensin II. Second, SARS-CoV was previously shown to directly upregulate p38 activity via a viral protein, similar to other RNA respiratory viruses that may hijack p38 activity to promote replication. Given the homology between SARS-CoV and SARS-CoV-2, the latter may employ a similar mechanism. Thus, SARS-CoV-2 may induce overwhelming inflammation by directly activating p38 and downregulating a key inhibitory pathway, while simultaneously taking advantage of p38 activity to replicate. Therapeutic inhibition of p38 could therefore attenuate COVID-19 infection. Interestingly, a prior preclinical study showed protective effects of p38 inhibition in a SARS-CoV mouse model. A number of p38 inhibitors are in the clinical stage and should be considered for clinical trials in serious COVID-19 infection.", "qid": 38, "docid": "qd5pzxtx", "rank": 53, "score": 0.861710786819458}, {"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": 38, "docid": "2o3dvi2d", "rank": 54, "score": 0.8616002202033997}, {"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": 55, "score": 0.861339807510376}, {"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": 38, "docid": "ete5n5pw", "rank": 56, "score": 0.861056923866272}, {"content": "Title: p38 MAPK inhibition: A promising therapeutic approach for COVID-19 Content: COVID-19, caused by the SARS-CoV-2 virus, is a major source of morbidity and mortality due to its inflammatory effects in the lungs and heart. The p38 MAPK pathway plays a crucial role in the release of pro-inflammatory cytokines such as IL-6 and has been implicated in acute lung injury and myocardial dysfunction. The overwhelming inflammatory response in COVID-19 infection may be caused by disproportionately upregulated p38 activity, explained by two mechanisms. First, angiotensin-converting enzyme 2 (ACE2) activity is lost during SARS-CoV-2 viral entry. ACE2 is highly expressed in the lungs and heart and converts Angiotensin II into Angiotensin 1-7. Angiotensin II signals proinflammatory, pro-vasoconstrictive, pro-thrombotic activity through p38 MAPK activation, which is countered by Angiotensin 1-7 downregulation of p38 activity. Loss of ACE2 upon viral entry may tip the balance towards destructive p38 signaling through Angiotensin II. Second, SARS-CoV was previously shown to directly upregulate p38 activity via a viral protein, similar to other RNA respiratory viruses that may hijack p38 activity to promote replication. Given the homology between SARS-CoV and SARS-CoV-2, the latter may employ a similar mechanism. Thus, SARS-CoV-2 may induce overwhelming inflammation by directly activating p38 and downregulating a key inhibitory pathway, while simultaneously taking advantage of p38 activity to replicate. Therapeutic inhibition of p38 could therefore attenuate COVID-19 infection. Interestingly, a prior preclinical study showed protective effects of p38 inhibition in a SARS-CoV mouse model. A number of p38 inhibitors are in the clinical stage and should be considered for clinical trials in serious COVID-19 infection.", "qid": 38, "docid": "12dfuqtq", "rank": 57, "score": 0.8609347939491272}, {"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": 38, "docid": "rhvv3l0l", "rank": 58, "score": 0.8606274127960205}, {"content": "Title: COVID-19: Review on latest available drugs and therapies against SARS-CoV-2. Coagulation and inflammation cross-talking Content: SARS-CoV-2 is the agent responsible for COVID-19. The infection can be dived into three phases: mild infection, the pulmonary phase and the inflammatory phase. Treatment options for the pulmonary phase include: Hydroxychloroquine, Remdesivir, Lopinavir/Ritonavir. The inflammatory phase includes therapeutic options like Tocilizumab, Anakinra, Baricitinib, Eculizumab, Emapalumab and Heparin. Human clinical trials are starting to show some results, in some cases like that of Remdesivir and corticosteroids these are controversial. Coagulopathy is a common complication in severe cases, inflammation and coagulation are intertwined and cross-talking between these two responses is known to happen. A possible amplification of this cross-talking is suggested to be implicated in the severe cases that show both a cytokine storm and coagulopathy.", "qid": 38, "docid": "ly2ytc6t", "rank": 59, "score": 0.8604226112365723}, {"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": 38, "docid": "f37cp6j3", "rank": 60, "score": 0.8603904247283936}, {"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": 61, "score": 0.8596883416175842}, {"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": 38, "docid": "528p64iu", "rank": 62, "score": 0.8596349358558655}, {"content": "Title: Possible Cause of Inflammatory Storm and Septic Shock in Patients Diagnosed with (COVID-19) Content: The novel coronavirus (SARS-CoV-2) infection which has been known as Coronavirus diseases 2019 COVID-19 has become an endemic emergent situation by the World Health Organization. So far, no successful specific treatment has been found for this disease. As has been reported, most of non-survivor patients with COVID-19 (70%) had septic shock which was significantly higher than survived ones. Although the exact pathophysiology of septic shock in these patients is still unclear, it seems to be possible that part of it would be due to the administration of empiric antibiotics with inflammatory properties especially in the absence of bacterial infection. Herein, we have reviewed possible molecular pathways of septic shock in the patients who have received antibiotics with inflammatory properties which mainly is release of interleukin 1\u00df (IL-1\u00df), IL-6, and tumor necrosis factor &#945; (TNF- &#945;) through different routes. Altogether, we highly recommend clinicians to look after those antibiotics with anti-inflammatory activity for both empiric antibiotic therapy and reducing the inflammation to prevent septic shock in patients with diagnosed COVID-19.", "qid": 38, "docid": "9k1fm84p", "rank": 63, "score": 0.8595893383026123}, {"content": "Title: COVID-19: review on latest available drugs and therapies against SARS-CoV-2. Coagulation and inflammation cross-talking Content: SARS-CoV-2 is the agent responsible for COVID-19. The infection can be dived into three phases: mild infection, the pulmonary phase and the inflammatory phase. Treatment options for the pulmonary phase include: Hydroxychloroquine, Remdesivir, Lopinavir/Ritonavir. The inflammatory phase includes therapeutic options like Tocilizumab, Anakinra, Baricitinib, Eculizumab, Emapalumab and Heparin. Human clinical trials are starting to show some results, in some cases like that of Remdesivir these are controversial. Coagulopathy is a common complication in severe cases, inflammation and coagulation are intertwined and cross-talking between these two responses is known to happen. A possible amplification of this cross-talking is suggested to be implicated in the severe cases that show both a cytokine storm and coagulopathy.", "qid": 38, "docid": "v59dpmuu", "rank": 64, "score": 0.8595737218856812}, {"content": "Title: SGLT2 inhibition and COVID-19: The road not taken Content: The COVID-19 pandemic, caused by SARS-CoV-2, is an immense challenge for global healthcare. Diabetes mellitus, hypertension and obesity have been shown to portend poor prognosis in COVID-19 despite no greater susceptibility to the infection (1). Chronic hypertension is commonly associated with vasculopathy which can predispose to severe infection. In patients with diabetes, severity is attributable to impaired innate, adaptive immunity, upregulation of ACE2 (entry receptor for SARS-CoV2) by acute hyperglycemia and diabetic vasculopathy. The background of chronic low grade inflammation characterised by increased levels of IL-6 and CRP in diabetes and obesity can also lead to an enhanced 'cytokine storm' in COVID-19 (2). ACE2 expression on endothelial cells has been reported to cause viral mediated endothelitis and precipitate vascular dysfunction manifesting as acute respiratory distress syndrome as well as myocarditis, heart failure, arrhythmias, myocardial infarction and renal failure (3). In patients with pre-existing comorbidities like hypertension, diabetes, obesity and chronic kidney disease, this new-onset organ dysfunction can have deleterious additive effects.", "qid": 38, "docid": "ojoqsdn1", "rank": 65, "score": 0.8593864440917969}, {"content": "Title: SGLT2 inhibition and COVID-19: The road not taken. Content: The COVID-19 pandemic, caused by SARS-CoV-2, is an immense challenge for global healthcare. Diabetes mellitus, hypertension and obesity have been shown to portend poor prognosis in COVID-19 despite no greater susceptibility to the infection (1). Chronic hypertension is commonly associated with vasculopathy which can predispose to severe infection. In patients with diabetes, severity is attributable to impaired innate, adaptive immunity, upregulation of ACE2 (entry receptor for SARS-CoV2) by acute hyperglycemia and diabetic vasculopathy. The background of chronic low grade inflammation characterised by increased levels of IL-6 and CRP in diabetes and obesity can also lead to an enhanced 'cytokine storm' in COVID-19 (2). ACE2 expression on endothelial cells has been reported to cause viral mediated endothelitis and precipitate vascular dysfunction manifesting as acute respiratory distress syndrome as well as myocarditis, heart failure, arrhythmias, myocardial infarction and renal failure (3). In patients with pre-existing comorbidities like hypertension, diabetes, obesity and chronic kidney disease, this new-onset organ dysfunction can have deleterious additive effects.", "qid": 38, "docid": "md9dbxb5", "rank": 66, "score": 0.8593864440917969}, {"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": 38, "docid": "smkpp89u", "rank": 67, "score": 0.8590632081031799}, {"content": "Title: Immune environment modulation in pneumonia patients caused by coronavirus: SARS-CoV, MERS-CoV and SARS-CoV-2 Content: Currently, we are on a global pandemic of Coronavirus disease-2019 (COVID-19) which causes fever, dry cough, fatigue and acute respiratory distress syndrome (ARDS) that may ultimately lead to the death of the infected. Current researches on COVID-19 continue to highlight the necessity for further understanding the virus-host synergies. In this study, we have highlighted the key cytokines induced by coronavirus infections. We have demonstrated that genes coding interleukins (Il-1&#945;, Il-1\u00df, Il-6, Il-10), chemokine (Ccl2, Ccl3, Ccl5, Ccl10), and interferon (Ifn-&#945;2, Ifn-\u00df1, Ifn2) upsurge significantly which in line with the elevated infiltration of T cells, NK cells and monocytes in SARS-Cov treated group at 24 hours. Also, interleukins (IL-6, IL-23&#945;, IL-10, IL-7, IL-1&#945;, IL-1\u00df) and interferon (IFN-&#945;2, IFN2, IFN-\u00ce\u00b3) have increased dramatically in MERS-Cov at 24 hours. A similar cytokine profile showed the cytokine storm served a critical role in the infection process. Subsequent investigation of 463 patients with COVID-19 disease revealed the decreased amount of total lymphocytes, CD3+, CD4+, and CD8+ T lymphocytes in the severe type patients which indicated COVID-19 can impose hard blows on human lymphocyte resulting in lethal pneumonia. Thus, taking control of changes in immune factors could be critical in the treatment of COVID-19.", "qid": 38, "docid": "xrcvyu87", "rank": 68, "score": 0.8590225577354431}, {"content": "Title: Estudios de imagen cardiaca en la pandemia COVID-19 Content: COVID-19 is an acute respiratory syndrome caused by coronavirus-2 (SARS COV2) The different cardiac imaging methods have issued specific recommendations for the different imaging methods in this pandemic, so it is essential to emphasize the recommendations for carrying out these studies", "qid": 38, "docid": "rcccwfl8", "rank": 69, "score": 0.8588594198226929}, {"content": "Title: Unraveling the mystery of Covid-19 Cytokine storm: From skin to organ systems Content: COVID-19 is a global pandemic that emerged from Wuhan, China. Besides pneumonia and acute respiratory distress syndrome, the disease leads to multisystem involvement in the form of myocarditis, arrhythmias, cardiac arrest, gastrointestinal symptoms, hypoxemic brain injury, acute liver and renal function impairment. There are also reports of cutaneous lesions in form of urticarial and maculopapular rashes, chilblain like fingers and toes (covid feet), livedoid vasculopathy and chicken-pox like or varicelliform vesicles. Clinically, many of these skin lesions are likely secondary to occlusion of small to medium blood vessels due to microthrombi formation or due to viral laden antigen-antibody immune complexes; and same explanation may hold true for possible hypoxemic injury simultaneously occurring in other vital organs like lungs, heart, brain and kidneys. The histopathology, immunoflorescence and RT-PCR analysis of skin biopsies can provide useful insights for ascertaining the pathogenesis of this complex viral syndrome. Apparently, it is interplay of disarmed cellular immunity and over-activated humoral immunity that culminates in end-organ changes. The morbidity and mortality can be significantly reduced by upgrading the cellular immunity and downgrading the humoral response; along with prevention of hypoxemic and reperfusion injuries by using antivirals, immunomodulators, antioxidants, anti-platelets and anticoagulants in judicious and phased manner. This article is protected by copyright. All rights reserved.", "qid": 38, "docid": "ve83421h", "rank": 70, "score": 0.8587003946304321}, {"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": 71, "score": 0.8586850762367249}, {"content": "Title: Estudios de imagen cardiaca en la pandemia COVID-19./ Cardiac imaging studies in the COVID-19 pandemic Content: COVID-19 is an acute respiratory syndrome caused by coronavirus-2 (SARS COV2). The different cardiac imaging methods have issued specific recommendations for the different imaging methods in this pandemic, so it is essential to emphasize the recommendations for carrying out these studies.", "qid": 38, "docid": "11q83ony", "rank": 72, "score": 0.8583308458328247}, {"content": "Title: Cardiac imaging studies in the COVID-19 pandemic. Content: COVID-19 is an acute respiratory syndrome caused by coronavirus-2 (SARS COV2). The different cardiac imaging methods have issued specific recommendations for the different imaging methods in this pandemic, so it is essential to emphasize the recommendations for carrying out these studies.", "qid": 38, "docid": "9vypr79o", "rank": 73, "score": 0.8583308458328247}, {"content": "Title: Hyperinflammation and derangement of renin-angiotensin-aldosterone system in COVID-19: A novel hypothesis for clinically suspected hypercoagulopathy and microvascular immunothrombosis Content: Early clinical evidence suggests that severe cases of coronavirus disease 2019 (COVID-19), caused by the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), are frequently characterized by hyperinflammation, imbalance of renin-angiotensin-aldosterone system, and a particular form of vasculopathy, thrombotic microangiopathy, and intravascular coagulopathy. In this paper, we present an immunothrombosis model of COVID-19. We discuss the underlying pathogenesis and the interaction between multiple systems, resulting in propagation of immunothrombosis, which through investigation in the coming weeks, may lead to both an improved understanding of COVID-19 pathophysiology and identification of innovative and efficient therapeutic targets to reverse the otherwise unfavorable clinical outcome of many of these patients.", "qid": 38, "docid": "p298vft5", "rank": 74, "score": 0.8577211499214172}, {"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": 75, "score": 0.8577039837837219}, {"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": 38, "docid": "ne1qvf5g", "rank": 76, "score": 0.8576085567474365}, {"content": "Title: Immune environment modulation in pneumonia patients caused by coronavirus: SARS-CoV, MERS-CoV and SARS-CoV-2 Content: Currently, we are on a global pandemic of Coronavirus disease-2019 (COVID-19) which causes fever, dry cough, fatigue and acute respiratory distress syndrome (ARDS) that may ultimately lead to the death of the infected. Current researches on COVID-19 continue to highlight the necessity for further understanding the virus-host synergies. In this study, we have highlighted the key cytokines induced by coronavirus infections. We have demonstrated that genes coding interleukins (Il-1\u03b1, Il-1\u03b2, Il-6, Il-10), chemokine (Ccl2, Ccl3, Ccl5, Ccl10), and interferon (Ifn-\u03b12, Ifn-\u03b21, Ifn2) upsurge significantly which in line with the elevated infiltration of T cells, NK cells and monocytes in SARS-Cov treated group at 24 hours. Also, interleukins (IL-6, IL-23\u03b1, IL-10, IL-7, IL-1\u03b1, IL-1\u03b2) and interferon (IFN-\u03b12, IFN2, IFN-\u03b3) have increased dramatically in MERS-Cov at 24 hours. A similar cytokine profile showed the cytokine storm served a critical role in the infection process. Subsequent investigation of 463 patients with COVID-19 disease revealed the decreased amount of total lymphocytes, CD3+, CD4+, and CD8+ T lymphocytes in the severe type patients which indicated COVID-19 can impose hard blows on human lymphocyte resulting in lethal pneumonia. Thus, taking control of changes in immune factors could be critical in the treatment of COVID-19.", "qid": 38, "docid": "2w5ws14b", "rank": 77, "score": 0.8573794364929199}, {"content": "Title: Coronavirus Disease 2019 (COVID-19): Cytokine Storms, Hyper-Inflammatory Phenotypes, and Acute Respiratory Distress Syndrome Content: Abstract Coronavirus Disease 2019 (COVID-19) was first identified in China at the end of 2019. Acute respiratory distress syndrome (ARDS) represents the most common and serious complication of COVID-19. Cytokine storms are a pathophysiological feature of COVID-19 and play an important role in distinguishing hyper-inflammatory subphenotypes of ARDS. Accordingly, in this review, we focus on hyper-inflammatory host responses in ARDS that play a critical role in the differentiated development of COVID-19. Furthermore, we discuss inflammation-related indicators that have the potential to identify hyper-inflammatory subphenotypes of COVID-19, especially for those with a high risk of ARDS. Finally, we explore the possibility of improving the quality of monitoring and treatment of COVID-19 patients and in reducing the incidence of critical illness and mortality via better distinguishing hyper- and hypo-inflammatory subphenotypes of COVID-19.", "qid": 38, "docid": "c5co9cfq", "rank": 78, "score": 0.8573215007781982}, {"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": 38, "docid": "ter67nri", "rank": 79, "score": 0.8573176860809326}, {"content": "Title: Immune Response, Inflammation, and the Clinical Spectrum of COVID-19 Content: The current COVID-19 pandemic began in December 2019 in Wuhan (China) and rapidly extended to become a global sanitary and economic emergency. Its etiological agent is the coronavirus SARS-CoV-2. COVID-19 presents a wide spectrum of clinical manifestations, which ranges from an asymptomatic infection to a severe pneumonia accompanied by multisystemic failure that can lead to a patient's death. The immune response to SARS-CoV-2 is known to involve all the components of the immune system that together appear responsible for viral elimination and recovery from the infection. Nonetheless, such immune responses are implicated in the disease's progression to a more severe and lethal process. This review describes the general aspects of both COVID-19 and its etiological agent SARS-CoV-2, stressing the similarities with other severe coronavirus infections, such as SARS and MERS, but more importantly, pointing toward the evidence supporting the hypothesis that the clinical spectrum of COVID-19 is a consequence of the corresponding variable spectrum of the immune responses to the virus. The critical point where progression of the disease ensues appears to center on loss of the immune regulation between protective and altered responses due to exacerbation of the inflammatory components. Finally, it appears possible to delineate certain major challenges deserving of exhaustive investigation to further understand COVID-19 immunopathogenesis, thus helping to design more effective diagnostic, therapeutic, and prophylactic strategies.", "qid": 38, "docid": "pjjrgn05", "rank": 80, "score": 0.8571563959121704}, {"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": 38, "docid": "7oaxtrul", "rank": 81, "score": 0.8570922017097473}, {"content": "Title: Biochemical indicators of coronavirus disease 2019 exacerbation and the clinical implications Content: Coronavirus Disease 2019 (COVID-19) has sparked a global pandemic, affecting more than 4 million people worldwide. The severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) can cause acute lung injury (ALI) and even acute respiratory distress syndrome (ARDS); with a fatality of 7.0 %. Accumulating evidence suggested that the progression of COVID-19 is associated with lymphopenia and excessive inflammation, and a subset of severe cases might exhibit cytokine storm triggered by secondary hemophagocytic lymphohistiocytosis (sHLH). Furthermore, secondary bacterial infection may contribute to the exacerbation of COVID-19. We recommend using both IL-10 and IL-6 as the indicators of cytokine storm, and monitoring the elevation of procalcitonin (PCT) as an alert for initiating antibacterial agents. Understanding the dynamic progression of SARS-CoV-2 infection is crucial to determine an effective treatment strategy to reduce the rising mortality of this global pandemic.", "qid": 38, "docid": "j25rvp1i", "rank": 82, "score": 0.8570553064346313}, {"content": "Title: The renin-angiotensin-aldosterone system: Role in pathogenesis and potential therapeutic target in COVID-19 Content: Coronavirus disease 2019 (COVID-19), caused by the SARS-CoV-2 novel coronavirus, has spread worldwide causing high fatality rates. Neither a vaccine nor specific therapeutic approaches are available, hindering the fight against this disease and making better understanding of its pathogenesis essential. Despite similarities between SARS-CoV-2 and SARS-CoV, the former has unique characteristics which represent a great challenge to physicians. The mechanism of COVID-19 infection and pathogenesis is still poorly understood. In the present review, we highlight possible pathways involved in the pathogenesis of COVID-19 and potential therapeutic targets, focusing on the role of the renin-angiotensin-aldosterone system.", "qid": 38, "docid": "bc2wpryp", "rank": 83, "score": 0.8568822145462036}, {"content": "Title: The renin-angiotensin-aldosterone system: Role in pathogenesis and potential therapeutic target in COVID-19. Content: Coronavirus disease 2019 (COVID-19), caused by the SARS-CoV-2 novel coronavirus, has spread worldwide causing high fatality rates. Neither a vaccine nor specific therapeutic approaches are available, hindering the fight against this disease and making better understanding of its pathogenesis essential. Despite similarities between SARS-CoV-2 and SARS-CoV, the former has unique characteristics which represent a great challenge to physicians. The mechanism of COVID-19 infection and pathogenesis is still poorly understood. In the present review, we highlight possible pathways involved in the pathogenesis of COVID-19 and potential therapeutic targets, focusing on the role of the renin-angiotensin-aldosterone system.", "qid": 38, "docid": "ep73us0e", "rank": 84, "score": 0.8568822145462036}, {"content": "Title: Electrical Storm in COVID-19 Content: Abstract COVID-19 is a global pandemic caused by SARS-CoV-2. Infection is associated with significant morbidity and mortality. Individuals with pre-existing cardiovascular disease or evidence of myocardial injury are at risk for severe disease and death. Little is understood about the mechanisms of myocardial injury or life-threatening cardiovascular sequelae.", "qid": 38, "docid": "98xisxg7", "rank": 85, "score": 0.8568652272224426}, {"content": "Title: Characteristics of inflammatory factors and lymphocyte subsets in patients with severe COVID-19 Content: To investigate the inflammatory factors and lymphocyte subsets which play an important role in the course of severe coronavirus disease 2019 (COVID-19). A total of 27 patients with severe COVID-19 who were admitted to Tongji Hospital in Wuhan from 1 to 21 February 2020 were recruited to the study. The characteristics of interleukin-1\u00df (IL-1\u00df), IL-2 receptor (IL-2R), IL-6, IL-8, IL-10, tumor necrosis factor-&#945; (TNF)-&#945;, C-reactive protein (CRP), serum ferritin and procalcitonin (PCT), and lymphocyte subsets of these patients were retrospectively compared before and after treatment. Before treatment, there was no significant difference in most inflammatory factors (IL-1\u00df, IL-2R, IL-6, IL-8, IL-10, CRP, and serum ferritin) between male and female patients. Levels of IL-2R, IL-6, TNF-&#945;, and CRP decreased significantly after treatment, followed by IL-8, IL-10, and PCT. Serum ferritin was increased in all patients before treatment but did not decrease significantly after treatment. IL-1\u00df was normal in most patients before treatment. Lymphopenia was common among these patients with severe COVID-19. Analysis of lymphocyte subsets showed that CD4+ and particularly CD8+ T lymphocytes increased significantly after treatment. However, B lymphocytes and natural killer cells showed no significant changes after treatment. A pro-inflammatory response and decreased level of T lymphocytes were associated with severe COVID-19.", "qid": 38, "docid": "zuf19lex", "rank": 86, "score": 0.8566985130310059}, {"content": "Title: Tackle the free radicals damage in COVID-19. Content: COVID-19 is a severe pandemic which has caused a devastating amount of loss in lives around the world, and yet we still don't know how to appropriately treat this disease. We know very little about the pathogenesis of SARS-CoV-2, the virus which induces the COVID-19. However, COVID-19 does share many similar symptoms with SARS and influenza. Previous scientific discoveries learned from lab animal models and clinical practices shed light on possible pathogenic mechanisms in COVID-19. In the past decades, accumulated scientific findings confirmed the pathogenic role of free radicals damage in respiratory virus infection. Astonishingly very few medical professionals mention the crucial role of free radical damage in COVID-19. This hypothesis aims to summarize the crucial pathogenic role of free radical damage in respiratory virus induced pneumonia and suggest an antioxidative therapeutic strategy for COVID-19.", "qid": 38, "docid": "8aiexhdd", "rank": 87, "score": 0.8566136360168457}, {"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": 38, "docid": "cv8r9pbl", "rank": 88, "score": 0.8564746975898743}, {"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": 89, "score": 0.8564249277114868}, {"content": "Title: COVID-19 as an Acute Inflammatory Disease Content: The 2019 coronavirus disease (COVID-19) pandemic caused by the virus severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2) has created an unprecedented global crisis for the infrastructure sectors, including economic, political, healthcare, education, and research systems. Although over 90% of infected individuals are asymptomatic or manifest noncritical symptoms and will recover from the infection, those individuals presenting with critical symptoms are in urgent need of effective treatment options. Emerging data related to mechanism of severity and potential therapies for patients presenting with severe symptoms are scattered and therefore require a comprehensive analysis to focus research on developing effective therapeutics. A critical literature review suggests that the severity of SARS-CoV-2 infection is associated with dysregulation of inflammatory immune responses, which in turn inhibits the development of protective immunity to the infection. Therefore, the use of therapeutics that modulate inflammation without compromising the adaptive immune response could be the most effective therapeutic strategy.", "qid": 38, "docid": "hczmytse", "rank": 90, "score": 0.8562940359115601}, {"content": "Title: COVID-19 as an Acute Inflammatory Disease. Content: The 2019 coronavirus disease (COVID-19) pandemic caused by the virus severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2) has created an unprecedented global crisis for the infrastructure sectors, including economic, political, healthcare, education, and research systems. Although over 90% of infected individuals are asymptomatic or manifest noncritical symptoms and will recover from the infection, those individuals presenting with critical symptoms are in urgent need of effective treatment options. Emerging data related to mechanism of severity and potential therapies for patients presenting with severe symptoms are scattered and therefore require a comprehensive analysis to focus research on developing effective therapeutics. A critical literature review suggests that the severity of SARS-CoV-2 infection is associated with dysregulation of inflammatory immune responses, which in turn inhibits the development of protective immunity to the infection. Therefore, the use of therapeutics that modulate inflammation without compromising the adaptive immune response could be the most effective therapeutic strategy.", "qid": 38, "docid": "70s35cip", "rank": 91, "score": 0.8562940359115601}, {"content": "Title: Rheumatologists\u2019 perspective on coronavirus disease 19 (COVID-19) and potential therapeutic targets Content: The ongoing pandemic coronavirus disease 19 (COVID-19) caused by the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) is a matter of global concern. Environmental factors such as air pollution and smoking and comorbid conditions (hypertension, diabetes mellitus and underlying cardio-respiratory illness) likely increase the severity of COVID-19. Rheumatic manifestations such as arthralgias and arthritis may be prevalent in about a seventh of individuals. COVID-19 can result in acute interstitial pneumonia, myocarditis, leucopenia (with lymphopenia) and thrombocytopenia, also seen in rheumatic diseases like lupus and Sjogren\u2019s syndrome. Severe disease in a subset of patients may be driven by cytokine storm, possibly due to secondary hemophagocytic lymphohistiocytosis (HLH), akin to that in systemic onset juvenile idiopathic arthritis or adult-onset Still\u2019s disease. In the absence of high-quality evidence in this emerging disease, understanding of pathogenesis may help postulate potential therapies. Angiotensin converting enzyme 2 (ACE2) appears important for viral entry into pneumocytes; dysbalance in ACE2 as caused by ACE inhibitors or ibuprofen may predispose to severe disease. Preliminary evidence suggests potential benefit with chloroquine or hydroxychloroquine. Antiviral drugs like lopinavir/ritonavir, favipiravir and remdesivir are also being explored. Cytokine storm and secondary HLH might require heightened immunosuppressive regimens. Current international society recommendations suggest that patients with rheumatic diseases on immunosuppressive therapy should not stop glucocorticoids during COVID-19 infection, although minimum possible doses may be used. Disease-modifying drugs should be continued; cessation may be considered during infection episodes as per standard practices. Development of a vaccine may be the only effective long-term protection against this disease.", "qid": 38, "docid": "njkh20sv", "rank": 92, "score": 0.8561925888061523}, {"content": "Title: [Therapy of coronavirus disease 2019 induced acute respiratory distress syndrome is different from traditional acute respiratory distress syndrome] Content: Coronavirus disease 2019 (COVID-19) has become a global public health emergency threatening people's lives around the world. Although the acute respiratory distress syndrome (ARDS) induced by COVID-19 is similar to the ARDS caused by other diseases in terms of pathophysiological basis and clinical manifestations, they are also different in many aspects, which lead to different clinical therapies. Therefore, understanding the differences and similarities of ARDS induced by COVID-19 and other diseases currently are the basis for clinicians to make decisions for the treatment of COVID-19 induced ARDS.", "qid": 38, "docid": "vcebp49l", "rank": 93, "score": 0.856093168258667}, {"content": "Title: [Therapy of coronavirus disease 2019 induced acute respiratory distress syndrome is different from traditional acute respiratory distress syndrome]. Content: Coronavirus disease 2019 (COVID-19) has become a global public health emergency threatening people's lives around the world. Although the acute respiratory distress syndrome (ARDS) induced by COVID-19 is similar to the ARDS caused by other diseases in terms of pathophysiological basis and clinical manifestations, they are also different in many aspects, which lead to different clinical therapies. Therefore, understanding the differences and similarities of ARDS induced by COVID-19 and other diseases currently are the basis for clinicians to make decisions for the treatment of COVID-19 induced ARDS.", "qid": 38, "docid": "xxklup4c", "rank": 94, "score": 0.856093168258667}, {"content": "Title: Histopathology and genetic susceptibility in COVID\u201019 pneumonia Content: The clinical features of COVID\u201019 range from a mild illness to patients with a very severe illness with acute hypoxemic respiratory failure requiring ventilation and Intensive Care Unit admission. Risk factors for a fatal disease include older age, respiratory disease, diabetes mellitus, obesity and hypertension. Little is known about the mechanisms behind observed episodes of sudden deterioration or the infrequent idiosyncratic clinical demise in otherwise healthy and young subjects. As in other diseases, the answer to some of these questions may in time be provided by genotyping as well careful clinical, serological, radiological and histopathological phenotyping, which enable mechanistic insights into the differences in pathogenesis and underlying immunological and tissue regenerative response patterns. We will aim to provide a brief overview of the existing evidence for such differences in host response and outcome, and generate hypotheses for divergent patterns and avenues for future research, by highlighting similarities and differences in histopathological appearance between COVID19 and influenza as well as previous coronavirus outbreaks, and by discussing predisposition through genetics and underlying disease.", "qid": 38, "docid": "mt939rqw", "rank": 95, "score": 0.8560712337493896}, {"content": "Title: COVID-19 - Toward a comprehensive understanding of the disease Content: The evidence on the pathophysiology of the novel coronavirus SARS-CoV-2 infection is rapidly growing. Understanding why some patients suffering from COVID-19 are getting so sick, while others are not, has become an informal imperative for researchers and clinicians around the globe. The answer to this question would allow rationalizing the fear surrounding this pandemic. Understanding of the pathophysiology of COVID-19 relies on an understanding of interplaying mechanisms, including SARS-CoV-2 virulence, human immune response, and complex inflammatory reactions with coagulation playing a major role. An interplay with bacterial co-infections, as well as the vascular system and microcirculation affected throughout the body should also be examined. More importantly, a compre-hensive understanding of pathological mechanisms of COVID-19 will increase the efficacy of therapy and decrease mortality. Herewith, presented is the current state of knowledge on COVID-19: beginning from the virus, its transmission, and mechanisms of entry into the human body, through the pathological effects on the cellular level, up to immunological reaction, systemic and organ presentation. Last but not least, currently available and possible future therapeutic and diagnostic options are briefly commented on.", "qid": 38, "docid": "edbtz6up", "rank": 96, "score": 0.8557596802711487}, {"content": "Title: COVID-19 Pandemic: Is Chronic Inflammation a Major Cause of Death? Content: Abstract Background. Today humanity is facing another infectious threat: a newly emerging virus SARS-CoV-2 causing COVID-19. It was already described that COVID-19 mortality among elderly people and people with such underlying conditions as obesity, cardiovascular diseases, cancer, chronic respiratory diseases, and diabetes s increased. Dysregulation of the immune responses vital for antiviral defense, which are typical for chronic inflammation, led us to a hypothesis that chronic inflammation is the main risk factor for increased susceptibility and mortality from COVID-19. Method. Based on the available information for 126 countries, statistical analysis to find out whether the difference in incidence and mortality within countries can be explained by the existing chronic inflammation among the countries population, was conducted. Results. A positive correlation between the percentage of people dying from chronic noncommunicable diseases and COVID-19 incidence (p<0.001) and mortality (p<0.001) within countries. Conclusion. The problem of COVID-19-caused high mortality rate may be a consequence of the high number of people having chronic low-grade inflammation as a precondition, and thus, one of the potential ways to reduce risk of morbidity and mortality is to focus on this widespread health problem, mainly occurring in developed countries and to take corresponding diagnostic, preventative, and treatment measures.", "qid": 38, "docid": "bmvdwa68", "rank": 97, "score": 0.8557336330413818}, {"content": "Title: AhR and IDO1 in pathogenesis of Covid-19 and the \"Systemic AhR Activation Syndrome:\" Translational review and therapeutic perspectives Content: Covid-19 is the acute illness caused by SARS-CoV-2 with initial clinical symptoms such as cough, fever, malaise, headache, and anosmia. After entry into cells, corona viruses (CoV) activate aryl hydrocarbon receptors (AhRs) by an indoleamine 2,3-dioxygenase (IDO1)-independent mechanism, bypassing the IDO1-kynurenine-AhR pathway. The IDO1-kynurenine-AhR signaling pathway is used by multiple viral, microbial and parasitic pathogens to activate AhRs and to establish infections. AhRs enhance their own activity through an IDO1-AhR-IDO1 positive feedback loop prolonging activation induced by pathogens. Direct activation of AhRs by CoV induces immediate and simultaneous up-regulation of diverse AhR-dependent downstream effectors, and this, in turn, results in a \"Systemic AhR Activation Syndrome\" (SAAS) consisting of inflammation, thromboembolism, and fibrosis, culminating in multiple organ injuries, and death. Activation of AhRs by CoV may lead to diverse sets of phenotypic disease pictures depending on time after infection, overall state of health, hormonal balance, age, gender, comorbidities, but also diet and environmental factors modulating AhRs. We hypothesize that elimination of factors known to up-regulate AhRs, or implementation of measures known to down-regulate AhRs, should decrease severity of infection. Although therapies selectively down-regulating both AhR and IDO1 are currently lacking, medications in clinical use such as dexamethasone may down-regulate both AhR and IDO1 genes, as calcitriol/vitamin D3 may down-regulate the AhR gene, and tocopherol/vitamin E may down-regulate the IDO1 gene. Supplementation of calcitriol should therefore be subjected to epidemiological studies and tested in prospective trials for prevention of CoV infections, as should tocopherol, whereas dexamethasone could be tried in interventional trials. Because lack of physical exercise activates AhRs via the IDO1-kynurenine-AhR signaling pathway increasing risk of infection, physical exercise should be encouraged during quarantines and stay-at-home orders during pandemic outbreaks. Understanding which factors affect gene expression of both AhR and IDO1 may help in designing therapies to prevent and treat humans suffering from Covid-19.", "qid": 38, "docid": "mm38i1gg", "rank": 98, "score": 0.8554638624191284}, {"content": "Title: AhR and IDO1 in pathogenesis of Covid-19 and the \"Systemic AhR Activation Syndrome\" Translational review and therapeutic perspectives. Content: Covid-19 is the acute illness caused by SARS-CoV-2 with initial clinical symptoms such as cough, fever, malaise, headache, and anosmia. After entry into cells, corona viruses (CoV) activate aryl hydrocarbon receptors (AhRs) by an indoleamine 2,3-dioxygenase (IDO1)-independent mechanism, bypassing the IDO1-kynurenine-AhR pathway. The IDO1-kynurenine-AhR signaling pathway is used by multiple viral, microbial and parasitic pathogens to activate AhRs and to establish infections. AhRs enhance their own activity through an IDO1-AhR-IDO1 positive feedback loop prolonging activation induced by pathogens. Direct activation of AhRs by CoV induces immediate and simultaneous up-regulation of diverse AhR-dependent downstream effectors, and this, in turn, results in a \"Systemic AhR Activation Syndrome\" (SAAS) consisting of inflammation, thromboembolism, and fibrosis, culminating in multiple organ injuries, and death. Activation of AhRs by CoV may lead to diverse sets of phenotypic disease pictures depending on time after infection, overall state of health, hormonal balance, age, gender, comorbidities, but also diet and environmental factors modulating AhRs. We hypothesize that elimination of factors known to up-regulate AhRs, or implementation of measures known to down-regulate AhRs, should decrease severity of infection. Although therapies selectively down-regulating both AhR and IDO1 are currently lacking, medications in clinical use such as dexamethasone may down-regulate both AhR and IDO1 genes, as calcitriol/vitamin D3 may down-regulate the AhR gene, and tocopherol/vitamin E may down-regulate the IDO1 gene. Supplementation of calcitriol should therefore be subjected to epidemiological studies and tested in prospective trials for prevention of CoV infections, as should tocopherol, whereas dexamethasone could be tried in interventional trials. Because lack of physical exercise activates AhRs via the IDO1-kynurenine-AhR signaling pathway increasing risk of infection, physical exercise should be encouraged during quarantines and stay-at-home orders during pandemic outbreaks. Understanding which factors affect gene expression of both AhR and IDO1 may help in designing therapies to prevent and treat humans suffering from Covid-19.", "qid": 38, "docid": "kaefedl1", "rank": 99, "score": 0.8554638624191284}, {"content": "Title: Innate Immunity in Coronavirus Infection ;\u0432\u0440\u043e\u0436\u0434\u0435\u043d\u043d\u044b\u0439 \u0418\u043c\u043c\u0443\u043d\u0438\u0442\u0435\u0442 \u041f\u0440\u0438 \u041a\u043e\u0440\u043e\u043d\u0430\u0432\u0438\u0440\u0443\u0441\u043d\u043e\u0439 \u0418\u043d\u0444\u0435\u043a\u0446\u0438\u0438 Content: Coronaviruses (CoVs) comprise a polymorphic group of respiratory viruses causing acute inflammatory diseases in domestic and agricultural animals (chicken, pig, buffalo, cat, dog) Until recently, this infection in humans was mainly observed during the autumn-winter period and characterized by a mild, often asymptomatic, course The situation changed dramatically in 2003, when SARS outbreak caused by pathogenic CoV (SARS-CoV) was recorded in China A decade later, a new CoV outbreak occurred in the form of the Middle East respiratory syndrome (MERS-CoV), whereas in December 2019, SARS-CoV-2 (COVID-19) cases were recorded, which transformed within the first months of 2020 into the pandemic In all three cases, CoV disease led to severe bronchopulmonary lesions, varying from dry, debilitating cough to acute respiratory distress syndrome (ARDS) At the same time, multiple changes in innate immunity were noted most often manifested as a pronounced inflammatory reaction in the lower respiratory tract, featured by damaged type II pneumocytes, apoptosis, hyalinization of alveolar membranes, focal or generalized pulmonary edema Destructive processes in the respiratory tract were accompanied by migration of monocytes/macrophages and granulocyte neutrophils to the inflammatory focus Such events were accompanied by production of pro-inflammatory cytokines, which magnitude could ascend up to a cytokine storm SARS-CoV is characterized by symptoms of secondary immunosuppression, manifested by the late onset of interferon production and activation of NLRP3 inflammasomes \u00e2\u20ac\u201c the key inflammatory factor The reason for such reaction may be accounted for by CoV arsenal containing extensive set of structural and inflammatory proteins exerting pro-inflammatory and immunosuppressive properties Delayed IFN production allowed CoV to replicate actively and freely, and when type I IFN synthesis was eventually triggered, its activity was detrimental and accompanied by an aggravated infection course Thus, SARS can surely be referred to immune-dependent infections with a marked immunopathological component The purpose of this review was to describe some mechanisms underlying formation of innate immune response to infection caused by pathogenic coronaviruses SARS-CoV, MERS-CoV and SARS-CoV-2 (COVID-19) 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"qid": 38, "docid": "t1gxo4mw", "rank": 100, "score": 0.8554041385650635}]}
{"query": "What is the mechanism of cytokine storm syndrome on the COVID-19?", "hits": [{"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": 1, "score": 0.9210485219955444}, {"content": "Title: Cytokine Storm in COVID19: A Neural Hypothesis Content: Cytokine storm in COVID-19 is characterized by an excessive inflammatory response to SARS-CoV-2 that is caused by a dysregulated immune system of the host. We are proposing a new hypothesis that SARS-CoV-2 mediated inflammation of nucleus tractus solitarius (NTS) may be responsible for the cytokine storm in COVID 19. The inflamed NTS may result in a dysregulated cholinergic anti-inflammatory pathway and hypothalamic-pituitary-adrenal axis.", "qid": 39, "docid": "ynrvowoc", "rank": 2, "score": 0.9202277660369873}, {"content": "Title: Cytokine Storm in COVID19: A Neural Hypothesis. Content: Cytokine storm in COVID-19 is characterized by an excessive inflammatory response to SARS-CoV-2 that is caused by a dysregulated immune system of the host. We are proposing a new hypothesis that SARS-CoV-2 mediated inflammation of nucleus tractus solitarius (NTS) may be responsible for the cytokine storm in COVID 19. The inflamed NTS may result in a dysregulated cholinergic anti-inflammatory pathway and hypothalamic-pituitary-adrenal axis.", "qid": 39, "docid": "e58nciq3", "rank": 3, "score": 0.9202277660369873}, {"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": 4, "score": 0.9188416004180908}, {"content": "Title: Tocilizumab Administration in Patients with SARS\u2010CoV\u20102 Infection: Subcutaneous Injection versus Intravenous Infusion Content: Recent studies have revealed that cytokine storm syndrome, which is caused by the activation of inflammatory cytokines, is a likely underlying pathophysiology in patients with severe COVID\u201019 that has been associated with a high mortality rate(1). This article is protected by copyright. All rights reserved.", "qid": 39, "docid": "me4tdzvl", "rank": 5, "score": 0.9056355953216553}, {"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": 6, "score": 0.9007997512817383}, {"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": 7, "score": 0.8997598886489868}, {"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": 8, "score": 0.897402286529541}, {"content": "Title: Alternative management of Covid-19 infection Content: Cytokine storm is a life-threatening complication of Covid-19 infection. Excessive cytokines are the products of hyperactive immune inflammatory response mounted by the host against the virus. There is no agreed treatment for cytokine storm. Three therapeutic agents with proven immune-modulatory properties in regular use in a wide range of inflammatory disorders (high dose intravenous immunoglobulin, Rituximab and thalidomide) are proposed for the treatment of cytokine storm. Safety and efficacy of the proposed treatment should be assessed by randomised controlled clinical trials. The use of the proposed treatment is expected to reduce the mortality rate and alter the overall management of the pandemic.", "qid": 39, "docid": "1hfnv35j", "rank": 9, "score": 0.8964883089065552}, {"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": 10, "score": 0.8958428502082825}, {"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": 11, "score": 0.8958428502082825}, {"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": 12, "score": 0.8932383060455322}, {"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": 0.8919503688812256}, {"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": 14, "score": 0.888263463973999}, {"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": 15, "score": 0.8878978490829468}, {"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": 39, "docid": "2skjqwis", "rank": 16, "score": 0.885660707950592}, {"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": 39, "docid": "dd836h0r", "rank": 17, "score": 0.8856606483459473}, {"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": 18, "score": 0.8855900764465332}, {"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": 19, "score": 0.8852947950363159}, {"content": "Title: Innate Immune Signaling and Proteolytic Pathways in the Resolution or Exacerbation of SARS-CoV-2 in Covid-19: Key Therapeutic Targets? Content: COVID-19 is caused by the Severe Acute Respiratory Syndrome (SARS) coronavirus (Cov)-2, an enveloped virus with a positive-polarity, single-stranded RNA genome. The initial outbreak of the pandemic began in December 2019, and it is affecting the human health of the global community. In common with previous pandemics (Influenza H1N1 and SARS-CoV) and the epidemics of Middle east respiratory syndrome (MERS)-CoV, CoVs target bronchial and alveolar epithelial cells. Virus protein ligands (e.g., haemagglutinin or trimeric spike glycoprotein for Influenza and CoV, respectively) interact with cellular receptors, such as (depending on the virus) either sialic acids, Dipeptidyl peptidase 4 (DPP4), or angiotensin-converting enzyme 2 (ACE2). Host proteases, e.g., cathepsins, furin, or members of the type II transmembrane serine proteases (TTSP) family, such as Transmembrane protease serine 2 (TMPRSS2), are involved in virus entry by proteolytically activating virus ligands. Also involved are Toll Like Receptor (TLR) family members, which upregulate anti-viral and pro-inflammatory mediators [interleukin (IL)-6 and IL-8 and type I and type III Interferons among others], through the activation of Nuclear Factor (NF)-kB. When these events (virus cellular entry and innate immune responses) are uncontrolled, a deleterious systemic response is sometimes encountered in infected patients, leading to the well-described \"cytokine storm\" and an ensuing multiple organ failure promoted by a downregulation of dendritic cell, macrophage, and T-cell function. We aim to describe how the lung and systemic host innate immune responses affect survival either positively, through downregulating initial viral load, or negatively, by triggering uncontrolled inflammation. An emphasis will be put on host cellular signaling pathways and proteases involved with a view on tackling these therapeutically.", "qid": 39, "docid": "ls88uo78", "rank": 20, "score": 0.8844749927520752}, {"content": "Title: Innate Immune Signaling and Proteolytic Pathways in the Resolution or Exacerbation of SARS-CoV-2 in Covid-19: Key Therapeutic Targets? Content: COVID-19 is caused by the Severe Acute Respiratory Syndrome (SARS) coronavirus (Cov)-2, an enveloped virus with a positive-polarity, single-stranded RNA genome. The initial outbreak of the pandemic began in December 2019, and it is affecting the human health of the global community. In common with previous pandemics (Influenza H1N1 and SARS-CoV) and the epidemics of Middle east respiratory syndrome (MERS)-CoV, CoVs target bronchial and alveolar epithelial cells. Virus protein ligands (e.g., haemagglutinin or trimeric spike glycoprotein for Influenza and CoV, respectively) interact with cellular receptors, such as (depending on the virus) either sialic acids, Dipeptidyl peptidase 4 (DPP4), or angiotensin-converting enzyme 2 (ACE2). Host proteases, e.g., cathepsins, furin, or members of the type II transmembrane serine proteases (TTSP) family, such as Transmembrane protease serine 2 (TMPRSS2), are involved in virus entry by proteolytically activating virus ligands. Also involved are Toll Like Receptor (TLR) family members, which upregulate anti-viral and pro-inflammatory mediators [interleukin (IL)-6 and IL-8 and type I and type III Interferons among others], through the activation of Nuclear Factor (NF)-kB. When these events (virus cellular entry and innate immune responses) are uncontrolled, a deleterious systemic response is sometimes encountered in infected patients, leading to the well-described \u201ccytokine storm\u201d and an ensuing multiple organ failure promoted by a downregulation of dendritic cell, macrophage, and T-cell function. We aim to describe how the lung and systemic host innate immune responses affect survival either positively, through downregulating initial viral load, or negatively, by triggering uncontrolled inflammation. An emphasis will be put on host cellular signaling pathways and proteases involved with a view on tackling these therapeutically.", "qid": 39, "docid": "5gz2dotn", "rank": 21, "score": 0.8843450546264648}, {"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": 22, "score": 0.8841269612312317}, {"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": 39, "docid": "be38b41o", "rank": 23, "score": 0.8837714195251465}, {"content": "Title: Role of inflammatory markers in corona virus disease (COVID-19) patients: A review. Content: IMPACT STATEMENT In late 2019, a novel virus called SARS-CoV-2, expanded globally from Wuhan, China and was declared a pandemic on 11 March 2020 by the WHO. The mechanism of virus entry inside the host cell