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20 | s4ty52kb | are patients taking Angiotensin-converting enzyme inhibitors (ACE) at increased risk for COVID-19? | A systematic review and meta-analysis to evaluate the clinical outcomes in COVID-19 patients on angiotensin-converting enzyme inhibitors or angiotensin receptor blockers 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, 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 = 0.53–1.41, 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. |
31 | h3oix9zc | How does the coronavirus differ from seasonal flu? | Animal models for the risk assessment of viral pandemic potential Pandemics affect human lives severely and globally. Experience predicts that there will be a pandemic for sure although the time is unknown. When a viral epidemic breaks out, assessing its pandemic risk is an important part of the process that characterizes genomic property, viral pathogenicity, transmission in animal model, and so forth. In this review, we intend to figure out how a pandemic may occur by looking into the past influenza pandemic events. We discuss interpretations of the experimental evidences resulted from animal model studies and extend implications of viral pandemic potentials and ingredients to emerging viral epidemics. Focusing on the pandemic potential of viral infectious diseases, we suggest what should be assessed to prevent global catastrophes from influenza virus, Middle East respiratory syndrome coronavirus, dengue and Zika viruses. |
36 | 9zm4per4 | What is the protein structure of the SARS-CoV-2 spike? | Prediction of RNA Pseudoknots Using Heuristic Modeling with Mapping and Sequential Folding Predicting RNA secondary structure is often the first step to determining the structure of RNA. Prediction approaches have historically avoided searching for pseudoknots because of the extreme combinatorial and time complexity of the problem. Yet neglecting pseudoknots limits the utility of such approaches. Here, an algorithm utilizing structure mapping and thermodynamics is introduced for RNA pseudoknot prediction that finds the minimum free energy and identifies information about the flexibility of the RNA. The heuristic approach takes advantage of the 5′ to 3′ folding direction of many biological RNA molecules and is consistent with the hierarchical folding hypothesis and the contact order model. Mapping methods are used to build and analyze the folded structure for pseudoknots and to add important 3D structural considerations. The program can predict some well known pseudoknot structures correctly. The results of this study suggest that many functional RNA sequences are optimized for proper folding. They also suggest directions we can proceed in the future to achieve even better results. |
49 | c51eyqpi | do individuals who recover from COVID-19 show sufficient immune response, including antibody levels and T-cell mediated immunity, to prevent re-infection? | Targeting innate immunity by blocking CD14: Novel approach to control inflammation and organ dysfunction in COVID-19 illness The SARS-CoV-2 pandemic has produced an unprecedented rush to develop new therapies, ranging from immunizations and antivirals to host-directed therapies to dampen potentially deleterious host inflammatory responses. With a sense of urgency, many groups have proposed repurposing approved drugs for other indications that might be deployed rapidly to control the viral infection or improve host responses. However, many of these therapies are based on drug availability rather than on a rational understanding of important steps in pathogenesis, particularly in the lungs, that lead to critical illness and life-threatening acute respiratory failure. Here we propose that the viral infection initially triggers a profound activation of innate immunity in the lungs that generates a self-perpetuating cytokine storm affecting the entire body. Inhibiting key proximal points in innate immunity pathways is feasible and offers a science-based approach to improving outcomes in moderate to severe COVID-19 illness. |
30 | gin58n77 | is remdesivir an effective treatment for COVID-19 | Core principles for infection prevention in hemodialysis centers during the COVID-19 pandemic |
14 | uicvudil | what evidence is there related to COVID-19 super spreaders | Evaluating transmission heterogeneity and super-spreading event of COVID-19 in a metropolis of China 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. |
47 | ru6yepyu | what are the health outcomes for children who contract COVID-19? | Ethical decision-making for children with neuromuscular disorders in the COVID-19 crisis. The sudden appearance and proliferation of COVID-19 has forced societies and governmental authorities across the world to confront the possibility of resource constraints when critical care facilities are overwhelmed by the sheer numbers of grievously ill patients. As governments and health care systems develop and update policies and guidelines regarding the allocation of resources, patients and families affected by chronic disabilities, including many neuromuscular disorders that affect children and young adults, have become alarmed at the possibility that they may be determined to have less favorable prognoses due to their underlying diagnoses and thus be assigned to lower priority groups. It is important for health care workers, policymakers, and government officials to be aware that the long term prognoses for children and young adults with neuromuscular disorders are often more promising than previously believed, due to a better understanding of the natural history of these diseases, benefits of multidisciplinary supportive care, and novel molecular therapies that can dramatically improve the disease course. Although the realities of a global pandemic have the potential to require a shift from our usual, highly individualistic standards of care to crisis standards of care, shifting priorities should nonetheless be informed by good facts. Resource allocation guidelines with the potential to affect children and young adults with neuromuscular disorders should take into account the known trajectory of acute respiratory illness in this population, and rely primarily on contemporary long-term outcome data. |
48 | 52rnzk4g | what are the benefits and risks of re-opening schools in the midst of the COVID-19 pandemic? | The prospects of sitting 'end of year' open book exams in the light of COVID-19: A medical student's perspective. Medical schools in the UK have been forced to dramatically restructure teaching and assessment amidst the Coronavirus (COVID-19) pandemic. As part of this, some have opted to assess progression through open book examinations (OBE). I aim to share my thoughts as an unsettled 4th year medical student about to embark on my first set of clinical exams conducted in this format. The difficulties associated with preparing for examinations under such unique and challenging circumstances cannot be underestimated. Working from home, during social distancing, surrounds students with the extra family stresses that we are all facing during this pandemic. This combined with a new, unfamiliar examination format will inevitably lead to students feeling daunted. While some would argue that an OBE may reward good problem solvers, students still require a strong foundation of knowledge. The luxury of reference will not be afforded in all clinical settings thus leading to concerns regarding students skimming over essential learning points. Furthermore, we cannot ignore the increased opportunity for academic misconduct resulting from an open book assessment format. Why are medical schools placing undue stress on students who could instead focus their attention on living compassionately for others during this difficult time? |
15 | 4evbeijx | how long can the coronavirus live outside the body | Novel Immunoinformatics Approaches to Design Multi-epitope Subunit Vaccine for Malaria by Investigating Anopheles Salivary Protein Malaria fever has been pervasive for quite a while in tropical developing regions causing high morbidity and mortality. The causal organism is a protozoan parasite of genus Plasmodium which spreads to the human host by the bite of hitherto infected female Anopheles mosquito. In the course of biting, a salivary protein of Anopheles helps in blood feeding behavior and having the ability to elicit the host immune response. This study represents a series of immunoinformatics approaches to design multi-epitope subunit vaccine using Anopheles mosquito salivary proteins. Designed subunit vaccine was evaluated for its immunogenicity, allergenicity and physiochemical parameters. To enhance the stability of vaccine protein, disulfide engineering was performed in a region of high mobility. Codon adaptation and in silico cloning was also performed to ensure the higher expression of designed subunit vaccine in E. coli K12 expression system. Finally, molecular docking and simulation study was performed for the vaccine protein and TLR-4 receptor, to determine the binding free energy and complex stability. Moreover, the designed subunit vaccine was found to induce anti-salivary immunity which may have the ability to prevent the entry of Plasmodium sporozoites into the human host. |