depends upon the cellular proteases including cathepsins, HAT, and TMPRSS2, which splits up the spike protein and causes further penetration. MERS coronavirus uses DPP4, while coronavirus HCoV-NL63 and SARS-CoV and SARS-CoV-2 employ ACE-2 as the key receptor. Cytokine storm syndrome was analyzed in critically ill nCOVID-19 patients and it is presented with high inflammatory mediators, systemic inflammation, and multiple organ failure. Among various inflammatory mediators, the level of interleukins (IL-2, IL-7, IL-10), G-CSF, MIP1A, MCP1, and TNF-\u03b1 was reported to be higher in critically ill patients. Understanding this molecular mechanism of ILs, T cells, and dendritic cells will be helpful to design immunotherapy and novel drugs for the treatment of nCOVID-19 infection.", "qid": 39, "docid": "8gzcrrml", "rank": 24, "score": 0.8833584785461426}, {"content": "Title: Immune environment modulation in pneumonia patients caused by coronavirus: SARS-CoV, MERS-CoV and SARS-CoV-2 Content: Currently, we are on a global pandemic of Coronavirus disease-2019 (COVID-19) which causes fever, dry cough, fatigue and acute respiratory distress syndrome (ARDS) that may ultimately lead to the death of the infected. Current researches on COVID-19 continue to highlight the necessity for further understanding the virus-host synergies. In this study, we have highlighted the key cytokines induced by coronavirus infections. We have demonstrated that genes coding interleukins (Il-1&#945;, Il-1\u00df, Il-6, Il-10), chemokine (Ccl2, Ccl3, Ccl5, Ccl10), and interferon (Ifn-&#945;2, Ifn-\u00df1, Ifn2) upsurge significantly which in line with the elevated infiltration of T cells, NK cells and monocytes in SARS-Cov treated group at 24 hours. Also, interleukins (IL-6, IL-23&#945;, IL-10, IL-7, IL-1&#945;, IL-1\u00df) and interferon (IFN-&#945;2, IFN2, IFN-\u00ce\u00b3) have increased dramatically in MERS-Cov at 24 hours. A similar cytokine profile showed the cytokine storm served a critical role in the infection process. Subsequent investigation of 463 patients with COVID-19 disease revealed the decreased amount of total lymphocytes, CD3+, CD4+, and CD8+ T lymphocytes in the severe type patients which indicated COVID-19 can impose hard blows on human lymphocyte resulting in lethal pneumonia. Thus, taking control of changes in immune factors could be critical in the treatment of COVID-19.", "qid": 39, "docid": "xrcvyu87", "rank": 25, "score": 0.8829467296600342}, {"content": "Title: Role of inflammatory markers in corona virus disease (COVID-19) patients: A review Content: IMPACT STATEMENT: In late 2019, a novel virus called SARS-CoV-2, expanded globally from Wuhan, China and was declared a pandemic on 11 March 2020 by the WHO. The mechanism of virus entry inside the host cell depends upon the cellular proteases including cathepsins, HAT, and TMPRSS2, which splits up the spike protein and causes further penetration. MERS coronavirus uses DPP4, while coronavirus HCoV-NL63 and SARS-CoV and SARS-CoV-2 employ ACE-2 as the key receptor. Cytokine storm syndrome was analyzed in critically ill nCOVID-19 patients and it is presented with high inflammatory mediators, systemic inflammation, and multiple organ failure. Among various inflammatory mediators, the level of interleukins (IL-2, IL-7, IL-10), G-CSF, MIP1A, MCP1, and TNF-&#945; was reported to be higher in critically ill patients. Understanding this molecular mechanism of ILs, T cells, and dendritic cells will be helpful to design immunotherapy and novel drugs for the treatment of nCOVID-19 infection.", "qid": 39, "docid": "qk5mrmrd", "rank": 26, "score": 0.8828954696655273}, {"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": 27, "score": 0.8824521899223328}, {"content": "Title: The Cytokine storm in COVID-19: An overview of the involvement of the chemokine/chemokine-receptor system Content: In 2019-2020 a new coronavirus named SARS-CoV-2 was identified as the causative agent of a several acute respiratory infection named COVID-19, which is causing a worldwide pandemic. There are still many unresolved questions regarding the pathogenesis of this disease and especially the reasons underlying the extremely different clinical course, ranging from asymptomatic forms to severe manifestations, including the Acute Respiratory Distress Syndrome (ARDS). SARS-CoV-2 showed phylogenetic similarities to both SARS-CoV and MERS-CoV viruses, and some of the clinical features are shared between COVID-19 and previously identified beta-coronavirus infections. Available evidence indicate that the so called \u201ccytokine storm\u201d an uncontrolled over-production of soluble markers of inflammation which, in turn, sustain an aberrant systemic inflammatory response, is a major responsible for the occurrence of ARDS. Chemokines are low molecular weight proteins with powerful chemoattractant activity which play a role in the immune cell recruitment during inflammation. This review will be aimed at providing an overview of the current knowledge on the involvement of the chemokine/chemokine-receptor system in the cytokine storm related to SARS-CoV-2 infection. Basic and clinical evidences obtained from previous SARS and MERS epidemics and available data from COVID-19 will be taken into account.", "qid": 39, "docid": "ex9nh1yi", "rank": 28, "score": 0.8818956613540649}, {"content": "Title: The cytokine storm in COVID-19: An overview of the involvement of the chemokine/chemokine-receptor system Content: In 2019-2020 a new coronavirus named SARS-CoV-2 was identified as the causative agent of a several acute respiratory infection named COVID-19, which is causing a worldwide pandemic. There are still many unresolved questions regarding the pathogenesis of this disease and especially the reasons underlying the extremely different clinical course, ranging from asymptomatic forms to severe manifestations, including the Acute Respiratory Distress Syndrome (ARDS). SARS-CoV-2 showed phylogenetic similarities to both SARS-CoV and MERS-CoV viruses, and some of the clinical features are shared between COVID-19 and previously identified beta-coronavirus infections. Available evidence indicate that the so called \"cytokine storm\" an uncontrolled over-production of soluble markers of inflammation which, in turn, sustain an aberrant systemic inflammatory response, is a major responsible for the occurrence of ARDS. Chemokines are low molecular weight proteins with powerful chemoattractant activity which play a role in the immune cell recruitment during inflammation. This review will be aimed at providing an overview of the current knowledge on the involvement of the chemokine/chemokine-receptor system in the cytokine storm related to SARS-CoV-2 infection. Basic and clinical evidences obtained from previous SARS and MERS epidemics and available data from COVID-19 will be taken into account.", "qid": 39, "docid": "9ch0wti7", "rank": 29, "score": 0.8810638785362244}, {"content": "Title: Immune environment modulation in pneumonia patients caused by coronavirus: SARS-CoV, MERS-CoV and SARS-CoV-2 Content: Currently, we are on a global pandemic of Coronavirus disease-2019 (COVID-19) which causes fever, dry cough, fatigue and acute respiratory distress syndrome (ARDS) that may ultimately lead to the death of the infected. Current researches on COVID-19 continue to highlight the necessity for further understanding the virus-host synergies. In this study, we have highlighted the key cytokines induced by coronavirus infections. We have demonstrated that genes coding interleukins (Il-1\u03b1, Il-1\u03b2, Il-6, Il-10), chemokine (Ccl2, Ccl3, Ccl5, Ccl10), and interferon (Ifn-\u03b12, Ifn-\u03b21, Ifn2) upsurge significantly which in line with the elevated infiltration of T cells, NK cells and monocytes in SARS-Cov treated group at 24 hours. Also, interleukins (IL-6, IL-23\u03b1, IL-10, IL-7, IL-1\u03b1, IL-1\u03b2) and interferon (IFN-\u03b12, IFN2, IFN-\u03b3) have increased dramatically in MERS-Cov at 24 hours. A similar cytokine profile showed the cytokine storm served a critical role in the infection process. Subsequent investigation of 463 patients with COVID-19 disease revealed the decreased amount of total lymphocytes, CD3+, CD4+, and CD8+ T lymphocytes in the severe type patients which indicated COVID-19 can impose hard blows on human lymphocyte resulting in lethal pneumonia. Thus, taking control of changes in immune factors could be critical in the treatment of COVID-19.", "qid": 39, "docid": "2w5ws14b", "rank": 30, "score": 0.8802628517150879}, {"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": 31, "score": 0.8778613209724426}, {"content": "Title: Biochemical indicators of coronavirus disease 2019 exacerbation and the clinical implications Content: Coronavirus Disease 2019 (COVID-19) has sparked a global pandemic, affecting more than 4 million people worldwide. The severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) can cause acute lung injury (ALI) and even acute respiratory distress syndrome (ARDS); with a fatality of 7.0 %. Accumulating evidence suggested that the progression of COVID-19 is associated with lymphopenia and excessive inflammation, and a subset of severe cases might exhibit cytokine storm triggered by secondary hemophagocytic lymphohistiocytosis (sHLH). Furthermore, secondary bacterial infection may contribute to the exacerbation of COVID-19. We recommend using both IL-10 and IL-6 as the indicators of cytokine storm, and monitoring the elevation of procalcitonin (PCT) as an alert for initiating antibacterial agents. Understanding the dynamic progression of SARS-CoV-2 infection is crucial to determine an effective treatment strategy to reduce the rising mortality of this global pandemic.", "qid": 39, "docid": "j25rvp1i", "rank": 32, "score": 0.8771295547485352}, {"content": "Title: Immune response in COVID-19: addressing a pharmacological challenge by targeting pathways triggered by SARS-CoV-2 Content: To date, no vaccines or effective drugs have been approved to prevent or treat COVID-19 and the current standard care relies on supportive treatments. Therefore, based on the fast and global spread of the virus, urgent investigations are warranted in order to develop preventive and therapeutic drugs. In this regard, treatments addressing the immunopathology of SARS-CoV-2 infection have become a major focus. Notably, while a rapid and well-coordinated immune response represents the first line of defense against viral infection, excessive inflammatory innate response and impaired adaptive host immune defense may lead to tissue damage both at the site of virus entry and at systemic level. Several studies highlight relevant changes occurring both in innate and adaptive immune system in COVID-19 patients. In particular, the massive cytokine and chemokine release, the so-called \u201ccytokine storm\u201d, clearly reflects a widespread uncontrolled dysregulation of the host immune defense. Although the prospective of counteracting cytokine storm is compelling, a major limitation relies on the limited understanding of the immune signaling pathways triggered by SARS-CoV-2 infection. The identification of signaling pathways altered during viral infections may help to unravel the most relevant molecular cascades implicated in biological processes mediating viral infections and to unveil key molecular players that may be targeted. Thus, given the key role of the immune system in COVID-19, a deeper understanding of the mechanism behind the immune dysregulation might give us clues for the clinical management of the severe cases and for preventing the transition from mild to severe stages.", "qid": 39, "docid": "hedpur93", "rank": 33, "score": 0.875821590423584}, {"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": 34, "score": 0.8747032880783081}, {"content": "Title: Immune response in COVID-19: addressing a pharmacological challenge by targeting pathways triggered by SARS-CoV-2 Content: To date, no vaccines or effective drugs have been approved to prevent or treat COVID-19 and the current standard care relies on supportive treatments. Therefore, based on the fast and global spread of the virus, urgent investigations are warranted in order to develop preventive and therapeutic drugs. In this regard, treatments addressing the immunopathology of SARS-CoV-2 infection have become a major focus. Notably, while a rapid and well-coordinated immune response represents the first line of defense against viral infection, excessive inflammatory innate response and impaired adaptive host immune defense may lead to tissue damage both at the site of virus entry and at systemic level. Several studies highlight relevant changes occurring both in innate and adaptive immune system in COVID-19 patients. In particular, the massive cytokine and chemokine release, the so-called \"cytokine storm\", clearly reflects a widespread uncontrolled dysregulation of the host immune defense. Although the prospective of counteracting cytokine storm is compelling, a major limitation relies on the limited understanding of the immune signaling pathways triggered by SARS-CoV-2 infection. The identification of signaling pathways altered during viral infections may help to unravel the most relevant molecular cascades implicated in biological processes mediating viral infections and to unveil key molecular players that may be targeted. Thus, given the key role of the immune system in COVID-19, a deeper understanding of the mechanism behind the immune dysregulation might give us clues for the clinical management of the severe cases and for preventing the transition from mild to severe stages.", "qid": 39, "docid": "lv7kt128", "rank": 35, "score": 0.8742598295211792}, {"content": "Title: Eficacia de los pulsos de corticoides en pacientes con s\u00edndrome de liberaci\u00f3n de citocinas inducido por infecci\u00f3n por SARS-CoV-2./ Eficacia de los pulsos de corticoides en pacientes con s\u00edndrome de liberaci\u00f3n de citocinas inducido por infecci\u00f3n por SARS-CoV-2./ Effectiveness of corticoid pulses in patients with cytokine storm syndrome induced by SARS-CoV-2 infection Content: INTRODUCTION: Cytokine storm syndrome (CSS) is a serious complication of COVID-19 patients. Treatment is tocilizumab. The use of glucocorticoids (GC) is controversial. In other very similar CSS, such as macrophage activation syndrome (MAS) and hemophagocytic syndrome (HFS), the main treatment are corticosteroids. Our objective is to evaluate the efficacy of GC in the CSS by COVID-19. PATIENTS: We included 92 patients with CSS associated to COVID-19 who received GC, GC, and tocilizumab and only tocilizumab. We determine CSS markers. We evaluated mortality, intubation, and a combined variable. RESULTS: In all cases the percentages of events were lower in the group of patients with GC was administered. The hazard ratio of the final variables with GC versus the group in which only tocilizumab was administered was lower as CGs were considered, with statistical significance for survival. DISCUSSION: The early use of GC pulses could control SLC, with a lower requirement to use tocilizumab and a decrease in events such as intubation and death.", "qid": 39, "docid": "ky6115jm", "rank": 36, "score": 0.8741956949234009}, {"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": 37, "score": 0.8736571669578552}, {"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": 38, "score": 0.8736571669578552}, {"content": "Title: COVID-19, immune system response, hyperinflammation and repurposing antirheumatic drugs Content: In the Wuhan Province of China, in December 2019, the novel coronavirus 2019 (COVID-19) has caused a severe involvement of the lower respiratory tract leading to an acute respiratory syndrome. Subsequently, coronavirus 2 (SARS-CoV-2) provoked a pandemic which is considered a life-threatening disease. The SARS-CoV-2, a family member of betacoronaviruses, possesses single-stranded positive-sense RNA with typical structural proteins, involving the envelope, membrane, nucleocapsid and spike proteins that are responsible for the viral infectivity, and nonstructural proteins. The effectual host immune response including innate and adaptive immunity against SARS-Cov-2 seems crucial to control and resolve the viral infection. However, the severity and outcome of the COVID-19 might be associated with the excessive production of proinflammatory cytokines \u201ccytokine storm\u201d leading to an acute respiratory distress syndrome. Regretfully, the exact pathophysiology and treatment, especially for the severe COVID-19, is still uncertain. The results of preliminary studies have shown that immune-modulatory or immune-suppressive treatments such as hydroxychloroquine, interleukin (IL)-6 and IL-1 antagonists, commonly used in rheumatology, might be considered as treatment choices for COVID-19, particularly in severe disease. In this review, to gain better information about appropriate anti-inflammatory treatments, mostly used in rheumatology for COVID-19, we have focused the attention on the structural features of SARS-CoV-2, the host immune response against SARS-CoV-2 and its association with the cytokine storm.", "qid": 39, "docid": "7ivw72l0", "rank": 39, "score": 0.873427152633667}, {"content": "Title: De Los Pulsos De Corticoides En Pacientes Con S\u00edndrome De Liberaci\u00f3n De Citoquinas Inducido Por Infecci\u00f3n Por Sars-Cov-2 Content: Abstract Introduction: cytokine storm syndrome (CSS) is a serious complication of COVID-19 patients. Treatment is tocilizumab. The use of glucocorticoids (GC) is controversial. In other very similar CSS, such as macrophage activation syndrome (MAS) and hemophagocytic syndrome (HFS), the main treatment are corticosteroids. Our objective is to evaluate the efficacy of GC in the CSS by COVID-19. Patients: we included 92 patients with CSS associated to COVID-19 who received GC, GC, and tocilizumab and only tocilizumab. We determine CSS markers. We evaluated mortality, intubation, and a combined variable. Results: in all cases the percentages of events were lower in the group of patients with GC was administered. The hazard ratio of the final variables with GC versus the group in which only tocilizumab was administered was lower as CGs were considered, with statistical significance for survival. Discussion: the early use of GC pulses could control SLC, with a lower requirement to use tocilizumab and a decrease in events such as intubation and death.", "qid": 39, "docid": "kcdb7nvs", "rank": 40, "score": 0.8734105229377747}, {"content": "Title: Eficacia de los pulsos de corticoides en pacientes con s\u00edndrome de liberaci\u00f3n de citocinas inducido por infecci\u00f3n por SARS-CoV-2 Content: INTRODUCTION: Cytokine storm syndrome (CSS) is a serious complication of COVID-19 patients Treatment is tocilizumab The use of glucocorticoids (GC) is controversial In other very similar CSS, such as macrophage activation syndrome (MAS) and hemophagocytic syndrome (HFS), the main treatment are corticosteroids Our objective is to evaluate the efficacy of GC in the CSS by COVID-19 PATIENTS: We included 92 patients with CSS associated to COVID-19 who received GC, GC, and tocilizumab and only tocilizumab We determine CSS markers We evaluated mortality, intubation, and a combined variable RESULTS: In all cases the percentages of events were lower in the group of patients with GC was administered The hazard ratio of the final variables with GC versus the group in which only tocilizumab was administered was lower as CGs were considered, with statistical significance for survival DISCUSSION: The early use of GC pulses could control SLC, with a lower requirement to use tocilizumab and a decrease in events such as intubation and death", "qid": 39, "docid": "teokh13r", "rank": 41, "score": 0.8733029365539551}, {"content": "Title: COVID 19: a clue from innate immunity Content: The recent COVID-19 pandemic has had a significant impact on our lives and has rapidly expanded to reach more than 4 million cases worldwide by May 2020. These cases are characterized by extreme variability, from a mild or asymptomatic form lasting for a few days up to severe forms of interstitial pneumonia that may require ventilatory therapy and can lead to patient death. Several hypotheses have been drawn up to understand the role of the interaction between the infectious agent and the immune system in the development of the disease and the most severe forms; the role of the cytokine storm seems important. Innate immunity, as one of the first elements of guest interaction with different infectious agents, could play an important role in the development of the cytokine storm and be responsible for boosting more severe forms. Therefore, it seems important to study also this important arm of the immune system to adequately understand the pathogenesis of the disease. Research on this topic is also needed to develop therapeutic strategies for treatment of this disease.", "qid": 39, "docid": "n21y5kps", "rank": 42, "score": 0.8727570176124573}, {"content": "Title: COVID 19: a clue from innate immunity Content: The recent COVID-19 pandemic has had a significant impact on our lives and has rapidly expanded to reach more than 4 million cases worldwide by May 2020. These cases are characterized by extreme variability, from a mild or asymptomatic form lasting for a few days up to severe forms of interstitial pneumonia that may require ventilatory therapy and can lead to patient death.Several hypotheses have been drawn up to understand the role of the interaction between the infectious agent and the immune system in the development of the disease and the most severe forms; the role of the cytokine storm seems important.Innate immunity, as one of the first elements of guest interaction with different infectious agents, could play an important role in the development of the cytokine storm and be responsible for boosting more severe forms. Therefore, it seems important to study also this important arm of the immune system to adequately understand the pathogenesis of the disease. Research on this topic is also needed to develop therapeutic strategies for treatment of this disease.", "qid": 39, "docid": "911ozh90", "rank": 43, "score": 0.8727570176124573}, {"content": "Title: Effectiveness of corticoid pulses in patients with cytokine storm syndrome induced by SARS-CoV-2 infection Content: Abstract Introduction Cytokine storm syndrome (CSS) is a serious complication of COVID-19 patients. Treatment is tocilizumab. The use of glucocorticoids (GC) is controversial. In other very similar CSS, such as macrophage activation syndrome (MAS) and hemophagocytic syndrome (HFS), the main treatment are corticosteroids. Our objective is to evaluate the efficacy of GC in the CSS by COVID-19. Patients We included 92 patients with CSS associated to COVID-19 who received GC, GC, and tocilizumab and only tocilizumab. We determine CSS markers. We evaluated mortality, intubation, and a combined variable. Results In all cases the percentages of events were lower in the group of patients with GC was administered. The hazard ratio of the final variables with GC versus the group in which only tocilizumab was administered was lower as CGs were considered, with statistical significance for survival. Discussion The early use of GC pulses could control SLC, with a lower requirement to use tocilizumab and a decrease in events such as intubation and death.", "qid": 39, "docid": "bn6j30t4", "rank": 44, "score": 0.8720317482948303}, {"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": 45, "score": 0.8717924356460571}, {"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": 46, "score": 0.870861828327179}, {"content": "Title: Can we use interleukin-6 (IL-6) blockade for coronavirus disease 2019 (COVID-19)-induced cytokine release syndrome (CRS)? Content: The emergent outbreak of coronavirus disease 2019 (COVID-19) has caused a global pandemic. Acute respiratory distress syndrome (ARDS) and multiorgan dysfunction are among the leading causes of death in critically ill patients with COVID-19. The elevated inflammatory cytokines suggest that a cytokine storm, also known as cytokine release syndrome (CRS), may play a major role in the pathology of COVID-19. However, the efficacy of corticosteroids, commonly utilized antiinflammatory agents, to treat COVID-19-induced CRS is controversial. There is an urgent need for novel therapies to treat COVID-19-induced CRS. Here, we discuss the pathogenesis of severe acute respiratory syndrome (SARS)-induced CRS, compare the CRS in COVID-19 with that in SARS and Middle East respiratory syndrome (MERS), and summarize the existing therapies for CRS. We propose to utilize interleukin-6 (IL-6) blockade to manage COVID-19-induced CRS and discuss several factors that should be taken into consideration for its clinical application.", "qid": 39, "docid": "uzfpv5rd", "rank": 47, "score": 0.8704831600189209}, {"content": "Title: COVID-19, immune system response, hyperinflammation and repurposing antirheumatic drugs Content: In the Wuhan Province of China, in December 2019, the novel coronavirus 2019 (COVID-19) has caused a severe involvement of the lower respiratory tract leading to an acute respiratory syndrome. Subsequently, coronavirus 2 (SARS-CoV-2) provoked a pandemic which is considered a life-threatening disease. The SARS-CoV-2, a family member of betacoronaviruses, possesses single-stranded positive-sense RNA with typical structural proteins, involving the envelope, membrane, nucleocapsid and spike proteins that are responsible for the viral infectivity, and nonstructural proteins. The effectual host immune response including innate and adaptive immunity against SARS-Cov-2 seems crucial to control and resolve the viral infection. However, the severity and outcome of the COVID-19 might be associated with the excessive production of proinflammatory cytokines \"cytokine storm\" leading to an acute respiratory distress syndrome. Regretfully, the exact pathophysiology and treatment, especially for the severe COVID-19, is still uncertain. The results of preliminary studies have shown that immune-modulatory or immune-suppressive treatments such as hydroxychloroquine, interleukin (IL)-6 and IL-1 antagonists, commonly used in rheumatology, might be considered as treatment choices for COVID-19, particularly in severe disease. In this review, to gain better information about appropriate anti-inflammatory treatments, mostly used in rheumatology for COVID-19, we have focused the attention on the structural features of SARS-CoV-2, the host immune response against SARS-CoV-2 and its association with the cytokine storm.", "qid": 39, "docid": "zm8hpuer", "rank": 48, "score": 0.8701436519622803}, {"content": "Title: Exuberant elevation of IP-10, MCP-3 and IL-1ra during SARS-CoV-2 infection is associated with disease severity and fatal outcome Content: The outbreak of Coronavirus Disease 2019 (COVID-19) caused by the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) emerged in Wuhan, December 2019, and continuously poses a serious threat to public health. Our previous study has shown that cytokine storm occurred during SARS-CoV-2 infection, while the detailed role of cytokines in the disease severity and progression remained unclear due to the limited case number. In this study, we examined 48 cytokines in the plasma samples from 53 COVID-19 cases, among whom 34 were severe cases, and the others moderate. Results showed that 14 cytokines were significantly elevated upon admission in COVID-19 cases. Moreover, IP-10, MCP-3, and IL-1ra were significantly higher in severe cases, and highly associated with the PaO2/FaO2 and Murray score. Furthermore, the three cytokines were independent predictors for the progression of COVID-19, and the combination of IP-10, MCP-3 and IL-1ra showed the biggest area under the curve (AUC) of the receiver-operating characteristics (ROC) calculations. Serial detection of IP-10, MCP-3 and IL-1ra in 14 severe cases showed that the continuous high levels of these cytokines were associated with disease deterioration and fatal outcome. In conclusion, we report three cytokines that closely associated with disease severity and outcome of COVID-19. These findings add to our understanding of the immunopathologic mechanisms of SARS-CoV-2 infection, which suggested novel therapeutic targets and strategy.", "qid": 39, "docid": "c3dxfet9", "rank": 49, "score": 0.8692357540130615}, {"content": "Title: Absence of severe complications from SARS-CoV-2 infection in children with rheumatic diseases treated with biologic drugs Content: We read with interest the Editorial by Cron and Chatam (1) suggesting a cytokine storm syndrome (CSS) occurring in response to SARS-CoV-2 infection and, consequently, a possible role for targeted approaches to blocking inflammatory cytokines.", "qid": 39, "docid": "iffgnr51", "rank": 50, "score": 0.8683551549911499}, {"content": "Title: Absence of severe complications from SARS-CoV-2 infection in children with rheumatic diseases treated with biologic drugs. Content: We read with interest the Editorial by Cron and Chatam (1) suggesting a cytokine storm syndrome (CSS) occurring in response to SARS-CoV-2 infection and, consequently, a possible role for targeted approaches to blocking inflammatory cytokines.", "qid": 39, "docid": "rzfa4ozr", "rank": 51, "score": 0.8683551549911499}, {"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": 52, "score": 0.867851734161377}, {"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": 53, "score": 0.8677281141281128}, {"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": 54, "score": 0.8672593235969543}, {"content": "Title: Can we use interleukin-6 (IL-6) blockade for coronavirus disease 2019 (COVID-19)-induced cytokine release syndrome (CRS)? Content: Abstract The emergent outbreak of coronavirus disease 2019 (COVID-19) has caused a global pandemic. Acute respiratory distress syndrome (ARDS) and multiorgan dysfunction are among the leading causes of death in critically ill patients with COVID-19. The elevated inflammatory cytokines suggest that a cytokine storm, also known as cytokine release syndrome (CRS), may play a major role in the pathology of COVID-19. However, the efficacy of corticosteroids, commonly utilized antiinflammatory agents, to treat COVID-19-induced CRS is controversial. There is an urgent need for novel therapies to treat COVID-19-induced CRS. Here, we discuss the pathogenesis of severe acute respiratory syndrome (SARS)-induced CRS, compare the CRS in COVID-19 with that in SARS and Middle East respiratory syndrome (MERS), and summarize the existing therapies for CRS. We propose to utilize interleukin-6 (IL-6) blockade to manage COVID-19-induced CRS and discuss several factors that should be taken into consideration for its clinical application.", "qid": 39, "docid": "6gwnhkn4", "rank": 55, "score": 0.8672574758529663}, {"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": 39, "docid": "5ad4rm3y", "rank": 56, "score": 0.8667988777160645}, {"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": 39, "docid": "1zq0aels", "rank": 57, "score": 0.8667988777160645}, {"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": 58, "score": 0.8664539456367493}, {"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": 59, "score": 0.8659559488296509}, {"content": "Title: COVID-19: Pathogenesis, cytokine storm and therapeutic potential of interferons Content: ABSTRACT The outbreak of the novel SARS-CoV-2 (severe acute respiratory syndrome coronavirus 2) responsible for coronavirus disease 2019 (COVID-19) has developed into a major health hazard across the globe. The rapid escalation of the COVID-19 and the considerable associated illness leading to death has transformed it into a critical global public health issue. The current clinical investigation in patients with COVID-19 has showed strong upregulation of cytokine and interferon production after critical infection with SARS-CoV2- induced pneumonia. The current research suggests that few groups of patients with COVID-19 might have a cytokine storm syndrome. Thus, identification and treatment of hyperinflammation using existing, approved therapies with proven safety profiles to address the immediate need to reduce the rising mortality. To date, no specific therapeutic drug or vaccine has been discovered to treat this COVID-19. Intensive research is in progress to identify a promising drug therapy. Hence, several options were proposed to control this fast-emerging pandemic, including antiviral drugs, vaccines, small-molecules, monoclonal antibodies, oligonucleotides, peptides, and interferons (IFNs).", "qid": 39, "docid": "3g06zxmx", "rank": 60, "score": 0.865809440612793}, {"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": 39, "docid": "ot5v8n0c", "rank": 61, "score": 0.8656905889511108}, {"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": 62, "score": 0.8656254410743713}, {"content": "Title: Induction of pro-inflammatory cytokines (IL-1 and IL-6) and lung inflammation by COVID-19: anti-inflammatory strategies Content: COVID-19 (coronavirus disease-19) involves humans as well as animals and may cause serious damage to the respiratory tract including the lung This pathogenic virus has been identified in swabs performed on the throat and nose of patients who suffer from or are suspected of the disease When COVID-19 infect the upper and lower respiratory tract it can cause mild or highly acute respiratory syndrome with consequent release of pro-inflammatory cytokines, including interleukin (IL)-1b and IL-6 The binding of COVID-19 to the Toll Like Receptor (TLR) causes the release of pro-IL-1b which is cleaved by caspase-1, followed by inflammasome activation and production of active mature IL-1b which is a mediator of lung inflammation, fever and fibrosis Suppression of pro-inflammatory IL-1 family members and IL-6 have been shown to have a therapeutic effect in many inflammatory diseases, including viral infections Cytokine IL-37 has the ability to suppress innate and acquired immune response and also has the capacity to inhibit inflammation by acting on IL-18Ra receptor IL-37 performs its immunosuppressive activity by acting on mTOR and increasing the adenosine monophosphate (AMP) kinase This cytokine inhibits class II histocompatibility complex (MHC) molecules and inflammation in inflammatory diseases by suppressing MyD88 and subsequently IL-1\u03b2, IL-6, TNF and CCL2 The suppression of IL-1b by IL-37 in inflammatory state induced by COVID-19 can have a new therapeutic effect previously unknown Another inhibitory cytokine is IL-38, the newest cytokine of the IL-1 family members, produced by several immune cells including B cells and macrophages IL-38 is also a suppressor cytokine which inhibits IL-1b and other pro-inflammatory IL-family members IL-38 is a potential therapeutic cytokine which inhibits inflammation in viral infections including that caused by COVID-19, providing a new relevant strategy", "qid": 39, "docid": "4gze6w35", "rank": 63, "score": 0.8651856780052185}, {"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": 64, "score": 0.865090548992157}, {"content": "Title: [Study on treatment of \"cytokine storm\" by anti-2019-nCoV prescriptions based on arachidonic acid metabolic pathway]. Content: Since the outbreak of 2019-nCoV, the epidemic has developed rapidly and the situation is grim. LANCET figured out that the 2019-nCoV is closely related to \"cytokine storm\". \"Cytokine storm\" is an excessive immune response of the body to external stimuli such as viruses and bacteria. As the virus attacking the body, it stimulates the secretion of a large number of inflammatory factors: interleukin(IL), interferon(IFN), C-X-C motif chemokine(CXCL) and so on, which lead to cytokine cascade reaction. With the exudation of inflammatory factors, cytokines increase abnormally in tissues and organs, interfering with the immune system, causing excessive immune response of the body, resulting in diffuse damage of lung cells, pulmonary fibrosis, and multiple organ damage, even death. Arachidonic acid(AA) metabolic pathway is principally used to synthesize inflammatory cytokines, such as monocyte chemotactic protein 1(MCP-1), tumor necrosis factor(TNF), IL, IFN, etc., which is closely related to the occurrence, development and regression of inflammation. Therefore, the inhibition of AA metabolism pathway is benefit for inhibiting the release of inflammatory factors in the body and alleviating the \"cytokine storm\". Based on the pharmacophore models of the targets on AA metabolic pathway, the traditional Chinese medicine database 2009(TCMD 2009) was screened. The potential herbs were ranked by the number of hit molecules, which were scored by pharmacophore fit value. In the end, we obtained the potential active prescriptions on \"cytokine storm\" according to the potential herbs in the \"National novel coronavirus pneumonia diagnosis and treatment plan(trial version sixth)\". The results showed that the hit components with the inhibitory effect on AA were magnolignan \u2160, lonicerin and physcion-8-O-\u03b2-D-glucopy-ranoside, which mostly extracted from Magnoliae Officinalis Cortex, Zingiberis Rhizoma Recens, Lonicerae Japonicae Flos, Rhei Radix et Rhizoma, Salviae Miltiorrhizae Radix et Rhizoma, Scutellariae Radix, Gardeniae Fructus, Ginseng Radix et Rhizoma, Arctii Fructus, Dryopteridis Crassirhizomatis Rhizoma, Paeoniaeradix Rubra, Dioscoreae Rhizoma. Finally the anti-2019-nCoV prescriptions were analyzed to obtain the potential active prescriptions on AA metabolic pathway, Huoxiang Zhengqi Capsules, Jinhua Qinggan Granules, Lianhua Qingwen Capsules, Qingfei Paidu Decoction, Xuebijing Injection, Reduning Injection and Tanreqing Injection were found that may prevent 2019-nCoV via regulate cytokines. This study intends to provide reference for clinical use of traditional Chinese medicine to resist new coronavirus.", "qid": 39, "docid": "2plg8f0u", "rank": 65, "score": 0.8648809194564819}, {"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": 66, "score": 0.8636410236358643}, {"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": 67, "score": 0.863510251045227}, {"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": 39, "docid": "6hzlbpxg", "rank": 68, "score": 0.8634761571884155}, {"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": 69, "score": 0.8630551695823669}, {"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": 39, "docid": "528p64iu", "rank": 70, "score": 0.862978458404541}, {"content": "Title: [Expert consensus on Corona Virus Disease 2019 with special blood purification technology] Content: The outbreak of Corona Virus Disease 2019 (COVID-19) has spread to more than 70 countries worldwide and there was a higher mortality in those who developed serious illness.Cytokine storm syndrome is an important pathophysiological basis for COVID-19 patients developing into severe or critical conditions. It was indicated in the diagnosis and treatment scheme, by the National Health Commission of the People's Republic of China, that blood purifications such as plasma exchange, plasma adsorption, hemoperfusion, hemofiltration and plasmafiltration could be considered for use in the critical patients with cytokine storm syndrome. This expert consensus, proposed by the Chinese Society of Nephrology and the Nephrology Committee of Chinese Research Hospital Association, is to guide and standardize the clinical application of blood purifications in the treatment of severe or critical patients with COVID-19.", "qid": 39, "docid": "euozpliw", "rank": 71, "score": 0.8628636598587036}, {"content": "Title: [Expert consensus on Corona Virus Disease 2019 with special blood purification technology]. Content: The outbreak of Corona Virus Disease 2019 (COVID-19) has spread to more than 70 countries worldwide and there was a higher mortality in those who developed serious illness.Cytokine storm syndrome is an important pathophysiological basis for COVID-19 patients developing into severe or critical conditions. It was indicated in the diagnosis and treatment scheme, by the National Health Commission of the People's Republic of China, that blood purifications such as plasma exchange, plasma adsorption, hemoperfusion, hemofiltration and plasmafiltration could be considered for use in the critical patients with cytokine storm syndrome. This expert consensus, proposed by the Chinese Society of Nephrology and the Nephrology Committee of Chinese Research Hospital Association, is to guide and standardize the clinical application of blood purifications in the treatment of severe or critical patients with COVID-19.", "qid": 39, "docid": "jqtoundb", "rank": 72, "score": 0.8628636598587036}, {"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": 73, "score": 0.862805962562561}, {"content": "Title: COVID-19: Review on latest available drugs and therapies against SARS-CoV-2. Coagulation and inflammation cross-talking Content: SARS-CoV-2 is the agent responsible for COVID-19. The infection can be dived into three phases: mild infection, the pulmonary phase and the inflammatory phase. Treatment options for the pulmonary phase include: Hydroxychloroquine, Remdesivir, Lopinavir/Ritonavir. The inflammatory phase includes therapeutic options like Tocilizumab, Anakinra, Baricitinib, Eculizumab, Emapalumab and Heparin. Human clinical trials are starting to show some results, in some cases like that of Remdesivir and corticosteroids these are controversial. Coagulopathy is a common complication in severe cases, inflammation and coagulation are intertwined and cross-talking between these two responses is known to happen. A possible amplification of this cross-talking is suggested to be implicated in the severe cases that show both a cytokine storm and coagulopathy.", "qid": 39, "docid": "ly2ytc6t", "rank": 74, "score": 0.8626306653022766}, {"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": 39, "docid": "r7ahl9gd", "rank": 75, "score": 0.8626130819320679}, {"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": 76, "score": 0.8624845743179321}, {"content": "Title: Implications for Neuromodulation Therapy to Control Inflammation and Related Organ Dysfunction in COVID-19 Content: COVID-19 is a syndrome that includes more than just isolated respiratory disease, as severe acute respiratory syndrome-coronavirus 2 (SARS-CoV2) also interacts with the cardiovascular, nervous, renal, and immune system at multiple levels, increasing morbidity in patients with underlying cardiometabolic conditions and inducing myocardial injury or dysfunction. Emerging evidence suggests that patients with the highest rate of morbidity and mortality following SARS-CoV2 infection have also developed a hyperinflammatory syndrome (also termed cytokine release syndrome). We lay out the potential contribution of a dysfunction in autonomic tone to the cytokine release syndrome and related multiorgan damage in COVID-19. We hypothesize that a cholinergic anti-inflammatory pathway could be targeted as a therapeutic avenue. Graphical Abstract .", "qid": 39, "docid": "u4vejodw", "rank": 77, "score": 0.8622604608535767}, {"content": "Title: COVID-19: review on latest available drugs and therapies against SARS-CoV-2. Coagulation and inflammation cross-talking Content: SARS-CoV-2 is the agent responsible for COVID-19. The infection can be dived into three phases: mild infection, the pulmonary phase and the inflammatory phase. Treatment options for the pulmonary phase include: Hydroxychloroquine, Remdesivir, Lopinavir/Ritonavir. The inflammatory phase includes therapeutic options like Tocilizumab, Anakinra, Baricitinib, Eculizumab, Emapalumab and Heparin. Human clinical trials are starting to show some results, in some cases like that of Remdesivir these are controversial. Coagulopathy is a common complication in severe cases, inflammation and coagulation are intertwined and cross-talking between these two responses is known to happen. A possible amplification of this cross-talking is suggested to be implicated in the severe cases that show both a cytokine storm and coagulopathy.", "qid": 39, "docid": "v59dpmuu", "rank": 78, "score": 0.8622010946273804}, {"content": "Title: New intriguing possibility for prevention of coronavirus pneumonitis: Natural purified polyphenols Content: COVID-19 is an infectious disease characterized by several important systemic problems such as severe pneumonia. One of mechanisms responsible of these systemic problems is the release of pro-inflammatory cytokines, such as interleukin (IL)-1beta and IL-6(Conti et al., 2020). The binding of virus to TRL (Toll Like Receptor) can determine the release of pro-IL-1beta with successive activation and production of active mature IL-1beta, responsible of lung inflammation, fever and fibrosis(Conti et al., 2020). The interstitial pneumonia is linked to an over-production of IL-6. Based on this principle, several researchers started the use of an anti-arthritis drug, tocilizumab, for its anti-IL-6 action.", "qid": 39, "docid": "z9c9r3xw", "rank": 79, "score": 0.8620865941047668}, {"content": "Title: A Putative Role of de-Mono-ADP-Ribosylation of STAT1 by the SARS-CoV-2 Nsp3 Protein in the Cytokine Storm Syndrome of COVID-19 Content: As more cases of COVID-19 are studied and treated worldwide, it had become apparent that the lethal and most severe cases of pneumonia are due to an out-of-control inflammatory response to the SARS-CoV-2 virus. I explored the putative causes of this specific feature through a detailed genomic comparison with the closest SARS-CoV-2 relatives isolated from bats, as well as previous coronavirus strains responsible for the previous epidemics (SARS-CoV and MERS-CoV). The high variability region of the nsp3 protein was confirmed to exhibit the most variations between closest strains. It was then studied in the context of physiological and molecular data available in the literature. A number of convergent findings suggest de-mono-ADP-ribosylation (de-MARylation) of STAT1 by the SARS-CoV-2 nsp3 as a putative cause of the cytokine storm observed in the most severe cases of COVID-19. This may suggest new therapeutic approaches and help in designing assays to predict the virulence of naturally circulating SARS-like animal coronaviruses.", "qid": 39, "docid": "5hz6vy3b", "rank": 80, "score": 0.8611874580383301}, {"content": "Title: A Putative Role of de-Mono-ADP-Ribosylation of STAT1 by the SARS-CoV-2 Nsp3 Protein in the Cytokine Storm Syndrome of COVID-19. Content: As more cases of COVID-19 are studied and treated worldwide, it had become apparent that the lethal and most severe cases of pneumonia are due to an out-of-control inflammatory response to the SARS-CoV-2 virus. I explored the putative causes of this specific feature through a detailed genomic comparison with the closest SARS-CoV-2 relatives isolated from bats, as well as previous coronavirus strains responsible for the previous epidemics (SARS-CoV and MERS-CoV). The high variability region of the nsp3 protein was confirmed to exhibit the most variations between closest strains. It was then studied in the context of physiological and molecular data available in the literature. A number of convergent findings suggest de-mono-ADP-ribosylation (de-MARylation) of STAT1 by the SARS-CoV-2 nsp3 as a putative cause of the cytokine storm observed in the most severe cases of COVID-19. This may suggest new therapeutic approaches and help in designing assays to predict the virulence of naturally circulating SARS-like animal coronaviruses.", "qid": 39, "docid": "m9bh06jn", "rank": 81, "score": 0.8611874580383301}, {"content": "Title: Extracorporeal blood purification treatment options for COVID-19: The role of immunoadsorption Content: The activation of the innate and adaptive immune systems by SARS-CoV-2 causes the release of several inflammatory cytokines, including IL-6. The inflammatory hypercytokinemia causes immunopathological changes in the lungs including vascular leakage, and alveolar edema. As a result of these changes in the lungs, hypoxia and acute respiratory distress syndrome occur in patients with COVID-19. Even though there are clinical trials on the development of therapeutics and vaccines, there are currently no licensed vaccines or therapeutics for COVID-19. Pharmacological approaches have shown poor results in sepsis-like syndromes caused by the hypercytokinemia. Suppressing the cytokine storm is an important way to prevent the organ damage in patients with COVID-19. Extracorporeal blood purification could be proposed as an adjunctive therapy for sepsis, aiming to control the associated dysregulation of the immune system, which is known to protect organ functions. Several extracorporeal blood purification therapies are now available, and most of them target endotoxins and/or the cytokines and aim improving the immune response. For this purpose, plasmapheresis and immunoadsorption may be an important adjunctive treatment option to manage the complications caused by cytokine storm in critically ill patients with COVID-19.", "qid": 39, "docid": "h1zsb2en", "rank": 82, "score": 0.8610239624977112}, {"content": "Title: SARS-CoV-2 infection: The role of cytokines in COVID-19 disease Content: COVID-19 disease, caused by infection with SARS-CoV-2, is related to a series of physiopathological mechanisms that mobilize a wide variety of biomolecules, mainly immunological in nature. In the most severe cases, the prognosis can be markedly worsened by the hyperproduction of mainly proinflammatory cytokines, such as IL-1, IL-6, IL-12, IFN-\u00ce\u00b3, and TNF-&#945;, preferentially targeting lung tissue. This study reviews published data on alterations in the expression of different cytokines in patients with COVID-19 who require admission to an intensive care unit. Data on the implication of cytokines in this disease and their effect on outcomes will support the design of more effective approaches to the management of COVID-19.", "qid": 39, "docid": "tgunokrk", "rank": 83, "score": 0.8606749773025513}, {"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": 84, "score": 0.860598087310791}, {"content": "Title: Induction of pro-inflammatory cytokines (IL-1 and IL-6) and lung inflammation by Coronavirus-19 (COVI-19 or SARS-CoV-2): anti-inflammatory strategies Content: Coronavirus-19 (COVI-19) involves humans as well as animals and may cause serious damage to the respiratory tract, including the lung: coronavirus disease (COVID-19). This pathogenic virus has been identified in swabs performed on the throat and nose of patients who suffer from or are suspected of the disease. When COVI-19 infect the upper and lower respiratory tract it can cause mild or highly acute respiratory syndrome with consequent release of pro-inflammatory cytokines, including interleukin (IL)-1\u00df and IL-6. The binding of COVI-19 to the Toll Like Receptor (TLR) causes the release of pro-IL-1\u00df which is cleaved by caspase-1, followed by inflammasome activation and production of active mature IL-1\u00df which is a mediator of lung inflammation, fever and fibrosis. Suppression of pro-inflammatory IL-1 family members and IL-6 have been shown to have a therapeutic effect in many inflammatory diseases, including viral infections. Cytokine IL-37 has the ability to suppress innate and acquired immune response and also has the capacity to inhibit inflammation by acting on IL-18R&#945; receptor. IL-37 performs its immunosuppressive activity by acting on mTOR and increasing the adenosine monophosphate (AMP) kinase. This cytokine inhibits class II histocompatibility complex (MHC) molecules and inflammation in inflammatory diseases by suppressing MyD88 and subsequently IL-1\u00df, IL-6, TNF and CCL2. The suppression of IL-1\u00df by IL-37 in inflammatory state induced by coronavirus-19 can have a new therapeutic effect previously unknown. Another inhibitory cytokine is IL-38, the newest cytokine of the IL-1 family members, produced by several immune cells including B cells and macrophages. IL-38 is also a suppressor cytokine which inhibits IL-1\u00df and other pro-inflammatory IL-family members. IL-38 is a potential therapeutic cytokine which inhibits inflammation in viral infections including that caused by coronavirus-19, providing a new relevant strategy.", "qid": 39, "docid": "sw4t9yaw", "rank": 85, "score": 0.860480785369873}, {"content": "Title: TNF\u03b1 inhibitor may be effective for severe COVID-19: learning from toxic epidermal necrolysis Content: Increased inflammatory cytokines [such as tumor necrosis factor alpha (TNF&#945;) and interleukin-6 (IL-6)] are observed in COVID-19 patients, especially in the severe group. The phenomenon of a cytokine storm may be the central inducer of apoptosis of alveolar epithelial cells, which leads to rapid progression in severe group patients. Given the similarities of clinical features and pathogenesis between toxic epidermal necrolysis (TEN) and COVID-19, we hypothesize that the application of etanercept, an inhibitor of TNF&#945;, could attenuate disease progression in severe group COVID-19 patients by suppressing systemic auto-inflammatory responses. The reviews of this paper are available via the supplemental material section.", "qid": 39, "docid": "2l2pmta1", "rank": 86, "score": 0.8601543307304382}, {"content": "Title: Lessons from dermatology about inflammatory responses in Covid-19 Content: The SARS-Cov-2 is a single-stranded RNA virus composed of 16 non-structural proteins (NSP 1-16) with specific roles in the replication of coronaviruses. NSP3 has the property to block host innate immune response and to promote cytokine expression. NSP5 can inhibit interferon (IFN) signalling and NSP16 prevents MAD5 recognition, depressing the innate immunity. Dendritic cells, monocytes, and macrophages are the first cell lineage against viruses' infections. The IFN type I is the danger signal for the human body during this clinical setting. Protective immune responses to viral infection are initiated by innate immune sensors that survey extracellular and intracellular space for foreign nucleic acids. In Covid-19 the pathogenesis is not yet fully understood, but viral and host factors seem to play a key role. Important points in severe Covid-19 are characterized by an upregulated innate immune response, hypercoagulopathy state, pulmonary tissue damage, neurological and/or gastrointestinal tract involvement, and fatal outcome in severe cases of macrophage activation syndrome, which produce a 'cytokine storm'. These systemic conditions share polymorphous cutaneous lesions where innate immune system is involved in the histopathological findings with acute respiratory distress syndrome, hypercoagulability, hyperferritinemia, increased serum levels of D-dimer, lactic dehydrogenase, reactive-C-protein and serum A amyloid. It is described that several polymorphous cutaneous lesions similar to erythema pernio, urticarial rashes, diffuse or disseminated erythema, livedo racemosa, blue toe syndrome, retiform purpura, vesicles lesions, and purpuric exanthema or exanthema with clinical aspects of symmetrical drug-related intertriginous and flexural exanthema. This review describes the complexity of Covid-19, its pathophysiological and clinical aspects.", "qid": 39, "docid": "qpblq9y8", "rank": 87, "score": 0.8600727319717407}, {"content": "Title: Lessons from dermatology about inflammatory responses in Covid-19. Content: The SARS-Cov-2 is a single-stranded RNA virus composed of 16 non-structural proteins (NSP 1-16) with specific roles in the replication of coronaviruses. NSP3 has the property to block host innate immune response and to promote cytokine expression. NSP5 can inhibit interferon (IFN) signalling and NSP16 prevents MAD5 recognition, depressing the innate immunity. Dendritic cells, monocytes, and macrophages are the first cell lineage against viruses' infections. The IFN type I is the danger signal for the human body during this clinical setting. Protective immune responses to viral infection are initiated by innate immune sensors that survey extracellular and intracellular space for foreign nucleic acids. In Covid-19 the pathogenesis is not yet fully understood, but viral and host factors seem to play a key role. Important points in severe Covid-19 are characterized by an upregulated innate immune response, hypercoagulopathy state, pulmonary tissue damage, neurological and/or gastrointestinal tract involvement, and fatal outcome in severe cases of macrophage activation syndrome, which produce a 'cytokine storm'. These systemic conditions share polymorphous cutaneous lesions where innate immune system is involved in the histopathological findings with acute respiratory distress syndrome, hypercoagulability, hyperferritinemia, increased serum levels of D-dimer, lactic dehydrogenase, reactive-C-protein and serum A amyloid. It is described that several polymorphous cutaneous lesions similar to erythema pernio, urticarial rashes, diffuse or disseminated erythema, livedo racemosa, blue toe syndrome, retiform purpura, vesicles lesions, and purpuric exanthema or exanthema with clinical aspects of symmetrical drug-related intertriginous and flexural exanthema. This review describes the complexity of Covid-19, its pathophysiological and clinical aspects.", "qid": 39, "docid": "d7q6u7vj", "rank": 88, "score": 0.860072672367096}, {"content": "Title: Implications for Neuromodulation Therapy to Control Inflammation and Related Organ Dysfunction in COVID-19 Content: COVID-19 is a syndrome that includes more than just isolated respiratory disease, as severe acute respiratory syndrome\u2013coronavirus 2 (SARS-CoV2) also interacts with the cardiovascular, nervous, renal, and immune system at multiple levels, increasing morbidity in patients with underlying cardiometabolic conditions and inducing myocardial injury or dysfunction. Emerging evidence suggests that patients with the highest rate of morbidity and mortality following SARS-CoV2 infection have also developed a hyperinflammatory syndrome (also termed cytokine release syndrome). We lay out the potential contribution of a dysfunction in autonomic tone to the cytokine release syndrome and related multiorgan damage in COVID-19. We hypothesize that a cholinergic anti-inflammatory pathway could be targeted as a therapeutic avenue. [Figure: see text]", "qid": 39, "docid": "q4of4qpo", "rank": 89, "score": 0.8595455288887024}, {"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": 90, "score": 0.8592343330383301}, {"content": "Title: Distinct infection process of SARS-CoV-2 in human bronchial epithelial cells line Content: COVID-19, caused by SARS-CoV-2, leads to a series of clinical symptoms of respiratory and pulmonary inflammatory reactions via unknown pathologic mechanisms related to the viral infection process in tracheal or bronchial epithelial cells. Investigation of this viral infection in the human bronchial epithelial cell line (16HBE) suggests that SARS-CoV-2 can enter these cells through interaction between its membrane-localized S protein with the ACE2 molecule on the host cell membrane. Further observation indicates distinct viral replication with a dynamic and moderate increase, whereby viral replication does not lead to a specific cytopathic effect but maintains a continuous release of progeny virions from infected cells. Although mRNA expression of various innate immune signaling molecules is altered in the cells, transcription of IFN&#945;, IFN\u00df and IFN\u00ce\u00b3 is unchanged. Furthermore, expression of some interleukins related to inflammatory reactions, such as IL-6, IL-2 and IL-8, is maintained at low levels, whereas that of interleukins involved in immune regulation is upregulated. Interestingly, IL-22, an interleukin that functions mainly in tissue repair, shows very high expression. Collectively, these data suggest a distinct infection process for this virus in respiratory epithelial cells, which may be linked to its clinicopathological mechanism. This article is protected by copyright. All rights reserved.", "qid": 39, "docid": "k4lfow9h", "rank": 91, "score": 0.859113335609436}, {"content": "Title: Rheumatologists and Pulmonologists at Temple University Weather the COVID-19 Storm Together Content: In recent commentaries from Lancet Rheumatology and The Journal of Rheumatology 1,2, the authors eloquently illustrated the connection between the coronavirus disease 2019 (COVID-19) infection, the subsequent cytokine storm (CS) that ensues in a number of patients, and the potential efficacy of biologics that rheumatologists routinely use in their practices. Moreover, those biologics were originally investigated by rheumatologists for the treatment of numerous rheumatic conditions, including macrophage activating syndrome (MAS), a similar form of storm that resembles the one occurring in patients with COVID-193.", "qid": 39, "docid": "qwhp9kz4", "rank": 92, "score": 0.8590186238288879}, {"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": 93, "score": 0.8589638471603394}, {"content": "Title: [Study on treatment of \"cytokine storm\" by anti-2019-nCoV prescriptions based on arachidonic acid metabolic pathway] Content: Since the outbreak of 2019-nCoV, the epidemic has developed rapidly and the situation is grim. LANCET figured out that the 2019-nCoV is closely related to &quot;cytokine storm&quot;. &quot;Cytokine storm&quot; is an excessive immune response of the body to external stimuli such as viruses and bacteria. As the virus attacking the body, it stimulates the secretion of a large number of inflammatory factors: interleukin(IL), interferon(IFN), C-X-C motif chemokine(CXCL) and so on, which lead to cytokine cascade reaction. With the exudation of inflammatory factors, cytokines increase abnormally in tissues and organs, interfering with the immune system, causing excessive immune response of the body, resulting in diffuse damage of lung cells, pulmonary fibrosis, and multiple organ damage, even death. Arachidonic acid(AA) metabolic pathway is principally used to synthesize inflammatory cytokines, such as monocyte chemotactic protein 1(MCP-1), tumor necrosis factor(TNF), IL, IFN, etc., which is closely related to the occurrence, development and regression of inflammation. Therefore, the inhibition of AA metabolism pathway is benefit for inhibiting the release of inflammatory factors in the body and alleviating the &quot;cytokine storm&quot;. Based on the pharmacophore models of the targets on AA metabolic pathway, the traditional Chinese medicine database 2009(TCMD 2009) was screened. The potential herbs were ranked by the number of hit molecules, which were scored by pharmacophore fit value. In the end, we obtained the potential active prescriptions on &quot;cytokine storm&quot; according to the potential herbs in the &quot;National novel coronavirus pneumonia diagnosis and treatment plan(trial version sixth)&quot;. The results showed that the hit components with the inhibitory effect on AA were magnolignan \u00e2 , lonicerin and physcion-8-O-\u00df-D-glucopy-ranoside, which mostly extracted from Magnoliae Officinalis Cortex, Zingiberis Rhizoma Recens, Lonicerae Japonicae Flos, Rhei Radix et Rhizoma, Salviae Miltiorrhizae Radix et Rhizoma, Scutellariae Radix, Gardeniae Fructus, Ginseng Radix et Rhizoma, Arctii Fructus, Dryopteridis Crassirhizomatis Rhizoma, Paeoniaeradix Rubra, Dioscoreae Rhizoma. Finally the anti-2019-nCoV prescriptions were analyzed to obtain the potential active prescriptions on AA metabolic pathway, Huoxiang Zhengqi Capsules, Jinhua Qinggan Granules, Lianhua Qingwen Capsules, Qingfei Paidu Decoction, Xuebijing Injection, Reduning Injection and Tanreqing Injection were found that may prevent 2019-nCoV via regulate cytokines. This study intends to provide reference for clinical use of traditional Chinese medicine to resist new coronavirus.", "qid": 39, "docid": "r5xyuweg", "rank": 94, "score": 0.858852744102478}, {"content": "Title: Immunomodulatory therapy for the management of severe COVID-19. Beyond the anti-viral therapy: A comprehensive review Content: Severe Acute Respiratory Syndrome related to Coronavirus-2 (SARS-CoV-2), coronavirus disease-2019 (COVID-19) may cause severe illness in 20% of patients. This may be in part due to an uncontrolled immune-response to SARS-CoV-2 infection triggering a systemic hyperinflammatory response, the so-called \u201ccytokine storm\u201d. The reduction of this inflammatory immune-response could be considered as a potential therapeutic target against severe COVID-19. The relationship between inflammation and clot activation must also be considered. Furthermore, we must keep in mind that currently, no specific antiviral treatment is available for SARS-CoV-2. While moderate-severe forms need in-hospital surveillance plus antivirals and/or hydroxychloroquine; in severe and life-threating subsets a high intensity anti-inflammatory and immunomodulatory therapy could be a therapeutic option. However, right data on the effectiveness of different immunomodulating drugs are scarce. Herein, we discuss the pathogenesis and the possible role played by drugs such as: antimalarials, anti-IL6, anti-IL-1, calcineurin and JAK inhibitors, corticosteroids, immunoglobulins, heparins, angiotensin-converting enzyme agonists and statins in severe COVID-19.", "qid": 39, "docid": "v44s8flj", "rank": 95, "score": 0.8586196303367615}, {"content": "Title: Humoral Immune Responses in COVID-19 Patients: A Window on the State of the Art Content: The novel SARS-CoV-2 is a recently emerging virus causing a human pandemic. A great variety of symptoms associated with COVID-19 disease, ranging from mild to severe symptoms, eventually leading to death. Specific SARS-CoV-2 RT-PCR is the standard method to screen symptomatic people; however, asymptomatic subjects and subjects with undetectable viral load escape from the screening, contributing to viral spread. Currently, the lock down imposed by many governments is an important measure to contain the spread, as there is no specific antiviral therapy or a vaccine and the main treatments are supportive. Therefore, there is urgent need to characterize the virus and the viral-mediated responses, in order to develop specific diagnostic and therapeutic tools to prevent viral transmission and efficiently cure COVID-19 patients. Here, we review the current studies on two viral mediated-responses, specifically the cytokine storm occurring in a subset of patients and the antibody response triggered by the infection. Further studies are needed to explore both the dynamics and the mechanisms of the humoral immune response in COVID-19 patients, in order to guide future vaccine design and antibody-based therapies for the management of the disease.", "qid": 39, "docid": "3tgvvq4o", "rank": 96, "score": 0.8585080504417419}, {"content": "Title: High IL\u20106/IFN\u2010\u03b3 ratio could be associated with severe disease in COVID\u201019 patients Content: Cytokines are important mediators of the inflammatory response, and during infection with SARS\u2010CoV\u20102 it has been suggested that there is a cytokine storm syndrome. In this study, a meta\u2010analysis was performed to investigate whether the IL\u20106/IFN\u2010\u03b3 ratio can help predict clinical severity in patients with COVID\u201019. This article is protected by copyright. All rights reserved.", "qid": 39, "docid": "z15l4pcq", "rank": 97, "score": 0.858393669128418}, {"content": "Title: Rheumatologists and Pulmonologists at Temple University weather the COVID-19 storm together. Content: In recent commentaries from Lancet Rheumatology and The Journal of Rhuematology (1-2) the authors eloquently illustrated the connection between COVID-19 infection, the subsequent cytokine storm (CS) that ensues in a number of patients and the potential efficacy of biologics that Rheumatologists routinely use in their practices. Moreover those biologics were originally investigated by Rheumatologists for the treatment of numerous rheumatic conditions, including macrophage activating syndrome (MAS), a similar form of storm that resembles the one occurring in COVID-19 patients (3).", "qid": 39, "docid": "1pujz3em", "rank": 98, "score": 0.8581967949867249}, {"content": "Title: Anticoagulant and antiarrhythmic effects of heparin in the treatment of COVID-19 patients Content: Most severe manifestations of COVID-19 cases, such as multiple organ failure and death, have been linked to coagulation dysfunction markers, such as platelet reduction and increases in prothrombin time, fibrin degradation products and, mainly, D-dimer [1]. A recent paper by Tang et al. [2] in this journal reported that heparin treatment reduced mortality of COVID-19 patients with elevated D-dimer; similar preliminary results have been reported elsewhere [3]. A mounting body of evidence shows that SARS-CoV-2 causes a \"cytokine storm\" [1,4] that activates the coagulation cascade, leading to thrombosis. Similar to the findings in severe sepsis, generalized deposition of intravascular thrombi compromises the blood supply of several organs, leading to organ failure [5].", "qid": 39, "docid": "0ehd4oct", "rank": 99, "score": 0.8580479025840759}, {"content": "Title: The Role of Cytokines including Interleukin-6 in COVID-19 induced Pneumonia and Macrophage Activation Syndrome-Like Disease Content: Severe COVID-19 associated pneumonia patients may exhibit features of systemic hyper-inflammation designated under the umbrella term of macrophage activation syndrome (MAS) or cytokine storm, also known as secondary haemophagocytic lymphohistocytosis (sHLH). This is distinct from HLH associated with immunodeficiency states termed primary HLH -with radically different therapy strategies in both situations. COVID-19 infection with MAS typically occurs in subjects with adult respiratory distress syndrome (ARDS) and historically, non-survival in ARDS was linked to sustained IL-6 and IL-1 elevation. We provide a model for the classification of MAS to stratify the MAS-like presentation in COVID-19 pneumonia and explore the complexities of discerning ARDS from MAS. We discuss the potential impact of timing of anti-cytokine therapy on viral clearance and the impact of such therapy on intra-pulmonary macrophage activation and emergent pulmonary vascular disease.", "qid": 39, "docid": "yfoipwuv", "rank": 100, "score": 0.8579839468002319}]}
{"query": "What are the observed mutations in the SARS-CoV-2 genome and how often do the mutations occur?", "hits": [{"content": "Title: Insights on early mutational events in SARS-CoV-2 virus reveal founder effects across geographical regions Content: Here we aim to describe early mutational events across samples from publicly available SARS-CoV-2 sequences from the sequence read archive repository. Up until March 27, 2020, we downloaded 53 illumina datasets, mostly from China, USA (Washington DC) and Australia (Victoria). Of 30 high quality datasets, 27 datasets (90%) contain at least a single founder mutation and most of the variants are missense (over 63%). Five-point mutations with clonal (founder) effect were found in USA sequencing samples. Sequencing samples from USA in GenBank present this signature with 50% allele frequencies among samples. Australian mutation signatures were more diverse than USA samples, but still, clonal events were found in those samples. Mutations in the helicase and orf1a coding regions from SARS-CoV-2 were predominant, among others, suggesting that these proteins are prone to evolve by natural selection. Finally, we firmly urge that primer sets for diagnosis be carefully designed, since rapidly occurring variants would affect the performance of the reverse transcribed quantitative PCR (RT-qPCR) based viral testing.", "qid": 40, "docid": "gfwqog3x", "rank": 1, "score": 0.8800382018089294}, {"content": "Title: Insights on early mutational events in SARS-CoV-2 virus reveal founder effects across geographical regions Content: Here we aim to describe early mutational events across samples from publicly available SARS-CoV-2 sequences from the sequence read archive and GenBank repositories. Up until 27 March 2020, we downloaded 50 illumina datasets, mostly from China, USA (WA State) and Australia (VIC). A total of 30 datasets (60%) contain at least a single founder mutation and most of the variants are missense (over 63%). Five-point mutations with clonal (founder) effect were found in USA next-generation sequencing samples. Sequencing samples from North America in GenBank (22 April 2020) present this signature with up to 39% allele frequencies among samples (n = 1,359). Australian variant signatures were more diverse than USA samples, but still, clonal events were found in these samples. Mutations in the helicase, encoded by the ORF1ab gene in SARS-CoV-2 were predominant, among others, suggesting that these regions are actively evolving. Finally, we firmly urge that primer sets for diagnosis be carefully designed, since rapidly occurring variants would affect the performance of the reverse transcribed quantitative PCR (RT-qPCR) based viral testing.", "qid": 40, "docid": "0xruezf2", "rank": 2, "score": 0.8789780735969543}, {"content": "Title: Comment on \u201cGenetic variants and source of introduction of SARS\u2010CoV\u20102 in South America\u201d Content: I read with great interest a recent study by Poterico and Mestanza1 who described mutations in 30 SARS-CoV-2 genomes from South American countries (Argentina, Brazil, Chile, Colombia, Ecuador, and Peru) This article is protected by copyright. All rights reserved.", "qid": 40, "docid": "09r8xd0u", "rank": 3, "score": 0.8735991716384888}, {"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": 4, "score": 0.8674945831298828}, {"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": 5, "score": 0.8643783330917358}, {"content": "Title: SARS-CoV-2 variants: Relevance for symptom granularity, epidemiology, immunity (herd, vaccines), virus origin and containment? Content: The origin of the SARS-CoV-2 virus remains enigmatic. It is likely to be a continuum resulting from inevitable mutations and recombination events. These genetic changes keep developing in the present epidemic. Mutations tending to deplete the genome in its cytosine content will progressively lead to attenuation as a consequence of Muller's ratchet, but this is counteracted by recombination when different mutants co-infect the same host, in particular, in clusters of infection. Monitoring as a function of time the genome sequences in closely related cases is critical to anticipate the future of SARS-CoV-2 and hence of COVID-19.", "qid": 40, "docid": "mtngelbr", "rank": 6, "score": 0.862855076789856}, {"content": "Title: Overwhelming Mutations or SNPs of SARS-CoV-2: A Point of Caution Content: \u2022 Mutation studies hits cause for the superior infectious rate of SARS-CoV-2. \u2022 SARS-CoV-2 is evolving rapidly with number of mutations and SNPs. \u2022 Mutations were found in the ACE2 binding region of SARS-CoV-2 spike glycoprotein. \u2022 ORF1ab, ORF8 and spike glycoprotein regions of SARS-CoV-2 are highly mutated. \u2022 Overwhelming mutations or SNPs of SARS-CoV-2 alerts drug treatment options.", "qid": 40, "docid": "sd0ah7k5", "rank": 7, "score": 0.8616576194763184}, {"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": 8, "score": 0.8608202934265137}, {"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": 9, "score": 0.8599759936332703}, {"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": 10, "score": 0.8584508895874023}, {"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": 11, "score": 0.8557027578353882}, {"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": 12, "score": 0.8552396893501282}, {"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": 13, "score": 0.8544899225234985}, {"content": "Title: SARS-CoV2 envelope protein: Non-synonymous mutations and its consequences Content: In the NCBI database, as on June 6, 2020, total number of available complete genome sequences of SARS-CoV2 across the world is 3617. The envelope protein of SARS-CoV2 possesses several non-synonymous mutations over the transmembrane domain and (C)-terminus in 15 (0.414%) genomes among 3617 available SARS-CoV2 genomes. More precisely, it is to be mentioned that 10(0.386%) out of 2588 genomes from the USA, 3(0.806%) from Asia, 1 (0.348%) from Europe and 1 (0.274%) from Oceania contain the missense mutations over the envelope proteins of SARS-CoV2 genomes. The C-terminus motif DLLV has been changed to DFLV and YLLV in the proteins QJR88103 (Australia: Victoria) and QKI36831 (China: Guangzhou) respectively, which might affect the binding of this motif with the host protein PALS1.", "qid": 40, "docid": "phl6ibbv", "rank": 14, "score": 0.8535300493240356}, {"content": "Title: Global genetic diversity patterns and transmissions of SARS-CoV-2 Content: Background: Since it was firstly discovered in China, the SARS-CoV-2 epidemic has caused a substantial health emergency and economic stress in the world. However, the global genetic diversity and transmissions are still unclear. Methods: 3050 SARS-CoV-2 genome sequences were retrieved from GIASID database. After aligned by MAFFT, the mutation patterns were identified by phylogenetic tree analysis. Results: We detected 17 high frequency (>6%) mutations in the 3050 sequences. Based on these mutations, we classed the SARS-CoV-2 into four main groups and 10 subgroups. We found that group A was mainly presented in Asia, group B was primarily detected in North America, group C was prevailingly appeared in Asia and Oceania and group D was principally emerged in Europe and Africa. Additionally, the distribution of these groups was different in age, but was similar in gender. Group A, group B1 and group C2 were declined over time, inversely, group B2, group C3 and group D were rising. At last, we found two apparent expansion stages (late Jan-2020 and late Feb-2020 to early Mar-2020, respectively). Notably, most of groups are quickly expanding, especially group D. Conclusions: We classed the SARS-CoV-2 into four main groups and 10 subgroups based on different mutation patterns at first time. The distribution of the 10 subgroups was different in geography, time and age, but not in gender. Most of groups are rapidly expanding, especially group D. Therefore, we should attach importance to these genetic diversity patterns of SARS-CoV-2 and take more targeted measures to constrain its spread.", "qid": 40, "docid": "r3t4bd78", "rank": 15, "score": 0.8529845476150513}, {"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": 16, "score": 0.851842999458313}, {"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": 17, "score": 0.851842999458313}, {"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": 18, "score": 0.8509076833724976}, {"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": 19, "score": 0.8501337766647339}, {"content": "Title: International expansion of a novel SARS-CoV-2 mutant Content: Letter to the editor. There is no abstract. The summary was showed: SARS-CoV-2 has inevitably mutated during its pandemic spread to cause unpredictable effects on COVID-19 and complicate epidemic control efforts. Here we report that a novel SARS-CoV-2 mutation (ORF3a) appears to be spreading worldwide, which deserves close attention.", "qid": 40, "docid": "alsiqv04", "rank": 20, "score": 0.8500480651855469}, {"content": "Title: Investigating the genomic landscape of novel coronavirus (2019-nCoV) to identify non-synonymous mutations for use in diagnosis and drug design Content: This study presents a comprehensive phylogenetic analysis of SARS-CoV2 isolates to understand discrete mutations that are occurring between patient samples. The analysis unravel various amino acid mutations in the viral proteins which may provide an explanation for varying treatment efficacies of different inhibitory drugs and a future direction towards a combinatorial treatment therapies based on the kind of mutation in the viral genome.", "qid": 40, "docid": "ttte21up", "rank": 21, "score": 0.8499610424041748}, {"content": "Title: SARS-CoV2 envelope protein: Non-synonymous mutations and its consequences Content: Abstract In the NCBI database, as on June 6, 2020, total number of available complete genome sequences of SARS-CoV2 across the world is 3617. The envelope protein of SARS-CoV2 possesses several non-synonymous mutations over the transmembrane domain and (C)-terminus in 15 (0.414%) genomes among 3617 available SARS-CoV2 genomes. More precisely, it is to be mentioned that 10(0.386%) out of 2588 genomes from the USA, 3(0.806%) from Asia, 1 (0.348%) from Europe and 1 (0.274%) from Oceania contain the missense mutations over the envelope proteins of SARS-CoV2 genomes. The C-terminus motif DLLV has been changed to DFLV and YLLV in the proteins QJR88103 (Australia: Victoria) and QKI36831 (China: Guangzhou) respectively, which might affect the binding of this motif with the host protein PALS1.", "qid": 40, "docid": "gnrnsxej", "rank": 22, "score": 0.8492263555526733}, {"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": 23, "score": 0.849166989326477}, {"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": 24, "score": 0.8491066694259644}, {"content": "Title: An overview of the genetic variations of the SARS-CoV-2 genomes isolated in Southeast Asian countries Content: Monitoring the mutation dynamics of human severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) is critical in understanding its infectivity, virulence and pathogenicity for development of a vaccine. In an \"age of mobility\", the pandemic highlights the importance and vulnerability of regionalisation and labour market interdependence in Southeast Asia. We intend to characterise the genetic variability of viral populations within the region to provide preliminary information for regional surveillance in the future. By analysing 142 complete genomes from South East Asian (SEA) countries, we identified three central variants distinguished by nucleotide and amino acid changes.", "qid": 40, "docid": "ewpfxpw2", "rank": 25, "score": 0.8476194143295288}, {"content": "Title: An overview of the genetic variations of the SARS-CoV-2 genomes isolated in Southeast Asian countries. Content: Monitoring the mutation dynamics of human severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) is critical in understanding its infectivity, virulence and pathogenicity for development of a vaccine. In an \"age of mobility\", the pandemic highlights the importance and vulnerability of regionalisation and labour market interdependence in Southeast Asia. We intend to characterise the genetic variability of viral populations within the region to provide preliminary information for regional surveillance in the future. By analysing 142 complete genomes from South East Asian (SEA) countries, we identified three central variants distinguished by nucleotide and amino acid changes.", "qid": 40, "docid": "zf3moii7", "rank": 26, "score": 0.8476194143295288}, {"content": "Title: The genomic variation landscape of globally-circulating clades of SARS-CoV-2 defines a genetic barcoding scheme Content: We describe fifteen major mutation events from 2,058 high-quality SARS-CoV-2 genomes deposited up to March 31st, 2020. These events define five major clades (G, I, S, D and V) of globally-circulating viral populations, representing 85.7% of all sequenced cases, which we can identify using a 10 nucleotide genetic classifier or barcode. We applied this barcode to 4,000 additional genomes deposited between March 31st and April 15th and classified successfully 95.6% of the clades demonstrating the utility of this approach. An analysis of amino acid variation in SARS-CoV-2 ORFs provided evidence of substitution events in the viral proteins involved in both host-entry and genome replication. The systematic monitoring of dynamic changes in the SARS-CoV-2 genomes of circulating virus populations over time can guide therapeutic and prophylactic strategies to manage and contain the virus and, also, with available efficacious antivirals and vaccines, aid in the monitoring of circulating genetic diversity as we proceed towards elimination of the agent. The barcode will add the necessary genetic resolution to facilitate tracking and monitoring of infection clusters to distinguish imported and indigenous cases and thereby aid public health measures seeking to interrupt transmission chains without the requirement for real-time complete genomes sequencing.", "qid": 40, "docid": "drqhuhk4", "rank": 27, "score": 0.847225546836853}, {"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": 28, "score": 0.8465803265571594}, {"content": "Title: We shouldn\u2019t worry when a virus mutates during disease outbreaks Content: Mutation. The word naturally conjures fears of unexpected and freakish changes. Ill-informed discussions of mutations thrive during virus outbreaks, including the ongoing spread of SARS-CoV-2. In reality, mutations are a natural part of the virus life cycle and rarely impact outbreaks dramatically.", "qid": 40, "docid": "73b58lcm", "rank": 29, "score": 0.8462616801261902}, {"content": "Title: An updated analysis of variations in SARS-CoV-2 genome Content: A novel pathogen, named SARS-CoV-2, has caused an unprecedented worldwide pandemic in the first half of 2020. As the SARS-CoV-2 genome sequences have become available, one of the important focus of scientists has become tracking variations in the viral genome. In this study, 30366 SARS-CoV-2 isolate genomes were aligned using the software developed by our group (ODOTool) and 11 variations in SARS-CoV-2 genome over 10% of whole isolates were discussed. Results indicated that, frequency rates of these 11 variations change between 3.56%\u201388.44 % and these rates differ greatly depending on the continents they have been reported. Despite some variations being in low frequency rate in some continents, C14408T and A23403G variations on Nsp12 and S protein, respectively, observed to be the most prominent variations all over the world, in general, and both cause missense mutations. It is also notable that most of isolates carry C14408T and A23403 variations simultaneously and also nearly all isolates carrying the G25563T variation on ORF3a, also carry C14408T and A23403 variations, although their location distributions are not similar. All these data should be considered towards development of vaccine and antiviral treatment strategies as well as tracing diversity of virus in all over the world.", "qid": 40, "docid": "od3c25qg", "rank": 30, "score": 0.845700740814209}, {"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": 31, "score": 0.8456900119781494}, {"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": 32, "score": 0.8455688953399658}, {"content": "Title: Genome-wide variations of SARS-CoV-2 infer evolution relationship and transmission route Content: In the epidemic evolution of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), the issues of mutation, origin, typing and the effect of mutation on molecular detection remain to be unrevealed. In order to identify the evolutionary relationship of SARS-CoV-2 and evaluate the detection efficiency of primers that are currently used in different countries, we retrieved genomic sequences of 373 SARS-CoV-2 strains from multiple databases and performed genome-wide variation analysis. According to the nucleotide C28144T variation, the SARS-CoV-2 can be divided into group A (117 strains) and group B (256 strains). The spike protein gene (S gene) coding region 1841 (total 23403) A1841G, formed a B1 subgroup (40 strains) in group B, of which 30 strains were from European and American countries in March (especially Washington, USA). These mutations are likely to be influenced by the environment or the immunization selection pressure of different populations. Although the mutation is not in the receptor binding region (RBD) and alkaline cleavage region, it may also affect the ability of transmission and pathogenicity; however, the significance is not yet clear. As the ratio of A / B strains in the epidemic months showed an increasing trend (0.35: 1 in January, 0.62: 1 in February and 0.76: 1 in March), it seems that the transmissibility of group A strains becomes stronger with time. Based on the variation of 11 nucleotide sites during the epidemic process, it is speculated that the Washington strain is more like an ancestor type, and the Wuhan strain is the offspring of the group A virus strain. By comparing the detection capabilities of primers in different countries, the SARS-CoV-2 nucleotide variation may only affect molecular detection of very few strains. The differences in the transmissibility, pathogenicity and clinical manifestations of different types of strains require further investigations.", "qid": 40, "docid": "blqzi69t", "rank": 33, "score": 0.8453969955444336}, {"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": 34, "score": 0.8452427387237549}, {"content": "Title: Decoding SARS-CoV-2 Transmission and Evolution and Ramifications for COVID-19 Diagnosis, Vaccine, and Medicine Content: Tremendous effort has been given to the development of diagnostic tests, preventive vaccines, and therapeutic medicines for coronavirus disease 2019 (COVID-19) caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). Much of this development has been based on the reference genome collected on January 5, 2020. Based on the genotyping of 15\u00e2\u0080\u00af140 genome samples collected up to June 1, 2020, we report that SARS-CoV-2 has undergone 8309 single mutations which can be clustered into six subtypes. We introduce mutation ratio and mutation h-index to characterize the protein conservativeness and unveil that SARS-CoV-2 envelope protein, main protease, and endoribonuclease protein are relatively conservative, while SARS-CoV-2 nucleocapsid protein, spike protein, and papain-like protease are relatively nonconservative. In particular, we have identified mutations on 40% of nucleotides in the nucleocapsid gene in the population level, signaling potential impacts on the ongoing development of COVID-19 diagnosis, vaccines, and antibody and small-molecular drugs.", "qid": 40, "docid": "lzrxdi6a", "rank": 35, "score": 0.8446651101112366}, {"content": "Title: Decoding SARS-CoV-2 Transmission and Evolution and Ramifications for COVID-19 Diagnosis, Vaccine, and Medicine Content: [Image: see text] Tremendous effort has been given to the development of diagnostic tests, preventive vaccines, and therapeutic medicines for coronavirus disease 2019 (COVID-19) caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). Much of this development has been based on the reference genome collected on January 5, 2020. Based on the genotyping of 15 140 genome samples collected up to June 1, 2020, we report that SARS-CoV-2 has undergone 8309 single mutations which can be clustered into six subtypes. We introduce mutation ratio and mutation h-index to characterize the protein conservativeness and unveil that SARS-CoV-2 envelope protein, main protease, and endoribonuclease protein are relatively conservative, while SARS-CoV-2 nucleocapsid protein, spike protein, and papain-like protease are relatively nonconservative. In particular, we have identified mutations on 40% of nucleotides in the nucleocapsid gene in the population level, signaling potential impacts on the ongoing development of COVID-19 diagnosis, vaccines, and antibody and small-molecular drugs.", "qid": 40, "docid": "13tc3loo", "rank": 36, "score": 0.8446028828620911}, {"content": "Title: Coronavirus3D: 3D structural visualization of COVID-19 genomic divergence Content: MOTIVATION: As the COVID-19 pandemics is spreading around the world, the SARS-CoV-2 virus is evolving with mutations that potentially change and fine-tune functions of the proteins coded in its genome. RESULTS: Coronavirus3D website integrates data on the SARS-CoV-2 virus mutations with information about 3D structures of its proteins, allowing users to visually analyze the mutations in their 3D context. AVAILABILITY: Coronavirus3D server is freely available at https://coronavirus3d.org.", "qid": 40, "docid": "b7e17hl9", "rank": 37, "score": 0.84424889087677}, {"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": 38, "score": 0.8442462682723999}, {"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": 39, "score": 0.8441715836524963}, {"content": "Title: Intra-host Variation and Evolutionary Dynamics of SARS-CoV-2 Population in COVID-19 Patients Content: As of middle May 2020, the causative agent of COVID-19, SARS-CoV-2, has infected over 4 million people with more than 300 thousand death as official reports1,2. The key to understanding the biology and virus-host interactions of SARS-CoV-2 requires the knowledge of mutation and evolution of this virus at both inter- and intra-host levels. However, despite quite a few polymorphic sites identified among SARS-CoV-2 populations, intra-host variant spectra and their evolutionary dynamics remain mostly unknown. Here, using deep sequencing data, we achieved and characterized consensus genomes and intra-host genomic variants from 32 serial samples collected from eight patients with COVID-19. The 32 consensus genomes revealed the coexistence of different genotypes within the same patient. We further identified 40 intra-host single nucleotide variants (iSNVs). Most (30/40) iSNVs presented in single patient, while ten iSNVs were found in at least two patients or identical to consensus variants. Comparison of allele frequencies of the iSNVs revealed genetic divergence between intra-host populations of the respiratory tract (RT) and gastrointestinal tract (GIT), mostly driven by bottleneck events among intra-host transmissions. Nonetheless, we observed a maintained viral genetic diversity within GIT, showing an increased population with accumulated mutations developed in the tissue-specific environments. The iSNVs identified here not only show spatial divergence of intra-host viral populations, but also provide new insights into the complex virus-host interactions.", "qid": 40, "docid": "st0yux3b", "rank": 40, "score": 0.8441416621208191}, {"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": 41, "score": 0.8430925607681274}, {"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": 42, "score": 0.8427969217300415}, {"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": 43, "score": 0.8419837951660156}, {"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": 44, "score": 0.8416386842727661}, {"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": 45, "score": 0.8407694101333618}, {"content": "Title: Decoding SARS-CoV-2 transmission, evolution and ramification on COVID-19 diagnosis, vaccine, and medicine Content: Tremendous effort has been given to the development of diagnostic tests, preventive vaccines, and therapeutic medicines for coronavirus disease 2019 (COVID-19) caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). Much of this development has been based on the reference genome collected on January 5, 2020. Based on the genotyping of 6156 genome samples collected up to April 24, 2020, we report that SARS-CoV-2 has had 4459 alarmingly mutations which can be clustered into five subtypes. We introduce mutation ratio and mutation $h$-index to characterize the protein conservativeness and unveil that SARS-CoV-2 envelope protein, main protease, and endoribonuclease protein are relatively conservative, while SARS-CoV-2 nucleocapsid protein, spike protein, and papain-like protease are relatively non-conservative. In particular, the nucleocapsid protein has more than half its genes changed in the past few months, signaling devastating impacts on the ongoing development of COVID-19 diagnosis, vaccines, and drugs.", "qid": 40, "docid": "u6ewlh16", "rank": 46, "score": 0.8402277231216431}, {"content": "Title: Comprehensive annotations of the mutational spectra of SARS-CoV-2 spike protein: a fast and accurate pipeline Content: In order to explore nonsynonymous mutations and deletions in the spike (S) protein of SARS-CoV-2, we comprehensively analyzed 35,750 complete S protein gene sequences from across six continents and five climate zones around the world, as documented in the GISAID database as of June 24th, 2020. Through a custom Python-based pipeline for analyzing mutations, we identified 27,801 (77.77 % of spike sequences) mutated strains compared to Wuhan-Hu-1 strain. 84.40% of these strains had only single amino-acid (aa) substitution mutations, but an outlier strain from Bosnia and Herzegovina (EPI_ISL_463893) was found to possess six aa substitutions. The D614G variant of the major G clade was found to be predominant across circulating strains in all climates. We also identified 988 unique aa substitution mutations distributed across 660 positions within the spike protein, with eleven sites showing high variability \u2013 these sites had four types of aa variations at each position. Besides, 17 in-frame deletions at four major regions (three in N-terminal domain and one just downstream of the RBD) may have possible impact on attenuation. Moreover, the mutational frequency differed significantly (p= 0.003, Kruskal\u2013Wallis test) among the SARS-CoV-2 strains worldwide. This study presents a fast and accurate pipeline for identifying nonsynonymous mutations and deletions from large dataset for any particular protein coding sequence and presents this S protein data as representative analysis. By using separate multi-sequence alignment with MAFFT, removing ambiguous sequences and in-frame stop codons, and utilizing pairwise alignment, this method can derive nonsynonymus mutations (Reference:Position:Strain). We believe this will aid in the surveillance of any proteins encoded by SARS-CoV-2, and will prove to be crucial in tracking the ever-increasing variation of many other divergent RNA viruses in the future.", "qid": 40, "docid": "1iqg0efn", "rank": 47, "score": 0.8401124477386475}, {"content": "Title: SARS-CoV-2: virus mutations in specific European populations Content: Abstract The SARS-CoV-2 virus is being intensively studied, particularly, its evolution in the increasingly available sequences between countries/continents with classical phylogenetic tree representation. More recently, certain protein mutations are correlated with specific functional impacts. Our clinical data from patients suggest different clinical symptoms between European countries. Among others, SARS-CoV-2 mutations could explain these disparities. Our analyses point out an association of diverse mutations, including co-evolving ones, in a few SARS-CoV-2 proteins, with specific countries. We therefore suggest combining clinical information from patients and the determination of the associated SARS-CoV-2 genome to better understand the specific symptoms.", "qid": 40, "docid": "y5th0mrf", "rank": 48, "score": 0.8392024040222168}, {"content": "Title: [Genetic variation analysis of SARS coronavirus]. Content: Severe acute respiratory syndrome (SARS)-associated coronavirus (SARS-CoV) has been verified as the causative agent of a worldwide outbreak of SARS. Since the observed per-base replication error-rate of RNA polymerase is about 3 x 10(-5), RNA virus populations typically contain genetic variants that form a heterogeneous virus pool. This feature confers great adaptability on viruses and is partly responsible for current difficulties of viral disease prevention and control, such as of HIV and HCV infections. SARS-CoV, a newly-identified single-strand RNA virus, has been identified with common variable property of RNA viruses. In this study, genetic variation of SARS-CoV is analyzed based on available documented data and our study. It suggests that SARS-CoV is of similar mutation frequency and dynamic mutant distributions like other RNA viruses, though relatively less identified variation number than those causing chronic infections. In contrast, the viral spike (S) gene exhibits high variation, while nucleocapsid (N) gene shows relative sequence conservation. No obvious correlation is observed between viral variation and clinical disease manifestation from present analyzed data.", "qid": 40, "docid": "8xu453f8", "rank": 49, "score": 0.839120626449585}, {"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": 50, "score": 0.8390033841133118}, {"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": 0.8389672040939331}, {"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": 52, "score": 0.8385276198387146}, {"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": 53, "score": 0.838221549987793}, {"content": "Title: Spike mutation pipeline reveals the emergence of a more transmissible form of SARS-CoV-2 Content: We have developed an analysis pipeline to facilitate real-time mutation tracking in SARS-CoV-2, focusing initially on the Spike (S) protein because it mediates infection of human cells and is the target of most vaccine strategies and antibody-based therapeutics. To date we have identified thirteen mutations in Spike that are accumulating. Mutations are considered in a broader phylogenetic context, geographically, and over time, to provide an early warning system to reveal mutations that may confer selective advantages in transmission or resistance to interventions. Each one is evaluated for evidence of positive selection, and the implications of the mutation are explored through structural modeling. The mutation Spike D614G is of urgent concern; it began spreading in Europe in early February, and when introduced to new regions it rapidly becomes the dominant form. Also, we present evidence of recombination between locally circulating strains, indicative of multiple strain infections. These finding have important implications for SARS-CoV-2 transmission, pathogenesis and immune interventions.", "qid": 40, "docid": "4hmecfi0", "rank": 54, "score": 0.8381341695785522}, {"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": 40, "docid": "uhru7rn8", "rank": 55, "score": 0.8380568027496338}, {"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": 56, "score": 0.8373743891716003}, {"content": "Title: SARS-CoV-2 amino acid substitutions widely spread in the human population are mainly located in highly conserved segments of the structural proteins Content: The Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) pandemic offers a unique opportunity to study the introduction and evolution of a pathogen into a completely na\u00efve human population. We identified and analysed the amino acid mutations that gained prominence worldwide in the early months of the pandemic. Eight mutations have been identified along the viral genome, mostly located in conserved segments of the structural proteins and showing low variability among coronavirus, which indicated that they might have a functional impact. At the moment of writing this paper, these mutations present a varied success in the SARS-CoV-2 virus population; ranging from a change in the spike protein that becomes absolutely prevalent, two mutations in the nucleocapsid protein showing frequencies around 25%, to a mutation in the matrix protein that nearly fades out after reaching a frequency of 20%.", "qid": 40, "docid": "0hldozml", "rank": 57, "score": 0.8369147181510925}, {"content": "Title: Attenuated SARS-CoV-2 variants with deletions at the S1/S2 junction Content: The emergence of SARS-CoV-2 has led to the current global coronavirus pandemic and more than one million infections since December 2019. The exact origin of SARS-CoV-2 remains elusive, but the presence of a distinct motif in the S1/S2 junction region suggests the possible acquisition of cleavage site(s) in the spike protein that promoted cross-species transmission. Through plaque purification of Vero-E6 cultured SARS-CoV-2, we found a series of variants which contain 15-30-bp deletions (Del-mut) or point mutations respectively at the S1/S2 junction. Examination of the original clinical specimen from which the isolate was derived, and 26 additional SARS-CoV-2 positive clinical specimens, failed to detect these variants. Infection of hamsters shows that one of the variants (Del-mut-1) which carries deletion of 10 amino acids (30bp) does not cause the body weight loss or more severe pathological changes in the lungs that is associated with wild type virus infection. We suggest that the unique cleavage motif promoting SARS-CoV-2 infection in humans may be under strong selective pressure, given that replication in permissive Vero-E6 cells leads to the loss of this adaptive function. It would be important to screen the prevalence of these variants in asymptomatic infected cases. The potential of the Del-mut variants as an attenuated vaccine or laboratory tool should be evaluated.", "qid": 40, "docid": "mgsaoz3j", "rank": 58, "score": 0.8368673324584961}, {"content": "Title: Genome Sequencing of a Severe Acute Respiratory Syndrome Coronavirus 2 Isolate Obtained from a South African Patient with Coronavirus Disease 2019 Content: As a contribution to the global efforts to track and trace the ongoing coronavirus pandemic, here we present the sequence, phylogenetic analysis, and modeling of nonsynonymous mutations for a severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) genome that was detected in a South African patient with coronavirus disease 2019 (COVID-19).", "qid": 40, "docid": "4bco5udc", "rank": 59, "score": 0.8367166519165039}, {"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": 60, "score": 0.8363310694694519}, {"content": "Title: Virus strain from a mild COVID-19 patient in Hangzhou represents a new trend in SARS-CoV-2 evolution potentially related to Furin cleavage site. Content: The mutations in the SARS-CoV-2 virus genome during the spread of COVID-19 have been unclear. In 788 COVID-19 patients from Zhejiang province, we observed decreased rate of severe/critical cases, increased liver/kidney damage, and prolonged period of nuclear acid positivity, compared with patients in Wuhan, China. To investigate the underlying mechanisms, we isolated one strain of SARS-CoV-2 (ZJ01) from a mild COVID-19 patient. Thirty-five specific gene mutations were identified by gene alignment. Further phylogenetic analysis and relative synonymous codon usage heat map results suggested that ZJ01 may be a potential evolutionary branch of SARS-CoV-2. We classified 54 virus strains collected globally based on the base (C or T) at positions 8824 and 28247. ZJ01 has T at both sites and is currently the only known TT type. The prediction of the Furin cleavage site (FCS) and sequence alignment of the virus family indicated that the FCS may be an important site of coronavirus evolution. ZJ01 mutations identified near the FCS (F1-2) caused changes in the structure and electrostatic distribution of the S surface protein, further affecting the binding capacity of Furin. Single-cell sequencing and ACE2-Furin co-expression results confirmed that the Furin expression was higher in the whole body, especially in glands, liver, kidneys, and colon. Thus, FCS may help SARS-CoV-2 infect these organs. The evolutionary pattern of SARS-CoV-2 towards FCS formation may result in its clinical symptom becoming closer to HKU-1 and OC43 (the source of FCS sequence-PRRA) caused mild flu-like symptoms, further showing potential in differentiating into mild COVID-19 subtypes.", "qid": 40, "docid": "0s7oq0uv", "rank": 61, "score": 0.8358029127120972}, {"content": "Title: Quality control of low-frequency variants in SARS-CoV-2 genomes Content: During the current outbreak of COVID-19, research labs around the globe submit sequences of the local SARS-CoV-2 genomes to the GISAID database to provide a comprehensive analysis of the variability and spread of the virus during the outbreak. We explored the variations in the submitted genomes and found a significant number of variants that can be seen only in one submission (singletons). While it is not completely clear whether these variants are erroneous or not, these variants show lower transition/transversion ratio. These singleton variants may influence the estimations of the viral mutation rate and tree topology. We suggest that genomes with multiple singletons even marked as high-covered should be considered with caution. We also provide a simple script for checking variant frequency against the database before submission.", "qid": 40, "docid": "lkdkdque", "rank": 62, "score": 0.8355492949485779}, {"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": 63, "score": 0.8348948955535889}, {"content": "Title: Virus strain from a mild COVID-19 patient in Hangzhou represents a new trend in SARS-CoV-2 evolution potentially related to Furin cleavage site Content: The mutations in the SARS-CoV-2 virus genome during COVID-19 dissemination are unclear. In 788 COVID-19 patients from Zhejiang province, we observed decreased rate of severe/critical cases compared with patients in Wuhan. For mechanisms exploration, we isolated one strain of SARS-CoV-2 (ZJ01) from a mild COVID-19 patient. Thirty-five specific gene mutations were identified. Phylogenetic and relative synonymous codon usage analysis suggested that ZJ01 may be a potential