11 | ix4zo0ha | what are the guidelines for triaging patients infected with coronavirus? | Could Intravenous Immunoglobulin Collected from Recovered Coronavirus Patients Protect against COVID-19 and Strengthen the Immune System of New Patients? The emergence of the novel coronavirus in Wuhan, China, which causes severe respiratory tract infections in humans (COVID-19), has become a global health concern. Most coronaviruses infect animals but can evolve into strains that cross the species barrier and infect humans. At the present, there is no single specific vaccine or efficient antiviral therapy against COVID-19. Recently, we showed that intravenous immunoglobulin (IVIg) treatment reduces inflammation of intestinal epithelial cells and eliminates overgrowth of the opportunistic human fungal pathogen Candida albicans in the murine gut. Immunotherapy with IVIg could be employed to neutralize COVID-19. However, the efficacy of IVIg would be better if the immune IgG antibodies were collected from patients who have recovered from COVID-19 in the same city, or the surrounding area, in order to increase the chance of neutralizing the virus. These immune IgG antibodies will be specific against COVID-19 by boosting the immune response in newly infected patients. Different procedures may be used to remove or inactivate any possible pathogens from the plasma of recovered coronavirus patient derived immune IgG, including solvent/detergent, 60 °C heat-treatment, and nanofiltration. Overall, immunotherapy with immune IgG antibodies combined with antiviral drugs may be an alternative treatment against COVID-19 until stronger options such as vaccines are available. |
5 | 5y8cc5eb | what drugs have been active against SARS-CoV or SARS-CoV-2 in animal studies? | Anti-RAS drugs and SARS-CoV-2 infection • There is no enough evidence to indicate that ACEIs and ARBs result in ACE2 upregulation. • The level of ACE2 expression is not completely related with the risk of COVID-19 infection. • There is currently no evidence that ACEI/ARB increase risk for COVID-19 infection from clinical trials. • It is not recommended that COVID-19 patients with hypertension or normal hypertensive patients at risk for exposure to stop using ACEI/ARB or change to other antihypertensive drugs. |
10 | md1o1od4 | has social distancing had an impact on slowing the spread of COVID-19? | Sepsis and septic shock: endothelial molecular pathogenesis associated with vascular microthrombotic disease In addition to protective "immune response", sepsis is characterized by destructive "endothelial response" of the host, leading to endotheliopathy and its molecular dysfunction. Complement activation generates membrane attack complex (MAC). MAC causes channel formation to the cell membrane of pathogen, leading to death of microorganisms. In the host, MAC also may induce channel formation to innocent bystander endothelial cells (ECs) and ECs cannot be protected. This provokes endotheliopathy, which activates two independent molecular pathways: inflammatory and microthrombotic. Activated inflammatory pathway promotes the release of inflammatory cytokines and triggers inflammation. Activated microthrombotic pathway mediates platelet activation and exocytosis of unusually large von Willebrand factor multimers (ULVWF) from ECs and initiates microthrombogenesis. Excessively released ULVWF become anchored to ECs as long elongated strings and recruit activated platelets to assemble platelet-ULVWF complexes and form "microthrombi". These microthrombi strings trigger disseminated intravascular microthrombosis (DIT), which is the underlying pathology of endotheliopathy-associated vascular microthrombotic disease (EA-VMTD). Sepsis-induced endotheliopathy promotes inflammation and DIT. Inflammation produces inflammatory response and DIT orchestrates consumptive thrombocytopenia, microangiopathic hemolytic anemia, and multiorgan dysfunction syndrome (MODS). Systemic inflammatory response syndrome (SIRS) is a combined phenotype of inflammation and endotheliopathy-associated (EA)-VMTD. Successful therapeutic design for sepsis can be achieved by counteracting the pathologic microthrombogenesis. |
33 | 51b7oh8s | What vaccine candidates are being tested for Covid-19? | 2019-nCoV - Towards a 4th generation vaccine The first report of the unusual manifestation of pneumonia-like symptoms in Wuhan City, China was made on 31 December 2019. Within one week, the Chinese authorities reported that they had identified the causative agent as a new member of the Coronavirus family, the same family of that was responsible for MERS and SARS not so many years ago. The new virus was called Novel Coronavirus 2019 (2019-nCoV). Three weeks later, the World Health Organization declared that 2019-nCoV was capable of direct human-to-human transmission, the virus had spread across several countries in three continents, and had infected close to two thousand people, of whom at least 1 in 5 quite severely. The number of fatalities was fast rising. Yet, the World Health Organization officially announced that there is still at present no recommended anti-nCoV vaccine for subject at-risk, nor treatment for patients with suspected or confirmed nCoV, let alone 2019-nCov. It is therefore timely and critical to propose new possible and practical approaches for preventive interventions for subjects at-risk, and for treatment of patients afflicted with 2019-nCov-induced disease (Corona Virus Disease 2019; COVID-19) before the present situation explodes into a worldwide pandemic. One such potential clinical protocol is proposed as a hypothesis. |
17 | k8ixv4aa | are there any clinical trials available for the coronavirus | The Acute Respiratory Infection Consortium: A Multi-Site, Multi-Disciplinary Clinical Research Network in the Department of Defense INTRODUCTION: Acute respiratory infections (ARI) result in substantial annual morbidity among military personnel and decrease operational readiness. Herein, we summarize the research efforts of the Infectious Disease Clinical Research Program (IDCRP) related to ARIs. METHODS: The ARI Research Area of the IDCRP was established in response to the 2009 emergence of pandemic influenza A/H1N1. That year, IDCRP investigators deployed the ARI Consortium Natural History Study (ARIC NHS), a multi-centered, longitudinal observational study to assess etiology, epidemiology, and clinical characteristics of influenza-like illness (ILI) and severe acute respiratory infections (SARI) in the U.S. military. The success of this initial effort spurred implementation of several new initiatives. These include the FluPlasma trial, designed to evaluate the efficacy of hyperimmune anti-influenza plasma for the treatment of severe influenza; the self-administered live-attenuated influenza vaccine (SNIF) trial, which assessed the immunogenicity and acceptance of a self-administered live-attenuated influenza vaccine in military personnel; the Study to Address Threats of ARI in Congregate Military Populations (ATARI), a prospective study of ILI transmission, etiology and epidemiology in recruits; and the Flu Breath Test (FBT) study, a preliminary study of exhaled volatile organic compounds (VOC) in influenza patients. In addition, the InFLUenza Patient-Reported Outcome (FLU-PRO) survey, a daily diary to measure influenza symptoms during clinical trials, was developed. Lastly, the Pragmatic Assessment of Influenza Vaccine Effectiveness in the DoD (PAIVED) study, a two-year randomized trial designed to compare the effectiveness of the three types of licensed vaccines, launched in Fall 2018. RESULTS: The on-going ARIC NHS has enrolled over 2000 ILI and SARI cases since its inception, providing data on burden and clinical manifestations of ARI in military personnel and their families. The FluPlasma 2 trial concluded subject enrollment in 2018. Preliminary results from ATARI study show a high frequency of respiratory viruses circulating during the first two weeks of recruit training. Based on assessment of FLU-PRO responses, which were found to be reliable and reproducible, the survey may be a useful tool in clinical trials and epidemiological studies. The Flu Breath Study will complete enrollment in 2019. Findings from PAIVED are intended to provide evidence needed for assessing influenza vaccination policy in the military. CONCLUSIONS: The ARI burden in the armed services remains significant every year and the threat is dynamic given emergent and evolving threats, such as influenzas. With strong successes to date, future initiatives of the ARI Research Area will focus on interventional studies, ARI transmission dynamics in congregate military settings, and determinants of risk of pandemic influenza and other emergent respiratory viruses. |
8 | c4cs14ja | how has lack of testing availability led to underreporting of true incidence of Covid-19? | Estimating SARS-CoV-2 seroprevalence and epidemiological parameters with uncertainty from serological surveys Establishing how many people have already been infected by SARS-CoV-2 is an urgent priority for controlling the COVID-19 pandemic. Patchy virological testing has hampered interpretation of confirmed case counts, and unknown rates of asymptomatic and mild infections make it challenging to develop evidence-based public health policies. Serological tests that identify past infection can be used to estimate cumulative incidence, but the relative accuracy and robustness of various sampling strategies has been unclear. Here, we used a flexible framework that integrates uncertainty from test characteristics, sample size, and heterogeneity in seroprevalence across tested subpopulations to compare estimates from sampling schemes. Using