evolutionary branch of SARS-CoV-2. We classified 54 global virus strains based on the base (C or T) at positions 8824 and 28247 while ZJ01 has T at both sites. The prediction of the Furin cleavage site (FCS) and sequence alignment indicated that the FCS may be an important site of coronavirus evolution. ZJ01 mutations identified near the FCS (F1-2) caused changes in the structure and electrostatic distribution of the S surface protein, further affecting the binding capacity of Furin. Single-cell sequencing and ACE2-Furin co-expression results confirmed that the Furin expression was especially higher in glands, liver, kidneys, and colon. The evolutionary pattern of SARS-CoV-2 towards FCS formation may result in its clinical symptom becoming closer to HKU-1 and OC43 caused mild flu-like symptoms, further showing its potential in differentiating into mild COVID-19 subtypes.", "qid": 40, "docid": "iljmhdd1", "rank": 64, "score": 0.8348019123077393}, {"content": "Title: Mutational patterns correlate with genome organization in SARS and other coronaviruses Content: Abstract Focused efforts by several international laboratories have resulted in the sequencing of the genome of the causative agent of severe acute respiratory syndrome (SARS), novel coronavirus SARS-CoV, in record time. Using cumulative skew diagrams, I found that mutational patterns in the SARS-CoV genome were strikingly different from other coronaviruses in terms of mutation rates, although they were in general agreement with the model of the coronavirus lifecycle. These findings might be relevant for the development of sequence-based diagnostics and the design of agents to treat SARS.", "qid": 40, "docid": "g68g6xxu", "rank": 65, "score": 0.8343502879142761}, {"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": 66, "score": 0.8342218399047852}, {"content": "Title: Molecular analysis of several in-house rRT-PCR protocols for SARS-CoV-2 detection in the context of genetic variability of the virus in Colombia. Content: The COVID-19 pandemic caused by SARS-CoV-2 is a public health problem unprecedented in the recent history of humanity. Different in-house real-time RT-PCR (rRT-PCR) methods for SARS-CoV-2 diagnosis and the appearance of genomes with mutations in primer regions have been reported. Hence, whole-genome data from locally-circulating SARS-CoV-2 strains contribute to the knowledge of its global variability and the development and fine-tuning of diagnostic protocols. To describe the genetic variability of Colombian SARS-CoV-2 genomes in hybridization regions of oligonucleotides of the main in-house methods for SARS-CoV-2 detection, RNA samples with confirmed SARS-CoV-2 molecular diagnosis were processed through next-generation sequencing. Primers/probes sequences from 13 target regions for SARS-CoV-2 detection suggested by 7 institutions and consolidated by WHO during the early stage of the pandemic were aligned with Muscle tool to assess the genetic variability potentially affecting their performance. Finally, the corresponding codon positions at the 3' end of each primer, the open reading frame inspection was identified for each gene/protein product. Complete SARS-CoV-2 genomes were obtained from 30 COVID-19 cases, representative of the current epidemiology in the country. Mismatches between at least one Colombian sequence and five oligonucleotides targeting the RdRP and N genes were observed. The 3' end of 4 primers aligned to the third codon position, showed high risk of nucleotide substitution and potential mismatches at this critical position. Genetic variability was detected in Colombian SARS-CoV-2 sequences in some of the primer/probe regions for in-house rRT-PCR diagnostic tests available at WHO COVID-19 technical guidelines; its impact on the performance and rates of false-negative results should be experimentally evaluated. The genomic surveillance of SARS-CoV-2 is highly recommended for the early identification of mutations in critical regions and to issue recommendations on specific diagnostic tests to ensure the coverage of locally-circulating genetic variants.", "qid": 40, "docid": "gs9zno1d", "rank": 67, "score": 0.834084153175354}, {"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": 68, "score": 0.8339565992355347}, {"content": "Title: Molecular analysis of several in-house rRT-PCR protocols for SARS-CoV-2 detection in the context of genetic variability of the virus in Colombia Content: The COVID-19 pandemic caused by SARS-CoV-2 is a public health problem unprecedented in the recent history of humanity. Different in-house real-time RT-PCR (rRT-PCR) methods for SARS-CoV-2 diagnosis and the appearance of genomes with mutations in primer regions have been reported. Hence, whole-genome data from locally-circulating SARS-CoV-2 strains contribute to the knowledge of its global variability and the development and fine tuning of diagnostic protocols. To describe the genetic variability of Colombian SARS-CoV-2 genomes in hybridization regions of oligonucleotides of the main in-house methods for SARS-CoV-2 detection, RNA samples with confirmed SARS-CoV-2 molecular diagnosis were processed through next-generation sequencing. Primers/probes sequences from 13 target regions for SARS-CoV-2 detection suggested by 7 institutions and consolidated by WHO during the early stage of the pandemic were aligned with Muscle tool to assess the genetic variability potentially affecting their performance. Finally, the corresponding codon positions at the 3' end of each primer, the open reading frame inspection was identified for each gene/protein product. Complete SARS-CoV-2 genomes were obtained from 30 COVID-19 cases, representative of the current epidemiology in the country. Mismatches between at least one Colombian sequence and five oligonucleotides targeting the RdRP and N genes were observed. The 3' end of 4 primers aligned to the third codon position, showed high risk of nucleotide substitution and potential mismatches at this critical position. Genetic variability was detected in Colombian SARS-CoV-2 sequences in some of the primer/probe regions for in-house rRT-PCR diagnostic tests available at WHO COVID-19 technical guidelines; its impact on the performance and rates of false-negative results should be experimentally evaluated. The genomic surveillance of SARS-CoV-2 is highly recommended for the early identification of mutations in critical regions and to issue recommendations on specific diagnostic tests to ensure the coverage of locally-circulating genetic variants.", "qid": 40, "docid": "vwzdijgg", "rank": 69, "score": 0.8339071869850159}, {"content": "Title: Molecular analysis of several in-house rRT-PCR protocols for SARS-CoV-2 detection in the context of genetic variability of the virus in Colombia Content: The COVID-19 pandemic caused by SARS-CoV-2 is a public health problem unprecedented in the recent history of humanity. Different in-house real-time RT-PCR (rRT-PCR) methods for SARS-CoV-2 diagnosis and the appearance of genomes with mutations in primer regions have been reported. Hence, whole-genome data from locally-circulating SARS-CoV-2 strains contribute to the knowledge of its global variability and the development and fine tuning of diagnostic protocols. To describe the genetic variability of Colombian SARS-CoV-2 genomes in hybridization regions of oligonucleotides of the main in-house methods for SARS-CoV-2 detection, RNA samples with confirmed SARS-CoV-2 molecular diagnosis were processed through next-generation sequencing. Primers/probes sequences from 13 target regions for SARS-CoV-2 detection suggested by 7 institutions and consolidated by WHO during the early stage of the pandemic were aligned with Muscle tool to assess the genetic variability potentially affecting their performance. Finally, the corresponding codon positions at the 3\u2032 end of each primer, the open reading frame inspection was identified for each gene/protein product. Complete SARS-CoV-2 genomes were obtained from 30 COVID-19 cases, representative of the current epidemiology in the country. Mismatches between at least one Colombian sequence and five oligonucleotides targeting the RdRP and N genes were observed. The 3\u2032 end of 4 primers aligned to the third codon position, showed high risk of nucleotide substitution and potential mismatches at this critical position. Genetic variability was detected in Colombian SARS-CoV-2 sequences in some of the primer/probe regions for in-house rRT-PCR diagnostic tests available at WHO COVID-19 technical guidelines; its impact on the performance and rates of false-negative results should be experimentally evaluated. The genomic surveillance of SARS-CoV-2 is highly recommended for the early identification of mutations in critical regions and to issue recommendations on specific diagnostic tests to ensure the coverage of locally-circulating genetic variants.", "qid": 40, "docid": "kr3y2k25", "rank": 70, "score": 0.8335554599761963}, {"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": 71, "score": 0.8333574533462524}, {"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": 72, "score": 0.8327498435974121}, {"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": 73, "score": 0.8327459096908569}, {"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": 74, "score": 0.8327146768569946}, {"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": 40, "docid": "t0cw7l2a", "rank": 75, "score": 0.8325061798095703}, {"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": 76, "score": 0.8323301076889038}, {"content": "Title: Time Series Prediction of COVID-19 by Mutation Rate Analysis using Recurrent Neural Network-based LSTM Model Content: SARS-CoV-2, a novel coronavirus mostly known as COVID-19 has created a global pandemic. The world is now immobilized by this infectious RNA virus. As of May 18, already more than 4.8 million people have been infected and 316k people died. This RNA virus has the ability to do the mutation in the human body. Accurate determination of mutation rates is essential to comprehend the evolution of this virus and to determine the risk of emergent infectious disease. This study explores the mutation rate of the whole genomic sequence gathered from the patient's dataset of different countries. The collected dataset is processed to determine the nucleotide mutation and codon mutation separately. Furthermore, based on the size of the dataset, the determined mutation rate is categorized for four different regions: China, Australia, The United States, and the rest of the World. It has been found that a huge amount of Thymine (T) and Adenine (A) are mutated to other nucleotides for all regions, but codons are not frequently mutating like nucleotides. A recurrent neural network-based Long Short Term Memory (LSTM) model has been applied to predict the future mutation rate of this virus. The LSTM model gives Root Mean Square Error (RMSE) of 0.06 in testing and 0.04 in training, which is an optimized value. Using this train and testing process, the nucleotide mutation rate of 400(th) patient in future time has been predicted. About 0.1% increment in mutation rate is found for mutating of nucleotides from T to C and G, C to G and G to T. While a decrement of 0.1% is seen for mutating of T to A, and A to C. It is found that this model can be used to predict day basis mutation rates if more patient data is available in updated time.", "qid": 40, "docid": "a9fi9ssg", "rank": 77, "score": 0.8320106267929077}, {"content": "Title: Discovery of a 382-nt deletion during the early evolution of SARS-CoV-2 Content: To date, the SARS-CoV-2 genome has been considered genetically more stable than SARS-CoV or MERS-CoV. Here we report a 382-nt deletion covering almost the entire open reading frame 8 (ORF8) of SARS-CoV-2 obtained from eight hospitalized patients in Singapore. The deletion also removes the ORF8 transcription-regulatory sequence (TRS), which in turn enhances the downstream transcription of the N gene. We also found that viruses with the deletion have been circulating for at least four weeks. During the SARS-CoV outbreak in 2003, a number of genetic variants were observed in the human population [1], and similar variation has since been observed across SARS-related CoVs in humans and bats. Overwhelmingly these viruses had mutations or deletions in ORF8, that have been associated with reduced replicative fitness of the virus [2]. This is also consistent with the observation that towards the end of the outbreak sequences obtained from human SARS cases possessed an ORF8 deletion that may be associated with host adaptation [1]. We therefore hypothesise that the major deletion revealed in this study may lead to an attenuated phenotype of SARS-CoV-2.", "qid": 40, "docid": "v5v9bjgs", "rank": 78, "score": 0.8310315608978271}, {"content": "Title: [The genome comparison of SARS-CoV and other coronaviruses]. Content: The genome comparison of inter-species and intra-species can give us much information about the origin and evolution of viruses. There are 137 mutation sites in the 17 genomes of SARS-CoV,and the mutation rate is about 8.04 x 10(-3) substitution/site/year. The distribution of the segregating sites is not steady,the most variable region appears in S1 protein,and the nucleotide sequence of RNA-dependent RNA polymerase has very few mutation sites. The substitution bias of nucleotide acids and amino acids indicates the non-random drift products. The comparison of genome structures of SARS-CoV and other coronaviruses shows that SARS-CoV and IBV share the same genome structure. Phylogenetic analyses of conserved genes of coronaviruses indicate that SARS-CoV is a new branch of coronaviruses and appears more close to the group II coronaviruses. Interestingly,SARS-CoV shares some different features with different groups of coronaviruses. Additional analyses show that the first ORFs between S and E genes of some coronaviruses are transmembrane proteins and share the common motif,indicating the possible common ancestor. From the host distribution of different groups of coronaviruses and the phylogeny of s2m,we can deduce that avian is the probable natural host of SARS-CoV.", "qid": 40, "docid": "6loaq8pq", "rank": 79, "score": 0.8307113647460938}, {"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": 80, "score": 0.8303898572921753}, {"content": "Title: Making sense of mutation: what D614G means for the COVID-19 pandemic remains unclear Content: Abstract Korber et al. (2020) found that a SARS-CoV-2 variant in the spike protein, D614G, rapidly became dominant around the world. While clinical and in vitro data suggest that D614G changes the virus phenotype, the impact of the mutation on transmission, disease, and vaccine and therapeutic development are largely unknown.", "qid": 40, "docid": "rwxhdg8r", "rank": 81, "score": 0.8303787708282471}, {"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": 82, "score": 0.8301115036010742}, {"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": 83, "score": 0.8301113843917847}, {"content": "Title: Multi-Omics and Integrated Network Approach to Unveil Evolutionary Patterns, Mutational Hotspots, Functional Crosstalk and Regulatory Interactions in SARS-CoV-2 Content: SARS-CoV-2 responsible for the pandemic of the Severe Acute Respiratory Syndrome resulting in infections and death of millions worldwide with maximum cases and mortality in USA. The current study focuses on understanding the population specific variations attributing its high rate of infections in specific geographical regions which may help in developing appropriate treatment strategies for COVID-19 pandemic. Rigorous phylogenetic network analysis of 245 complete SARS-CoV-2 genomes inferred five central clades named a (ancestral), b, c, d and e (subtype e1 & e2) showing both divergent and linear evolution types. The clade d & e2 were found exclusively comprising of USA strains with highest known mutations. Clades were distinguished by ten co-mutational combinations in proteins; Nsp3, ORF8, Nsp13, S, Nsp12, Nsp2 and Nsp6 generated by Amino Acid Variations (AAV). Our analysis revealed that only 67.46 % of SNP mutations were carried by amino acid at phenotypic level. T1103P mutation in Nsp3 was predicted to increase the protein stability in 238 strains except six strains which were marked as ancestral type; whereas com (P5731L & Y5768C) in Nsp13 were found in 64 genomes of USA highlighting its 100% co-occurrence. Docking study highlighted mutation (D7611G) caused reduction in binding of Spike proteins with ACE2, but it also showed better interaction with TMPRSS2 receptor which may contribute to its high transmissibility in USA strains. In addition, we found host proteins, MYO5A, MYO5B & MYO5C had maximum interaction with viral hub proteins (Nucleocapsid, Spike & Membrane). Thus, blocking the internalization pathway by inhibiting MYO-5 proteins which could be an effective target for COVID-19 treatment. The functional annotations of the Host-Pathogen Interaction (HPI) network were found to be highly associated with hypoxia and thrombotic conditions confirming the vulnerability and severity of infection in the patients. We also considered the presence of CpG islands in Nsp1 and N proteins which may confers the ability of SARS-CoV-2 to enter and trigger methyltransferase activity inside host cell.", "qid": 40, "docid": "m2px0pyj", "rank": 84, "score": 0.8299661874771118}, {"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": 85, "score": 0.8299205899238586}, {"content": "Title: Coding variants in ACE2 and TMPRSS2 are not major drivers of COVID-19 severity in UK Biobank subjects. Content: There is wide individual variation in response to infection with SARS-CoV-2 and this may be influenced by ethnicity. It is plausible that coding variants in the ACE2 and TMPRSS2 genes might contribute to this variation. Exome sequence data was obtained for 49,953 UK Biobank subjects of whom 74 had tested positive for SARS-CoV-2 and could be presumed to have severe disease because mildly affected subjects were not tested in the relevant period. A weighted burden analysis was carried out using SCOREASSOC to determine whether there were differences between these cases and the other sequenced subjects in the overall burden of rare, damaging variants in ACE2 or TMPRSS2. There were no significant differences in weighted burden scores between cases and controls for either gene. There were no individual DNA sequence variants with a markedly different frequency between cases and controls. Genetic variants affecting the structure and function of the ACE2 and TMPRSS2 proteins are not a major determinant of whether infection with SARS-CoV-2 results in severe symptoms. This research has been conducted using the UK Biobank Resource.", "qid": 40, "docid": "b08rzif3", "rank": 86, "score": 0.8298735022544861}, {"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": 40, "docid": "g1zxlaer", "rank": 87, "score": 0.8298127055168152}, {"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": 88, "score": 0.8294988870620728}, {"content": "Title: Genetic diversity and evolution of SARS-CoV-2 Content: Abstract COVID-19 is a viral respiratory illness caused by a new coronavirus called SARS-CoV-2. The World Health Organization declared the SARS-CoV-2 outbreak a global public health emergency. We performed genetic analyses of eighty-six complete or near-complete genomes of SARS-CoV-2 and revealed many mutations and deletions on coding and non-coding regions. These observations provided evidence of the genetic diversity and rapid evolution of this novel coronavirus.", "qid": 40, "docid": "0nh58odf", "rank": 89, "score": 0.8284684419631958}, {"content": "Title: A Global Effort to Define the Human Genetics of Protective Immunity to SARS-CoV-2 Infection Content: SARS-CoV-2 infection displays immense inter-individual clinical variability, ranging from silent infection to lethal disease. The role of human genetics in determining clinical response to the virus remains unclear. Studies of outliers-individuals remaining uninfected despite viral exposure and healthy young patients with life-threatening disease-present a unique opportunity to reveal human genetic determinants of infection and disease.", "qid": 40, "docid": "zfwwqhxq", "rank": 90, "score": 0.8284220099449158}, {"content": "Title: Implications of SARS-CoV-2 Genetic Diversity and Mutations on Pathogenicity of COVID-19 and Biomedical Interventions Content: ABSTRACT Objective Coronavirus disease 2019 (COVID-19) has caused an unprecedented global health emergency. The COVID-19 pandemic has claimed over 350,000 human lives within five months of its emergence, especially in the USA and the European continent. This study analysed the implications of the genetic diversity and mutations in SARS-CoV-2 on its virulence diversity and investigated how these factors could affect the successful development and application of antiviral chemotherapy, immunotherapy, serodiagnosis, and vaccination. Methods All the suitable and eligible full text articles published between 31st December 2019 and 31st May 2020 were filtered and extracted from \u201cPubMed\u201d, \u201cScopus\u201d, \u201cWeb of Science\u201d, and \u201cHinari\u201d and were critically reviewed. We used the Medical Subject Headings (MeSH) terms \u201cCOVID-19, \u201cMutation\u201d, \u201cGenetic diversity\u201d, \u201cSARS-CoV-2\u201d, \u201cVirulence\u201d, \u201cPathogenicity\u201d, \u201cEvolution\u201d and \u201cSARS-CoV-2 transmission\u201d for this search. Results Our search showed that SARS-CoV-2 has persistently undergone significant mutations in various parts of its non-structural proteins (NSPs), including NSP2 and NSP3, S protein, and RNA-dependent RNA polymerase (RdRp). In particular, the S protein was found to be the key determinant of evolution, transmission, and virulence of SARS-CoV-2, and could be a potential target for vaccine development. Additionally, RdRp could be a major target in the development of antivirals for the treatment of COVID-19. Conclusion Given the critical importance of mutations in the pathogenicity of SARS-CoV-2 and in the development of sero-diagnostics, antivirals, and vaccines, this study recommends continuous molecular surveillance of SARS-CoV-2. This approach would potentially prompt identification of new mutants and their impact on ongoing biomedical interventions and COVID-19 control measures.", "qid": 40, "docid": "ajr7g7pm", "rank": 91, "score": 0.8283456563949585}, {"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": 92, "score": 0.8282954692840576}, {"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": 93, "score": 0.8282076120376587}, {"content": "Title: SARS\u2010CoV\u20102 variants: Relevance for symptom granularity, epidemiology, immunity (herd, vaccines), virus origin and containment? Content: The origin of the SARS\u2010CoV\u20102 virus remains enigmatic. It is likely to be a continuum resulting from inevitable mutations and recombination events. These genetic changes keep developing in the present epidemic. Mutations tending to deplete the genome in its cytosine content will progressively lead to attenuation as a consequence of Muller's ratchet, but this is counteracted by recombination when different mutants co\u2010infect the same host, in particular, in clusters of infection. Monitoring as a function of time the genome sequences in closely related cases is critical to anticipate the future of SARS\u2010CoV\u20102 and hence of COVID\u201019.", "qid": 40, "docid": "lj8t52yl", "rank": 94, "score": 0.8279721140861511}, {"content": "Title: Genetic lesions within the 3a gene of SARS-CoV Content: A series of frameshift mutations within the 3a gene has been observed in culture-derived severe acute respiratory syndrome coronavirus (SARS-CoV). We report here that viral RNA from clinical samples obtained from SARS-CoV infected patients also contains a heterogeneous population of wild-type and mutant 3a transcripts.", "qid": 40, "docid": "covwyddp", "rank": 95, "score": 0.8279136419296265}, {"content": "Title: Genetic diversity and evolution of SARS-CoV-2 Content: COVID-19 is a viral respiratory illness caused by a new coronavirus called SARS-CoV-2. The World Health Organization declared the SARS-CoV-2 outbreak a global public health emergency. We performed genetic analyses of eighty-six complete or near-complete genomes of SARS-CoV-2 and revealed many mutations and deletions on coding and non-coding regions. These observations provided evidence of the genetic diversity and rapid evolution of this novel coronavirus.", "qid": 40, "docid": "can1e8ro", "rank": 96, "score": 0.8278454542160034}, {"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": 97, "score": 0.8275376558303833}, {"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": 98, "score": 0.8272629976272583}, {"content": "Title: Intra-host site-specific polymorphisms of SARS-CoV-2 is consistent across multiple samples and methodologies Content: Despite the potential relevance to clinical outcome, intra-host dynamics of SARS-CoV-2 are unclear. Here, we quantify and characterize intra-host variation in SARS-CoV-2 raw sequence data uploaded to SRA as of 14 April 2020, and compare results between two sequencing methods (amplicon and RNA-Seq). Raw fastq files were quality filtered and trimmed using Trimmomatic, mapped to the WuhanHu1 reference genome using Bowtie2, and variants called with bcftools mpileup. To ensure sufficient coverage, we only included samples with 10X coverage for >90% of the genome (n=406 samples), and only variants with a depth >=10. Derived (i.e. non-reference) alleles were found at 408 sites. The number of polymorphic sites (i.e. sites with multiple alleles) within samples ranged from 0-13, with 72% of samples (295/406) having at least one polymorphic site. Correlation between number of polymorphic sites and coverage was very low for both sequencing methods (R2 < 0.1, p < 0.05). Polymorphisms were observed >1 sample at 66 sites (range: 2-38 samples). The minor allele frequency (MAF) at each shared polymorphic site was 0.03% - 48.5%. 33/66 sites occurred in ORF1a1b, and 37/66 changes were non-synonymous. At 10/66 sites, derived alleles were found in samples sequenced using both methods. Polymorphic amplicon samples were found at 10/10 positions, while polymorphic RNA-Seq samples were found at 7/10 positions. In conclusion, our results suggest that intra-host variation is prevalent among clinical samples. While mutations resulting from amplification and/or sequencing errors cannot be excluded, the observation of shared polymorphic sites with high MAF across multiple samples and sequencing methods is consistent with true underlying variation. Further investigation into intra-host evolutionary dynamics, particularly with longitudinal sampling, is critical for broader understanding of disease progression.", "qid": 40, "docid": "zugrtvyo", "rank": 99, "score": 0.8270514011383057}, {"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": 100, "score": 0.8269954919815063}]}
{"query": "What are the impacts of COVID-19 among African-Americans that differ from the rest of the U.S. population?", "hits": [{"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": 1, "score": 0.893439769744873}, {"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": 2, "score": 0.8834717273712158}, {"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": 3, "score": 0.8834717273712158}, {"content": "Title: COVID-19: A Closer Lens. Content: Generations of nurses to come, now called heroes in the media, will have challenges in providing care for persons during this global pandemic. COVID-19 has impacted all demographics, regardless of race, gender, or socioeconomic class globally. African Americans have experienced a disproportionate number of deaths related to COVID-19 in the New Orleans and surrounding Metropolitan areas. According to the Louisiana Department of Health (2020), fifty-seven percent (57.40%) of the deaths in Louisiana related to COVID-19 have been African American (Black) and fifty-five percent (55.2%) have been males as of May 11, 2020. Social determinants of health are the conditions in which people age and the conditions they are born, grow, age and work. These conditions include neighborhoods, schools, and places of employment. These circumstances are shaped by the distribution of money, power, and resources at global, national, and local levels (World Health Organization, 2020). Years later the same community that comprised \"pre-and post-Katrina\" are now facing this pandemic.", "qid": 41, "docid": "b7x39b3m", "rank": 4, "score": 0.8810549974441528}, {"content": "Title: COVID-19: A Closer Lens Content: Generations of nurses to come, now called heroes in the media, will have challenges in providing care for persons during this global pandemic. COVID-19 has impacted all demographics, regardless of race, gender, or socioeconomic class globally. African Americans have experienced a disproportionate number of deaths related to COVID-19 in the New Orleans and surrounding Metropolitan areas. According to the Louisiana Department of Health (2020), fifty-seven percent (57.40%) of the deaths in Louisiana related to COVID-19 have been African American (Black) and fifty-five percent (55.2%) have been males as of May 11, 2020. Social determinants of health are the conditions in which people age and the conditions they are born, grow, age and work. These conditions include neighborhoods, schools, and places of employment. These circumstances are shaped by the distribution of money, power, and resources at global, national, and local levels (World Health Organization, 2020). Years later the same community that comprised \"pre-and post-Katrina\" are now facing this pandemic.", "qid": 41, "docid": "peys32ve", "rank": 5, "score": 0.8810549378395081}, {"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": 6, "score": 0.8809687495231628}, {"content": "Title: COVID-19 and the Widening Gap in Health Inequity Content: The coronavirus disease 2019 (COVID-19) pandemic has brought to light significant health inequities that have existed in our society for decades. Blacks, Hispanics, Native Americans, and immigrants are the populations most likely to experience disparities related to burden of disease, health care, and health outcomes. Increasingly, national and state statistics on COVID-19 report disproportionately higher mortality rates in blacks. There has never been a more pressing time for us to enact progressive and far-reaching changes in social, economic, and political policies that will shape programs aimed at improving the health of all people living in the United States.", "qid": 41, "docid": "3omm8wkv", "rank": 7, "score": 0.8795178532600403}, {"content": "Title: COVID-19 and the Widening Gap in Health Inequity. Content: The coronavirus disease 2019 (COVID-19) pandemic has brought to light significant health inequities that have existed in our society for decades. Blacks, Hispanics, Native Americans, and immigrants are the populations most likely to experience disparities related to burden of disease, health care, and health outcomes. Increasingly, national and state statistics on COVID-19 report disproportionately higher mortality rates in blacks. There has never been a more pressing time for us to enact progressive and far-reaching changes in social, economic, and political policies that will shape programs aimed at improving the health of all people living in the United States.", "qid": 41, "docid": "sza8r2e1", "rank": 8, "score": 0.8795178532600403}, {"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": 9, "score": 0.8790919780731201}, {"content": "Title: Racial Disparities in COVID-19 Deaths Reveal Harsh Truths About Structural Inequality in America. Content: The Coronavirus disease 2019 (COVID-19) pandemic has unveiled the stark racial disparities that are present in United States (US) and other developed countries today. In recent weeks, several states have released demographic data that highlights the disproportionate rate of COVID-19 infections in racial/ethnic minorities1 . These disparities are likely a result of the structural inequities that minorities face due to factors such as racism, neighborhood segregation, income, housing and education inequality, and poor access to medical care.", "qid": 41, "docid": "a2kjjsq1", "rank": 10, "score": 0.8762096762657166}, {"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": 11, "score": 0.8752734661102295}, {"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": 12, "score": 0.8749061822891235}, {"content": "Title: Policy Recommendations to Address High Risk of COVID-19 Among Immigrants Content: The health and economic consequences of COVID-19 will be devastatingly widespread, but the populations that will suffer most are those who have experienced longstanding health disparities. For example, emerging evidence strongly suggests that incidence and case fatality rates are higher among Blacks than Whites.1 Immigrants are among the groups most likely to experience disproportionate effects from COVID-19. Unlike race/ethnicity, however, nativity and citizenship status are not included on the Centers for Disease Control and Prevention's (CDC's) coronavirus case report form,2 so data regarding testing and spread across immigrant groups are likely to remain scarce. Information from other health and social surveys-including data that I present in Table 1-suggest that noncitizens experience barriers to physical distancing that will place them at high risk of contracting COVID-19 and have high levels of disadvantage that leave them vulnerable to its economic effects. I recommend three policy changes to address the high health and economic risk among noncitizens, goals that are in the best interest of public health and the broader economy. (Am J Public Health. Published online ahead of print June 25, 2020: e1-e3. doi:10.2105/AJPH.2020.305792).", "qid": 41, "docid": "71rhjy74", "rank": 13, "score": 0.8733544945716858}, {"content": "Title: Policy Recommendations to Address High Risk of COVID-19 Among Immigrants. Content: The health and economic consequences of COVID-19 will be devastatingly widespread, but the populations that will suffer most are those who have experienced longstanding health disparities. For example, emerging evidence strongly suggests that incidence and case fatality rates are higher among Blacks than Whites.1 Immigrants are among the groups most likely to experience disproportionate effects from COVID-19. Unlike race/ethnicity, however, nativity and citizenship status are not included on the Centers for Disease Control and Prevention's (CDC's) coronavirus case report form,2 so data regarding testing and spread across immigrant groups are likely to remain scarce. Information from other health and social surveys-including data that I present in Table 1-suggest that noncitizens experience barriers to physical distancing that will place them at high risk of contracting COVID-19 and have high levels of disadvantage that leave them vulnerable to its economic effects. I recommend three policy changes to address the high health and economic risk among noncitizens, goals that are in the best interest of public health and the broader economy. (Am J Public Health. Published online ahead of print June 25, 2020: e1-e3. doi:10.2105/AJPH.2020.305792).", "qid": 41, "docid": "bb8u9nmj", "rank": 14, "score": 0.8733544945716858}, {"content": "Title: Disparities In Outcomes Among COVID-19 Patients In A Large Health Care System In California. Content: As the coronavirus disease (COVID-19) pandemic spreads throughout the United States, evidence is mounting that racial and ethnic minorities and socioeconomically disadvantaged groups are bearing a disproportionate burden of illness and death. We conducted a retrospective cohort analysis of COVID-19 patients at Sutter Health, a large integrated health care system in northern California, to measure potential disparities. We used Sutter's integrated electronic health record to identify adults with suspected and confirmed COVID-19, and used multivariable logistic regression to assess risk of hospitalization, adjusting for known risk factors, such as race/ethnicity, sex, age, health, and socioeconomic variables. We analyzed 1,052 confirmed cases of COVID-19 from January 1-April 8, 2020. Among our findings, we observed that, compared with non-Hispanic white patients, African Americans had 2.7 times the odds of hospitalization, after adjusting for age, sex, comorbidities, and income. We explore possible explanations for this, including societal factors that either result in barriers to timely access to care or create circumstances in which patients view delaying care as the most sensible option. Our study provides real-world evidence that there are racial and ethnic disparities in the presentation of COVID-19. [Editor's Note: This Fast Track Ahead Of Print article is the accepted version of the peer-reviewed manuscript. The final edited version will appear in an upcoming issue of Health Affairs.].", "qid": 41, "docid": "s0xhfla6", "rank": 15, "score": 0.871640682220459}, {"content": "Title: Social Vulnerability and Racial Inequality in COVID-19 Deaths in Chicago Content: Although the current COVID-19 crisis is felt globally, at the local level, COVID-19 has disproportionately affected poor, highly segregated African American communities in Chicago. To understand the emerging pattern of racial inequality in the effects of COVID-19, we examined the relative burden of social vulnerability and health risk factors. We found significant spatial clusters of social vulnerability and risk factors, both of which are significantly associated with the increased COVID-19-related death rate. We also found that a higher percentage of African Americans was associated with increased levels of social vulnerability and risk factors. In addition, the proportion of African American residents has an independent effect on the COVID-19 death rate. We argue that existing inequity is often highlighted in emergency conditions. The disproportionate effects of COVID-19 in African American communities are a reflection of racial inequality and social exclusion that existed before the COVID-19 crisis.", "qid": 41, "docid": "aa9zegjr", "rank": 16, "score": 0.8706291317939758}, {"content": "Title: Social Vulnerability and Racial Inequality in COVID-19 Deaths in Chicago. Content: Although the current COVID-19 crisis is felt globally, at the local level, COVID-19 has disproportionately affected poor, highly segregated African American communities in Chicago. To understand the emerging pattern of racial inequality in the effects of COVID-19, we examined the relative burden of social vulnerability and health risk factors. We found significant spatial clusters of social vulnerability and risk factors, both of which are significantly associated with the increased COVID-19-related death rate. We also found that a higher percentage of African Americans was associated with increased levels of social vulnerability and risk factors. In addition, the proportion of African American residents has an independent effect on the COVID-19 death rate. We argue that existing inequity is often highlighted in emergency conditions. The disproportionate effects of COVID-19 in African American communities are a reflection of racial inequality and social exclusion that existed before the COVID-19 crisis.", "qid": 41, "docid": "gn8uwuca", "rank": 17, "score": 0.8706291317939758}, {"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": 18, "score": 0.8700557947158813}, {"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": 19, "score": 0.8666857481002808}, {"content": "Title: Similarities and differences in COVID-19 awareness, concern, and symptoms by race and ethnicity in the United States: A cross-sectional survey Content: BACKGROUND: Existing health disparities based on race and ethnicity in the United States are contributing to disparities in morbidity and mortality in the COVID-19 pandemic. We conducted an online survey of American adults to assess similarities and differences by race and ethnicity groups with respect to COVID-19 symptoms, estimates of the extent of the pandemic, knowledge of control measures, and stigma. OBJECTIVE: Describe similarities and differences in COVID-19 symptoms, knowledge, and beliefs by race and ethnicity among adults in the US. METHODS: We conducted a cross-sectional survey from March 27, 2020 through April 1, 2020. Participants were recruited on social media platforms and completed the survey on a secure, online survey platform. We used chi square tests to compare characteristics related to COVID-19 by race and ethnicity. Statistical tests were corrected using the Holm Bonferroni correction to account for multiple comparisons. RESULTS: A total of 1,435 (3.6% Asian, 11.0% non-Hispanic Black, 38.2% Hispanic, 40.9% non-Hispanic white, and 6.3% other or multiple races) participants completed the survey. Only one symptom (sore throat) was found to be different based on race and ethnicity (p = 0.003), which was less frequently reported by Asian (5.8%), non-Hispanic Black (5.7%), and other/multiple race (8.9%) participants compared to those who were Hispanic (18.1%) or non-Hispanic white (16.2%). Non-Hispanic white and Asian participants were more likely to estimate that the number of current cases was at least 100,000 (p = 0.004) and were more likely to answer all 14 COVID-19 knowledge scale questions correctly (Asian, 25.0%; non-Hispanic White, 30.7%) compared to Hispanic (19.7%) and non-Hispanic Black (15.8%) participants. CONCLUSIONS: We observed differences with respect to knowledge of appropriate methods to prevent infection by the novel coronavirus that causes COVID-19. Deficits in knowledge of proper control methods might further exacerbate existing race/ethnicity disparities. Additional research is needed to identify trusted sources of information in Hispanic and non-Hispanic Black communities and effective messaging to disseminate correct COVID-19 prevention and treatment information.", "qid": 41, "docid": "y1shr2xa", "rank": 20, "score": 0.8654573559761047}, {"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": 21, "score": 0.8654211759567261}, {"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": 22, "score": 0.8642538785934448}, {"content": "Title: Six feet apart or six feet under: The impact of COVID-19 on the Black community Content: To date, 110,000+ people in the United States have died from the COVID-19 pandemic. In this paper, the authors will discuss COVID-19 relative to Black people and their overrepresentation among those who are infected and died from the disease. Their dying, death, and grief experiences are explored through a cultural and spiritual lens. The physical distancing, social isolation, misinformation, and restrictive burials and cremations now elicited by this unprecedented pandemic have had diminished familial, cultural, emotional, and economic impacts on the Black community. Implications for public health and Black peoples' involvement in the political process are also addressed.", "qid": 41, "docid": "i2b9py8e", "rank": 23, "score": 0.8634788393974304}, {"content": "Title: Six feet apart or six feet under: The impact of COVID-19 on the Black community. Content: To date, 110,000+ people in the United States have died from the COVID-19 pandemic. In this paper, the authors will discuss COVID-19 relative to Black people and their overrepresentation among those who are infected and died from the disease. Their dying, death, and grief experiences are explored through a cultural and spiritual lens. The physical distancing, social isolation, misinformation, and restrictive burials and cremations now elicited by this unprecedented pandemic have had diminished familial, cultural, emotional, and economic impacts on the Black community. Implications for public health and Black peoples' involvement in the political process are also addressed.", "qid": 41, "docid": "phcd8b4m", "rank": 24, "score": 0.8634788393974304}, {"content": "Title: The COVID-19 Pandemic: a Call to Action to Identify and Address Racial and Ethnic Disparities Content: The Coronavirus disease 2019 (COVID-19) pandemic has significantly impacted and devastated the world. As the infection spreads, the projected mortality and economic devastation are unprecedented. In particular, racial and ethnic minorities may be at a particular disadvantage as many already assume the status of a marginalized group. Black Americans have a long-standing history of disadvantage and are in a vulnerable position to experience the impact of this crisis and the myth of Black immunity to COVID-19 is detrimental to promoting and maintaining preventative measures. We are the first to present the earliest available data in the peer-reviewed literature on the racial and ethnic distribution of COVID-19-confirmed cases and fatalities in the state of Connecticut. We also seek to explode the myth of Black immunity to the virus. Finally, we call for a National Commission on COVID-19 Racial and Ethnic Health Disparities to further explore and respond to the unique challenges that the crisis presents for Black and Brown communities.", "qid": 41, "docid": "orz4be90", "rank": 25, "score": 0.8632832765579224}, {"content": "Title: Disparities In Outcomes Among COVID-19 Patients In A Large Health Care System In California Content: As the novel coronavirus disease (COVID-19) pandemic spreads throughout the United States, evidence is mounting that racial and ethnic minorities and socioeconomically disadvantaged groups are bearing a disproportionate burden of illness and death. We conducted a retrospective cohort analysis of COVID-19 patients at Sutter Health, a large integrated health system in northern California, to measure potential disparities. We used Sutter's integrated electronic health record to identify adults with suspected and confirmed COVID-19, and we used multivariable logistic regression to assess risk of hospitalization, adjusting for known risk factors, such as race/ethnicity, sex, age, health, and socioeconomic variables. We analyzed 1,052 confirmed cases of COVID-19 from the period January 1-April 8, 2020. Among our findings, we observed that compared with non-Hispanic white patients, non-Hispanic African American patients had 2.7 times the odds of hospitalization, after adjustment for age, sex, comorbidities, and income. We explore possible explanations for this, including societal factors that either result in barriers to timely access to care or create circumstances in which patients view delaying care as the most sensible option. Our study provides real-world evidence of racial and ethnic disparities in the presentation of COVID-19.", "qid": 41, "docid": "xdy9c88p", "rank": 26, "score": 0.863205075263977}, {"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": 27, "score": 0.8621608018875122}, {"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": 28, "score": 0.8619081974029541}, {"content": "Title: Covid-19 by Race and Ethnicity: A National Cohort Study of 6 Million United States Veterans Content: BACKGROUND: There is growing concern that racial and ethnic minority communities around the world are experiencing a disproportionate burden of morbidity and mortality from symptomatic SARS-Cov-2 infection or coronavirus disease 2019 (Covid-19). Most studies investigating racial and ethnic disparities to date have focused on hospitalized patients or have not characterized who received testing or those who tested positive for Covid-19. OBJECTIVE: To compare patterns of testing and test results for coronavirus 2019 (Covid-19) and subsequent mortality by race and ethnicity in the largest integrated healthcare system in the United States. DESIGN: Retrospective cohort study. SETTING: United States Department of Veterans Affairs (VA). PARTICIPANTS: 5,834,543 individuals in care, among whom 62,098 were tested and 5,630 tested positive for Covid-19 between February 8 and May 4, 2020. EXPOSURES: Self-reported race/ethnicity. MAIN OUTCOME MEASURES: We evaluated associations between race/ethnicity and receipt of Covid-19 testing, a positive test result, and 30-day mortality, accounting for a wide range of demographic and clinical risk factors including comorbid conditions, site of care, and urban versus rural residence. RESULTS: Among all individuals in care, 74% were non-Hispanic white (white), 19% non-Hispanic black (black), and 7% Hispanic. Compared with white individuals, black and Hispanic individuals were more likely to be tested for Covid-19 (tests per 1000: white=9.0, [95% CI 8.9 to 9.1]; black=16.4, [16.2 to 16.7]; and Hispanic=12.2, [11.9 to 12.5]). While individuals from minority backgrounds were more likely to test positive (black vs white: OR 1.96, 95% CI 1.81 to 2.12; Hispanic vs white: OR 1.73, 95% CI 1.53 to 1.96), 30-day mortality did not differ by race/ethnicity (black vs white: OR 0.93, 95% CI 0.64 to 1.33; Hispanic vs white: OR 1.07, 95% CI 0.61 to 1.87). CONCLUSIONS: Black and Hispanic individuals are experiencing an excess burden of Covid-19 not entirely explained by underlying medical conditions or where they live or receive care. While there was no observed difference in mortality by race or ethnicity, our findings may underestimate risk in the broader US population as health disparities tend to be reduced in VA.", "qid": 41, "docid": "tnp0lrrh", "rank": 29, "score": 0.8615343570709229}, {"content": "Title: Inequity and the disproportionate impact of COVID-19 on communities of color in the United States: The need for a trauma-informed social justice response. Content: COVID-19 has had disproportionate contagion and fatality in Black, Latino, and Native American communities and among the poor in the United States. Toxic stress resulting from racial and social inequities have been magnified during the pandemic, with implications for poor physical and mental health and socioeconomic outcomes. It is imperative that our country focus and invest in addressing health inequities and work across sectors to build self-efficacy and long-term capacity within communities and systems of care serving the most disenfranchised, now and in the aftermath of the COVID-19 epidemic. (PsycInfo Database Record (c) 2020 APA, all rights reserved).", "qid": 41, "docid": "q7telkky", "rank": 30, "score": 0.8615256547927856}, {"content": "Title: Inequity and the disproportionate impact of COVID-19 on communities of color in the United States: The need for a trauma-informed social justice response Content: COVID-19 has had disproportionate contagion and fatality in Black, Latino, and Native American communities and among the poor in the United States. Toxic stress resulting from racial and social inequities have been magnified during the pandemic, with implications for poor physical and mental health and socioeconomic outcomes. It is imperative that our country focus and invest in addressing health inequities and work across sectors to build self-efficacy and long-term capacity within communities and systems of care serving the most disenfranchised, now and in the aftermath of the COVID-19 epidemic. (PsycInfo Database Record (c) 2020 APA, all rights reserved).", "qid": 41, "docid": "81crwncn", "rank": 31, "score": 0.8615255951881409}, {"content": "Title: Multivariate Analysis of Factors Affecting COVID-19 Case and Death Rate in U.S. Counties: The Significant Effects of Black Race and Temperature Content: Objectives: Coronavirus disease-19 (COVID-19) has spread rapidly around the world, and many risk factors including patient demographics, social determinants of health, environmental variables, underlying health conditions, and adherence to social distancing have been hypothesized to affect case and death rates. However, little has been done to account for the potential confounding effects of these factors. Using a large multivariate analysis, this study illuminates modulators of COVID-19 incidence and mortality in U.S. counties while controlling for risk factors across multiple domains. Methods: Data on COVID-19 and various risk factors in all U.S. counties was collected from publicly available data sources through April 14, 2020. Counties with at least 50 COVID-19 cases were included in case analyses and those with at least 10 deaths were included in mortality models. The 661 counties meeting inclusion criteria for number of cases were grouped into quartiles and comparisons of risk factors were made using t-tests between the highest and lowest quartiles. Similar comparisons for 217 counties were made for above average and below average deaths/100,000. Adjusted linear and logistic regression analyses were performed to evaluate the independent effects of factors that significantly impacted cases and deaths. Results: Univariate analyses demonstrated numerous significant differences between cohorts for both cases and deaths. Risk factors associated with increased cases and/or deaths per 100,000 included increased GDP per capita, decreased social distancing, increased age, increased percent Black, decreased percent Hispanic, decreased percent Asian, decreased health, increased poverty, increased diabetes, increased coronary heart disease, increased physical inactivity, increased alcohol consumption, increased tobacco use, and decreased access to primary care. Multivariate regression analyses demonstrated Black race is a risk factor for worse COVID-19 outcome independent of comorbidities, poverty, access to health care, and other mitigating factors. Lower daily temperatures was also an independent risk factor in case load but not deaths. Conclusions: U.S. counties with a higher proportion of Black residents are associated with increased COVID-19 cases and deaths. However, the various suggested mechanisms, such as socioeconomic and healthcare predispositions, did not appear to drive the effect of race in our model. Counties with higher average daily temperatures are also associated with decreased COVID-19 cases but not deaths. Several theories are posited to explain these findings, including prevalence of vitamin D deficiency. Additional studies are needed to further understand these effects.", "qid": 41, "docid": "vp4kq39i", "rank": 32, "score": 0.8608736991882324}, {"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": 33, "score": 0.8605761528015137}, {"content": "Title: Even more to handle: Additional sources of stress and trauma for clients from marginalized racial and ethnic groups in the United States during the COVID-19 pandemic Content: In addition the general