the same framework and making the assumption that serological positivity indicates immune protection, we propagated these estimates and uncertainty through dynamical models to assess the uncertainty in the epidemiological parameters needed to evaluate public health interventions. We examined the relative accuracy of convenience samples versus structured surveys to estimate population seroprevalence, and found that sampling schemes informed by demographics and contact networks outperform uniform sampling. The framework can be adapted to optimize the design of serological surveys given particular test characteristics and capacity, population demography, sampling strategy, and modeling approach, and can be tailored to support decision-making around introducing or removing interventions. |
46 | m7sawt31 | what evidence is there for dexamethasone as a treatment for COVID-19? | A systematic review on the efficacy and safety of chloroquine for the treatment of COVID-19 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. |
38 | p05a8zjy | What is the mechanism of inflammatory response and pathogenesis of COVID-19 cases? | Virus spread and voter model on random graphs with multiple type nodes When modelling epidemics or spread of information on online social networks, it is crucial to include not just the density of the connections through which infections can be transmitted, but also the variability of susceptibility. Different people have different chance to be infected by a disease (due to age or general health conditions), or, in case of opinions, ones are easier to be convinced by others, or stronger at sharing their opinions. The goal of this work is to examine the effect of multiple types of nodes on various random graphs such as Erd\H{o}s--R\'enyi random graphs, preferential attachment random graphs and geometric random graphs. We used two models for the dynamics: SEIR model with vaccination and a version of voter model for exchanging opinions. In the first case, among others, various vaccination strategies are compared to each other, while in the second case we studied sevaral initial configurations to find the key positions where the most effective nodes should be placed to disseminate opinions. |
28 | zp4uy1v7 | what evidence is there for the value of hydroxychloroquine in treating Covid-19? | CORONAVIRUSES (CORONAVIRIDAE) |
16 | waqyr9tq | how long does coronavirus remain stable on surfaces? | Coronavirus infection of rat dorsal root ganglia: Ultrastructural characterization of viral replication, transfer, and the early response of satellite cells Abstract Swine hemagglutinating encephalomyelitis virus (HEV) has been shown to have a capability to gain access to the cell bodies of sensory neurons after peripheral inoculation, resulting in ganglionic infection. It is not clearly understood how this virus is replicated within and released from the sensory neurons, and it remains to know how satellite cells response to the HEV invasion. By ultrastructurally examining HEV-infected rat dorsal root ganglia, we found that HEV in the cell bodies of infected neurons budded from endoplasmic reticulum–Golgi intermediate compartments, and were assembled either individually within small vesicles or in groups within large vesicles. The progeny virions were released from the sensory neurons mainly by smooth-surfaced vesicle-mediated secretory pathway, which occurred predominantly at the perikaryal projections and infoldings of sensory neurons. Released HEV particles were subsequently taken up by the adjacent satellite cells. Almost all virus particles in the cytoplasm of satellite cells were contained in groups within vesicles and lysosome-like structures, suggesting that these glial cells may restrict the local diffusion of HEV. These observations give some insights into the pathogenesis of coronavirus infection and are thought to help understand the interactions between sensory neurons and their satellite cells. |
9 | nhjruvnd | how has COVID-19 affected Canada | The date predicted 200.000 cases of Covid-19 in Spain using SutteARIMA The aim of this study is predicted 200.000 cases of Covid-19 in Spain. Covid-19 Spanish confirmed data obtained from Worldometer from 01 March 2020 - 17 April 2020. The data from 01 March 2020 - 10 April 2020 using to fitting with data from 11 April - 17 April 2020. For the evaluation of the forecasting accuracy measures, we use mean absolute percentage error (MAPE). Based on the results of SutteARIMA fitting data, the accuracy of SutteARIMA for the period 11 April 2020 - 17 April 2020 is 0.61% and we forecast 20.000 confirmed cases of Spain by the WHO situation report day 90/91 which is 19 April 2020 / 20 April 2020. |
42 | xfsbaxnx | Does Vitamin D impact COVID-19 prevention and treatment? | The COVID-19 outbreak: The issue of face masks |
21 | mcrf27ew | what are the mortality rates overall and in specific populations | A geroscience perspective on COVID-19 mortality A novel coronavirus, SARS-CoV-2, emerged in December 2019, leading within a few months to a global pandemic. COVID-19, the disease caused by this highly contagious virus, can have serious health consequences, though risks of complications are highly age-dependent. Rates of hospitalization and death are less than 0.1% in children, but increase to 10% or more in older people. Moreover, at all ages, men are more likely than women to suffer serious consequences from COVID-19. These patterns are familiar to the geroscience community. The effects of age and sex on mortality rates from COVID-19 mirror the effects of aging on almost all major causes of mortality. These similarities are explored here, and underscore the need to consider the role of basic biological mechanisms of aging on potential treatment and outcomes of COVID-19. |
1 | w8ewm8ve | what is the origin of COVID-19 | How to handle patients with autoimmune rheumatic and inflammatory bowel diseases in the COVID-19 era: An expert opinion • A correct patient risk stratification is of paramount importance for the proper management of economic and human resources. • It's fundamental to prioritize clinical trials evaluating dosing, prophylaxis, and treatment with immunosuppressant in COVID-19 in order to avoid either an overuse and a treatment shortage. • Future controlled studies may highlight in our patients a potential preventive role of immunosuppressant therapies in the development of severe forms of Covid-19. • Despite the overall risk of infection in rheumatic and gastroenterological diseases a conclusive association between these diseases and COVID −19 remains questionable. |
26 | isbq1fqt | what are the initial symptoms of Covid-19? | Diarrhea during COVID-19 infection: pathogenesis, epidemiology, prevention and management Abstract Background and aims The severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2 / COVID-19) pandemic is a worldwide emergency. An increasing number of diarrhea cases is reported. Here we investigate the epidemiology, clinical presentation, molecular mechanisms, management, and prevention of SARS-CoV-2 associated diarrhea. Methods We searched on PubMed, EMBASE, and Web of Science up to March 2020 to identify studies documenting diarrhea and mechansism of intestinal inflammation in patients with confirmed diagnosis of SARS-CoV-2 infection. Results Clinical studies show an incidence rate of diarrhea ranging from 2% to 50% of cases. It may precede or trail respiratory symptoms. A pooled analysis revealed an overall percentage of diarrhea onset of 10.4%. SARS-CoV uses the the angiotensin-converting enzyme 2 (ACE2) and the serine protease TMPRSS2 for S protein priming. ACE2 and TMPRSS2 are not only expressed in lung, but also in the small intestinal epithelia. ACE2 is expressed furthermore in the upper esophagus, liver, and colon. SARS-CoV-2 binding affinity to ACE2 is significantly higher (10-20 times) compared with SARS-CoV. Several reports indicate viral RNA shedding in stool detectable longer time period than in nasopharyngeal swabs. Current treatment is supportive, but several options appear promising and are the subject of investigation. Conclusion Diarrhea is a frequent presenting symptom in patients infected with SARS-CoV-2. Increasing evidence indicates possible fecal oral transmission, indicating the need for a rapid and effective modification of the screening and diagnostic algorithms. The optimal methods to prevent, manage, and treat diarrhea in COVID-19 infected patients are subjects of intensive research. |
48 | 5p8gkbi7 | what are the benefits and risks of re-opening schools in the midst of the COVID-19 pandemic? | Are pangolins the intermediate host of the 2019 novel coronavirus (2019-nCoV) ? The outbreak of 2019-nCoV pneumonia (COVID-19) in the city of Wuhan, China has resulted in more than 70,000 laboratory confirmed cases, and recent studies showed that 2019-nCoV (SARS-CoV-2) could be of bat origin but involve other potential intermediate hosts. In this study, we assembled the genomes of coronaviruses identified in sick pangolins. The molecular and phylogenetic analyses showed that pangolin Coronaviruses (pangolin-CoV) are genetically related to both the 2019-nCoV and bat Coronaviruses but do not support the 2019-nCoV arose directly from the pangolin-CoV. Our study also suggested that pangolin be natural host of Betacoronavirus, with a potential to infect humans. Large surveillance of coronaviruses in pangolins could improve our understanding of the spectrum of coronaviruses in pangolins. Conservation of wildlife and limits of the exposures of humans to wildlife will be important to minimize the spillover risks of coronaviruses from wild animals to humans. |