stressors occurring as a result of the COVID-19 pandemic, individuals who are members of marginalized racial or ethnic minority groups in the United States may face additional stressors, such as pandemic-related, racially-based prejudice and discrimination and the magnification of pre-existing health disparities and their effects. Such stressors may increase pandemic-related and general health risks both directly and indirectly and increase the risk for both general and traumatic stress. These stressors and their historical and social contexts are discussed, and implications for clinicians are provided.", "qid": 41, "docid": "z3j9sbzf", "rank": 34, "score": 0.8603257536888123}, {"content": "Title: Assessing Differential Impacts of COVID-19 on Black Communities Content: PURPOSE: Given incomplete data reporting by race, we used data on COVID-19 cases and deaths in US counties to describe racial disparities in COVID-19 disease and death and associated determinants. METHODS: Using publicly available data (accessed April 13, 2020), predictors of COVID-19 cases and deaths were compared between disproportionately (>13%) black and all other (<13% black) counties. Rate ratios were calculated and population attributable fractions (PAF) were estimated using COVID-19 cases and deaths via zero-inflated negative binomial regression model. National maps with county-level data and an interactive scatterplot of COVID-19 cases were generated. RESULTS: Nearly ninety-seven percent of disproportionately black counties (656/677) reported a case and 49% (330/677) reported a death versus 81% (1987/2,465) and 28% (684/ 2465), respectively, for all other counties. Counties with higher proportions of black people have higher prevalence of comorbidities and greater air pollution. Counties with higher proportions of black residents had more COVID-19 diagnoses (RR 1.24, 95% CI 1.17-1.33) and deaths (RR 1.18, 95% CI 1.00-1.40), after adjusting for county-level characteristics such as age, poverty, comorbidities, and epidemic duration. COVID-19 deaths were higher in disproportionally black rural and small metro counties. The PAF of COVID-19 diagnosis due to lack of health insurance was 3.3% for counties with <13% black residents and 4.2% for counties with >13% black residents. CONCLUSIONS: Nearly twenty-two percent of US counties are disproportionately black and they accounted for 52% of COVID-19 diagnoses and 58% of COVID-19 deaths nationally. County-level comparisons can both inform COVID-19 responses and identify epidemic hot spots. Social conditions, structural racism, and other factors elevate risk for COVID-19 diagnoses and deaths in black communities.", "qid": 41, "docid": "kr86wlax", "rank": 35, "score": 0.8592684268951416}, {"content": "Title: Assessing Differential Impacts of COVID-19 on Black Communities Content: Purpose: Given incomplete data reporting by race, we used data on COVID-19 cases and deaths in US counties to describe racial disparities in COVID-19 disease and death and associated determinants. Methods: Using publicly available data (accessed April 13, 2020), predictors of COVID-19 cases and deaths were compared between disproportionately (>13%) black and all other (<13% black) counties. Rate ratios were calculated and population attributable fractions (PAF) were estimated using COVID-19 cases and deaths via zero-inflated negative binomial regression model. National maps with county-level data and an interactive scatterplot of COVID-19 cases were generated. Results: Nearly ninety-seven percent of disproportionately black counties (656/677) reported a case and 49% (330/677) reported a death versus 81% (1987/2,465) and 28% (684/ 2465), respectively, for all other counties. Counties with higher proportions of black people have higher prevalence of comorbidities and greater air pollution. Counties with higher proportions of black residents had more COVID-19 diagnoses (RR 1.24, 95% CI 1.17-1.33) and deaths (RR 1.18, 95% CI 1.00-1.40), after adjusting for county-level characteristics such as age, poverty, comorbidities, and epidemic duration. COVID-19 deaths were higher in disproportionally black rural and small metro counties. The PAF of COVID-19 diagnosis due to lack of health insurance was 3.3% for counties with <13% black residents and 4.2% for counties with >13% black residents. Conclusions: Nearly twenty-two percent of US counties are disproportionately black and they accounted for 52% of COVID-19 diagnoses and 58% of COVID-19 deaths nationally. County-level comparisons can both inform COVID-19 responses and identify epidemic hot spots. Social conditions, structural racism, and other factors elevate risk for COVID-19 diagnoses and deaths in black communities.", "qid": 41, "docid": "dl3vkqas", "rank": 36, "score": 0.8592684268951416}, {"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": 37, "score": 0.8590776324272156}, {"content": "Title: Hospitalization and Mortality among Black Patients and White Patients with Covid-19 Content: BACKGROUND: Many reports on coronavirus disease 2019 (Covid-19) have highlighted age- and sex-related differences in health outcomes. More information is needed about racial and ethnic differences in outcomes from Covid-19. METHODS: In this retrospective cohort study, we analyzed data from patients seen within an integrated-delivery health system (Ochsner Health) in Louisiana between March 1 and April 11, 2020, who tested positive for severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2, the virus that causes Covid-19) on qualitative polymerase-chain-reaction assay. The Ochsner Health population is 31% black non-Hispanic and 65% white non-Hispanic. The primary outcomes were hospitalization and in-hospital death. RESULTS: A total of 3626 patients tested positive, of whom 145 were excluded (84 had missing data on race or ethnic group, 9 were Hispanic, and 52 were Asian or of another race or ethnic group). Of the 3481 Covid-19-positive patients included in our analyses, 60.0% were female, 70.4% were black non-Hispanic, and 29.6% were white non-Hispanic. Black patients had higher prevalences of obesity, diabetes, hypertension, and chronic kidney disease than white patients. A total of 39.7% of Covid-19-positive patients (1382 patients) were hospitalized, 76.9% of whom were black. In multivariable analyses, black race, increasing age, a higher score on the Charlson Comorbidity Index (indicating a greater burden of illness), public insurance (Medicare or Medicaid), residence in a low-income area, and obesity were associated with increased odds of hospital admission. Among the 326 patients who died from Covid-19, 70.6% were black. In adjusted time-to-event analyses, variables that were associated with higher in-hospital mortality were increasing age and presentation with an elevated respiratory rate; elevated levels of venous lactate, creatinine, or procalcitonin; or low platelet or lymphocyte counts. However, black race was not independently associated with higher mortality (hazard ratio for death vs. white race, 0.89; 95% confidence interval, 0.68 to 1.17). CONCLUSIONS: In a large cohort in Louisiana, 76.9% of the patients who were hospitalized with Covid-19 and 70.6% of those who died were black, whereas blacks comprise only 31% of the Ochsner Health population. Black race was not associated with higher in-hospital mortality than white race, after adjustment for differences in sociodemographic and clinical characteristics on admission.", "qid": 41, "docid": "e76foj38", "rank": 38, "score": 0.8586599826812744}, {"content": "Title: Black-White Risk Differentials in COVID-19 (SARS-COV2) Transmission, Mortality and Case Fatality in the United States: Translational Epidemiologic Perspective and Challenges Content: BACKGROUND: Social and health inequities predispose vulnerable populations to adverse morbidity and mortality outcomes of epidemics and pandemics. While racial disparities in cumulative incidence (CmI) and mortality from the influenza pandemics of 1918 and 2009 implicated Blacks with survival disadvantage relative to Whites in the United States, COVID-19 currently indicates comparable disparities. We aimed to: (a) assess COVID-19 CmI by race, (b) determine the Black-White case fatality (CF) and risk differentials, and (c) apply explanatory model for mortality risk differentials. METHODS: COVID-19 data on confirmed cases and deaths by selective states health departments were assessed using a cross-sectional ecologic design. Chi-square was used for CF independence, while binomial regression model for the Black-White risk differentials. RESULTS: The COVID-19 mortality CmI indicated Blacks/AA with 34% of the total mortality in the United States, albeit their 13% population size. The COVID-19 CF was higher among Blacks/AA relative to Whites; Maryland, (2.7% vs. 2.5%), Wisconsin (7.4% vs. 4.8%), Illinois (4.8% vs. 4.2%), Chicago (5.9% vs. 3.2%), Detroit (Michigan), 7.2% and St. John the Baptist Parish (Louisiana), 7.9%. Blacks/AA compared to Whites in Michigan were 15% more likely to die, CmI risk ratio (CmIRR) = 1.15, 95% CI, 1.01-1.32. Blacks/AA relative to Whites in Illinois were 13% more likely to die, CmIRR = 1.13, 95% CI, 0.93-1.39, while Blacks/AA compared to Whites in Wisconsin were 51% more likely to die, CmIRR = 1.51, 95% CI, 1.10-2.10. In Chicago, Blacks/AA were more than twice as likely to die, CmIRR = 2.24, 95% CI, 1.36-3.88. CONCLUSION: Substantial racial/ethnic disparities are observed in COVID-19 CF and mortality with Blacks/AA disproportionately affected across the United States.", "qid": 41, "docid": "9cy1jrw9", "rank": 39, "score": 0.8585325479507446}, {"content": "Title: The association of race and COVID-19 mortality Content: BACKGROUND: COVID-19 mortality disproportionately affects the Black population in the United States (US). To explore this association a cohort study was undertaken. METHODS: We assembled a cohort of 505,992 patients receiving ambulatory care at Bronx Montefiore Health System (BMHS) between 1/1/18 and 1/1/20 to evaluate the relative risk of hospitalization and death in two time-periods, the pre-COVID time-period (1/1/20\u20132/15/20) and COVID time-period (3/1/20\u20134/15/20). COVID testing, hospitalization and mortality were determined with the Black and Hispanic patient population compared separately to the White population using logistic modeling. Evaluation of the interaction of pre-COVID and COVID time periods and race, with respect to mortality was completed. FINDINGS: A total of 9,286/505,992 (1.8%) patients were hospitalized during either or both pre-COVID or COVID periods. Compared to Whites the relative risk of hospitalization of Black patients did not increase in the COVID period (p for interaction=0.12). In the pre- COVID period, compared to Whites, the odds of death for Blacks and Hispanics adjusted for comorbidity was statistically equivalent. In the COVID period compared to Whites the adjusted odds of death for Blacks was 1.6 (95% CI 1.2\u20132.0, p = 0.001). There was a significant increase in Black mortality risk from pre-COVID to COVID periods (p for interaction=0.02). Adjustment for relevant clinical and social indices attenuated but did not fully explain the observed difference in Black mortality. INTERPRETATION: The BMHS COVID experience demonstrates that Blacks do have a higher mortality with COVID incompletely explained by age, multiple reported comorbidities and available metrics of sociodemographic disparity. FUNDING: N/A", "qid": 41, "docid": "ncfo2v89", "rank": 40, "score": 0.858012855052948}, {"content": "Title: Hospitalization and Mortality among Black Patients and White Patients with Covid-19 Content: BACKGROUND: Many reports on coronavirus disease 2019 (Covid-19) have highlighted age- and sex-related differences in health outcomes. More information is needed about racial and ethnic differences in outcomes from Covid-19. METHODS: In this retrospective cohort study, we analyzed data from patients seen within an integrated-delivery health system (Ochsner Health) in Louisiana between March 1 and April 11, 2020, who tested positive for severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2, the virus that causes Covid-19) on qualitative polymerase-chain-reaction assay. The Ochsner Health population is 31% black non-Hispanic and 65% white non-Hispanic. The primary outcomes were hospitalization and in-hospital death. RESULTS: A total of 3626 patients tested positive, of whom 145 were excluded (84 had missing data on race or ethnic group, 9 were Hispanic, and 52 were Asian or of another race or ethnic group). Of the 3481 Covid-19\u2013positive patients included in our analyses, 60.0% were female, 70.4% were black non-Hispanic, and 29.6% were white non-Hispanic. Black patients had higher prevalences of obesity, diabetes, hypertension, and chronic kidney disease than white patients. A total of 39.7% of Covid-19\u2013positive patients (1382 patients) were hospitalized, 76.9% of whom were black. In multivariable analyses, black race, increasing age, a higher score on the Charlson Comorbidity Index (indicating a greater burden of illness), public insurance (Medicare or Medicaid), residence in a low-income area, and obesity were associated with increased odds of hospital admission. Among the 326 patients who died from Covid-19, 70.6% were black. In adjusted time-to-event analyses, variables that were associated with higher in-hospital mortality were increasing age and presentation with an elevated respiratory rate; elevated levels of venous lactate, creatinine, or procalcitonin; or low platelet or lymphocyte counts. However, black race was not independently associated with higher mortality (hazard ratio for death vs. white race, 0.89; 95% confidence interval, 0.68 to 1.17). CONCLUSIONS: In a large cohort in Louisiana, 76.9% of the patients who were hospitalized with Covid-19 and 70.6% of those who died were black, whereas blacks comprise only 31% of the Ochsner Health population. Black race was not associated with higher in-hospital mortality than white race, after adjustment for differences in sociodemographic and clinical characteristics on admission.", "qid": 41, "docid": "fm8koqjd", "rank": 41, "score": 0.8579033613204956}, {"content": "Title: Black\u2013White Risk Differentials in COVID-19 (SARS-COV2) Transmission, Mortality and Case Fatality in the United States: Translational Epidemiologic Perspective and Challenges Content: Background: Social and health inequities predispose vulnerable populations to adverse morbidity and mortality outcomes of epidemics and pandemics. While racial disparities in cumulative incidence (CmI) and mortality from the influenza pandemics of 1918 and 2009 implicated Blacks with survival disadvantage relative to Whites in the United States, COVID-19 currently indicates comparable disparities. We aimed to: (a) assess COVID-19 CmI by race, (b) determine the Black\u2013White case fatality (CF) and risk differentials, and (c) apply explanatory model for mortality risk differentials. Methods: COVID-19 data on confirmed cases and deaths by selective states health departments were assessed using a cross-sectional ecologic design. Chi-square was used for CF independence, while binomial regression model for the Black\u2013White risk differentials. Results: The COVID-19 mortality CmI indicated Blacks/AA with 34% of the total mortality in the United States, albeit their 13% population size. The COVID-19 CF was higher among Blacks/AA relative to Whites; Maryland, (2.7% vs. 2.5%), Wisconsin (7.4% vs. 4.8%), Illinois (4.8% vs. 4.2%), Chicago (5.9% vs. 3.2%), Detroit (Michigan), 7.2% and St. John the Baptist Parish (Louisiana), 7.9%. Blacks/AA compared to Whites in Michigan were 15% more likely to die, CmI risk ratio (CmIRR) = 1.15, 95% CI, 1.01\u20131.32. Blacks/AA relative to Whites in Illinois were 13% more likely to die, CmIRR = 1.13, 95% CI, 0.93\u20131.39, while Blacks/AA compared to Whites in Wisconsin were 51% more likely to die, CmIRR = 1.51, 95% CI, 1.10\u20132.10. In Chicago, Blacks/AA were more than twice as likely to die, CmIRR = 2.24, 95% CI, 1.36\u20133.88. Conclusion: Substantial racial/ethnic disparities are observed in COVID-19 CF and mortality with Blacks/AA disproportionately affected across the United States.", "qid": 41, "docid": "96001cps", "rank": 42, "score": 0.8575226068496704}, {"content": "Title: Similarities and Differences in COVID-19 Awareness, Concern, and Symptoms by Race and Ethnicity in the United States: Cross-Sectional Survey Content: BACKGROUND: Existing health disparities based on race and ethnicity in the United States are contributing to disparities in morbidity and mortality during the coronavirus disease (COVID-19) pandemic. We conducted an online survey of American adults to assess similarities and differences by race and ethnicity with respect to COVID-19 symptoms, estimates of the extent of the pandemic, knowledge of control measures, and stigma. OBJECTIVE: The aim of this study was to describe similarities and differences in COVID-19 symptoms, knowledge, and beliefs by race and ethnicity among adults in the United States. METHODS: We conducted a cross-sectional survey from March 27, 2020 through April 1, 2020. Participants were recruited on social media platforms and completed the survey on a secure web-based survey platform. We used chi-square tests to compare characteristics related to COVID-19 by race and ethnicity. Statistical tests were corrected using the Holm Bonferroni correction to account for multiple comparisons. RESULTS: A total of 1435 participants completed the survey; 52 (3.6%) were Asian, 158 (11.0%) were non-Hispanic Black, 548 (38.2%) were Hispanic, 587 (40.9%) were non-Hispanic White, and 90 (6.3%) identified as other or multiple races. Only one symptom (sore throat) was found to be different based on race and ethnicity (P=.003); this symptom was less frequently reported by Asian (3/52, 5.8%), non-Hispanic Black (9/158, 5.7%), and other/multiple race (8/90, 8.9%) participants compared to those who were Hispanic (99/548, 18.1%) or non-Hispanic White (95/587, 16.2%). Non-Hispanic White and Asian participants were more likely to estimate that the number of current cases was at least 100,000 (P=.004) and were more likely to answer all 14 COVID-19 knowledge scale questions correctly (Asian participants, 13/52, 25.0%; non-Hispanic White participants, 180/587, 30.7%) compared to Hispanic (108/548, 19.7%) and non-Hispanic Black (25/158, 15.8%) participants. CONCLUSIONS: We observed differences with respect to knowledge of appropriate methods to prevent infection by the novel coronavirus that causes COVID-19. Deficits in knowledge of proper control methods may further exacerbate existing race/ethnicity disparities. Additional research is needed to identify trusted sources of information in Hispanic and non-Hispanic Black communities and create effective messaging to disseminate correct COVID-19 prevention and treatment information.", "qid": 41, "docid": "961h5r54", "rank": 43, "score": 0.8573367595672607}, {"content": "Title: County-Level Proportions of Black and Hispanic populations, and Socioeconomic Characteristics in Association with Confirmed COVID-19 Cases and Deaths in the United States Content: Objectives. The objective of this study was to investigate potential county-level disparities among racial/ethnic and economic groups in COVID-19 burden which was measured using confirmed cases and deaths in 100,000 population. Design. Secondary data analysis Using county-level data for 3,142 US counties was conducted in 2020. Hierarchical linear regression and concentration curve analyses were performed. The combined association of COVID-19 cases and deaths was examined separately by sociodemographic and economic characteristics of the county population. Data from the American Community Survey (ACS) 5-year estimates (2014-2018), Area Health Resources File (AHRF) 2018-2019, and 2020 COVID-19 data from Johns Hopkins University were used in this study. Results. After adjusting for covariates, US counties with a higher proportion of the black population, and a higher proportion of adults with less than high school diploma had disproportionately higher COVID-19 cases and deaths ({beta}>0, p<0.05). A higher proportion of the Hispanic population was associated with higher confirmed cases ({beta}= 1.03, 95% CI= 0.57-1.5), and higher housing cost to household income ratio was associated with higher deaths ({beta}= 3.74, 95% CI= 2.14-5.37). This can potentially aggravate the existing health disparities among these population groups. Conclusions. Identification of disproportionately impacted population groups can pave the way towards narrowing the disparity gaps and guide policymakers and stakeholders in designing and implementing population group-specific interventions to mitigate the negative consequences of COVID-19 pandemic.", "qid": 41, "docid": "qcgttpqq", "rank": 44, "score": 0.8573230504989624}, {"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": 45, "score": 0.8568562269210815}, {"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": 46, "score": 0.8567390441894531}, {"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": 47, "score": 0.8547587394714355}, {"content": "Title: Fear of COVID-19 and the mental health consequences in America. Content: The intent of this work was to examine the intersection of COVID-19 fear with social vulnerabilities and mental health consequences among adults living in the United States. Data are from a nationally representative sample (n = 10,368) of U.S. adults surveyed online during demographic subgroups (gender, age, income, race and ethnicity, geography). The sample week of March 23, 2020. The sample was poststratification weighted to ensure a balanced representation across social and demographic subgroups (gender, age, income, race or ethnicity, geography). The sample comprised 51% female; 23% non-White; 18% Hispanic; 25% of households with children under 18 years of age; 55% unmarried; and nearly 20% unemployed, laid off, or furloughed at the time of the interview. Respondents were fearful, averaging a score of nearly 7 on a scale of 10 when asked how fearful they were of COVID-19. Preliminary analysis suggests clear spatial diffusion of COVID-19 fear. Fear appears to be concentrated in regions with the highest reported COVID-19 cases. Significant differences across several U.S. census regions are noted (p < .01). Additionally, significant bivariate relationships were found between socially vulnerable respondents (female, Asians, Hispanic, foreign-born, families with children) and fear, as well as with mental health consequences (anxiety and depressive symptoms). Depressive symptoms, on average, were high (16+ on the Center for Epidemiologic Studies Depression scale), and more than 25% of the sample reported moderate to severe anxiety symptoms. More in-depth psychosocial research is needed using nationally representative samples that can help to inform potential mental health risks, as well as by targeting specific mental health interventions. (PsycInfo Database Record (c) 2020 APA, all rights reserved).", "qid": 41, "docid": "9sqw617i", "rank": 48, "score": 0.8543294668197632}, {"content": "Title: Fear of COVID-19 and the mental health consequences in America Content: The intent of this work was to examine the intersection of COVID-19 fear with social vulnerabilities and mental health consequences among adults living in the United States. Data are from a nationally representative sample (n = 10,368) of U.S. adults surveyed online during demographic subgroups (gender, age, income, race and ethnicity, geography). The sample week of March 23, 2020. The sample was poststratification weighted to ensure a balanced representation across social and demographic subgroups (gender, age, income, race or ethnicity, geography). The sample comprised 51% female; 23% non-White; 18% Hispanic; 25% of households with children under 18 years of age; 55% unmarried; and nearly 20% unemployed, laid off, or furloughed at the time of the interview. Respondents were fearful, averaging a score of nearly 7 on a scale of 10 when asked how fearful they were of COVID-19. Preliminary analysis suggests clear spatial diffusion of COVID-19 fear. Fear appears to be concentrated in regions with the highest reported COVID-19 cases. Significant differences across several U.S. census regions are noted (p < .01). Additionally, significant bivariate relationships were found between socially vulnerable respondents (female, Asians, Hispanic, foreign-born, families with children) and fear, as well as with mental health consequences (anxiety and depressive symptoms). Depressive symptoms, on average, were high (16+ on the Center for Epidemiologic Studies Depression scale), and more than 25% of the sample reported moderate to severe anxiety symptoms. More in-depth psychosocial research is needed using nationally representative samples that can help to inform potential mental health risks, as well as by targeting specific mental health interventions. (PsycInfo Database Record (c) 2020 APA, all rights reserved).", "qid": 41, "docid": "7f9sbdsb", "rank": 49, "score": 0.8543293476104736}, {"content": "Title: Characteristics and Clinical Outcomes of Adult Patients Hospitalized with COVID-19 - Georgia, March 2020. Content: SARS-CoV-2, the novel coronavirus that causes coronavirus disease 2019 (COVID-19), was first detected in the United States during January 2020 (1). Since then, >980,000 cases have been reported in the United States, including >55,000 associated deaths as of April 28, 2020 (2). Detailed data on demographic characteristics, underlying medical conditions, and clinical outcomes for persons hospitalized with COVID-19 are needed to inform prevention strategies and community-specific intervention messages. For this report, CDC, the Georgia Department of Public Health, and eight Georgia hospitals (seven in metropolitan Atlanta and one in southern Georgia) summarized medical record-abstracted data for hospitalized adult patients with laboratory-confirmed* COVID-19 who were admitted during March 2020. Among 305 hospitalized patients with COVID-19, 61.6% were aged <65 years, 50.5% were female, and 83.2% with known race/ethnicity were non-Hispanic black (black). Over a quarter of patients (26.2%) did not have conditions thought to put them at higher risk for severe disease, including being aged \u226565 years. The proportion of hospitalized patients who were black was higher than expected based on overall hospital admissions. In an adjusted time-to-event analysis, black patients were not more likely than were nonblack patients to receive invasive mechanical ventilation\u2020 (IMV) or to die during hospitalization (hazard ratio [HR] = 0.63; 95% confidence interval [CI] = 0.35-1.13). Given the overrepresentation of black patients within this hospitalized cohort, it is important for public health officials to ensure that prevention activities prioritize communities and racial/ethnic groups most affected by COVID-19. Clinicians and public officials should be aware that all adults, regardless of underlying conditions or age, are at risk for serious illness from COVID-19.", "qid": 41, "docid": "vvuaegse", "rank": 50, "score": 0.8541275262832642}, {"content": "Title: Clinical, Behavioral and Social Factors Associated with Racial Disparities in Hospitalized and Ambulatory COVID-19 Patients from an Integrated Health Care System in Georgia Content: Introduction: Racial and ethnic minorities have shouldered a disproportioned burden of coronavirus disease 2019 (COVID-19) infection to date in the US, but data on the various drivers of these disparities is limited. Objectives: To describe the characteristics and outcomes of COVID-19 patients and explore factors associated with hospitalization risk by race. Methods: Case series of 448 consecutive patients with confirmed COVID-19 seen at Kaiser Permanente Georgia (KPGA), an integrated health care system serving the Atlanta metropolitan area, from March 3 to May 12, 2020. KPGA members with laboratory-confirmed COVID-19. Multivariable analyses for hospitalization risk also included an additional 3489 persons under investigation (PUI) with suspected infection. COVID-19 treatment and outcomes, underlying comorbidities and quality of care management metrics, socio-demographic and other individual and community-level social determinants of health (SDOH) indicators. Results: Of 448 COVID-19 positive members, 68,3% was non-Hispanic Black (n=306), 18% non-Hispanic White (n=81) and 13,7% Other race (n=61). Median age was 54 [IQR 43-63) years. Overall, 224 patients were hospitalized, median age 60 (50-69) years. Black race was a significant factor in the Confirmed + PUI, female and male models (ORs from 1.98 to 2.19). Obesity was associated with higher hospitalization odds in the confirmed, confirmed + PUI, Black and male models (ORs from 1.78 to 2.77). Chronic disease control metrics (diabetes, hypertension, hyperlipidemia) were associated with lower odds of hospitalization ranging from 48% to 35% in the confirmed + PUI and Black models. Self-reported physical inactivity was associated with 50% higher hospitalization odds in the Black and Female models. Residence in the Northeast region of Atlanta was associated with lower hospitalization odds in the Confirmed + PUI, White and female models (ORs from 0.22 to 0.64) Conclusions: We found that non-Hispanic Black KPGA members had a disproportionately higher risk of infection and, after adjusting for covariates, twice the risk of hospitalization compared to other race groups. We found no significant differences in clinical outcomes or mortality across race/ethnicity groups. In addition to age, sex and comorbidity burden, pre-pandemic self-reported exercise, metrics on quality of care and control of underlying cardio-metabolic diseases, and location of residence in Atlanta were significantly associated with hospitalization risk by race groups. Beyond well-known physiologic and clinical factors, individual and community-level social indicators and health behaviors must be considered as interventions designed to reduce COVID-19 disparities and the systemic effects of racism are implemented.", "qid": 41, "docid": "ix2cbs4j", "rank": 51, "score": 0.853905975818634}, {"content": "Title: Understanding COVID-19 Risks and Vulnerabilities among Black Communities in America: The Lethal Force of Syndemics Content: Black communities in the United States are bearing the brunt of the COVID-19 pandemic and the underlying conditions that exacerbate its negative consequences. Syndemic theory provides a useful framework for understanding how such interacting epidemics to develop under conditions of health and social disparity. Multiple historical and present-day factors have created the syndemic conditions within which Black Americans experience the lethal force of COVID-19. These factors include racism and its manifestations (e.g., chattel slavery, mortgage redlining, political gerrymandering, lack of Medicaid expansion, employment discrimination, and healthcare provider bias). Improving racial disparities in COVID-19 will require that we implement policies that address structural racism at the root of these disparities.", "qid": 41, "docid": "vs4qb91t", "rank": 52, "score": 0.8533152937889099}, {"content": "Title: Race, Socioeconomic Deprivation, and Hospitalization for COVID-19 in English participants of a National Biobank Content: Preliminary reports suggest that the Coronavirus Disease 2019 (COVID-19) pandemic has led to disproportionate morbidity and mortality among historically disadvantaged populations. The extent to which these disparities are related to socioeconomic versus biologic factors is largely unknown. We investigate the racial and socioeconomic associations of COVID-19 hospitalization among 418,794 participants of the UK Biobank, of whom 549 (0.13%) had been hospitalized. Both black participants (odds ratio 3.4; 95%CI 2.4-4.9) and Asian participants (odds ratio 2.1; 95%CI 1.5-3.2) were at substantially increased risk as compared to white participants. We further observed a striking gradient in COVID-19 hospitalization rates according to the Townsend Deprivation Index - a composite measure of socioeconomic deprivation - and household income. Adjusting for such factors led to only modest attenuation of the increased risk in black participants, adjusted odds ratio 3.1 (95%CI 2.0-4.8). These observations confirm and extend earlier preliminary and lay press reports of higher morbidity in non-white individuals in the context of a large population of participants in a national biobank. The extent to which this increased risk relates to variation in pre-existing comorbidities, differences in testing or hospitalization patterns, or additional disparities in social determinants of health warrants further study.", "qid": 41, "docid": "yw8o3c1l", "rank": 53, "score": 0.8531354665756226}, {"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": 54, "score": 0.8529417514801025}, {"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": 55, "score": 0.8525121808052063}, {"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": 56, "score": 0.852401614189148}, {"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": 57, "score": 0.8523823022842407}, {"content": "Title: Mental health and COVID-19: is the virus racist? Content: COVID-19 has changed our lives and it appears to be especially harmful for some groups more than others. Black and Asian ethnic minorities are at particular risk and have reported greater mortality and intensive care needs. Mental illnesses are more common among Black and ethnic minorities, as are crisis care pathways including compulsory admission. This editorial sets out what might underlie these two phenomena, explaining how societal structures and disadvantage generate and can escalate inequalities in crises.", "qid": 41, "docid": "aku7m0i5", "rank": 58, "score": 0.851935088634491}, {"content": "Title: For us, COVID-19 is personal Content: We are colleagues and friends working together in busy emergency departments in Washington DC. As Black physicians working in urban America, we do not find the recent deluge of news reports chronicling the disproportionate effect that the coronavirus disease (COVID-19) pandemic is having on the disenfranchised and minority populations in our country shocking. We have long been witness to and are in a constant state of alarm over the legal, medical, educational, social and economic inequities faced by the most vulnerable residents of this country.", "qid": 41, "docid": "2djys8ky", "rank": 59, "score": 0.8514869213104248}, {"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": 60, "score": 0.8513956069946289}, {"content": "Title: Mental health ramifications of the COVID-19 pandemic for Black Americans: Clinical and research recommendations Content: Mental health clinicians and researchers must be prepared to address the unique needs of Black Americans who have been disproportionately affected by the COVID-19 pandemic. Race-conscious and culturally competent interventions that consider factors such as discrimination, distrust of health care providers, and historical and racial trauma as well as protective factors including social support and culturally sanctioned coping strategies are needed. Research to accurately assess and design treatments for the mental health consequences of COVID-19 among Black Americans is warranted. (PsycInfo Database Record (c) 2020 APA, all rights reserved).", "qid": 41, "docid": "ef494his", "rank": 61, "score": 0.8507416248321533}, {"content": "Title: Mental health ramifications of the COVID-19 pandemic for Black Americans: Clinical and research recommendations. Content: Mental health clinicians and researchers must be prepared to address the unique needs of Black Americans who have been disproportionately affected by the COVID-19 pandemic. Race-conscious and culturally competent interventions that consider factors such as discrimination, distrust of health care providers, and historical and racial trauma as well as protective factors including social support and culturally sanctioned coping strategies are needed. Research to accurately assess and design treatments for the mental health consequences of COVID-19 among Black Americans is warranted. (PsycInfo Database Record (c) 2020 APA, all rights reserved).", "qid": 41, "docid": "4q97416a", "rank": 62, "score": 0.8507416248321533}, {"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": 63, "score": 0.8507348299026489}, {"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": 64, "score": 0.8503581285476685}, {"content": "Title: Caring for patients with posttraumatic stress and substance use disorders during the COVID-19 pandemic Content: Although COVID-19 is a physical illness, it has had large impacts on mental health. For many individuals, social distancing has led to social isolation; individuals with posttraumatic stress disorder and substance use disorders are at a particular risk for negative outcomes due to the global pandemic. Here, we discuss the impacts we have noticed and procedures we have implemented to care for this population during the pandemic. (PsycInfo Database Record (c) 2020 APA, all rights reserved).", "qid": 41, "docid": "pfrnlvda", "rank": 65, "score": 0.8498413562774658}, {"content": "Title: Caring for patients with posttraumatic stress and substance use disorders during the COVID-19 pandemic. Content: Although COVID-19 is a physical illness, it has had large impacts on mental health. For many individuals, social distancing has led to social isolation; individuals with posttraumatic stress disorder and substance use disorders are at a particular risk for negative outcomes due to the global pandemic. Here, we discuss the impacts we have noticed and procedures we have implemented to care for this population during the pandemic. (PsycInfo Database Record (c) 2020 APA, all rights reserved).", "qid": 41, "docid": "7uodxlrz", "rank": 66, "score": 0.8498413562774658}, {"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": 67, "score": 0.8496937155723572}, {"content": "Title: Racial and Ethnic Digital Divides in Posting COVID-19 Content on Social Media Among US Adults: Secondary Survey Analysis Content: BACKGROUND: Public health surveillance experts are leveraging user-generated content on social media to track the spread and effects of COVID-19. However, racial and ethnic digital divides, which are disparities among people who have internet access and post on social media, can bias inferences. This bias is particularly problematic in the context of the COVID-19 pandemic because due to structural inequalities, members of racial and ethnic minority groups are disproportionately vulnerable to contracting the virus and to the deleterious economic and social effects from mitigation efforts. Further, important demographic intersections with race and ethnicity, such as gender and age, are rarely investigated in work characterizing social media users; however, they reflect additional axes of inequality shaping differential exposure to COVID-19 and its effects. OBJECTIVE: The aim of this study was to characterize how the race and ethnicity of US adults are associated with their odds of posting COVID-19 content on social media and how gender and age modify these odds. METHODS: We performed a secondary analysis of a survey conducted by the Pew Research Center from March 19 to 24, 2020, using a national probability sample (N=10,510). Respondents were recruited from an online panel, where panelists without an internet-enabled device were given one to keep at no cost. The binary dependent variable was responses to an item asking whether respondents \u201cused social media to share or post information about the coronavirus.\u201d We used survey-weighted logistic regressions to estimate the odds of responding in the affirmative based on the race and ethnicity of respondents (white, black, Latino, other race/ethnicity), adjusted for covariates measuring sociodemographic background and COVID-19 experiences. We examined how gender (female, male) and age (18 to 30 years, 31 to 50 years, 51 to 64 years, and 65 years and older) intersected with race and ethnicity by estimating interactions. RESULTS: Respondents who identified as black (odds ratio [OR] 1.29, 95% CI 1.02-1.64; P=.03), Latino (OR 1.66, 95% CI 1.36-2.04; P<.001), or other races/ethnicities (OR 1.33, 95% CI 1.02-1.72; P=.03) had higher odds than respondents who identified as white of reporting that they posted COVID-19 content on social media. Women had higher odds of posting than men regardless of race and ethnicity (OR 1.58, 95% CI 1.39-1.80; P<.001). Among men, respondents who identified as black, Latino, or members of other races/ethnicities were significantly more likely to post than respondents who identified as white. Older adults (65 years or older) had significantly lower odds (OR 0.73, 95% CI 0.57-0.94; P=.01) of posting compared to younger adults (18-29 years), particularly among those identifying as other races/ethnicities. Latino respondents were the most likely to report posting across all age groups. CONCLUSIONS: In the United States, members of racial and ethnic minority groups are most likely to contribute to COVID-19 content on social media, particularly among groups traditionally less likely to use social media (older adults and men). The next step is to ensure that data collection procedures capture this diversity by encompassing a breadth of search criteria and social media platforms.", "qid": 41, "docid": "fambtykj", "rank": 68, "score": 0.849165141582489}, {"content": "Title: Racial and Ethnic Digital Divides in Posting COVID-19 Content on Social Media Among US Adults: Secondary Survey Analysis Content: BACKGROUND: Public health surveillance experts are leveraging user-generated content on social media to track the spread and effects of COVID-19. However, racial and ethnic digital divides, which are disparities among people who have internet access and post on social media, can bias inferences. This bias is particularly problematic in the context of the COVID-19 pandemic because due to structural inequalities, members of racial and ethnic minority groups are disproportionately vulnerable to contracting the virus and to the deleterious economic and social effects from mitigation efforts. Further, important demographic intersections with race and ethnicity, such as gender and age, are rarely investigated in work characterizing social media users; however, they reflect additional axes of inequality shaping differential exposure to COVID-19 and its effects. OBJECTIVE: The aim of this study was to characterize how the race and ethnicity of US adults are associated with their odds of posting COVID-19 content on social media and how gender and age modify these odds. METHODS: We performed a secondary analysis of a survey conducted by the Pew Research Center from March 19 to 24, 2020, using a national probability sample (N=10,510). Respondents were recruited from an online panel, where panelists without an internet-enabled device were given one to keep at no cost. The binary dependent variable was responses to an item asking whether respondents \"used social media to share or post information about the coronavirus.\" We used survey-weighted logistic regressions to estimate the odds of responding in the affirmative based on the race and ethnicity of respondents (white, black, Latino, other race/ethnicity), adjusted for covariates measuring sociodemographic background and COVID-19 experiences. We examined how gender (female, male) and age (18 to 30 years, 31 to 50 years, 51 to 64 years, and 65 years and older) intersected with race and ethnicity by estimating interactions. RESULTS: Respondents who identified as black (odds ratio [OR] 1.29, 95% CI 1.02-1.64; P=.03), Latino (OR 1.66, 95% CI 1.36-2.04; P<.001), or other races/ethnicities (OR 1.33, 95% CI 1.02-1.72; P=.03) had higher odds than respondents who identified as white of reporting that they posted COVID-19 content on social media. Women had higher odds of posting than men regardless of race and ethnicity (OR 1.58, 95% CI 1.39-1.80; P<.001). Among men, respondents who identified as black, Latino, or members of other races/ethnicities were significantly more likely to post than respondents who identified as white. Older adults (65 years or older) had significantly lower odds (OR 0.73, 95% CI 0.57-0.94; P=.01) of posting compared to younger adults (18-29 years), particularly among those identifying as other races/ethnicities. Latino respondents were the most likely to report posting across all age groups. CONCLUSIONS: In the United States, members of racial and ethnic minority groups are most likely to contribute to COVID-19 content on social media, particularly among groups traditionally less likely to use social media (older adults and men). The next step is to ensure that data collection procedures capture this diversity by encompassing a breadth of search criteria and social media platforms.", "qid": 41, "docid": "d6hfczkq", "rank": 69, "score": 0.8489562273025513}, {"content": "Title: Racial and ethnic determinants of Covid-19 risk Content: Background Racial and ethnic minorities have disproportionately high hospitalization rates and mortality related to the novel coronavirus disease 2019 (Covid-19). There are comparatively scant data on race and ethnicity as determinants of infection risk. Methods We used a smartphone application (beginning March 24, 2020 in the United Kingdom [U.K.] and March 29, 2020 in the United States [U.S.]) to recruit 2,414,601 participants who reported their race/ethnicity through May 25, 2020 and employed logistic regression to determine the adjusted odds ratios (aORs) and 95% confidence intervals (CIs) for a positive Covid-19 test among racial and ethnic groups. Results We documented 8,858 self-reported cases of Covid-19 among 2,259,841 non-Hispanic white; 79 among 9,615 Hispanic; 186 among 18,176 Black; 598 among 63,316 Asian; and 347 among 63,653 other racial minority participants. Compared with non-Hispanic white participants, the risk for a positive Covid-19 test was increased across racial minorities (aORs ranging from 1.24 to 3.51). After adjustment for socioeconomic indices and Covid-19 exposure risk factors, the associations (aOR [95% CI]) were attenuated but remained significant for Hispanic (1.58 [1.24-2.02]) and Black participants (2.56 [1.93-3.39]) in the U.S. and South Asian (1.52 [1.38-1.67]) and Middle Eastern participants (1.56 [1.25-1.95]) in the U.K. A higher risk of Covid-19 and seeking or receiving treatment was also observed for several racial/ethnic minority subgroups. Conclusions Our results demonstrate an increase in Covid-19 risk among racial and ethnic minorities not completely explained by other risk factors for Covid-19, comorbidities, and sociodemographic characteristics. Further research investigating these disparities are needed to inform public health measures.", "qid": 41, "docid": "lt9748vk", "rank": 70, "score": 0.8486729860305786}, {"content": "Title: Race, socioeconomic deprivation, and hospitalization for COVID-19 in English participants of a national biobank Content: Preliminary reports suggest that the Coronavirus Disease 2019 (COVID\u2212 19) pandemic has led to disproportionate morbidity and mortality among historically disadvantaged populations. We investigate the racial and socioeconomic associations of COVID\u2212 19 hospitalization among 418,794 participants of the UK Biobank, of whom 549 (0.13%) had been hospitalized. Both Black participants (odds ratio 3.7; 95%CI 2.5\u20135.3) and Asian participants (odds ratio 2.2; 95%CI 1.5\u20133.2) were at substantially increased risk as compared to White participants. We further observed a striking gradient in COVID\u2212 19 hospitalization rates according to the Townsend Deprivation Index \u2212 a composite measure of socioeconomic deprivation \u2212 and household income. Adjusting for socioeconomic factors and cardiorespiratory comorbidities led to only modest attenuation of the increased risk in Black participants, adjusted odds ratio 2.4 (95%CI 1.5\u20133.7). These observations confirm and extend earlier preliminary and lay press reports of higher morbidity in non-White individuals in the context of a large population of participants in a national biobank. The extent to which this increased risk relates to variation in pre-existing comorbidities, differences in testing or hospitalization patterns, or additional disparities in social determinants of health warrants further study.", "qid": 41, "docid": "5qph7yen", "rank": 71, "score": 0.8485497236251831}, {"content": "Title: Absence of Skin of Colour Images in Publications of COVID-19 Skin Manifestations Content: There are now over 1 million confirmed cases of COVID-19 globally with more than 270,000 recorded deaths to date. COVID-19 has been shown to disproportionately impact people of colour both in the United Kingdom and in the United States where blacks make up 13.4% of the population but 30% of COVID-19 cases. Mounting evidence shows that COVID-19 impacts several organ systems, including the skin.", "qid": 41, "docid": "33uqbusb", "rank": 72, "score": 0.8477805852890015}, {"content": "Title: Assessing racial and ethnic disparities using a COVID-19 outcomes continuum for New York State Content: PURPOSE: Heightened COVID-19 mortality among Black non-Hispanic and Hispanic communities (relative to white non-Hispanic) is well established. This study aims to estimate the relative contributions to fatality disparities in terms of differences in SARS-CoV-2 infections, diagnoses, and disease severity. METHODS: We constructed COVID-19 outcome continua (similar to the HIV care continuum) for white non-Hispanic, Black non-Hispanic, and Hispanic adults in New York State. For each stage in the COVID-19 outcome continua (population, infection experience, diagnosis, hospitalization, fatality), we synthesized the most recent publicly-available data. We described each continuum using overall percentages, fatality rates, and relative changes between stages, with comparisons between race and ethnicity using risk ratios. RESULTS: Estimated per-population COVID-19 fatality rates were 0.03%, 0.18%, and 0.12% for white non-Hispanic, Black non-Hispanic, and Hispanic adults. The 3.48-fold disparity for Hispanic, relative to white, communities was explained by differences in infection-experience, whereas the 5.38-fold disparity for non-Hispanic Black, relative to white, communities was primarily driven by differences in both infection-experience and in the need for hospitalization, given infection. CONCLUSIONS: These findings suggest the most impactful stages upon which to intervene with programs and policies to build COVID-19 health equity.", "qid": 41, "docid": "k2wojibt", "rank": 73, "score": 0.8476068377494812}, {"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": 74, "score": 0.8475310206413269}, {"content": "Title: Ethnic Disparities in Hospitalization for COVID-19: a Community-Based Cohort Study in the UK Content: IMPORTANCE: Differentials in COVID-19 incidence, hospitalization and mortality according to ethnicity are being reported but their origin is uncertain. OBJECTIVE: We aimed to explain any ethnic differentials in COVID-19 hospitalization based on socioeconomic, lifestyle, mental and physical health factors. DESIGN: Prospective cohort study with national registry linkage to hospitalisation for COVID-19. SETTING: Community-dwelling. PARTICIPANTS: 340,966 men and women (mean age 56.2 (SD=8.1) years; 54.3% women) residing in England from the UK Biobank study. EXPOSURES: Ethnicity classified as White, Black, Asian, and Others. MAIN OUTCOME(S) AND MEASURE(S): Cases of COVID-19 serious enough to warrant a hospital admission in England from 16-March-2020 to 26-April-2020. RESULTS: There were 640 COVID-19 cases (571/324,306 White, 31/4,485 Black, 21/5,732 Asian, 17/5,803 Other). Compared to the White study members and after adjusting for age and sex, Black individuals had over a 4-fold increased risk of being hospitalised (odds ratio; 95% confidence interval: =4.32; 3.00-6.23), and there was a doubling of risk in the Asian group (2.12; 1.37, 3.28) and the \u2018other\u2019 non-white group (1.84; 1.13, 2.99). After controlling for 15 confounding factors which included neighbourhood deprivation, education, number in household, smoking, markers of body size, inflammation, and glycated haemoglobin, these effect estimates were attenuated by 33% for Blacks, 52% for Asians and 43% for Other, but remained raised for Blacks (2.66; 1.82, 3.91), Asian (1.43; 0.91, 2.26) and other non-white groups (1.41; 0.87, 2.31). CONCLUSIONS AND RELEVANCE: Our findings show clear ethnic differences in risk of hospitalization for COVID-19 which do not appear to be fully explained by known explanatory factors. If replicated, our results have implications for health policy, including the targeting of prevention advice and vaccination coverage.", "qid": 41, "docid": "7g7yt23q", "rank": 75, "score": 0.8474771976470947}, {"content": "Title: A culturally specific mental health and spirituality approach for African Americans facing the COVID-19 pandemic Content: A series of 15-min videos were produced to provide resources to pastors in African-American communities to aid them in conveying accurate public and mental health information about COVID-19. Video presenters included trusted experts in public and mental health and pastors with considerable experience responding to the needs of the African-American community during the COVID-19 pandemic. Four culturally specific core themes to consider when providing care to African Americans who are at increased risk during the pandemic were identified: ritual disruption, negative reactions for not following public health guidelines, trauma, and culture and trust. (PsycInfo Database Record (c) 2020 APA, all rights reserved).", "qid": 41, "docid": "5c6nwrdo", "rank": 76, "score": 0.847350001335144}, {"content": "Title: A culturally specific mental health and spirituality approach for African Americans facing the COVID-19 pandemic. Content: A series of 15-min videos were produced to provide resources to pastors in African-American communities to aid them in conveying accurate public and mental health information about COVID-19. Video presenters included trusted experts in public and mental health and pastors with considerable experience responding to the needs of the African-American community during the COVID-19 pandemic. Four culturally specific core themes to consider when providing care to African Americans who are at increased risk during the pandemic were identified: ritual disruption, negative reactions for not following public health guidelines, trauma, and culture and trust. (PsycInfo Database Record (c) 2020 APA, all rights reserved).", "qid": 41, "docid": "juzi9th6", "rank": 77, "score": 0.847350001335144}, {"content": "Title: Factors Associated with Hospitalization and Disease Severity in a Racially and Ethnically Diverse Population of COVID-19 Patients Content: Background: The coronavirus disease (COVID-19) first identified in Wuhan in December 2019 became a pandemic within a few months of its discovery. The impact of COVID-19 is due to both its rapid spread and its severity, but the determinants of severity have not been fully delineated. Objective: Identify factors associated with hospitalization and disease severity in a racially and ethnically diverse cohort of COVID-19 patients. Methods: We analyzed data from COVID-19 patients diagnosed at the University of Cincinnati health system from March 13, 2020 to May 31, 2020. Severe COVID-19 was defined as admission to intensive care unit or death. Logistic regression modeling adjusted for covariates was used to identify the factors associated with hospitalization and severe COVID-19. Results: Among the 689 COVID-19 patients included in our study, 29.2% were non-Hispanic White, 25.5% were non-Hispanic Black, 32.5% were Hispanic, and 12.8% were of other race/ethnicity. About 31.3% of patients were hospitalized and 13.2% had severe disease. In adjusted analyses, the sociodemographic factors associated with hospitalization and/or disease severity included older age, non-Hispanic Black or Hispanic race/ethnicity (compared non-Hispanic White), and smoking. The following comorbidities: diabetes, hypercholesterolemia, asthma, chronic obstructive pulmonary disease (COPD), chronic kidney disease, cardiovascular diseases, osteoarthritis, and vitamin D deficiency, were associated with hospitalization and/or disease severity. Hematological disorders such as anemia, coagulation disorders, and thrombocytopenia were associated with higher odds of both hospitalization and disease severity. Conclusion: This study confirms race and ethnicity as predictors of severe COVID-19 and identifies clinical risk factors not previously reported such a vitamin D deficiency, hypercholesterolemia, osteoarthritis, and anemia.", "qid": 41, "docid": "7hnh85wy", "rank": 78, "score": 0.846897304058075}, {"content": "Title: Characteristics Associated with Hospitalization Among Patients with COVID-19 \u2014 Metropolitan Atlanta, Georgia, March\u2013April 2020 Content: The first reported U.S. case of coronavirus disease 2019 (COVID-19) was detected in January 2020 (1). As of June 15, 2020, approximately 2 million cases and 115,000 COVID-19-associated deaths have been reported in the United States.