6 | 1gt0n6uo | what types of rapid testing for Covid-19 have been developed? | Value of chest CT screening in the early COVID-19 outbreak/ 中华放射学杂志 Objective@#In view of the difficulty of the shortage of new coronavirus nucleal acid test in the early COVID-19 outbreak, to explore the application value of chest CT in screening COVID-19 patients.@*Methods@#Retrospective analysis was performed on the data of patients with fever who received chest CT and new coronavirus nucleal acid test during January 25, 2020 to February 2, 2020 in Zhongnan Hospital of Wuhan University. A total of 587 patients were enrolled, including 290 males and 297 females, aged from 11.0 to 96.0 (51.3±17.1) years old. Take the nucleic acid test results as the gold standard, the sensitivity, specificity and rate of missed diagnosis of CT screening COVID-19 were calculated.@*Results@#Among the 587 patients, there were 433 positive cases (73.8%, 433/587) and 154 negative cases (26.2%, 154/587) of novel coronavirus nucleic acid test. Using CT screening, 494 cases (84.2%, 494/587) were positive and 93 cases (15.8%, 93/587) were negative. The sensitivity of CT screening COVID-19 was 97.7% (423/433), specificity was 53.9% (83/154) and rate of missed diagnosis was 2.3% (10/433).@*Conclusions@#In the early COVID-19 outbreak, CT screening has the advantages of high sensitivity and low rate of missed diagnosis of COVID-19, which can compensate for the shortage of new coronavirus nucleal acid test and can be used as the basis for rapid screening for early prevention and control of COVID-19 outbreak. |
32 | vg0wg0w4 | Does SARS-CoV-2 have any subtypes, and if so what are they? | Coronaviridae and SARS-associated Coronavirus Strain HSR1 During the recent severe acute respiratory (SARS) outbreak, the etiologic agent was identified as a new coronavirus (CoV). We have isolated a SARS-associated CoV (SARS-CoV) strain by injecting Vero cells with a sputum specimen from an Italian patient affected by a severe pneumonia; the patient traveled from Vietnam to Italy in March 2003. Ultrastructural analysis of infected Vero cells showed the virions within cell vesicles and around the cell membrane. The full-length viral genome sequence was similar to those derived from the Hong-Kong Hotel M isolate. By using both real-time reverse transcription–polymerase chain reaction TaqMan assay and an infectivity plaque assay, we determined that approximately 360 viral genomes were required to generate a PFU. In addition, heparin (100 μg/mL) inhibited infection of Vero cells by 50%. Overall, the molecular and biologic characteristics of the strain HSR1 provide evidence that SARS-CoV forms a fourth genetic coronavirus group with distinct genomic and biologic features. |
34 | xlw7tize | What are the longer-term complications of those who recover from COVID-19? | Co-stimulation: novel methods for preventing viral-induced lung inflammation Respiratory infections cause significant morbidity and mortality worldwide. Although an immune response is required to eliminate respiratory pathogens, if unchecked, it can damage surrounding tissues and block primary lung function. Based on our knowledge of immune T-cell activation, there are several pathways to which immune intervention could be applied. However, relatively few interventions target only those immune cells that are responding to antigens. OX40 and 4-1BB are members of the tumour necrosis factor receptor family and are expressed on the surface of T cells in several inflammatory conditions. Recently, the inhibition of OX40 has proved beneficial during influenza virus infection. This review highlights the recent advances in the manipulation of such molecules and how they have been applied to inflammatory conditions that are caused by viruses in the lung. |
15 | jqf3e2np | how long can the coronavirus live outside the body | Negligible risk of the COVID-19 resurgence caused by work resuming in China (outside Hubei): a statistical probability study The COVID-19 outbreak in China appears to reach the late stage since late March 2020, and a stepwise restoration of economic operations is implemented. Risk assessment for such economic restoration is of significance. Here, we estimated the probability of COVID-19 resurgence caused by work resuming in typical provinces/cities and found that such probability is very limited (<5% for all the regions except Beijing). Our work may inform provincial governments to make risk level-based, differentiated control measures. |