* Reports of U.S. patients hospitalized with SARS-CoV-2 infection (the virus that causes COVID-19) describe high proportions of older, male, and black persons (2-4). Similarly, when comparing hospitalized patients with catchment area populations or nonhospitalized COVID-19 patients, high proportions have underlying conditions, including diabetes mellitus, hypertension, obesity, cardiovascular disease, chronic kidney disease, or chronic respiratory disease (3,4). For this report, data were abstracted from the medical records of 220 hospitalized and 311 nonhospitalized patients aged \u226518 years with laboratory-confirmed COVID-19 from six acute care hospitals and associated outpatient clinics in metropolitan Atlanta, Georgia. Multivariable analyses were performed to identify patient characteristics associated with hospitalization. The following characteristics were independently associated with hospitalization: age \u226565 years (adjusted odds ratio [aOR] = 3.4), black race (aOR = 3.2), having diabetes mellitus (aOR = 3.1), lack of insurance (aOR = 2.8), male sex (aOR = 2.4), smoking (aOR = 2.3), and obesity (aOR = 1.9). Infection with SARS-CoV-2 can lead to severe outcomes, including death, and measures to protect persons from infection, such as staying at home, social distancing (5), and awareness and management of underlying conditions should be emphasized for those at highest risk for hospitalization with COVID-19. Measures that prevent the spread of infection to others, such as wearing cloth face coverings (6), should be used whenever possible to protect groups at high risk. Potential barriers to the ability to adhere to these measures need to be addressed.", "qid": 41, "docid": "9wn91fj2", "rank": 79, "score": 0.8468776345252991}, {"content": "Title: Assessing Differential Impacts of COVID-19 on Black Communities Content: Purpose Given incomplete data reporting by race, we used data on COVID-19 cases and deaths in US counties to describe racial disparities in COVID-19 disease and death and associated determinants. Methods Using publicly available data (accessed April 13, 2020), predictors of COVID-19 cases and deaths were compared between disproportionately (>13%) black and all other (<13% black) counties. Rate ratios were calculated and population attributable fractions (PAF) were estimated using COVID-19 cases and deaths via zero-inflated negative binomial regression model. National maps with county-level data and an interactive scatterplot of COVID-19 cases were generated. Results Nearly ninety-seven percent of disproportionately black counties (656/677) reported a case and 49% (330/677) reported a death versus 81% (1987/2,465) and 28% (684/ 2465), respectively, for all other counties. Counties with higher proportions of black people have higher prevalence of comorbidities and greater air pollution. Counties with higher proportions of black residents had more COVID-19 diagnoses (RR 1.24, 95% CI 1.17-1.33) and deaths (RR 1.18, 95% CI 1.00-1.40), after adjusting for county-level characteristics such as age, poverty, comorbidities, and epidemic duration. COVID-19 deaths were higher in disproportionally black rural and small metro counties. The PAF of COVID-19 diagnosis due to lack of health insurance was 3.3% for counties with <13% black residents and 4.2% for counties with >13% black residents. Conclusions Nearly twenty-two percent of US counties are disproportionately black and they accounted for 52% of COVID-19 diagnoses and 58% of COVID-19 deaths nationally. County-level comparisons can both inform COVID-19 responses and identify epidemic hot spots. Social conditions, structural racism, and other factors elevate risk for COVID-19 diagnoses and deaths in black communities.", "qid": 41, "docid": "p5owyivo", "rank": 80, "score": 0.846387505531311}, {"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": 81, "score": 0.8460832238197327}, {"content": "Title: Psychological and social impact of COVID-19 Content: The high numbers of COVID-19 infections and deaths, economic difficulties, uncertainty about the future, as well as the approaches needed to contain the spread of the virus are all playing critical roles in the short and long-term social and psychological impact of the COVID-19 pandemic. Inequities based on race and socioeconomic status influence the rates of infection and deaths and steps that are needed to achieve recovery. This commentary focuses on similarities and differences after other disasters and efforts being initiated to provide support and recovery. (PsycInfo Database Record (c) 2020 APA, all rights reserved).", "qid": 41, "docid": "nj2dllu3", "rank": 82, "score": 0.8457702398300171}, {"content": "Title: Psychological and social impact of COVID-19. Content: The high numbers of COVID-19 infections and deaths, economic difficulties, uncertainty about the future, as well as the approaches needed to contain the spread of the virus are all playing critical roles in the short and long-term social and psychological impact of the COVID-19 pandemic. Inequities based on race and socioeconomic status influence the rates of infection and deaths and steps that are needed to achieve recovery. This commentary focuses on similarities and differences after other disasters and efforts being initiated to provide support and recovery. (PsycInfo Database Record (c) 2020 APA, all rights reserved).", "qid": 41, "docid": "hdy4h13e", "rank": 83, "score": 0.8457702398300171}, {"content": "Title: Ethnicity, comorbidity, socioeconomic status, and their associations with COVID-19 infection in England: a cohort analysis of UK Biobank data Content: Objectives: Recent data suggest higher COVID-19 rates and severity in Black, Asian, and minority ethnic (BAME) communities. The mechanisms underlying such associations remain unclear. We aimed to study the association between ethnicity and risk of COVID-19 infection and disentangle any correlation with socioeconomic deprivation or previous comorbidity. Design: Prospective cohort. Setting: UK Biobank linked to Hospital Episode Statistics (HES) and COVID-19 tests until 14 April 2020. Participants: UK Biobank participants from England, excluding drop-outs and deaths. Main measures: COVID-19 infection based on a positive PCR test. Ethnicity was self-reported and classified using Office of National Statistics groups. Socioeconomic status was based on index of multiple deprivation quintiles. Comorbidities were self-reported and completed from HES. Analyses: Multivariable Poisson analysis to estimate incidence rate ratios of COVID-19 infection according to ethnicity, adjusted for socioeconomic status, alcohol drinking, smoking, body mass index, age, sex, and comorbidity. Results: 415,582 participants were included, with 1,416 tested and 651 positive for COVID-19. The incidence of COVID-19 was 0.61% (95% CI: 0.46%-0.82%) in Black/Black British participants, 0.32% (0.19%-0.56%) in other ethnicities, 0.32% (0.23%-0.47%) in Asian/Asian British, 0.30% (0.11%-0.80%) in Chinese, 0.16% (0.06%-0.41%) in mixed, and 0.14% (0.13%-0.15%) in White. Compared with White participants, Black/Black British participants had an adjusted relative risk (RR) of 3.30 (2.39-4.55), Chinese participants 3.00 (1.11-8.06), Asian/Asian British participants 2.04 (1.36-3.07), other ethnicities 1.93 (1.08-3.45), and mixed ethnicities 1.07 (0.40-2.86). Socioeconomic status (adjusted RR 1.93 (1.51-2.46) for the most deprived), obesity (adjusted RR 1.04 (1.02-1.05) per kg/m2) and comorbid hypertension, chronic obstructive pulmonary disease, asthma, and specific renal diseases were also associated with increased risk of COVID-19. Conclusions: COVID-19 rates in the UK are higher in BAME communities, those living in deprived areas, obese patients, and patients with previous comorbidity. Public health strategies are needed to reduce COVID-19 infections among the most susceptible groups.", "qid": 41, "docid": "tjqd1srq", "rank": 84, "score": 0.8456571102142334}, {"content": "Title: Racial disparities in knowledge, attitudes and practices related to COVID-19 in the USA Content: BACKGROUND: Recent reports indicate racial disparities in the rates of infection and mortality from the 2019 novel coronavirus (coronavirus disease 2019 [COVID-19]). The aim of this study was to determine whether disparities exist in the levels of knowledge, attitudes and practices (KAPs) related to COVID-19. METHODS: We analyzed data from 1216 adults in the March 2020 Kaiser Family Foundation 'Coronavirus Poll', to determine levels of KAPs across different groups. Univariate and multivariate regression analysis was used to identify predictors of KAPs. RESULTS: In contrast to White respondents, Non-White respondents were more likely to have low knowledge (58% versus 30%; P < 0.001) and low attitude scores (52% versus 27%; P < 0.001), but high practice scores (81% versus 59%; P < 0.001). By multivariate regression, White race (odds ratio [OR] 3.06; 95% confidence interval [CI]: 1.70-5.50), higher level of education (OR 1.80; 95% CI: 1.46-2.23) and higher income (OR 2.06; 95% CI: 1.58-2.70) were associated with high knowledge of COVID-19. Race, sex, education, income, health insurance status and political views were all associated with KAPs. CONCLUSIONS: Racial and socioeconomic disparity exists in the levels of KAPs related to COVID-19. More work is needed to identify educational tools that tailor to specific racial and socioeconomic groups.", "qid": 41, "docid": "q12m8a8z", "rank": 85, "score": 0.8456298112869263}, {"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": 41, "docid": "de6vwlh5", "rank": 86, "score": 0.8443760275840759}, {"content": "Title: Ethnic disparities in hospitalisation for COVID-19 in England: The role of socioeconomic factors, mental health, and inflammatory and pro-inflammatory factors in a community-based cohort study Content: BACKGROUND: Differentials in COVID-19 hospitalisations and mortality according to ethnicity have been reported but their origin is uncertain. We examined the role of socioeconomic, mental health, and pro-inflammatory factors in a community-based sample. METHODS: We used data on 340,966 men and women (mean age 56.2 years) from the UK Biobank study, a prospective cohort study with linkage to hospitalisation for COVID-19. Logistic regression models were used to estimate associations between ethnicity and hospitalisation for COVID-19. RESULTS: There were 640 COVID-19 cases (571/324,306 White, 31/4,485 Black, 21/5,732 Asian, 17/5,803 Other). Compared to the White study members and after adjusting for age and sex, Black individuals had over a 4-fold increased risk of COVID-19 infection (odds ratio; 95% confidence interval: 4.32; 3.00-6.23), and there was a doubling of risk in the Asian group (2.12; 1.37, 3.28) and the 'other' non-white group (1.84; 1.13, 2.99). After controlling for potential explanatory factors which included neighbourhood deprivation, household crowding, smoking, body size, inflammation, glycated haemoglobin, and mental illness, these effect estimates were attenuated by 33% for Blacks, 52% for Asians and 43% for Other, but remained raised for Blacks (2.66; 1.82, 3.91), Asian (1.43; 0.91, 2.26) and other non-white groups (1.41; 0.87, 2.31). CONCLUSIONS: There were clear ethnic differences in risk of COVID-19 hospitalisation and these do not appear to be fully explained by measured factors. If replicated, our results have implications for health policy, including the targeting of prevention advice and vaccination coverage.", "qid": 41, "docid": "mqnim7pe", "rank": 87, "score": 0.844169020652771}, {"content": "Title: Multivariate Analysis of Black Race and Environmental Temperature on COVID-19 In the US Content: BACKGROUND: There has been much interest in environmental temperature and race as modulators of Coronavirus disease-19 (COVID-19) infection and mortality. However, in the United States race and temperature correlate with various other social determinants of health, comorbidities, and environmental influences that could be responsible for noted effects. This study investigates the independent effects of race and environmental temperature on COVID-19 incidence and mortality in United States counties. METHODS: Data on COVID-19 and risk factors in all United States counties was collected. 661 counties with at least 50 COVID-19 cases and 217 with at least 10 deaths were included in analyses. Upper and lower quartiles for cases/100,000 people and halves for deaths/100,000 people were compared with t-tests. Adjusted linear and logistic regression analyses were performed to evaluate the independent effects of race and environmental temperature. RESULTS: Multivariate regression analyses demonstrated Black race is a risk factor for increased COVID-19 cases (OR=1.22, 95% CI: 1.09-1.40, P=0.001) and deaths independent of comorbidities, poverty, access to health care, and other risk factors. Higher environmental temperature independently reduced caseload (OR=0.81, 95% CI: 0.71-0.91, P=0.0009), but not deaths. CONCLUSIONS: Higher environmental temperatures correlated with reduced COVID-19 cases, but this benefit does not yet appear in mortality models. Black race was an independent risk factor for increased COVID-19 cases and deaths. Thus, many proposed mechanisms through which Black race might increase risk for COVID-19, such as socioeconomic and healthcare-related predispositions, are inadequate in explaining the full magnitude of this health disparity.", "qid": 41, "docid": "0wspp086", "rank": 88, "score": 0.843993067741394}, {"content": "Title: Differential occupational risk for COVID-19 and other infection exposure according to race and ethnicity Content: BACKGROUND: There are racial and ethnic disparities in the risk of contracting COVID-19. This study sought to assess how occupational segregation according to race and ethnicity may contribute to the risk of COVID-19. METHODS: Data about employment in 2019 by industry and occupation and race and ethnicity were obtained from the Bureau of Labor Statistics Current Population Survey. This data was combined with information about industries according to whether they were likely or possibly essential during the COVID-19 pandemic and the frequency of exposure to infections and close proximity to others by occupation. The percentage of workers employed in essential industries and occupations with a high risk of infection and close proximity to others by race and ethnicity was calculated. RESULTS: People of color were more likely to be employed in essential industries and in occupations with more exposure to infections and close proximity to others. Black workers in particular faced an elevated risk for all of these factors. CONCLUSION: Occupational segregation into high-risk industries and occupations likely contributes to differential risk with respect to COVID-19. Providing adequate projection to workers may help to reduce these disparities.", "qid": 41, "docid": "8ffds4yc", "rank": 89, "score": 0.8431140184402466}, {"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": 90, "score": 0.8428318500518799}, {"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": 91, "score": 0.842128336429596}, {"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": 41, "docid": "9d7vxjys", "rank": 92, "score": 0.8419421911239624}, {"content": "Title: COVID-19: Unique public health issues facing Black, Asian and minority ethnic communities Content: The 2019 coronavirus disease is a serious public health emergency, with serious adverse implications for populations, healthcare systems, and economies globally. Recently, concerns have been raised about possible association between ethnicity, incidence and outcomes of COVID-19 arisen from early government data. In this review, we will explore the possible association using both recent COVID-19 studies and studies of previous pandemics. We call for data on ethnicity to be routinely collected by governments, as part of an international collaboration, alongside other patient demographics and further research to robustly determine the magnitude of association. Moreover, governments must learn from previous pandemics and recommended strategies to mitigate risks on minority ethnicities due to socioeconomic disadvantages.", "qid": 41, "docid": "xzc7bwe3", "rank": 93, "score": 0.8418164253234863}, {"content": "Title: Ethnic Disparities in Hospitalisation for COVID-19 in England: The Role of Socioeconomic Factors, Mental Health, and Inflammatory and Pro-inflammatory Factors in a Community-based Cohort Study Content: BACKGROUND: Differentials in COVID-19 hospitalisations and mortality according to ethnicity have been reported but their origin is uncertain. We examined the role of socioeconomic, mental health, and pro-inflammatory factors in a community-based sample. METHODS: We used data on 340,966 men and women (mean age 56.2 years) from the UK Biobank study, a prospective cohort study with linkage to hospitalisation for COVID-19. Logistic regression models were used to estimate associations between ethnicity and hospitalisation for COVID-19. RESULTS: There were 640 COVID-19 cases (571/324,306 White, 31/4,485 Black, 21/5,732 Asian, 17/5,803 Other). Compared to the White study members and after adjusting for age and sex, Black individuals had over a 4-fold increased risk of COVID-19 infection (odds ratio; 95% confidence interval: 4.32; 3.00-6.23), and there was a doubling of risk in the Asian group (2.12; 1.37, 3.28) and the \u2018other\u2019 non-white group (1.84; 1.13, 2.99). After controlling for potential explanatory factors which included neighbourhood deprivation, household crowding, smoking, body size, inflammation, glycated haemoglobin, and mental illness, these effect estimates were attenuated by 33% for Blacks, 52% for Asians and 43% for Other, but remained raised for Blacks (2.66; 1.82, 3.91), Asian (1.43; 0.91, 2.26) and other non-white groups (1.41; 0.87, 2.31). CONCLUSIONS: There were clear ethnic differences in risk of COVID-19 hospitalisation and these do not appear to be fully explained by measured factors. If replicated, our results have implications for health policy, including the targeting of prevention advice and vaccination coverage.", "qid": 41, "docid": "qq9nf8dr", "rank": 94, "score": 0.8410176038742065}, {"content": "Title: Racial disparities in knowledge, attitudes and practices related to COVID-19 in the USA Content: BACKGROUND: Recent reports indicate racial disparities in the rates of infection and mortality from the 2019 novel coronavirus (coronavirus disease 2019 [COVID-19]). The aim of this study was to determine whether disparities exist in the levels of knowledge, attitudes and practices (KAPs) related to COVID-19. METHODS: We analyzed data from 1216 adults in the March 2020 Kaiser Family Foundation \u2018Coronavirus Poll\u2019, to determine levels of KAPs across different groups. Univariate and multivariate regression analysis was used to identify predictors of KAPs. RESULTS: In contrast to White respondents, Non-White respondents were more likely to have low knowledge (58% versus 30%; P < 0.001) and low attitude scores (52% versus 27%; P < 0.001), but high practice scores (81% versus 59%; P < 0.001). By multivariate regression, White race (odds ratio [OR] 3.06; 95% confidence interval [CI]: 1.70\u20135.50), higher level of education (OR 1.80; 95% CI: 1.46\u20132.23) and higher income (OR 2.06; 95% CI: 1.58\u20132.70) were associated with high knowledge of COVID-19. Race, sex, education, income, health insurance status and political views were all associated with KAPs. CONCLUSIONS: Racial and socioeconomic disparity exists in the levels of KAPs related to COVID-19. More work is needed to identify educational tools that tailor to specific racial and socioeconomic groups.", "qid": 41, "docid": "6nr3ufkv", "rank": 95, "score": 0.8409851789474487}, {"content": "Title: Coronavirus disease 19 in minority populations of Newark, New Jersey Content: BACKGROUND: The purpose of this study is to report the clinical features and outcomes of Black/African American (AA) and Latino Hispanic patients with Coronavirus disease 2019 (COVID-19) hospitalized in an inter-city hospital in the state of New Jersey. METHODS: This is a retrospective cohort study of AA and Latino Hispanic patients with COVID-19 admitted to a 665-bed quaternary care, teaching hospital located in Newark, New Jersey. The study included patients who had completed hospitalization between March 10, 2020, and April 10, 2020. We reviewed demographics, socioeconomic variables and incidence of in-hospital mortality and morbidity. Logistic regression was used to identify predictor of in-hospital death. RESULTS: Out of 416 patients, 251 (60%) had completed hospitalization as of April 10, 2020. The incidence of In-hospital mortality was 38.6% (n = 97). Most common symptoms at initial presentation were dyspnea 39% (n = 162) followed by cough 38%(n = 156) and fever 34% (n = 143). Patients were in the highest quartile for population's density, number of housing units and disproportionately fell into the lowest median income quartile for the state of New Jersey. The incidence of septic shock, acute kidney injury (AKI) requiring hemodialysis and admission to an intensive care unit (ICU) was 24% (n = 59), 21% (n = 52), 33% (n = 82) respectively. Independent predictors of in-hospital mortality were older age, lower serum Hemoglobin < 10 mg/dl, elevated serum Ferritin and Creatinine phosphokinase levels > 1200 U/L and > 1000 U/L. CONCLUSIONS: Findings from an inter-city hospital's experience with COVID-19 among underserved minority populations showed that, more than one of every three patients were at risk for in-hospital death or morbidity. Older age and elevated inflammatory markers at presentation were associated with in-hospital death.", "qid": 41, "docid": "g7cqx652", "rank": 96, "score": 0.8406952619552612}, {"content": "Title: For us, COVID\u201019 is personal Content: We are colleagues and friends working together in busy emergency departments in Washington DC. As Black physicians working in urban America, we do not find the recent deluge of news reports chronicling the disproportionate effect that the coronavirus disease (COVID\u201019) pandemic is having on the disenfranchised and minority populations in our country shocking. We have long been witness to and are in a constant state of alarm over the legal, medical, educational, social and economic inequities faced by the most vulnerable residents of this country.", "qid": 41, "docid": "13hperkz", "rank": 97, "score": 0.8406622409820557}, {"content": "Title: Reaching the Hispanic Community About COVID-19 Through Existing Chronic Disease Prevention Programs Content: Publicly available data on racial and ethnic disparities related to coronavirus disease 2019 (COVID-19) are now surfacing, and these data suggest that the novel virus has disproportionately sickened Hispanic communities in the United States. We discuss why Hispanic communities are highly vulnerable to COVID-19 and how adaptations were made to existing infrastructure for Penn State Project ECHO (Extension for Community Healthcare Outcomes) and Better Together REACH (a community-academic coalition using grant funds from Racial and Ethnic Approaches to Community Health) to address these needs. We also describe programming to support COVID-19 efforts for Hispanic communities by using chronic disease prevention programs and opportunities for replication across the country.", "qid": 41, "docid": "9c8w5hwc", "rank": 98, "score": 0.8405731916427612}, {"content": "Title: COVID\u201019: Shedding light on racial and health inequities in the USA Content: The sudden and rapid advancement of the novel Coronavirus (COVID-19) pandemic has led to an unanticipated and unprecedented global crisis. Since its emergence in the United States, there is increasing discussion surrounding the impact of the virus among vulnerable populations. Older adults, young children, and persons with chronic medical or mental health conditions, persons with disabilities, pregnant women, immunocompromised persons and those who are institutionalized or homeless are considered most vulnerable to death and lost quality of life (World Health Organization, 2020).", "qid": 41, "docid": "4prhmi8f", "rank": 99, "score": 0.8402423858642578}, {"content": "Title: Reaching the Hispanic Community About COVID-19 Through Existing Chronic Disease Prevention Programs Content: Publicly available data on racial and ethnic disparities related to coronavirus disease 2019 (COVID-19) are now surfacing, and these data suggest that the novel virus has disproportionately sickened Hispanic communities in the United States. We discuss why Hispanic communities are highly vulnerable to COVID-19 and how adaptations were made to existing infrastructure for Penn State Project ECHO (Extension for Community Healthcare Outcomes) and Better Together REACH (a community\u2013academic coalition using grant funds from Racial and Ethnic Approaches to Community Health) to address these needs. We also describe programming to support COVID-19 efforts for Hispanic communities by using chronic disease prevention programs and opportunities for replication across the country.", "qid": 41, "docid": "t671fl4d", "rank": 100, "score": 0.8399406671524048}]}
{"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": 0.9089176654815674}, {"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": 2, "score": 0.9049673080444336}, {"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": 3, "score": 0.9049294590950012}, {"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": 4, "score": 0.9032316207885742}, {"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": 5, "score": 0.8982445597648621}, {"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": 6, "score": 0.8971987962722778}, {"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": 7, "score": 0.8971936106681824}, {"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": 8, "score": 0.895307719707489}, {"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": 9, "score": 0.8946443796157837}, {"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": 10, "score": 0.8928412199020386}, {"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": 11, "score": 0.8926963806152344}, {"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": 12, "score": 0.8917158842086792}, {"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": 13, "score": 0.8893822431564331}, {"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": 14, "score": 0.888508677482605}, {"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": 15, "score": 0.8869308233261108}, {"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": 16, "score": 0.8865426778793335}, {"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": 17, "score": 0.8855929970741272}, {"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": 18, "score": 0.882725715637207}, {"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": 19, "score": 0.8827255964279175}, {"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": 20, "score": 0.8825381994247437}, {"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": 21, "score": 0.8780879974365234}, {"content": "Title: 25-Hydroxyvitamin D Concentrations Are Lower in Patients with Positive PCR for SARS-CoV-2 Content: Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) causes coronavirus disease 2019 (COVID-19), with a clinical outcome ranging from mild to severe, including death. To date, it is unclear why some patients develop severe symptoms. Many authors have suggested the involvement of vitamin D in reducing the risk of infections; thus, we retrospectively investigated the 25-hydroxyvitamin D (25(OH)D) concentrations in plasma obtained from a cohort of patients from Switzerland. In this cohort, significantly lower 25(OH)D levels (p = 0.004) were found in PCR-positive for SARS-CoV-2 (median value 11.1 ng/mL) patients compared with negative patients (24.6 ng/mL); this was also confirmed by stratifying patients according to age >70 years. On the basis of this preliminary observation, vitamin D supplementation might be a useful measure to reduce the risk of infection. Randomized controlled trials and large population studies should be conducted to evaluate these recommendations and to confirm our preliminary observation.", "qid": 42, "docid": "xsaj0fzu", "rank": 22, "score": 0.8770320415496826}, {"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": 23, "score": 0.8760361671447754}, {"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": 24, "score": 0.8757346868515015}, {"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": 25, "score": 0.8754634261131287}, {"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": 26, "score": 0.8737996816635132}, {"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": 27, "score": 0.8731384873390198}, {"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": 28, "score": 0.8731384873390198}, {"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": 29, "score": 0.870841383934021}, {"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": 30, "score": 0.8704227805137634}, {"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": 31, "score": 0.8699342012405396}, {"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": 32, "score": 0.8688575625419617}, {"content": "Title: Vitamin D Insufficiency is Prevalent in Severe COVID-19 Content: Background: COVID-19 is a major pandemic that has killed more than 196,000 people. The COVID-19 disease course is strikingly divergent. Approximately 80-85% of patients experience mild or no symptoms, while the remainder develop severe disease. The mechanisms underlying these divergent outcomes are unclear. Emerging health disparities data regarding African American and homeless populations suggest that vitamin D insufficiency (VDI) may be an underlying driver of COVID-19 severity. To better define the VDI-COVID-19 link, we determined the prevalence of VDI among our COVID-19 intensive care unit (ICU) patients. Methods: In an Institutional Review Board approved study performed at a single, tertiary care academic medical center, the medical records of COVID-19 patients were retrospectively reviewed. Subjects were included for whom serum 25-hydroxycholecalcifoerol (25OHD) levels were determined. COVID-19-relevant data were compiled and analyzed. We determined the frequency of VDI among COVID-19 patients to evaluate the likelihood of a VDI-COVID-19 relationship. Results: Twenty COVID-19 patients with serum 25OHD levels were identified; 65.0% required ICU admission.The VDI prevalence in ICU patients was 84.6%, vs. 57.1% in floor patients. Strikingly, 100% of ICU patients less than 75 years old had VDI. Coagulopathy was present in 62.5% of ICU COVID-19 patients, and 92.3% were lymphocytopenic. Conclusions: VDI is highly prevalent in severe COVID-19 patients. VDI and severe COVID-19 share numerous associations including hypertension, obesity, male sex, advanced age, concentration in northern climates, coagulopathy, and immune dysfunction. Thus, we suggest that prospective, randomized controlled studies of VDI in COVID-19 patients are warranted.", "qid": 42, "docid": "3ajeiteq", "rank": 33, "score": 0.8686380386352539}, {"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": 34, "score": 0.8686137795448303}, {"content": "Title: Low serum 25-hydroxyvitamin D (25[OH]D) levels in patients hospitalised with COVID-19 are associated with greater disease severity Content: OBJECTIVES: Vitamin D deficiency (VDD) has been proposed to play a role in Coronavirus Disease 2019 (COVID-19) pathophysiology. We aim to evaluate our implementation of a local protocol for treatment of VDD among patients hospitalized for COVID-19; to assess the prevalence of VDD among COVID-19 inpatients, and examine potential associations with disease severity and fatality. DESIGN AND PARTICIPANTS: We conducted a retrospective interim audit of a local clinical care pathway for 134 inpatients with COVID-19. Prevalence of VDD, compliance with local treatment protocol and relationship of baseline serum 25(OH)D with markers of COVID-19 severity and fatality were analysed. RESULTS: 55.8% of eligible patients received Colecalciferol replacement, albeit not all according to the suggested protocol. Patients admitted to ITU were younger than those managed on medical wards (61.1 years \u00b1 11.8 vs. 76.4 years \u00b1 14.9, respectively, p<0.001), with greater prevalence of hypertension, higher baseline respiratory rate, National Early Warning Score-2 and C-Reactive protein level. While mean serum 25(OH)D levels were comparable (p=0.3), only 19% of ITU patients had 25(OH)D levels greater than 50 nmol/L vs. 39.1% of non-ITU patients (p=0.02). However, there was no association with fatality, potentially due to small sample size and prompt diagnosis and treatment of VDD. CONCLUSIONS: Higher prevalence of VDD was observed in patients requiring ITU admission compared to patients managed on medical wards. Larger prospective studies and/or clinical trials are needed to validate and extend our observations.", "qid": 42, "docid": "rtkb45lx", "rank": 35, "score": 0.8680208921432495}, {"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": 36, "score": 0.8670907020568848}, {"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": 37, "score": 0.8660358190536499}, {"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": 38, "score": 0.8660358190536499}, {"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": 39, "score": 0.8626483678817749}, {"content": "Title: Low serum 25\u2010hydroxyvitamin D (25[OH]D) levels in patients hospitalised with COVID\u201019 are associated with greater disease severity Content: OBJECTIVES: Vitamin D deficiency (VDD) has been proposed to play a role in Coronavirus Disease 2019 (COVID\u201019) pathophysiology. We aim to evaluate our implementation of a local protocol for treatment of VDD among patients hospitalized for COVID\u201019; to assess the prevalence of VDD among COVID\u201019 inpatients, and examine potential associations with disease severity and fatality. DESIGN AND PARTICIPANTS: We conducted a retrospective interim audit of a local clinical care pathway for 134 inpatients with COVID\u201019. Prevalence of VDD, compliance with local treatment protocol and relationship of baseline serum 25(OH)D with markers of COVID\u201019 severity and fatality were analysed. RESULTS: 55.8% of eligible patients received Colecalciferol replacement, albeit not all according to the suggested protocol. Patients admitted to ITU were younger than those managed on medical wards (61.1 years \u00b1 11.8 vs. 76.4 years \u00b1 14.9, respectively, p<0.001), with greater prevalence of hypertension, higher baseline respiratory rate, National Early Warning Score\u20102 and C\u2010Reactive protein level. While mean serum 25(OH)D levels were comparable (p=0.3), only 19% of ITU patients had 25(OH)D levels greater than 50 nmol/L vs. 39.1% of non\u2010ITU patients (p=0.02). However, there was no association with fatality, potentially due to small sample size and prompt diagnosis and treatment of VDD. CONCLUSIONS: Higher prevalence of VDD was observed in patients requiring ITU admission compared to patients managed on medical wards. Larger prospective studies and/or clinical trials are needed to validate and extend our observations.", "qid": 42, "docid": "tw6f5h2q", "rank": 40, "score": 0.8621651530265808}, {"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": 41, "score": 0.8620240688323975}, {"content": "Title: Vitamin D and COVID-19 Content: Epidemiological data report that several countries with a high prevalence of hypovitaminosis D may have increased susceptibility to complications and mortality due to COVID-19 infection. These reports, however, have limitations given that they derive from observational studies. Nevertheless, while awaiting more robust data, clinicians should treat patients with vitamin D deficiency irrespective of whether or not it has a link with respiratory infections.", "qid": 42, "docid": "kfrhwsjb", "rank": 42, "score": 0.8611470460891724}, {"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": 43, "score": 0.8603194952011108}, {"content": "Title: Calcitriol, the active form of vitamin D, is a promising candidate for COVID-19 prophylaxis Content: COVID-19, the disease caused by SARS-CoV-2 (1), was declared a pandemic by the World Health Organization (WHO) in March 2020 (2). While awaiting a vaccine, several antivirals are being used to manage the disease with limited success (3, 4). To expand this arsenal, we screened 4 compound libraries: a United States Food and Drug Administration (FDA) approved drug library, an angiotensin converting enzyme-2 (ACE2) targeted compound library, a flavonoid compound library as well as a natural product library. Of the 121 compounds identified with activity against SARS-CoV-2, 7 were shortlisted for validation. We show for the first time that the active form of Vitamin D, calcitriol, exhibits significant potent activity against SARS-CoV-2. This finding paves the way for consideration of host-directed therapies for ring prophylaxis of contacts of SARS-CoV-2 patients.", "qid": 42, "docid": "sbon3aes", "rank": 44, "score": 0.8594352006912231}, {"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": 45, "score": 0.8561543226242065}, {"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": 46, "score": 0.8556919693946838}, {"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": 47, "score": 0.8548893928527832}, {"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": 48, "score": 0.854805588722229}, {"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": 49, "score": 0.85341477394104}, {"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": 50, "score": 0.8529038429260254}, {"content": "Title: Evidence of Protective Role of Ultraviolet-B (UVB) Radiation in Reducing COVID-19 Deaths Content: Background: Research is ongoing to identify an effective way to prevent or treat COVID-19, but thus far these efforts have not yet identified a possible solution. Prior studies indicate the protective role of Ultraviolet-B (UVB) radiation in human health, mediated by vitamin D synthesis. In this study, we empirically outline a negative association of UVB radiation as measured by the ultraviolet index (UVI) with the number of deaths attributed to COVID-19 (COVID-19 deaths). Methods: We carry out an observational study, applying a fixed-effect log-linear regression model to a panel dataset of 64 countries over a period of 78 days (n=4992). We use the cumulative number of COVID-19 deaths and case-fatality rate (CFR) as the main dependent variables to test our hypothesis and isolate UVI effect from potential confounding factors such as underlying time trends, country-specific time-constant and time-varying factors such as weather. Findings: After controlling for time-constant and time-varying factors, we find that a permanent unit increase in UVI is associated with a 2.2 percentage points decline in daily growth rates of cumulative COVID-19 deaths [p < 0.01], as well as a 1.9 percentage points, decline in the daily growth rates of CFR [p < 0.05]. These results represent a significant percentage reduction in terms of the daily growth rates of cumulative COVID-19 deaths (-22.92%) and CFR (-73.08%). Our results are consistent across different model specifications. Interpretation: We find a significant negative association between UVI and COVID-19 deaths, indicating evidence of the protective role of UVB in mitigating COVID-19 deaths. If confirmed via clinical studies, then the possibility of mitigating COVID-19 deaths via sensible sunlight exposure or vitamin D intervention will be very attractive because it is cost-effective and widely available.", "qid": 42, "docid": "6u3kepat", "rank": 51, "score": 0.8516372442245483}, {"content": "Title: Can Vitamins, as Epigenetic Modifiers, Enhance Immunity in COVID-19 Patients with Non-communicable Disease? Content: PURPOSE OF REVIEW: The highly infectious transmissible disease, the novel SARS-CoV-2, causing the coronavirus disease (COVID-19), has a median incubation time of 5 to 15 days. The symptoms vary from person to person and many are \u201chidden carriers.\u201d Few people experience immediate reaction and even death within 48 h of infection. However, many show mild to chronic symptoms and recover. Nevertheless, the death rate due to COVID-19 transmission is high especially among patients with non-communicable diseases. The purpose of this review is to provide evidence to consider vitamins as epigenetic modifiers to enhance immunity and reduce inflammatory response in COVID-19 patients with non-communicable diseases. RECENT FINDINGS: Clinical evidence has suggested the risk of getting infected is high among individuals with non-communicable diseases such as cardiovascular disease, type-2 diabetes, cancer, acute respiratory distress syndrome, and renal disease, as well as the elderly with high mortality rate among the cohort. The impact is due to an already compromised immune system of patients. Every patient has a different response to COVID-19, which shows that the ability to combat the deadly virus varies individually. Thus, treatment can be personalized and adjusted to help protect and combat COVID-19 infections, especially in individuals with non-communicable diseases. SUMMARY: Based on current published scientific and medical evidence, the suggestions made in this article for combination of vitamin therapy as epigenetic modifiers to control the unregulated inflammatory and cytokine marker expressions, further needs to be clinically proven. Future research and clinical trials can apply the suggestions given in this article to support metabolic activities in patients and enhance the immune response.", "qid": 42, "docid": "n6x0r58i", "rank": 52, "score": 0.8507845997810364}, {"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": 53, "score": 0.8498166799545288}, {"content": "Title: Can vitamins and/or supplements provide hope against coronavirus? Content: Severe acute respiratory syndrome coronavirus-2 (SARS-COV-2) quickly became a global pandemic and has been responsible, so far, for infecting 5.8 million and claiming the lives of more than 350,000. While certain medications initially garnered attention as potential treatment options, further studies failed to demonstrate great promise but did demonstrate the need to reduce the cytokine storm experienced by patients with this potentially life-threatening virus. Unfortunately, there is no cure on the horizon, but members of the medical community are beginning to evaluate the potential role of vitamins and supplements as potential treatment options or addition to other treatments. The goal of this narrative review is to evaluate current and ongoing clinical trials of vitamins and supplements, alone or in combination with each other or other therapies, for the treatment of coronavirus disease-2019 (COVID-19).", "qid": 42, "docid": "wp7593di", "rank": 54, "score": 0.8464165925979614}, {"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": 55, "score": 0.8460987210273743}, {"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": 56, "score": 0.8459519147872925}, {"content": "Title: Ultraviolet and COVID-19 pandemic Content: BACKGROUND: COVID-19 virus causes coronavirus disease. AIMS: It is a highly contagious viral infection. PATIENTS/METHODS/RESULTS/CONCLUSION: In this article, we will discuss the potential phototherapy problems and also alternative options for dermatologists, ultraviolet treatment against COVID-19 virus, and vitamin D-associated problems in these coronavirus days.", "qid": 42, "docid": "w143rf7h", "rank": 57, "score": 0.8437135219573975}, {"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": 58, "score": 0.8427814841270447}, {"content": "Title: COVID-19 and MS disease-modifying therapies Content: OBJECTIVE: To address concerns regarding the effect of MS disease-modifying therapies (DMTs) on the expression of coronavirus 2019 (COVID-19). METHODS: Review of the current state of knowledge regarding the viral etiology of COVID-19, mechanisms of injury by SARS-CoV-2 infection, and the effect of individual DMTs on the risk of infection and COVID-19 disease expression. RESULTS: Although data are limited, MS DMTs do not obviously increase the risk of acquiring symptomatic SARS-CoV-2 infection. The severe morbidity and mortality of SARS-CoV-2 appear to be largely the consequence of an overly robust immune response rather than the consequence of unchecked viral replication. The effects of specific MS DMTs on the immune response that may increase the risk of impaired viral clearance and their potential counterbalancing beneficial effects on the development of COVID-19\u2013associated acute respiratory distress syndrome are reviewed. CONCLUSION: Although there is currently insufficient real-world experience to definitively answer the question of the effect of a specific MS DMT on COVID-19, registries presently in nascent form should provide these answers. This review provides an approach to addressing these concerns while the data are being accumulated. Early insights suggest that the risk of infection and associated morbidity of COVID-19 in this population is little different than that of the population at large.", "qid": 42, "docid": "yio7v83p", "rank": 59, "score": 0.8420696258544922}, {"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": 60, "score": 0.8419976830482483}, {"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": 61, "score": 0.8414754271507263}, {"content": "Title: COVID-19 and MS disease-modifying therapies Content: OBJECTIVE: To address concerns regarding the effect of MS disease-modifying therapies (DMTs) on the expression of coronavirus 2019 (COVID-19). METHODS: Review of the current state of knowledge regarding the viral etiology of COVID-19, mechanisms of injury by SARS-CoV-2 infection, and the effect of individual DMTs on the risk of infection and COVID-19 disease expression. RESULTS: Although data are limited, MS DMTs do not obviously increase the risk of acquiring symptomatic SARS-CoV-2 infection. The severe morbidity and mortality of SARS-CoV-2 appear to be largely the consequence of an overly robust immune response rather than the consequence of unchecked viral replication. The effects of specific MS DMTs on the immune response that may increase the risk of impaired viral clearance and their potential counterbalancing beneficial effects on the development of COVID-19-associated acute respiratory distress syndrome are reviewed. CONCLUSION: Although there is currently insufficient real-world experience to definitively answer the question of the effect of a specific MS DMT on COVID-19, registries presently in nascent form should provide these answers. This review provides an approach to addressing these concerns while the data are being accumulated. Early insights suggest that the risk of infection and associated morbidity of COVID-19 in this population is little different than that of the population at large.", "qid": 42, "docid": "3lsn0qgl", "rank": 62, "score": 0.8409353494644165}, {"content": "Title: Low plasma 25(OH) vitamin D3 level is associated with increased risk of COVID-19 infection: an Israeli population-based study Content: Aim: To evaluate associations of plasma 25(OH)D status with the likelihood of coronavirus disease (COVID-19) infection and hospitalization. Methods: The study population included the 14,000 members of Leumit Health Services who were tested for COVID-19 infection from February 1st to April 30th, 2020, and who had at least one previous blood test for plasma 25(OH)D level. \"Suboptimal\" or \"low\" plasma 25(OH)D level was defined as plasma 25-hydroxyvitamin D, or 25(OH)D, concentration below 30 ng/mL. Results: Of 7,807 individuals, 782 (10.1%) were COVID-19-positive, and 7,025 (89.9%) COVID-19-negative. The mean plasma vitamin D level was significantly lower among those who tested positive than negative for COVID-19 [19.00 ng/mL (95% confidence interval [CI] 18.41-19.59) vs. 20.55 (95% CI 20.32-20.78)]. Univariate analysis demonstrated an association between low plasma 25(OH)D level and increased likelihood of COVID-19 infection [crude odds ratio (OR) of 1.58 (95% CI 1.24-2.01, p<0.001)], and of hospitalization due to the SARS-CoV-2 virus [crude OR of 2.09 (95% CI 1.01-4.30, p<0.05)]. In multivariate analyses that controlled for demographic variables and psychiatric and somatic disorders, the adjusted OR of COVID-19 infection [1.45 (95% CI 1.08-1.95, p<0.001)], and of hospitalization due to the SARS-CoV-2 virus [1.95 (95% CI 0.98-4.845, p=0.061)] were preserved. In the multivariate analyses, age over 50 years, male gender and low-medium socioeconomic status were also positively associated with the risk of COVID-19 infection; age over 50 years was positively associated with the likelihood of hospitalization due to COVID-19.", "qid": 42, "docid": "5xhc3h0z", "rank": 63, "score": 0.8407446146011353}, {"content": "Title: AhR and IDO1 in pathogenesis of Covid-19 and the \"Systemic AhR Activation Syndrome:\" Translational review and therapeutic perspectives Content: Covid-19 is the acute illness caused by SARS-CoV-2 with initial clinical symptoms such as cough, fever, malaise, headache, and anosmia. After entry into cells, corona viruses (CoV) activate aryl hydrocarbon receptors (AhRs) by an indoleamine 2,3-dioxygenase (IDO1)-independent mechanism, bypassing the IDO1-kynurenine-AhR pathway. The IDO1-kynurenine-AhR signaling pathway is used by multiple viral, microbial and parasitic pathogens to activate AhRs and to establish infections. AhRs enhance their own activity through an IDO1-AhR-IDO1 positive feedback loop prolonging activation induced by pathogens. Direct activation of AhRs by CoV induces immediate and simultaneous up-regulation of diverse AhR-dependent downstream effectors, and this, in turn, results in a \"Systemic AhR Activation Syndrome\" (SAAS) consisting of inflammation, thromboembolism, and fibrosis, culminating in multiple organ injuries, and death. Activation of AhRs by CoV may lead to diverse sets of phenotypic disease pictures depending on time after infection, overall state of health, hormonal balance, age, gender, comorbidities, but also diet and environmental factors modulating AhRs. We hypothesize that elimination of factors known to up-regulate AhRs, or implementation of measures known to down-regulate AhRs, should decrease severity of infection. Although therapies selectively down-regulating both AhR and IDO1 are currently lacking, medications in clinical use such as dexamethasone may down-regulate both AhR and IDO1 genes, as calcitriol/vitamin D3 may down-regulate the AhR gene, and tocopherol/vitamin E may down-regulate the IDO1 gene. Supplementation of calcitriol should therefore be subjected to epidemiological studies and tested in prospective trials for prevention of CoV infections, as should tocopherol, whereas dexamethasone could be tried in interventional trials. Because lack of physical exercise activates AhRs via the IDO1-kynurenine-AhR signaling pathway increasing risk of infection, physical exercise should be encouraged during quarantines and stay-at-home orders during pandemic outbreaks. Understanding which factors affect gene expression of both AhR and IDO1 may help in designing therapies to prevent and treat humans suffering from Covid-19.", "qid": 42, "docid": "mm38i1gg", "rank": 64, "score": 0.8402950763702393}, {"content": "Title: AhR and IDO1 in pathogenesis of Covid-19 and the \"Systemic AhR Activation Syndrome\" Translational review and therapeutic perspectives. Content: Covid-19 is the acute illness caused by SARS-CoV-2 with initial clinical symptoms such as cough, fever, malaise, headache, and anosmia. After entry into cells, corona viruses (CoV) activate aryl hydrocarbon receptors (AhRs) by an indoleamine 2,3-dioxygenase (IDO1)-independent mechanism, bypassing the IDO1-kynurenine-AhR pathway. The IDO1-kynurenine-AhR signaling pathway is used by multiple viral, microbial and parasitic pathogens to activate AhRs and to establish infections. AhRs enhance their own activity through an IDO1-AhR-IDO1 positive feedback loop prolonging activation induced by pathogens. Direct activation of AhRs by CoV induces immediate and simultaneous up-regulation of diverse AhR-dependent downstream effectors, and this, in turn, results in a \"Systemic AhR Activation Syndrome\" (SAAS) consisting of inflammation, thromboembolism, and fibrosis, culminating in multiple organ injuries, and death. Activation of AhRs by CoV may lead to diverse sets of phenotypic disease pictures depending on time after infection, overall state of health, hormonal balance, age, gender, comorbidities, but also diet and environmental factors modulating AhRs. We hypothesize that elimination of factors known to up-regulate AhRs, or implementation of measures known to down-regulate AhRs, should decrease severity of infection. Although therapies selectively down-regulating both AhR and IDO1 are currently lacking, medications in clinical use such as dexamethasone may down-regulate both AhR and IDO1 genes, as calcitriol/vitamin D3 may down-regulate the AhR gene, and tocopherol/vitamin E may down-regulate the IDO1 gene. Supplementation of calcitriol should therefore be subjected to epidemiological studies and tested in prospective trials for prevention of CoV infections, as should tocopherol, whereas dexamethasone could be tried in interventional trials. Because lack of physical exercise activates AhRs via the IDO1-kynurenine-AhR signaling pathway increasing risk of infection, physical exercise should be encouraged during quarantines and stay-at-home orders during pandemic outbreaks. Understanding which factors affect gene expression of both AhR and IDO1 may help in designing therapies to prevent and treat humans suffering from Covid-19.", "qid": 42, "docid": "kaefedl1", "rank": 65, "score": 0.8402950763702393}, {"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": 42, "docid": "jt7ctj2z", "rank": 66, "score": 0.8401163816452026}, {"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": 67, "score": 0.839991569519043}, {"content": "Title: COVID-19 in Parkinson's Disease Patients Living in Lombardy, Italy Content: BACKGROUND: It is unknown whether patients with PD are at greater risk of COVID-19, what their risk factors are, and whether their clinical manifestations differ from the general population. OBJECTIVES: The study aimed to address all these issues. METHODS: In a case-controlled survey, we interviewed 1,486 PD patients attending a single tertiary center in Lombardy, Italy and 1,207 family members (controls). RESULTS: One hundred five (7.1%) and 92 controls (7.6%) were identified as COVID-19 cases. COVID-19 patients were younger, more likely to suffer from chronic obstructive pulmonary disease, to be obese, and vitamin D nonsupplemented than unaffected patients. Six patients (5.7%) and 7 family members (7.6%) died from COVID-19. Patients were less likely to report shortness of breath and require hospitalization. CONCLUSIONS: In an unselected large cohort of nonadvanced PD patients, COVID-19 risk and mortality did not differ from the general population, but symptoms appeared to be milder. The possible protective role of vitamin D supplementation warrants future studies. \u00a9 2020 International Parkinson and Movement Disorder Society.", "qid": 42, "docid": "dfqqogqp", "rank": 68, "score": 0.8396292924880981}, {"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": 42, "docid": "0croajal", "rank": 69, "score": 0.8390969038009644}, {"content": "Title: Ultraviolet and COVID\u201019 pandemic Content: BACKGROUND: COVID\u201019 virus causes coronavirus disease. AIMS: It is a highly contagious viral infection. PATIENTS/METHODS/RESULTS/CONCLUSION: In this article, we will discuss the potential phototherapy problems and also alternative options for dermatologists, ultraviolet treatment against COVID\u201019 virus, and vitamin D\u2013associated problems in these coronavirus days.", "qid": 42, "docid": "c2gll4d1", "rank": 70, "score": 0.8388425707817078}, {"content": "Title: Strengthening the Immune System and Reducing Inflammation and Oxidative Stress through Diet and Nutrition: Considerations during the COVID-19 Crisis Content: The coronavirus-disease 2019 (COVID-19) was announced as a global pandemic by the World Health Organization. Challenges arise concerning how to optimally support the immune system in the general population, especially under self-confinement. An optimal immune response depends on an adequate diet and nutrition in order to keep infection at bay. For example, sufficient protein intake is crucial for optimal antibody production. Low micronutrient status, such as of vitamin A or zinc, has been associated with increased infection risk. Frequently, poor nutrient status is associated with inflammation and oxidative stress, which in turn can impact the immune system. Dietary constituents with especially high anti-inflammatory and antioxidant capacity include vitamin C, vitamin E, and phytochemicals such as carotenoids and polyphenols. Several of these can interact with transcription factors such as NF-kB and Nrf-2, related to anti-inflammatory and antioxidant effects, respectively. Vitamin D in particular may perturb viral cellular infection via interacting with cell entry receptors (angiotensin converting enzyme 2), ACE2. Dietary fiber, fermented by the gut microbiota into short-chain fatty acids, has also been shown to produce anti-inflammatory effects. In this review, we highlight the importance of an optimal status of relevant nutrients to effectively reduce inflammation and oxidative stress, thereby strengthening the immune system during the COVID-19 crisis.", "qid": 42, "docid": "q2l53631", "rank": 71, "score": 0.8377552032470703}, {"content": "Title: Strengthening the Immune System and Reducing Inflammation and Oxidative Stress through Diet and Nutrition: Considerations during the COVID-19 Crisis. Content: The coronavirus-disease 2019 (COVID-19) was announced as a global pandemic by the World Health Organization. Challenges arise concerning how to optimally support the immune system in the general population, especially under self-confinement. An optimal immune response depends on an adequate diet and nutrition in order to keep infection at bay. For example, sufficient protein intake is crucial for optimal antibody production. Low micronutrient status, such as of vitamin A or zinc, has been associated with increased infection risk. Frequently, poor nutrient status is associated with inflammation and oxidative stress, which in turn can impact the immune system. Dietary constituents with especially high anti-inflammatory and antioxidant capacity include vitamin C, vitamin E, and phytochemicals such as carotenoids and polyphenols. Several of these can interact with transcription factors such as NF-kB and Nrf-2, related to anti-inflammatory and antioxidant effects, respectively. Vitamin D in particular may perturb viral cellular infection via interacting with cell entry receptors (angiotensin converting enzyme 2), ACE2. Dietary fiber, fermented by the gut microbiota into short-chain fatty acids, has also been shown to produce anti-inflammatory effects. In this review, we highlight the importance of an optimal status of relevant nutrients to effectively reduce inflammation and oxidative stress, thereby strengthening the immune system during the COVID-19 crisis.", "qid": 42, "docid": "cvouxqxy", "rank": 72, "score": 0.8377552032470703}, {"content": "Title: Serum 25-Hydroxyvitamin D and the Incidence of Acute Viral Respiratory Tract Infections in Healthy Adults Content: BACKGROUND: Declining serum concentrations of 25-hydroxyvitamin D seen in the fall and winter as distance increases from the equator may be a factor in the seasonal increased prevalence of influenza and other viral infections. This study was done to determine if serum 25-hydroxyvitamin D concentrations correlated with the incidence of acute viral respiratory tract infections. METHODOLOGY/FINDINGS: In this prospective cohort study serial monthly concentrations of 25-hydroxyvitamin D were measured over the fall and winter 2009\u20132010 in 198 healthy adults, blinded to the nature of the substance being measured. The participants were evaluated for the development of any acute respiratory tract infections by investigators blinded to the 25-hydroxyvitamin D concentrations. The incidence of infection in participants with different concentrations of vitamin D was determined. One hundred ninety-five (98.5%) of the enrolled participants completed the study. Light skin pigmentation, lean body mass, and supplementation with vitamin D were found to correlate with higher concentrations of 25-hydroxyvitamin D. Concentrations of 38 ng/ml or more were associated with a significant (p<0.0001) two-fold reduction in the risk of developing acute respiratory tract infections and with a marked reduction in the percentages of days ill. CONCLUSIONS/SIGNIFICANCE: Maintenance of a 25-hydroxyvitamin D serum concentration of 38 ng/ml or higher should significantly reduce the incidence of acute viral respiratory tract infections and the burden of illness caused thereby, at least during the fall and winter in temperate zones. The findings of the present study provide direction for and call for future interventional studies examining the efficacy of vitamin D supplementation in reducing the incidence and severity of specific viral infections, including influenza, in the general population and in subpopulations with lower 25-hydroxyvitamin D concentrations, such as pregnant women, dark skinned individuals, and the obese.", "qid": 42, "docid": "zz7e17wp", "rank": 73, "score": 0.8363151550292969}, {"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": 74, "score": 0.8358587026596069}, {"content": "Title: Viramina D e coronavirus: un nuovo campo di impiego?/ [Vitamin D and coronavirus: a new field of use?] Content: Given the succession of communications in scientific and popular circuits, tending to take for granted a role for vitamin D in the control of the coronavirus pandemic, the authors conducted an analysis of the literature currently available in order to recognize what is supported by opinions personal and what evidence of effectiveness. At the end of the bibliographic survey there is the current absence of evidence of efficacy in favor of vitamin D in the treatment of coronavirus infection in its various expressions. The diffusion of personal opinions as if they were evidence can be a disturbing factor for adequate assistance and for correct research.", "qid": 42, "docid": "gfyx3nz2", "rank": 75, "score": 0.8354219198226929}, {"content": "Title: [Vitamin D and coronavirus: a new field of use?] Content: Given the succession of communications in scientific and popular circuits, tending to take for granted a role for vitamin D in the control of the coronavirus pandemic, the authors conducted an analysis of the literature currently available in order to recognize what is supported by opinions personal and what evidence of effectiveness. At the end of the bibliographic survey there is the current absence of evidence of efficacy in favor of vitamin D in the treatment of coronavirus infection in its various expressions. The diffusion of personal opinions as if they were evidence can be a disturbing factor for adequate assistance and for correct research.", "qid": 42, "docid": "34f1ie66", "rank": 76, "score": 0.8354219198226929}, {"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": 77, "score": 0.8344775438308716}, {"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": 42, "docid": "9eug7szt", "rank": 78, "score": 0.834450364112854}, {"content": "Title: Does Lockdown Decrease the Protective Role of ultraviolet-B (UVB) Radiation in Reducing COVID-19 Deaths? Content: Background: Nations are imposing unprecedented measures at large-scale to contain the spread of COVID-19 pandemic. Recent studies indicate that measures such as lockdowns may have slowed down the growth of COVID-19. However, in addition to substantial economic and social costs, these measures also limit the exposure to Ultraviolet-B radiation (UVB). Emerging observational evidence indicate the protective role of UVB and vitamin D in reducing the severity and mortality of COVID-19 deaths. In this observational study, we empirically outline the independent protective roles of lockdown and UVB exposure as measured by ultraviolet index (UVI), whilst also examining whether the severity of lockdown is associated with a reduction in the protective role. Methods. We apply a log-linear fixed-effects model to a panel dataset of 162 countries over a period of 108 days (n=6049). We use the cumulative number of COVID-19 deaths as the dependent variable and isolate the mitigating influence of lockdown severity on the association between UVI and growth-rates of COVID-19 deaths from time-constant country-specific and time-varying country-specific potentially confounding factors. Findings: After controlling for time-constant and time-varying factors, we find that a unit increase in UVI and lockdown severity are independently associated with 17% [-1.8 percentage points] and 77% [-7.9 percentage points] decline in COVID-19 deaths growth rate, indicating their respective protective roles. However, the widely utilized and least severe lockdown (recommendation to not leave the house) already fully mitigates the protective role of UVI by 95% [1.8 percentage points] indicating its downside. Interpretation: We find that lockdown severity and UVI are independently associated with a slowdown in the daily growth rates of cumulative COVID-19 deaths. However, we find consistent evidence that increase in lockdown severity is associated with a significant reduction in the protective role of UVI in reducing COVID-19 deaths. Our results suggest that lockdowns in conjunction with adequate exposure to UVB radiation might have provided even more substantial health benefits, than lockdowns alone. For example, we estimate that there would be 21% fewer deaths on average with sufficient UVB exposure while people were recommended not to leave their house. Therefore, our study outlines the importance of considering UVB exposure, especially while implementing lockdowns and may support policy decision making in countries imposing such measures.", "qid": 42, "docid": "z6cp42aa", "rank": 79, "score": 0.8342395424842834}, {"content": "Title: A Rapid Advice Guideline for the Prevention of Novel Coronavirus Through Nutritional Intervention Content: PURPOSE OF REVIEW: An unexpected and sudden outbreak of a novel infection known as a coronavirus (COVID-19) has imposed important problems to global well-being and economy. Based upon current researches, this virus is spreading from one human to another through respiratory droplets, i.e. cough and sneeze. Till now, there has not been any specific treatment found for this virus. Hence, there is a critical need to discover alternative techniques to cope with the current scenario. RECENT FINDINGS: This review conducted an online search for prevention of coronavirus infection with the help of nutritional interventions. It has been observed that the effect of the virus is mostly on the individual with low immunity, individual affected with diseases like diabetes, and individual using any immune-suppressed drug or having past history of major surgeries or severe medical conditions. SUMMARY: Therefore, consuming foods which boost immunity helps in preventing respiratory-related disorder or suppressing diseases-related problems, which could be helpful in controlling the spread of this virus. In conclusion, it has been suggested that before the beginning of generalised treatments and interventions in each infected patient, nutritional status should be evaluated, as it can help in creating a specific nutrition intervention for the infected individual.", "qid": 42, "docid": "yzb1o7am", "rank": 80, "score": 0.8338249325752258}, {"content": "Title: Can dapagliflozin have a protective effect against COVID-19 infection? A hypothesis Content: Abstract It has been reported that frequent occurrence of COVID-19 infection in these patients is associated with low cytosolic pH. During virus infection, serum lactate dehydrogenase (LDH) level excessively rises. LDH is a cytosolic enzyme and the serum level increases as the cell break down. When anaerobic conditions develop, lactate formation increases from pyruvate. Cell pH is regulated by very complex mechanisms. When lactate increases in the extracellular area, this symporter carries lactate and H+ ion into the cell, and the intracellular pH quickly becomes acidic. Paradoxically, Na+/H+ exchanger activation takes place. While H+ ion is thrown out of the cell, Na+ and Ca+2 enter the cell. When Na+ and Ca+2 increase in the cell, the cells swell and die. Dapagliflozin is a sodium-glucose cotransporter-2 inhibitor. Dapagliflozin has been reported to reduce lactate levels by various mechanisms. Also, it reduces oxygen consumption in tissues and causes the use of glucose in the aerobic pathway, thereby reducing lactate production. A lactate decrease in the environment reduces the activation of lactate/H+ symporter. Thus, the H ion pumping into the cell by this symporter is reduced and the cytosolic pH is maintained. Dapagliflozin also directly inhibits NHE. Thus, Na+ and Ca+2 flow to the cell are inhibited. Dapagliflozin provides the continuation of the structure and functions of the cells. Dapagliflozin can prevent the severe course of COVID-19 infection by preventing the lowering of cytosolic pH and reducing the viral load.", "qid": 42, "docid": "9lc9lckp", "rank": 81, "score": 0.8335441946983337}, {"content": "Title: Coronavirus Disease 2019: A Comprehensive Review of Etiology, Pathogenesis, Diagnosis, and Ongoing Clinical Trials Content: Coronavirus disease 2019 (COVID-19) is an acute respiratory viral infection caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). The disease outbreak started in China in late December 2019 and quickly spread to the rest of the world, resulting in a pandemic. The incidence of cases is increasing every day, affecting millions of people around the globe and resulting in a public health emergency. Furthermore, disease management has been challenging for the clinicians and other medical personnel in terms of treatment options and availability of personal protective equipment. The off-label use of drugs such as hydroxychloroquine and emergency use authorization of remdesivir can hopefully help the clinicians while treating critically ill patients. The use of convalescent serum has also shown some interim benefit until a definitive treatment and preventive options are uncovered, such as vaccines and other effective treatment regimens.", "qid": 42, "docid": "au5akuop", "rank": 82, "score": 0.8334981799125671}, {"content": "Title: Managing the supportive care needs of those affected by COVID-19 Content: Globally, the number of people affected by coronavirus disease 2019 (COVID-19) is rapidly increasing. In most (>80%), the illness is relatively mild and can be self-managed out of hospital. However, in about 20% the illness causes respiratory compromise severe enough to require hospital admission [1]. Patients with severe and critical disease need full active treatment. This may include oxygen for hypoxaemia and ventilatory support, along with optimal management of complications, e.g. super-imposed bacterial infection, and any underlying co-morbidities, e.g. chronic obstructive pulmonary disease, congestive heart failure. To date, no antiviral agent has shown to be effective in treating the disease [2].", "qid": 42, "docid": "9mo6h3l3", "rank": 83, "score": 0.8331226110458374}, {"content": "Title: Can dapagliflozin have a protective effect against COVID-19 infection? A hypothesis Content: It has been reported that frequent occurrence of COVID-19 infection in these patients is associated with low cytosolic pH. During virus infection, serum lactate dehydrogenase (LDH) level excessively rises. LDH is a cytosolic enzyme and the serum level increases as the cell break down. When anaerobic conditions develop, lactate formation increases from pyruvate. Cell pH is regulated by very complex mechanisms. When lactate increases in the extracellular area, this symporter carries lactate and H+ ion into the cell, and the intracellular pH quickly becomes acidic. Paradoxically, Na+/H+ exchanger activation takes place. While H+ ion is thrown out of the cell, Na+ and Ca+2 enter the cell. When Na+ and Ca+2 increase in the cell, the cells swell and die. Dapagliflozin is a sodium-glucose cotransporter-2 inhibitor. Dapagliflozin has been reported to reduce lactate levels by various mechanisms. Also, it reduces oxygen consumption in tissues and causes the use of glucose in the aerobic pathway, thereby reducing lactate production. A lactate decrease in the environment reduces the activation of lactate/H+ symporter. Thus, the H ion pumping into the cell by this symporter is reduced and the cytosolic pH is maintained. Dapagliflozin also directly inhibits NHE. Thus, Na+ and Ca+2 flow to the cell are inhibited. Dapagliflozin provides the continuation of the structure and functions of the cells. Dapagliflozin can prevent the severe course of COVID-19 infection by preventing the lowering of cytosolic pH and reducing the viral load.", "qid": 42, "docid": "5wm0v7e1", "rank": 84, "score": 0.8327319622039795}, {"content": "Title: Public health measures to slow community spread of COVID-19 ;The Journal of Infectious Diseases ;Oxford Academic Content: COVID-19 was initially identified in an outbreak of viral pneumonia in Wuhan in December 2019, and has now been recognized in 77 countries with over 90,000 laboratory-confirmed cases and over 3,000 deaths as of 3 March 2020 [1] The epidemiology of COVID-19 has recently become clearer as incident cases continue to rise and researchers refine estimates of the severity, transmissibility, and populations affected Based on available data, COVID-19 is efficiently transmitted in the community, and the proportion of infections leading to severe illness is particularly high among adults \u226550 years of age and among individuals with comorbid health conditions Although rare, severe cases have also been reported among younger individuals Thus far, the estimated basic reproductive number (R0) of COVID-19 is higher than that of influenza [2], as is the case fatality risk for adults and older individuals An estimated 80% of COVID-19 cases are mild [1] This is not a glass half full statistic, as 20% of infections result in clinically severe cases that have the potential to overwhelm already overburdened health facilities Given the lack of vaccines and effective antivirals, nonpharmaceutical interventions (NPIs) are the most effective available interventions for local and global control and mitigation of COVID-19 To date, measures aimed at slowing introduction of infection globally have included travel restrictions, isolation of confirmed cases, and quarantine of exposed persons In the United States, NPIs have reduced the number of infected persons entering the country, but recent outbreaks in multiple US states make it clear that these measures have delayed but not prevented community transmission In 2009, NPIs were able to delay large epidemic waves of pandemic influenza A(H1N1)pdm09 in some locations until after the summer, since influenza transmission tends to be reduced by higher temperatures and humidity It is unclear whether COVID-19 transmission will be heavily affected by seasonal weather variation, given that transmission is now occurring in multiple tropical and sub-tropical locations", "qid": 42, "docid": "lu9mum1d", "rank": 85, "score": 0.8326513767242432}, {"content": "Title: Diabetes and COVID-19 Content: According to previous reports, diabetes seems to be a risk factor which worsens the serious clinical events caused by COVID-19. But is diabetes per se a risk factor that increases the probability of getting the virus? This paper will discuss this point. There are not many research data on antidiabetic drugs in this context. The potential influence of glucose-lowering agents on the severity of COVID-19 has not been described yet. Dipeptidylpeptidase-4 (DPP-4) is a cell surface protein ubiquitously expressed in many tissues and it is also a soluble molecule found in serum/plasma fluids. DPP-4 is involved in infection of cells by some viruses. This paper reviews data about the use of DPP-4 inhibitors and others diabetes drugs on COVID-19 patients. As such, no available evidence has yet suggested that glucose-lowering drugs - including those targeting DPP4-related pathways - produce any significant harm or benefit in the context of human infections. However, insulin must remain the first-choice agent in the management of critically ill-hospitalized patients, while it is recommended to suspend other agents in unstable patients. This paper provides related French and international recommendations for people with diabetes who got infected by COVID-19 and upholds that infections may alter glucose control and may require additional vigilance.", "qid": 42, "docid": "1gswvgya", "rank": 86, "score": 0.832546591758728}, {"content": "Title: SARS-CoV-2 and DPP4 inhibition: Is it time to pray for Janus Bifrons? Content: Diabetes could be a risk factor for severity and mortality in patients with coronavirus disease 2019 COVID-19. It has been hypothesized that DPP4 inhibition, a therapy currently available for type 2 diabetes, might represent a target for decreasing the risk of the acute respiratory complications of the COVID-19 infection but (1) lack of demonstration of SARS-CoV2 binding to DPP4 (2) possible protective role of sDPP4 in Middle East respiratory Syndrome (MERS-CoV) (3) demonstrated inhibition and downregulation of DPP4 by HIV1 and MERS-CoV and (4) not exclusive role of the receptor binding in tropism of the Coronavirus family, support that DPP4 inhibition at present doesn't represent a plausible approach to mitigate COVID-19.", "qid": 42, "docid": "5k61tlva", "rank": 87, "score": 0.8322844505310059}, {"content": "Title: Diabetes and COVID-19 Content: Summary According to previous reports, diabetes seems to be a risk factor which worsens the serious clinical events caused by COVID-19. But is diabetes per se a risk factor that increases the probability of getting the virus? This paper will discuss this point. There are not many research data on antidiabetic drugs in this context. The potential influence of glucose-lowering agents on the severity of COVID-19 has not been described yet. Dipeptidylpeptidase-4 (DPP-4) is a cell surface protein ubiquitously expressed in many tissues and it is also a soluble molecule found in serum/plasma fluids. DPP-4 is involved in infection of cells by some viruses. This paper reviews data about the use of DPP-4 inhibitors and others diabetes drugs on COVID-19 patients. As such, no available evidence has yet suggested that glucose-lowering drugs \u2013 including those targeting DPP4-related pathways \u2013 produce any significant harm or benefit in the context of human infections. However, insulin must remain the first-choice agent in the management of critically ill-hospitalized patients, while it is recommended to suspend other agents in unstable patients. This paper provides related French and international recommendations for people with diabetes who got infected by COVID-19 and upholds that infections may alter glucose control and may require additional vigilance.", "qid": 42, "docid": "o99mtt0v", "rank": 88, "score": 0.8322216272354126}, {"content": "Title: Integrative pharmacological mechanism of vitamin C combined with glycyrrhizic acid against COVID-19: findings of bioinformatics analyses. Content: OBJECTIVE Coronavirus disease 2019 (COVID-19) is a fatal and fast-spreading viral infection. To date, the number of COVID-19 patients worldwide has crossed over six million with over three hundred and seventy thousand deaths (according to the data from World Health Organization; updated on 2 June 2020). Although COVID-19 can be rapidly diagnosed, efficient clinical treatment of COVID-19 remains unavailable, resulting in high fatality. Some clinical trials have identified vitamin C (VC) as a potent compound pneumonia management. In addition, glycyrrhizic acid (GA) is clinically as an anti-inflammatory medicine against pneumonia-induced inflammatory stress. We hypothesized that the combination of VC and GA is a potential option for treating COVID-19. METHODS The aim of this study was to determine pharmacological targets and molecular mechanisms of VC + GA treatment for COVID-19, using bioinformational network pharmacology. RESULTS We uncovered optimal targets, biological processes and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathways of VC + GA against COVID-19. Our findings suggested that combinatorial VC and GA treatment for COVID-19 was associated with elevation of immunity and suppression of inflammatory stress, including activation of the T cell receptor signaling pathway, regulation of Fc gamma R-mediated phagocytosis, ErbB signaling pathway and vascular endothelial growth factor signaling pathway. We also identified 17 core targets of VC + GA, which suggest as antimicrobial function. CONCLUSIONS For the first time, our study uncovered the pharmacological mechanism underlying combined VC and GA treatment for COVID-19. These results should benefit efforts to address the most pressing problem currently facing the world.", "qid": 42, "docid": "3cz34tk4", "rank": 89, "score": 0.8321321606636047}, {"content": "Title: A Rapid Advice Guideline for the Prevention of Novel Coronavirus Through Nutritional Intervention Content: PURPOSE OF REVIEW: An unexpected and sudden outbreak of a novel infection known as a coronavirus (COVID-19) has imposed important problems to global well-being and economy. Based upon current researches, this virus is spreading from one human to another through respiratory droplets, i.e. cough and sneeze. Till now, there has not been any specific treatment found for this virus. Hence, there is a critical need to discover alternative techniques to cope with the current scenario. RECENT FINDINGS: This review conducted an online search for prevention of coronavirus infection with the help of nutritional interventions. It has been observed that the effect of the virus is mostly on the individual with low immunity, individual affected with diseases like diabetes, and individual using any immune-suppressed drug or having past history of major surgeries or severe medical conditions. Therefore, consuming foods which boost immunity helps in preventing respiratory-related disorder or suppressing diseases-related problems, which could be helpful in controlling the spread of this virus. In conclusion, it has been suggested that before the beginning of generalised treatments and interventions in each infected patient, nutritional status should be evaluated, as it can help in creating a specific nutrition intervention for the infected individual.", "qid": 42, "docid": "t6wl35aw", "rank": 90, "score": 0.8320333957672119}, {"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": 42, "docid": "cn3bpmwj", "rank": 91, "score": 0.8315454721450806}, {"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": 92, "score": 0.8308061957359314}, {"content": "Title: Metronidazole;a Potential Novel Addition to the COVID-19 Treatment Regimen Content: Coronavirus disease 2019 or COVID-19 has rapidly emerged as a global pandemic This viral infection involves the upper respiratory tract and could lead to severe pneumonia with respiratory distress or even death Certain studies have found higher initial plasma levels of most pro-inflammatory cytokines during the course of the infection In this context, both in vitro and in vivo studies have revealed that metronidazole could decrease the levels of several cytokines, which are known to increase during the COVID-19 infection, including interleukin (IL)8, IL6, IL1B, tumor necrosis factor (TNF)alpha, IL12, IL1alpha, and interferon (IFN)gamma, as well as the levels of C-reactive protein (CRP) and neutrophil count Furthermore, the drug could decrease neutrophil-generated reactive oxygen species during inflammation Metronidazole could counteract majority of the immunopathological manifestations of the COVID-19 infection Therefore, studies with a large sample size are required to determine the efficacy of metronidazole in the treatment of COVID-19 infection", "qid": 42, "docid": "wwhfyemy", "rank": 93, "score": 0.830245316028595}, {"content": "Title: Is hydroxychloroquine beneficial for COVID-19 patients? Content: The outbreak of coronavirus disease 2019 (COVID-19) caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) was first reported in December 2019. As similar cases rapidly emerged around the world(1\u20133), the World Health Organization (WHO) declared a public health emergency of international concern on January 30, 2020 and pronounced the rapidly spreading coronavirus outbreak as a pandemic on March 11, 2020(4). The virus has reached almost all countries of the globe. As of June 3, 2020, the accumulated confirmed cases reached 6,479,405 with more than 383,013 deaths worldwide. The urgent and emergency care of COVID-19 patients calls for effective drugs, in addition to the beneficial effects of remdesivir(5), to control the disease and halt the pandemic.", "qid": 42, "docid": "hqkrer9m", "rank": 94, "score": 0.8302199840545654}, {"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": 42, "docid": "rn1t7612", "rank": 95, "score": 0.8298715353012085}, {"content": "Title: Ultraviolet A Radiation and COVID-19 Deaths: A Multi Country Study Content: Objectives To determine whether UVA exposure might be associated with COVID-19 deaths Design Ecological model and meta-analysis Setting 2,474 counties of the contiguous USA, 6,755 municipalities in Italy, 6,274 areas in England. Data were collected during their Vitamin D winter (monthly mean UVvitd of under 165 KJ/m2) from Jan to April 2020. Participants The at-risk population is the total county population, with measures to incorporate spatial infection into the model. The model is adjusted for: age, ethnicity, socioeconomic deprivation, long term PM2.5, and UV weighted by the vitamin D action spectrum. Main outcome measures We derive UVA measures for each area and estimate their relationship with COVID-19 mortality with a random effect for States, in a multilevel zero-inflated negative binomial model. In the USA and England death certificates had to record COVID-19. In Italy excess deaths in 2020 over expected from 2015-19. Data sources Satellite derived mean daily UVA dataset from Japan Aerospace Exploration Agency. Data on deaths compiled by Center for Disease Control (USA), Office for National Statistics (England) and Italian Institute of Statistics. Results Daily mean UVA (January-April 2020) varied between 450 to 1,000 KJ/m2 across the three countries. Our fully adjusted model showed an inverse correlation between UVA and COVID-19 mortality with a Mortality Risk Ratio (MRR) of 0.73 (0.62 to 0.87)per 100KJ/m2 increase UVA in the USA, 0.81 (0.71 to 0.93) in Italy and 0.51 (0.39 to 0.66) in England. Pooled MRR was 0.68 (0.53 to 0.66). Conclusions Our analysis, replicated in 3 independent national datasets, suggests ambient UVA exposure is associated with lower COVID-19 specific mortality. This effect is independent of vitamin D, as it occurred at irradiances below that likely to induce significant cutaneous vitamin D3 synthesis. Causal interpretations must be made cautiously in observational studies. Nonetheless this study suggests strategies for reduction of COVID-19 mortality", "qid": 42, "docid": "ruw45n81", "rank": 96, "score": 0.8297139406204224}, {"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": 42, "docid": "tsms3303", "rank": 97, "score": 0.8295890688896179}, {"content": "Title: Advice regarding COVID\u201019 and use of immunomodulators, in patients with severe dermatological diseases Content: Coronavirus disease 2019 (COVID-19) is the disease caused by the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), as named by the International Committee on Taxonomy of Viruses (ICTV). There is very limited evidence base to formulate specific advice for dermatology patients on immunomodulators with regards to COVID-19. The following is based on expert opinion, taking into account known risks of influenza (a negative sense single-stranded RNA virus) and other, positive-sense single-stranded, RNA virus infections (such as SARS, MERS, and the common cold). An Australia/New Zealand consensus document is in development.", "qid": 42, "docid": "nfjxp783", "rank": 98, "score": 0.8290760517120361}, {"content": "Title: COVID-19 treatment by repurposing drugs until the vaccine is in sight Content: Corona virus disease (COVID-19) has created pandemic in the world as declared by WHO on March 12, 2020. It is a viral disease caused by SARS-CoV 2 virus and has affected large populations in over 120 countries. There is no specific treatment available and management is empirical. Until such time that an effective vaccine is available for COVID-19 viral infection, one can repurpose known therapeutic drug molecules such as angiotensin receptor 2 blocker, a commonly used antihypertensive drug, to control COVID-19 virus from gaining entry into the host cell by blocking the angiotensin receptor. Clinical trials should also be undertaken to use statins, which are lipid-lowering drugs but have anti-inflammatory and immunomodulatory properties to prevent acute lung injury in COVID-19 infection.", "qid": 42, "docid": "f5vtticw", "rank": 99, "score": 0.8287169933319092}, {"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": 42, "docid": "a0drmmf7", "rank": 100, "score": 0.8280335068702698}]}
{"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": 0.8755218982696533}, {"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": 2, "score": 0.8719422817230225}, {"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": 3, "score": 0.8687469363212585}, {"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": 4, "score": 0.8681350946426392}, {"content": "Title: Social stigma in the time of Coronavirus Content: The COVID-19 pandemic has dramatically changed the lives of people around the globe since it appeared in Wuhan, China, at the beginning of December 2019. The burden of disease and its death toll have had an unprecedented impact on the healthcare, economic, and financial systems of low-, middle-, and high-income countries [1\u20133]. Peoples\u2019 lives have been disrupted and negatively impacted by COVID-19-related suffering and lockdowns at community and household level.", "qid": 43, "docid": "bhmt5l8y", "rank": 5, "score": 0.8666013479232788}, {"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": 6, "score": 0.860993504524231}, {"content": "Title: The hidden disaster of COVID-19: Intimate partner violence Content: The hidden and often unspoken impact of the 2019 novel coronavirus (COVID-19) has been the prevalence of intimate partner violence (IPV). This commentary addresses this issue and highlights a study undertaken to address this public health issue by generating empirical research on the relationship between COVID-19 and IPV. (PsycInfo Database Record (c) 2020 APA, all rights reserved).", "qid": 43, "docid": "35izipky", "rank": 7, "score": 0.8586212396621704}, {"content": "Title: The hidden disaster of COVID-19: Intimate partner violence. Content: The hidden and often unspoken impact of the 2019 novel coronavirus (COVID-19) has been the prevalence of intimate partner violence (IPV). This commentary addresses this issue and highlights a study undertaken to address this public health issue by generating empirical research on the relationship between COVID-19 and IPV. (PsycInfo Database Record (c) 2020 APA, all rights reserved).", "qid": 43, "docid": "meey1l87", "rank": 8, "score": 0.8586212396621704}, {"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": 9, "score": 0.8578699827194214}, {"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": 10, "score": 0.8575451374053955}, {"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": 11, "score": 0.8568315505981445}, {"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": 43, "docid": "9d7vxjys", "rank": 12, "score": 0.8553203344345093}, {"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": 13, "score": 0.855111837387085}, {"content": "Title: When \"Shelter-in-Place\" Isn't Shelter That's Safe: A Rapid Analysis of Domestic Violence Case Differences During the COVID-19 Pandemic and Stay-at-Home Orders Content: Purpose: This study explored the COVID-19 pandemic's impacts on domestic violence (DV) with the following research questions: 1) Did DV occurring during the pandemic differ on certain variables from cases occurring on a typical day the previous year? 2) Did DV occurring after the implementation of shelter-in-place orders differ (on these same variables) from cases occurring prior to shelter-in-place orders? Methods: Two logistic regression models were developed to predict DV case differences before and during the pandemic. DV reports (N=4618) were collected from the Chicago Police Department. Cases from March 2019 and March 2020 were analyzed based on multiple variables. One model was set to predict case differences since the pandemic began, and another model was set to predict case differences during the shelter-in-place period later that month. Results: Both models were significant with multiple significant predictors. During the pandemic period, cases with arrests were 3% less likely to have occurred, and cases at residential locations were 22% more likely to have occurred. During the shelter-in-place period, cases at residential locations were 64% more likely to have occurred, and cases with child victims were 67% less likely to have occurred. Conclusions: This study offers a rapid analysis of DV case differences since the pandemic and shelter-in-place began. Additional variables and data sources could improve model explanatory power. Research, policy, and practice in this area must pivot to focus on protecting children whose access to mandated reporters has decreased and moving victims out of dangerous living situations into safe spaces.", "qid": 43, "docid": "c3xcmkuc", "rank": 14, "score": 0.8537930250167847}, {"content": "Title: COVID-19 and cancer research Content: The COVID-19 pandemic has had a devastating effect on human lives and society. The accompanying editorial summarises some of the major effects on cancer patients and impacts on cancer research. These may be mitigated by appropriate responses from governments, research funders, charities, universities, industry and the public. It is already clear that different approaches to management have drastically different outcomes.", "qid": 43, "docid": "boyxyt88", "rank": 15, "score": 0.8473833799362183}, {"content": "Title: Counting the cost of COVID-19 Content: Coronavirus disease 2019 (COVID-19) is the name given by the World Health Organization (WHO) to the highly contagious and infectious disease caused by the Novel Corona Virus or SARS-CoV-2, which was first reported on 31 December 2019 in Wuhan city of the capital of China's Hubei province. Due to the rapid increase in the number of infections worldwide, the WHO in March 2020, declared COVID-19 as a pandemic. Historically, first coronavirus had surfaced in 1965 with symptoms of common cold. Since then five different strands of this virus have emerged, most lethal of them was the Severe Acute Respiratory Syndrome (SARS), which infected about eight thousand people, killing ten percent of them. The COVID-19 is not the most deadly pandemic world has ever witnessed as the Spanish influenza pandemic, during 1918\u201319, killed more than fifty million people. Indeed COVID-19 has turned out to be the most lethal of all coronaviruses as it has infected at least three million people killing more than two hundred thousands of them in the first 4 months of its spread. Many politicians and social scientists have dubbed the depression, being caused by COVID-19, worse than that caused by the Second World War. In this article, we shall analyze economic, social, cultural, educational and political impact of the COVID-19.", "qid": 43, "docid": "gs7j6fxo", "rank": 16, "score": 0.8453727960586548}, {"content": "Title: Caring for patients with posttraumatic stress and substance use disorders during the COVID-19 pandemic Content: Although COVID-19 is a physical illness, it has had large impacts on mental health. For many individuals, social distancing has led to social isolation; individuals with posttraumatic stress disorder and substance use disorders are at a particular risk for negative outcomes due to the global pandemic. Here, we discuss the impacts we have noticed and procedures we have implemented to care for this population during the pandemic. (PsycInfo Database Record (c) 2020 APA, all rights reserved).", "qid": 43, "docid": "pfrnlvda", "rank": 17, "score": 0.8442866206169128}, {"content": "Title: Caring for patients with posttraumatic stress and substance use disorders during the COVID-19 pandemic. Content: Although COVID-19 is a physical illness, it has had large impacts on mental health. For many individuals, social distancing has led to social isolation; individuals with posttraumatic stress disorder and substance use disorders are at a particular risk for negative outcomes due to the global pandemic. Here, we discuss the impacts we have noticed and procedures we have implemented to care for this population during the pandemic. (PsycInfo Database Record (c) 2020 APA, all rights reserved).", "qid": 43, "docid": "7uodxlrz", "rank": 18, "score": 0.8442866206169128}, {"content": "Title: COVID\u201019: Shedding light on racial and health inequities in the USA Content: The sudden and rapid advancement of the novel Coronavirus (COVID-19) pandemic has led to an unanticipated and unprecedented global crisis. Since its emergence in the United States, there is increasing discussion surrounding the impact of the virus among vulnerable populations. Older adults, young children, and persons with chronic medical or mental health conditions, persons with disabilities, pregnant women, immunocompromised persons and those who are institutionalized or homeless are considered most vulnerable to death and lost quality of life (World Health Organization, 2020).", "qid": 43, "docid": "4prhmi8f", "rank": 19, "score": 0.8420512676239014}, {"content": "Title: Gambling during the COVID-19 crisis - A cause for concern? Content: : The COVID-19 pandemic has the potential to worsen mental health problems in the general population, including increasing engagement in addictive behaviors. Here, we describe observations suggesting that the current crisis and its sequelae may worsen problem gambling. The current pandemic may impact financial and psychological well-being due to social isolation during spatial distancing, and these stressors in conjunction with substantial changes in gambling markets (land-based, online) during the pandemic may significantly influence gambling behaviors. This situation calls for rapid research initiatives in this area and preventive and regulatory measures by multiple stakeholders.", "qid": 43, "docid": "3mzvv6l3", "rank": 20, "score": 0.8418262004852295}, {"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": 21, "score": 0.8413671851158142}, {"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": 22, "score": 0.8408999443054199}, {"content": "Title: People experiencing homelessness urgently need to be recognised as a high risk group for COVID-19. Content: History shows that pandemics rarely impact on the population equally - the 14th century Black Death plague reduced the global population by a third, with the greatest number of deaths occurring among the poor.1 Fast forward six centuries, and the same pandemic inequities are prevailing due to COVID-19; with Smith and Judd articulating that \"while COVID-19 has the potential to impact everyone in society, these impacts will be felt differentially\u2026 the most vulnerable will be hardest hit\"2 in their recent Health Promotion Journal of Australia editorial.", "qid": 43, "docid": "qz4qsm32", "rank": 23, "score": 0.8405880928039551}, {"content": "Title: Gambling during the COVID-19 crisis - A cause for concern? Content: The COVID-19 pandemic has the potential to worsen mental health problems in the general population, including increasing engagement in addictive behaviors. Here, we describe observations suggesting that the current crisis and its sequelae may worsen problem gambling. The current pandemic may impact financial and psychological well-being due to social isolation during spatial distancing, and these stressors in conjunction with substantial changes in gambling markets (land-based, online) during the pandemic may significantly influence gambling behaviors. This situation calls for rapid research initiatives in this area and preventive and regulatory measures by multiple stakeholders.", "qid": 43, "docid": "rvcrya5i", "rank": 24, "score": 0.8397945165634155}, {"content": "Title: Scientific Publications During the COVID-19 Pandemic Content: \u2022 COVID-19 pandemics has shocked our world in a few months, not only by attacking individual health, but also public health and economic systems, the way people relate to each other, but has also changed scientific and editorial practices.", "qid": 43, "docid": "9uo0hsst", "rank": 25, "score": 0.8389862775802612}, {"content": "Title: Heterogeneous mental health consequences of COVID-19: Costs and benefits Content: In this commentary, I argue that the mental health impact of COVID-19 will show substantial variation across individuals, contexts, and time. Further, one key contributor to this variation will be the proximal and long-term impact of COVID-19 on the social environment. In addition to the mental health costs of the pandemic, it is likely that a subset of people will experience improved social and mental health functioning. (PsycInfo Database Record (c) 2020 APA, all rights reserved).", "qid": 43, "docid": "ingq7m2m", "rank": 26, "score": 0.8383369445800781}, {"content": "Title: Heterogeneous mental health consequences of COVID-19: Costs and benefits. Content: In this commentary, I argue that the mental health impact of COVID-19 will show substantial variation across individuals, contexts, and time. Further, one key contributor to this variation will be the proximal and long-term impact of COVID-19 on the social environment. In addition to the mental health costs of the pandemic, it is likely that a subset of people will experience improved social and mental health functioning. (PsycInfo Database Record (c) 2020 APA, all rights reserved).", "qid": 43, "docid": "u02vjcjs", "rank": 27, "score": 0.8383369445800781}, {"content": "Title: An Invited Commentary on \u2018 Evidence Based Management Guideline for the COVID-19 Pandemic- Review article\u2019 Content: Abstract COVID 19 been declared recently as a pandemic, to date has affected over 1,8881,365 with over 119,403 deaths in accordance to the global pandemic Real-Time Report. In this paper, the prime motive is to enlighten the key variables to the public on the pandemic and essential key points to note and practice in accordance to standard regulation to curb the aggressive COVID-19 pandemic. Author Summary To date over one(1) million persons have been affected indicating exponential spread of the disease and more rigorous implementation and adherence to more strengthen restrictions of social distancing would mitigate the spread of the pandemic disease and may prove to be even tedious.", "qid": 43, "docid": "l726qv1g", "rank": 28, "score": 0.8380487561225891}, {"content": "Title: Coronavirus and Quarantine: Catalysts of Domestic Violence Content: The pandemic of COVID-19 has resulted in quarantines imposed all around the world; these and other restrictions could produce an increase in domestic violence.", "qid": 43, "docid": "luef3iok", "rank": 29, "score": 0.8364872336387634}, {"content": "Title: Coronavirus and Quarantine: Catalysts of Domestic Violence. Content: The pandemic of COVID-19 has resulted in quarantines imposed all around the world; these and other restrictions could produce an increase in domestic violence.", "qid": 43, "docid": "427mkwsj", "rank": 30, "score": 0.8364872336387634}, {"content": "Title: Inequity and the disproportionate impact of COVID-19 on communities of color in the United States: The need for a trauma-informed social justice response. Content: COVID-19 has had disproportionate contagion and fatality in Black, Latino, and Native American communities and among the poor in the United States. Toxic stress resulting from racial and social inequities have been magnified during the pandemic, with implications for poor physical and mental health and socioeconomic outcomes. It is imperative that our country focus and invest in addressing health inequities and work across sectors to build self-efficacy and long-term capacity within communities and systems of care serving the most disenfranchised, now and in the aftermath of the COVID-19 epidemic. (PsycInfo Database Record (c) 2020 APA, all rights reserved).", "qid": 43, "docid": "q7telkky", "rank": 31, "score": 0.8364227414131165}, {"content": "Title: Inequity and the disproportionate impact of COVID-19 on communities of color in the United States: The need for a trauma-informed social justice response Content: COVID-19 has had disproportionate contagion and fatality in Black, Latino, and Native American communities and among the poor in the United States. Toxic stress resulting from racial and social inequities have been magnified during the pandemic, with implications for poor physical and mental health and socioeconomic outcomes. It is imperative that our country focus and invest in addressing health inequities and work across sectors to build self-efficacy and long-term capacity within communities and systems of care serving the most disenfranchised, now and in the aftermath of the COVID-19 epidemic. (PsycInfo Database Record (c) 2020 APA, all rights reserved).", "qid": 43, "docid": "81crwncn", "rank": 32, "score": 0.8364226222038269}, {"content": "Title: An Invited Commentary on 'Evidence Based Management Guideline for the COVID-19 pandemic- Review article' Content: COVID 19 been declared recently as a pandemic, to date has affected over 1,8881,365 with over 119,403 deaths in accordance to the global pandemic Real-Time Report. In this paper, the prime motive is to enlighten the key variables to the public on the pandemic and essential key points to note and practice in accordance to standard regulation to curb the aggressive COVID-19 pandemic.", "qid": 43, "docid": "n3yt9knx", "rank": 33, "score": 0.8360805511474609}, {"content": "Title: Effects of COVID-19 on Business and Research Content: Abstract The COVID-19 outbreak is a sharp reminder that pandemics, like other rarely occurring catastrophes, have happened in the past and will continue to happen in the future. Even if we cannot prevent dangerous viruses from emerging, we should prepare to dampen their effects on society. The current outbreak has had severe economic consequences across the globe, and it does not look like any country will be unaffected. This not only has consequences for the economy; all of society is affected, which has led to dramatic changes in how businesses act and consumers behave. This special issue is a global effort to address some of the pandemic-related issues affecting society. In total, there are 12 papers that cover different industry sectors (e.g., tourism, retail, higher education), changes in consumer behavior and businesses, ethical issues, and aspects related to employees and leadership.", "qid": 43, "docid": "7ofgekoj", "rank": 34, "score": 0.8360074162483215}, {"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": 43, "docid": "53b4lrk2", "rank": 35, "score": 0.8358228206634521}, {"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": 36, "score": 0.8358199000358582}, {"content": "Title: Child protection in the time of COVID-19 Content: As the number of cases of coronavirus disease 2019 (COVID-19) caused by the virus SARS-CoV-2 rises exponentially in Australia with consequences for the health system and society at large, we need to remember that during this pandemic that necessary social distancing measures, effective school closures and rising unemployment levels may lead to an increased risk for child abuse and neglect.", "qid": 43, "docid": "e3tgppzf", "rank": 37, "score": 0.8350033164024353}, {"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": 38, "score": 0.8342183828353882}, {"content": "Title: COVID-19 and finance: Agendas for future research Content: This paper highlights the enormous economic and social impact of COVID-19 with respect to articles that have either prognosticated such a large-scale event, and its economic consequences, or have assessed the impacts of other epidemics and pandemics. A consideration of possible impacts of COVID-19 on financial markets and institutions, either directly or indirectly, is briefly outlined by drawing on a variety of literatures. A consideration of the characteristics of COVID-19, along with what research suggests have been the impacts of other past events that in some ways roughly parallel COVID-19, points toward avenues of future investigation.", "qid": 43, "docid": "3sem1q9e", "rank": 39, "score": 0.834100067615509}, {"content": "Title: Isolation, social stress, low socioeconomic status and its relationship to immune response in Covid-19 pandemic context Content: The coronavirus disease 2019 (COVID-19) outbreak was first reported December 2019, in Wuhan, China, and has since spread worldwide. Social distancing or isolation measures were taken to mitigate the pandemic. Furthermore, stress and low socioeconomic status in humans confer increased vulnerability to morbidity and mortality, what can be biologically observed. This condition tends to remain during the Covid-19 pandemic. Social disruption stress (SDR) raises important questions regarding the functioning of the immune system, and the release of several stress hormones.A molecular pattern, conserved transcriptional response to adversity (CTRA), is thought to have evolved to defend against physical injury during periods of heightened risk. Chronic CTRA activation could leave an organism vulnerable to viral infections, leading to increased pro-inflammatory gene expression and a suppression of anti-viral gene expression. The activation of such transcriptional status is related to conditions of social stress through either hostile human contact, or increased predatory vulnerability due to separation from the social group and also low socioeconomic status. This review aims to point out questions for government officials, researchers and health professionals to better target their actions during a pandemic and encourage studies for a better understanding of these characteristics.", "qid": 43, "docid": "xai98wd5", "rank": 40, "score": 0.8337954878807068}, {"content": "Title: A commentary on the Nigerian response to the COVID-19 pandemic Content: In this commentary, we review the emergence of the COVID-19 pandemic in Nigeria and how aspects of the socioeconomic context and responses from the government and general public may contribute to its persistence. We also suggest mechanisms for the adverse mental health impacts of the pandemic and highlight the need for data and strengthening social infrastructure. (PsycInfo Database Record (c) 2020 APA, all rights reserved).", "qid": 43, "docid": "nf5sqrbe", "rank": 41, "score": 0.8335871696472168}, {"content": "Title: A commentary on the Nigerian response to the COVID-19 pandemic. Content: In this commentary, we review the emergence of the COVID-19 pandemic in Nigeria and how aspects of the socioeconomic context and responses from the government and general public may contribute to its persistence. We also suggest mechanisms for the adverse mental health impacts of the pandemic and highlight the need for data and strengthening social infrastructure. (PsycInfo Database Record (c) 2020 APA, all rights reserved).", "qid": 43, "docid": "zu5zr4sd", "rank": 42, "score": 0.8335871696472168}, {"content": "Title: COVID-19 and finance: Agendas for future research Content: Abstract This paper highlights the enormous economic and social impact of COVID-19 with respect to articles that have either prognosticated such a large-scale event, and its economic consequences, or have assessed the impacts of other epidemics and pandemics. A consideration of possible impacts of COVID-19 on financial markets and institutions, either directly or indirectly, is briefly outlined by drawing on a variety of literatures. A consideration of the characteristics of COVID-19, along with what research suggests have been the impacts of other past events that in some ways roughly parallel COVID-19, points toward avenues of future investigation.", "qid": 43, "docid": "s8fvqcel", "rank": 43, "score": 0.833579957485199}, {"content": "Title: Know Your Epidemic, Know Your Response: Covid-19 in the United States Content: We document that during the week of March 10-16, the Covid-19 pandemic fundamentally affected the perceptions of U.S. residents about the health risks and socioeconomic consequences entailed by the pandemic. During this week, it seems, \"everything changed.\" Not only did the pandemic progress rapidly across the United States, but U.S. residents started to realize that the threat was real: increasing Covid-19 caseloads heightened perceptions of infection risks and excess mortality risks, concerns about the economic implications increased substantially, and behavioral responses became widespread as the pandemic expanded rapidly in the U.S. In early to mid-March 2020, average perceptions about the coronavirus infection risks are broadly consistent with projections about the pandemic, while expectations about dying conditional on infection and expectations about Covid-19-related excess mortality during the next months are possibly too pessimistic. However, some aspects of Covid-19 perceptions are disconcerting from the perspective of implementing and sustaining an effective societal response to the pandemic. For instance, the education gradient in expected infection risks entails the possibility of having different perceptions of the reality of the pandemic between people with and without a college education, potentially resulting in two different levels of behavioral and policy-responses across individuals and regions. Unless addressed by effective health communication that reaches individuals across all social strata, some of the misperceptions about Covid-19 epidemic raise concerns about the ability of the United States to implement and sustain the widespread and harsh policies that are required to curtail the pandemic. Our analyses also reveal perceptions of becoming infected with the virus, and dying from Covid-19, were driven upwards by a rapidly increasing national caseload, and perceptions of the economic consequences and the adaptation of social distancing were affected by both national and state-level cases.", "qid": 43, "docid": "9nfz9m2p", "rank": 44, "score": 0.8333624005317688}, {"content": "Title: Pandemic Pulse: Unraveling and Modeling Social Signals during the COVID-19 Pandemic Content: We present and begin to explore a collection of social data that represents part of the COVID-19 pandemic's effects on the United States. This data is collected from a range of sources and includes longitudinal trends of news topics, social distancing behaviors, community mobility changes, web searches, and more. This multimodal effort enables new opportunities for analyzing the impacts such a pandemic has on the pulse of society. Our preliminary results show that the number of COVID-19-related news articles published immediately after the World Health Organization declared the pandemic on March 11, and that since that time have steadily decreased---regardless of changes in the number of cases or public policies. Additionally, we found that politically moderate and scientifically-grounded sources have, relative to baselines measured before the beginning of the pandemic, published a lower proportion of COVID-19 news than more politically extreme sources. We suggest that further analysis of these multimodal signals could produce meaningful social insights and present an interactive dashboard to aid further exploration.", "qid": 43, "docid": "71qh6yjr", "rank": 45, "score": 0.8330373764038086}, {"content": "Title: Coronavirus and interpersonal violence: A need for digital mental health resources Content: Since the declaration of COVID-19 restrictions and lockdowns, countries across the world have seen an increase in reports of interpersonal violence. During these trying times, digital mental health resources tailored to interpersonal violence are needed. Through the use of online platforms such as websites, mobile applications, and social media, survivors and perpetrators alike can access tools that help them manage stressors induced by the coronavirus as well as practice emotional regulation techniques and communication strategies at home. (PsycInfo Database Record (c) 2020 APA, all rights reserved).", "qid": 43, "docid": "p6uroywe", "rank": 46, "score": 0.8326314687728882}, {"content": "Title: Coronavirus and interpersonal violence: A need for digital mental health resources. Content: Since the declaration of COVID-19 restrictions and lockdowns, countries across the world have seen an increase in reports of interpersonal violence. During these trying times, digital mental health resources tailored to interpersonal violence are needed. Through the use of online platforms such as websites, mobile applications, and social media, survivors and perpetrators alike can access tools that help them manage stressors induced by the coronavirus as well as practice emotional regulation techniques and communication strategies at home. (PsycInfo Database Record (c) 2020 APA, all rights reserved).", "qid": 43, "docid": "0xc276mq", "rank": 47, "score": 0.8326314687728882}, {"content": "Title: Estimates of the Potential Impact of the COVID-19 Pandemic on Sexual and Reproductive Health In Low- and Middle-Income Countries Content: The novel coronavirus (SARS-CoV-2) that causes COVID-19 has spread rapidly since emerging in late 2019, leading the World Health Organization (WHO) to declare the disease a global pandemic on March 11, 2020. Governments around the world have had to quickly adapt and respond to curb transmission of the virus and to provide care for the many who have been infected. The strain that the outbreak imposes on health systems will undoubtedly impact the sexual and reproductive health of individuals living in low- and middle-income countries (LMICs); however, sexual and reproductive health will also be affected by societal responses to the pandemic, such as local or national lockdowns that force health services to shut down if they are not deemed essential, as well as the consequences of physical distancing, travel restrictions and economic slowdowns.", "qid": 43, "docid": "swykkjr7", "rank": 48, "score": 0.8325411081314087}, {"content": "Title: Estimates of the Potential Impact of the COVID-19 Pandemic on Sexual and Reproductive Health In Low- and Middle-Income Countries. Content: The novel coronavirus (SARS-CoV-2) that causes COVID-19 has spread rapidly since emerging in late 2019, leading the World Health Organization (WHO) to declare the disease a global pandemic on March 11, 2020. Governments around the world have had to quickly adapt and respond to curb transmission of the virus and to provide care for the many who have been infected. The strain that the outbreak imposes on health systems will undoubtedly impact the sexual and reproductive health of individuals living in low- and middle-income countries (LMICs); however, sexual and reproductive health will also be affected by societal responses to the pandemic, such as local or national lockdowns that force health services to shut down if they are not deemed essential, as well as the consequences of physical distancing, travel restrictions and economic slowdowns.", "qid": 43, "docid": "48hsdymv", "rank": 49, "score": 0.8325411081314087}, {"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": 43, "docid": "2r0a357c", "rank": 50, "score": 0.832160234451294}, {"content": "Title: Impact of the COVID-19 pandemic on the sexual behavior of the population. The vision of the east and the west Content: The COVID-19 pandemic has radically changed the way of life around the World. The state of alarm has forced the population to stay at home, radically changing both interpersonal and partner relationships; work at home, social distancing, the continued presence of children at home, fear of infection and not being able to physically meet with others have changed most people's sexual habits. We conducted a review by exploring the impact of the COVID-19 pandemic on sexual behavior in the population from three different countries: Iran, Italy and Spain from each country's perspective. The impact of the coronavirus will be very important in the sexual life of the people and we will attend in the next months or years, to some changes in the relationships at all the levels. The pandemic will negatively affect sexual behaviors due to multiple contact restrictions. In the future, we will be able to assess these effects in more detail.", "qid": 43, "docid": "1cg6wnpj", "rank": 51, "score": 0.8319156765937805}, {"content": "Title: Impact of the COVID-19 pandemic on the sexual behavior of the population. The vision of the east and the west. Content: The COVID-19 pandemic has radically changed the way of life around the World. The state of alarm has forced the population to stay at home, radically changing both interpersonal and partner relationships; work at home, social distancing, the continued presence of children at home, fear of infection and not being able to physically meet with others have changed most people's sexual habits. We conducted a review by exploring the impact of the COVID-19 pandemic on sexual behavior in the population from three different countries: Iran, Italy and Spain from each country's perspective. The impact of the coronavirus will be very important in the sexual life of the people and we will attend in the next months or years, to some changes in the relationships at all the levels. The pandemic will negatively affect sexual behaviors due to multiple contact restrictions. In the future, we will be able to assess these effects in more detail.", "qid": 43, "docid": "6lan923i", "rank": 52, "score": 0.8319156765937805}, {"content": "Title: Home is not always a haven: The domestic violence crisis amid the COVID-19 pandemic Content: The novel coronavirus (SARS-CoV-2) and the associated disease it causes, COVID-19, have caused unprecedented social disruption. Due to sweeping stay-at-home orders across the United States and internationally, many victims and survivors of domestic violence (DV), now forced to be isolated with their abusers, run the risk of new or escalating violence. Numerous advocates, organizations, and service centers anticipated this: Upticks in domestic violence were reported in many regions soon after stay-at-home directives were announced. In this commentary, we delineate some of the recent events leading up to the reported spike in DV; review literature on previously documented disaster-related DV surges; and discuss some of the unique challenges, dilemmas, and risks victims and survivors face during this pandemic. We conclude with recommendations to allocate resources to DV front-liners and utilize existing DV guidelines for disaster preparedness, response, and recovery. (PsycInfo Database Record (c) 2020 APA, all rights reserved).", "qid": 43, "docid": "ypzpui37", "rank": 53, "score": 0.8318519592285156}, {"content": "Title: Home is not always a haven: The domestic violence crisis amid the COVID-19 pandemic. Content: The novel coronavirus (SARS-CoV-2) and the associated disease it causes, COVID-19, have caused unprecedented social disruption. Due to sweeping stay-at-home orders across the United States and internationally, many victims and survivors of domestic violence (DV), now forced to be isolated with their abusers, run the risk of new or escalating violence. Numerous advocates, organizations, and service centers anticipated this: Upticks in domestic violence were reported in many regions soon after stay-at-home directives were announced. In this commentary, we delineate some of the recent events leading up to the reported spike in DV; review literature on previously documented disaster-related DV surges; and discuss some of the unique challenges, dilemmas, and risks victims and survivors face during this pandemic. We conclude with recommendations to allocate resources to DV front-liners and utilize existing DV guidelines for disaster preparedness, response, and recovery. (PsycInfo Database Record (c) 2020 APA, all rights reserved).", "qid": 43, "docid": "54mxjzfc", "rank": 54, "score": 0.8318518996238708}, {"content": "Title: COVID-19, tuberculosis, and poverty: preventing a perfect storm Content: The COVID-19 pandemic is likely to be the defining global health crisis of our generation. As the United Nations Development Programme highlighted in their recent call to action, the impact of this pandemic will extend beyond the immediate medical consequences to have far-reaching and long-lasting social and economic impacts, threatening to disproportionately affect poorer people in poorer countries [1]. Income losses are anticipated to exceed $220 billion in developing countries, where many people live day-to-day without access to social protection, and food security is precarious [1]. Strikingly, a recent United Nations study suggests that the social and economic consequences of the COVID-19 pandemic could increase the number of people living in poverty by as much as half a billion, with the majority of these newly poor people living in Africa, South-East Asia, and Central and South America [2].", "qid": 43, "docid": "19k558op", "rank": 55, "score": 0.8317766785621643}, {"content": "Title: The socio-economic implications of the coronavirus pandemic (COVID-19): A review Content: The COVID-19 pandemic has resulted in over 4.3 million confirmed cases and over 290,000 deaths globally. It has also sparked fears of an impending economic crisis and recession. Social distancing, self-isolation and travel restrictions have lead to a reduced workforce across all economic sectors and caused many jobs to be lost. Schools have closed down, and the need for commodities and manufactured products has decreased. In contrast, the need for medical supplies has significantly increased. The food sector is also facing increased demand due to panic-buying and stockpiling of food products. In response to this global outbreak, we summarise the socio-economic effects of COVID-19 on individual aspects of the world economy.", "qid": 43, "docid": "2waylxke", "rank": 56, "score": 0.831763744354248}, {"content": "Title: Economic Consequences of the COVID-19 Outbreak: the Need for Epidemic Preparedness Content: COVID-19 is not only a global pandemic and public health crisis; it has also severely affected the global economy and financial markets. Significant reductions in income, a rise in unemployment, and disruptions in the transportation, service, and manufacturing industries are among the consequences of the disease mitigation measures that have been implemented in many countries. It has become clear that most governments in the world underestimated the risks of rapid COVID-19 spread and were mostly reactive in their crisis response. As disease outbreaks are not likely to disappear in the near future, proactive international actions are required to not only save lives but also protect economic prosperity.", "qid": 43, "docid": "1ts0734u", "rank": 57, "score": 0.8313136100769043}, {"content": "Title: It\u2019s F**ing Chaos: COVID-19\u2019s Impact on Juvenile Delinquency and Juvenile Justice Content: An early examination of the impact of COVID-19 on juvenile delinquency and juvenile justice in America, this review provides initial scholarship to rapidly evolving areas of research. Our appraisals of these topics are made after nearly 2 months of national COVID-19 mitigation measures, like social distancing and limited \u201cnon-essential\u201d movement outside the home but also as states are gradually lifting stricter directives and reopening economic sectors. We consider the impact of these pandemic-related changes on twenty-first century youths, their behaviors, and their separate justice system. To forecast the immediate future, we draw from decades of research on juvenile delinquency and the justice system, as well as from reported patterns of reactions and responses to an unprecedented and ongoing situation. As post-pandemic studies on juvenile delinquency and juvenile justice proliferate, we urge careful consideration as to how they might influence societal and the system responses to youths\u2019 delinquency. Additional practical implications are discussed.", "qid": 43, "docid": "judp4703", "rank": 58, "score": 0.8312715291976929}, {"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": 43, "docid": "880lwnde", "rank": 59, "score": 0.8312230110168457}, {"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": 60, "score": 0.8304266929626465}, {"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": 61, "score": 0.83030104637146}, {"content": "Title: COVID-19-related self-harm and suicidality among individuals with mental disorders Content: Abstract The coronavirus disease (COVID-19) pandemic has created an unprecedented public health emergency Extraordinary measures have been implemented to reduce the spread of the virus, including mass quarantines and social distancing However, these preventive measures come at a price Economic stress, social isolation, decreased access to community activities, etc , is the new reality for a large part of the global community, and may have detrimental effects on mental health", "qid": 43, "docid": "itefsyv4", "rank": 62, "score": 0.8302379250526428}, {"content": "Title: Abuse, self-harm and suicidal ideation in the UK during the COVID-19 pandemic Content: This study explored patterns of abuse, self-harm and thoughts of suicide/self-harm in the UK during the first month of the COVID-19 pandemic using data from the COVID-19 Social Study (n=44 775), a non-probability sample weighted to population proportions. The reported frequency of abuse, self-harm and thoughts of suicide/self-harm was higher among women, Black, Asian and minority ethnic (BAME) groups and people experiencing socioeconomic disadvantage, unemployment, disability, chronic physical illnesses, mental disorders and COVID-19 diagnosis. Psychiatric medications were the most common type of support being used, but fewer than half of those affected were accessing formal or informal support.", "qid": 43, "docid": "bi0t9ylg", "rank": 63, "score": 0.8301011919975281}, {"content": "Title: On the frontlines: Protecting low-wage workers during COVID-19 Content: An examination of the trajectory of the coronavirus disease (COVID-19) pandemic and its subsequent economic impacts has revealed that this crisis will impact low-wage workers more severely than all others. The present commentary highlights the unique factors associated with low-wage work that make these workers particularly vulnerable to the effects of the pandemic, identifies potential adverse effects on the mental health of this population, and provides recommendations to maintain the safety, wellbeing, and dignity of low-wage workers. (PsycInfo Database Record (c) 2020 APA, all rights reserved).", "qid": 43, "docid": "tzkr88ce", "rank": 64, "score": 0.8299520015716553}, {"content": "Title: On the frontlines: Protecting low-wage workers during COVID-19. Content: An examination of the trajectory of the coronavirus disease (COVID-19) pandemic and its subsequent economic impacts has revealed that this crisis will impact low-wage workers more severely than all others. The present commentary highlights the unique factors associated with low-wage work that make these workers particularly vulnerable to the effects of the pandemic, identifies potential adverse effects on the mental health of this population, and provides recommendations to maintain the safety, wellbeing, and dignity of low-wage workers. (PsycInfo Database Record (c) 2020 APA, all rights reserved).", "qid": 43, "docid": "45kzk8wn", "rank": 65, "score": 0.8299520015716553}, {"content": "Title: Psychological and social impact of COVID-19 Content: The high numbers of COVID-19 infections and deaths, economic difficulties, uncertainty about the future, as well as the approaches needed to contain the spread of the virus are all playing critical roles in the short and long-term social and psychological impact of the COVID-19 pandemic. Inequities based on race and socioeconomic status influence the rates of infection and deaths and steps that are needed to achieve recovery. This commentary focuses on similarities and differences after other disasters and efforts being initiated to provide support and recovery. (PsycInfo Database Record (c) 2020 APA, all rights reserved).", "qid": 43, "docid": "nj2dllu3", "rank": 66, "score": 0.8298958539962769}, {"content": "Title: Psychological and social impact of COVID-19. Content: The high numbers of COVID-19 infections and deaths, economic difficulties, uncertainty about the future, as well as the approaches needed to contain the spread of the virus are all playing critical roles in the short and long-term social and psychological impact of the COVID-19 pandemic. Inequities based on race and socioeconomic status influence the rates of infection and deaths and steps that are needed to achieve recovery. This commentary focuses on similarities and differences after other disasters and efforts being initiated to provide support and recovery. (PsycInfo Database Record (c) 2020 APA, all rights reserved).", "qid": 43, "docid": "hdy4h13e", "rank": 67, "score": 0.8298958539962769}, {"content": "Title: On order and disorder during the COVID-19 pandemic Content: In this paper, we analyse the conditions under which the COVID-19 pandemic will lead either to social order (adherence to measures put in place by authorities to control the pandemic) or to social disorder (resistance to such measures and the emergence of open conflict). Using examples from different countries (principally the United Kingdom, the United States, and France), we first isolate three factors which determine whether people accept or reject control measures. These are the historical context of state-public relations, the nature of leadership during the pandemic and procedural justice in the development and operation of these measures. Second, we analyse the way the crisis is policed and how forms of policing determine whether dissent will escalate into open conflict. We conclude by considering the prospects for order/disorder as the pandemic unfolds.", "qid": 43, "docid": "bnjpsjr9", "rank": 68, "score": 0.8294013738632202}, {"content": "Title: Police Stress, Mental Health, and Resiliency during the COVID-19 Pandemic Content: The COVID-19 pandemic created social upheaval and altered norms for all members of society, but its effects on first responders have been particularly profound. Law enforcement officers have been expected to coordinate local shutdowns, encourage social distancing, and enforce stay-at-home mandates all while completing the responsibilities for which they are already understaffed and underfunded. The impact of the COVID-19 pandemic on officer stress, mental health, resiliency, and misconduct is explored drawing insight from reactions to the HIV epidemic over two decades earlier and the terrorist attacks of September 11, 2001. COVID-19 policing is hypothesized to serve as a significant stressor for officers and compound the general and organizational stress associated with the occupation. Avenues for providing officer support are discussed and recommendations for research into the phenomenon presented.", "qid": 43, "docid": "e44nuhh9", "rank": 69, "score": 0.829230546951294}, {"content": "Title: COVID-19 and the Widening Gap in Health Inequity Content: The coronavirus disease 2019 (COVID-19) pandemic has brought to light significant health inequities that have existed in our society for decades. Blacks, Hispanics, Native Americans, and immigrants are the populations most likely to experience disparities related to burden of disease, health care, and health outcomes. Increasingly, national and state statistics on COVID-19 report disproportionately higher mortality rates in blacks. There has never been a more pressing time for us to enact progressive and far-reaching changes in social, economic, and political policies that will shape programs aimed at improving the health of all people living in the United States.", "qid": 43, "docid": "3omm8wkv", "rank": 70, "score": 0.829149603843689}, {"content": "Title: COVID-19 and the Widening Gap in Health Inequity. Content: The coronavirus disease 2019 (COVID-19) pandemic has brought to light significant health inequities that have existed in our society for decades. Blacks, Hispanics, Native Americans, and immigrants are the populations most likely to experience disparities related to burden of disease, health care, and health outcomes. Increasingly, national and state statistics on COVID-19 report disproportionately higher mortality rates in blacks. There has never been a more pressing time for us to enact progressive and far-reaching changes in social, economic, and political policies that will shape programs aimed at improving the health of all people living in the United States.", "qid": 43, "docid": "sza8r2e1", "rank": 71, "score": 0.829149603843689}, {"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": 43, "docid": "6wqxcshu", "rank": 72, "score": 0.8290425539016724}, {"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": 73, "score": 0.8288376927375793}, {"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": 43, "docid": "y9vx7coj", "rank": 74, "score": 0.828231692314148}, {"content": "Title: Predictive Modeling on the Number of Covid-19 Death Toll in the United States Considering the Effects of Coronavirus-Related Changes and Covid-19 Recovered Cases Content: COVID-19 is caused by a coronavirus called SARS-CoV-2. Many countries around the world implemented their own policies and restrictions designed to limit the spread of Covid-19 in recent months. Businesses and schools transitioned into working and learning remotely. In the United States, many states were under strict orders to stay home at least in the month of April. In recent weeks, there are some significant changes related restrictions include social-distancing, reopening states, and staying-at-home orders. The United States surpassed 2 million coronavirus cases on Monday, June 15, 2020 less than five months after the first case was confirmed in the country. The virus has killed at least 115,000 people in the United States as of Monday, June 15, 2020, according to data from Johns Hopkins University. With the recent easing of coronavirus-related restrictions and changes on business and social activity such as stay-at-home, social distancing since late May 2020 hoping to restore economic and business activities, new Covid-19 outbreaks are on the rise in many states across the country. Some researchers expressed concern that the process of easing restrictions and relaxing stay-at-home orders too soon could quickly surge the number of infected Covid-19 cases as well as the death toll in the United States. Some of these increases, however, could be due to more testing sites in the communities while others may be are the results of easing restrictions due to recent reopening and changed policies, though the number of daily death toll does not appear to be going down in recent days due to Covid-19 in the U.S. This raises the challenging question: * How can policy decision-makers and community leaders make the decision to implement public policies and restrictions and keep or lift staying-at-home orders of ongoing Covid-19 pandemic for their communities in a scientific way? In this study, we aim to develop models addressing the effects of recent Covid-19 related changes in the communities such as reopening states, practicing social-distancing, and staying-at-home orders. Our models account for the fact that changes to these policies which can lead to a surge of coronavius cases and deaths, especially in the United States. Specifically, in this paper we develop a novel generalized mathematical model and several explicit models considering the effects of recent reopening states, staying-at-home orders and social-distancing practice of different communities along with a set of selected indicators such as the total number of coronavirus recovered and new cases that can estimate the daily death toll and total number of deaths in the United States related to Covid-19 virus. We compare the modeling results among the developed models based on several existing criteria. The model also can be used to predict the number of death toll in Italy and the United Kingdom (UK). The results show very encouraging predictability for the proposed models in this study. The model predicts that 128,500 to 140,100 people in the United States will have died of Covid-19 by July 4, 2020. The model also predicts that between 137,900 and 154,000 people will have died of Covid-19 by July 31, and 148,500 to 169,700 will have died by the end of August 2020, as a result of the SARS-CoV-2 coronavirus that causes COVID-19 based on the Covid-19 death data available on June 13, 2020. The model also predicts that 34,900 to 37,200 people in Italy will have died of Covid-19 by July 4, and 36,900 to 40,400 people will have died by the end of August based on the data available on June 13, 2020. The model also predicts that between 43,500 and 46,700 people in the United Kingdom will have died of Covid-19 by July 4, and 48,700 to 51,900 people will have died by the end of August, as a result of the SARS-CoV-2 coronavirus that causes COVID-19 based on the data available on June 13, 2020. The model can serve as a framework to help policy makers a scientific approach in quantifying decision-makings related to Covid-19 affairs.", "qid": 43, "docid": "4o8bedj8", "rank": 75, "score": 0.8281184434890747}, {"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": 43, "docid": "5zg5g77w", "rank": 76, "score": 0.8278125524520874}, {"content": "Title: On the dynamics emerging from pandemics and infodemics Content: This position paper discusses emerging behavioral, social, and economic dynamics related to the COVID-19 pandemic and puts particular emphasis on two emerging issues: First, delayed effects (or second strikes) of pandemics caused by dread risk effects are discussed whereby two factors which might influence the existence of such effects are identified, namely the accessibility of (mis-)information and the effects of policy decisions on adaptive behavior. Second, the issue of individual preparedness to hazardous events is discussed. As events such as the COVID-19 pandemic unfolds complex behavioral patterns which are hard to predict, sophisticated models which account for behavioral, social, and economic dynamics are required to assess the effectivity and efficiency of decision-making.", "qid": 43, "docid": "op7ygiuv", "rank": 77, "score": 0.827613353729248}, {"content": "Title: The economic impact of the Coronavirus 2019 (Covid-2019): Implications for the mining industry Content: The Coronavirus 2019 (Covid-19) global pandemic has not only caused infections and deaths, but it has also wreaked havoc with the global economy on a scale not seen since at least the Great Depression. Covid-19 has the potential to destroy individual livelihoods, businesses, industries and entire economies. The mining sector is not immune to these impacts, and the crisis has the potential to have severe consequences in the short, medium and long-term for the industry. Understanding these impacts, and analysing their significance for the industry, and the role it plays in wider economic development is a crucial task for academic research.", "qid": 43, "docid": "mf2vqro7", "rank": 78, "score": 0.8274569511413574}, {"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": 79, "score": 0.8271504044532776}, {"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": 80, "score": 0.8271504044532776}, {"content": "Title: Psychopathological problems related to the COVID\u201019 pandemic and possible prevention with music therapy Content: COVID-19 is having a profound effect on societies worldwide and the impact that it is having on children cannot be underestimated. Although Brodin (1) stated that the disease tends to be mild in children, psychopathological considerations allow us to assume that the pandemic will have a high risk of long-term paediatric psychiatric sequelae and interdisciplinary preventative measures are needed.", "qid": 43, "docid": "0mxv8h06", "rank": 81, "score": 0.8271340727806091}, {"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": 43, "docid": "uczrmgq3", "rank": 82, "score": 0.8266997337341309}, {"content": "Title: Why communities must be at the centre of the Coronavirus disease 2019 response: Lessons from Ebola and human immunodeficiency virus in Africa Content: As the Coronavirus disease 2019 (COVID-19) pandemic has spread globally, with no effective treatment or vaccine yet available, governments in many countries have put in place social interventions to control the outbreak. The various lockdown measures may have devastating impacts on economies and livelihoods. This approach risks undermining public trust in government responses and therefore undermines efforts to promote behaviour change, which is key to the success of social interventions. Important lessons can be drawn from past Ebola outbreaks and the human immunodeficiency virus pandemic on how communities should be central to COVID-19 responses. Communities are complex and only their members can inform public health experts about their lived realities, the community's understanding of the outbreak and what will work locally to reduce transmission. The public should be encouraged to take positive actions to ensure their own health and well-being, rather than made to feel powerless. Communities should be supported to develop their own response plans, community leaders should be recognised as vital assets, community representatives should have equal inclusion in strategic meetings and greater empathy should be built into decision-making processes.", "qid": 43, "docid": "n5u6b097", "rank": 83, "score": 0.8265587091445923}, {"content": "Title: Does COVID-19 really call for an overhaul of nursing curricula or promoting the power, status and representation of nursing? Content: The COVID-19 pandemic has presented us with many well documented challenges as well as causing death, disability and economic devastation. All around the globe people were caught unprepared for the pandemic despite the warnings of public health experts. Many of these warnings were not considered serious and moves towards nationalism and populism have challenged global collaboration.", "qid": 43, "docid": "k10hrqwe", "rank": 84, "score": 0.8264645338058472}, {"content": "Title: Global Data Science Project for COVID-19 Summary Report Content: This paper aims at providing the summary of the Global Data Science Project (GDSC) for COVID-19. as on May 31 2020. COVID-19 has largely impacted on our societies through both direct and indirect effects transmitted by the policy measures to counter the spread of viruses. We quantitatively analysed the multifaceted impacts of the COVID-19 pandemic on our societies including people's mobility, health, and social behaviour changes. People's mobility has changed significantly due to the implementation of travel restriction and quarantine measurements. Indeed, the physical distance has widened at international (cross-border), national and regional level. At international level, due to the travel restrictions, the number of international flights has plunged overall at around 88 percent during March. In particular, the number of flights connecting Europe dropped drastically in mid of March after the United States announced travel restrictions to Europe and the EU and participating countries agreed to close borders, at 84 percent decline compared to March 10th. Similarly, we examined the impacts of quarantine measures in the major city: Tokyo (Japan), New York City (the United States), and Barcelona (Spain). Within all three cities, we found the significant decline in traffic volume. We also identified the increased concern for mental health through the analysis of posts on social networking services such as Twitter and Instagram. Notably, in the beginning of April 2020, the number of post with #depression on Instagram doubled, which might reflect the rise in mental health awareness among Instagram users. Besides, we identified the changes in a wide range of people's social behaviors, as well as economic impacts through the analysis of Instagram data and primary survey data.", "qid": 43, "docid": "ltbvpv8b", "rank": 85, "score": 0.8264601230621338}, {"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": 43, "docid": "3ly4f8dy", "rank": 86, "score": 0.825942873954773}, {"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": 43, "docid": "hwlr3qfz", "rank": 87, "score": 0.825942873954773}, {"content": "Title: Modelling information-dependent social behaviors in response to lockdowns: the case of COVID-19 epidemic in Italy Content: The COVID-19 pandemic started in January 2020 has not only threatened world public health, but severely impacted almost every facet of lives including behavioral and psychological aspects. In this paper we focus on the 'human element' and propose a mathematical model to investigate the effects on the COVID-19 epidemic of social behavioral changes in response to lockdowns. We consider a SEIR-like epidemic model where that contact and quarantine rates are assumed to depend on the available information and rumors about the disease status in the community. The model is applied to the case of COVID-19 epidemic in Italy. We consider the period that stretches between February 24, 2020 when the first bulletin by the Italian Civil Protection was reported and May 18, 2020 when the lockdown restrictions have been mostly removed. The role played by the information-related parameters is determined by evaluating how they affect suitable outbreak-severity indicators. We estimated that citizens compliance with mitigation measures played a decisive role in curbing the epidemic curve by preventing a duplication of deaths and about 46% more contagions.", "qid": 43, "docid": "ylcv4zvl", "rank": 88, "score": 0.8257055282592773}, {"content": "Title: Lifestyle at Time of COVID-19: How Could Quarantine Affect Cardiovascular Risk Content: COVID-19 is causing a global pandemic with a high number of deaths and infected people. To contain the diffusion of COVID-19 virus, governments have enforced restrictions on outdoor activities or even collective quarantine on the population. Quarantine carries some long-term effects on cardiovascular disease, mainly related to unhealthy lifestyle and anxiety.", "qid": 43, "docid": "pigamjae", "rank": 89, "score": 0.8256781697273254}, {"content": "Title: Traffic Impacts of the COVID-19 Pandemic: Statewide Analysis of Social Separation and Activity Restriction Content: The COVID-19 pandemic resulted in significant social and economic impacts throughout the world In addition to the health consequences, the impacts on travel behavior have also been sudden and wide ranging This study describes the drastic changes in human behavior using the analysis of highway volume data as a representation of personal activity and interaction Same-day traffic volumes for 2019 and 2020 across Florida were analyzed to identify spatial and temporal changes in behavior resulting from the disease or fear of it and statewide directives to limit person-to-person interaction Compared to similar days in 2019, overall statewide traffic volume dropped by 47 5% Although decreases were evident across the state, there were also differences between rural and urban areas and between highways and arterials both in terms of the timing and extent The data and analyses help to demonstrate the early impacts of the pandemic and may be useful for operational and strategic planning of recovery efforts and for dealing with future pandemics", "qid": 43, "docid": "wszd5kqk", "rank": 90, "score": 0.8255209922790527}, {"content": "Title: Echoes of 2009 H1N1 Influenza Pandemic in the COVID Pandemic Content: The severe acute respiratory syndrome-related coronavirus-2 (SARS-CoV2) pandemic that has engulfed the globe has had incredible effects on health care systems and economic activity. Social distancing and school closures have played a central role in public health efforts to counter the coronavirus disease 2019 (COVID)-19 pandemic. The most recent global pandemic prior to COVID-19 was the 2009 pandemic, hemagglutinin type 1 and neuraminidase type 1 (H1N1) influenza. The course of events in 2009 offer some rich lessons that could be applied to the current COVID-19 pandemic. This commentary highlights some of the most relevant points and a discussion of possible outcomes of the COVID-19 pandemic.", "qid": 43, "docid": "iw48r2za", "rank": 91, "score": 0.8253474235534668}, {"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": 92, "score": 0.8252878189086914}, {"content": "Title: COVID-19 and the other pandemic: populations made vulnerable by systemic inequity Content: Greater than the coronavirus disease 2019 (COVID-19) crisis, systemic inequity in social determinants of health is the pandemic that has long fostered vulnerability to disease and poor health outcomes in the USA. Our response has major implications for the health of our nations.", "qid": 43, "docid": "aceu86at", "rank": 93, "score": 0.8252432942390442}, {"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": 43, "docid": "h0yzj1ro", "rank": 94, "score": 0.8251226544380188}, {"content": "Title: A phased approach to unlocking during the COVID-19 pandemic-Lessons from trend analysis Content: BACKGROUND: The COVID-19 pandemic has led to radical political control of social behaviour. The purpose of this paper is to explore data trends from the pandemic regarding infection rates/policy impact and draw learning points for informing the unlocking process. METHODS: The daily published cases in England in each of 149 Upper Tier Local Authority (UTLA) areas were converted to Average Daily Infection Rate (ADIR), an R value-the number of further people infected by one infected person during their infectious phase with Rate of Change of Infection Rate (RCIR) also calculated. Stepwise regression was carried out to see what local factors could be linked to differences in local infection rates. FINDINGS: By the 19th April 2020 the infection R has fallen from 2.8 on 23rd March before the lockdown and has stabilised at about 0.8 sufficient for suppression. However, there remain significant variations between England regions. Regression analysis across UTLAs found that the only factor relating to reduction in ADIR was the historic number of confirmed number infection/000 population, There is, however, wide variation between Upper Tier Local Authorities (UTLA) areas. Extrapolation of these results showed that unreported community infection may be 150 times higher than reported cases, providing evidence that by the end of the 2nd week in April, 26.8% of the population may already have had the disease and so have increased immunity. INTERPRETATION: Analysis of current case data using infectious ratio has provided novel insight into the current national state and can be used to make better-informed decisions about future management of restricted social behaviour and movement.", "qid": 43, "docid": "ayccccvg", "rank": 95, "score": 0.8251181840896606}, {"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": 43, "docid": "ctg6waey", "rank": 96, "score": 0.8248834609985352}, {"content": "Title: Disease and age-related inequalities in paediatric research, funding and communication: lessons from the COVID-19 pandemic Content: COVID-19 has already caused millions of infections, thousands of deaths and countless indirect and poorly estimated consequences on other diseases and the global economy. All ages are potentially susceptible, but the virus has had a lower direct impact on children, with fewer severe cases and low mortality rates. However, the reasons for this are still unclear and we cannot rule out children's role in transmitting the disease. The serious impact that restrictive measures have had on children's lives have not been fully considered. Because children are less affected by COVID-19, the scientific community, health agencies and governments have not focused much attention on them during this pandemic.", "qid": 43, "docid": "w3hgmfzb", "rank": 97, "score": 0.8248505592346191}, {"content": "Title: Is the effect of COVID-19 on children underestimated in low- and middle- income countries? Content: The COVID-19 pandemic has had a huge impact on health and society, worldwide. While most high income countries are felt to be reaching their COVID-19 peak, most low- and middle-income countries (LMICs), particularly sub-Saharan countries, are anticipating an exponential growth of cases.(1) Overall it has been documented that children are less affected.(2) However, in this commentary we describe how in Kenya, a LMIC in sub-Saharan Africa, COVID-19 is likely to have far-reaching direct and indirect implications on children.", "qid": 43, "docid": "gyj7wqjn", "rank": 98, "score": 0.8246431350708008}, {"content": "Title: The Institutional and Cultural Context of Cross-National Variation in COVID-19 Outbreaks Content: Background. The COVID-19 pandemic poses an unprecedented and cascading threat to the health and economic prosperity of the world's population. Objectives. To understand whether the institutional and cultural context influences the COVID-19 outbreak. Methods. At the ecological level, regression coefficients are examined to figure out contextual variables influencing the pandemic's exponential growth rate across 96 countries. Results. While a strong institutional context is negatively associated with the outbreak (B = -0.55 ... -0.64, p < 0.001), the pandemic's growth rate is steeper in countries with a quality education system (B = 0.33, p < 0.001). Countries with an older population are more affected (B = 0.46, p < 0.001). Societies with individualistic (rather than collectivistic) values experience a flatter rate of pathogen proliferation (B = -0.31, p < 0.001), similarly for higher levels of power distance (B = -0.32, p < 0.001). Hedonistic values, that is seeking indulgence and not enduring restraints, are positively related to the outbreak (B = 0.23, p = 0.001). Conclusions. The results emphasize the need for public policy makers to pay close attention to the institutional and cultural context in their respective countries when instigating measures aimed at constricting the pandemic's growth.", "qid": 43, "docid": "dr8x59s1", "rank": 99, "score": 0.8242202997207642}, {"content": "Title: Health behaviour changes during COVID-19 and the potential consequences: A mini-review Content: The COVID-19 pandemic has brought about profound changes to social behaviour. While calls to identify mental health effects that may stem from these changes should be heeded, there is also a need to examine potential changes with respect to health behaviours. Media reports have signalled dramatic shifts in sleep, substance use, physical activity and diet, which may have subsequent downstream mental health consequences. We briefly discuss the interplay between health behaviours and mental health, and the possible changes in these areas resulting from anti-pandemic measures. We also highlight a call for greater research efforts to address the short and long-term consequences of changes to health behaviours.", "qid": 43, "docid": "nypmshw5", "rank": 100, "score": 0.8238714933395386}]}