42 | 7pkusbl7 | Does Vitamin D impact COVID-19 prevention and treatment? | Description of COVID-19 in HIV-infected individuals: a single-centre, prospective cohort BACKGROUND: Information about incidence, clinical characteristics, and outcomes of HIV-infected individuals with severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection is scarce. We characterised individuals with COVID-19 among a cohort of HIV-infected adults in Madrid. METHODS: In this observational prospective study, we included all consecutive HIV-infected individuals (aged ≥18 years) who had suspected or confirmed COVID-19 as of April 30, 2020, at the Hospital Universitario Ramón y Cajal (Madrid, Spain). We compared the characteristics of HIV-infected individuals with COVID-19 with a sample of HIV-infected individuals assessed before the COVID-19 pandemic, and described the outcomes of individuals with COVID-19. FINDINGS: 51 HIV-infected individuals were diagnosed with COVID-19 (incidence 1·8%, 95% CI 1·3-2·3). Mean age of patients was 53·3 years (SD 9·5); eight (16%) were women, and 43 (84%) men. 35 (69%) cases of co-infection had laboratory confirmed COVID-19, and 28 (55%) required hospital admission. Age and CD4 cell counts in 51 patients diagnosed with COVID-19 were similar to those in 1288 HIV-infected individuals without; however, 32 (63%) with COVID-19 had at least one comorbidity (mostly hypertension and diabetes) compared with 495 (38%) without COVID-19 (p=0·00059). 37 (73%) patients had received tenofovir before COVID-19 diagnosis compared with 487 (38%) of those without COVID-19 (p=0·0036); 11 (22%) in the COVID-19 group had previous protease inhibitor use (mostly darunavir) compared with 175 (14%; p=0·578). Clinical, analytical, and radiological presentation of COVID-19 in HIV-infected individuals was similar to that described in the general population. Six (12%) individuals were critically ill, two of whom had CD4 counts of less than 200 cells per µL, and two (4%) died. SARS-CoV-2 RT-PCR remained positive after a median of 40 days from symptoms onset in six (32%) individuals, four of whom had severe disease or low nadir CD4 cell counts. INTERPRETATION: HIV-infected individuals should not be considered to be protected from SARS-CoV-2 infection or to have lower risk of severe disease. Generally, they should receive the same treatment approach applied to the general population. FUNDING: None. |
21 | xyowl659 | what are the mortality rates overall and in specific populations | Real-time estimation and prediction of mortality caused by COVID-19 with patient information based algorithm Abstract The global COVID-19 outbreak is worrisome both for its high rate of spread, and the high case fatality rate reported by early studies and now in Italy. We report a new methodology, the Patient Information Based Algorithm (PIBA), for estimating the death rate of a disease in real-time using publicly available data collected during an outbreak. PIBA estimated the death rate based on data of the patients in Wuhan and then in other cities throughout China. The estimated days from hospital admission to death was 13 (standard deviation (SD), 6 days). The death rates based on PIBA were used to predict the daily numbers of deaths since the week of February 25, 2020, in China overall, Hubei province, Wuhan city, and the rest of the country except Hubei province. The death rate of COVID-19 ranges from 0.75% to 3% and may decrease in the future. The results showed that the real death numbers had fallen into the predicted ranges. In addition, using the preliminary data from China, the PIBA method was successfully used to estimate the death rate and predict the death numbers of the Korean population. In conclusion, PIBA can be used to efficiently estimate the death rate of a new infectious disease in real-time and to predict future deaths. The spread of 2019-nCoV and its case fatality rate may vary in regions with different climates and temperatures from Hubei and Wuhan. PIBA model can be built based on known information of early patients in different countries. |
28 | mlwrfkm4 | what evidence is there for the value of hydroxychloroquine in treating Covid-19? | Estimating the Risks from COVID-19 Infection in Adult Chemotherapy Patients The SARS-CoV-2 (COVID-19) novel coronavirus represents a significant health risk, particularly in older patients. Cancer is one of the leading causes of death in most rich countries, and delivering chemotherapy may be associated with increased risk in the presence of a pandemic infection. Estimating this risk is crucial in making decisions about balancing risks and benefits from administering chemotherapy. However, there are no specific data about chemotherapy risks per se. Here we develop a simple model to estimate the potential harms in patients undergoing chemotherapy during a COVID outbreak. We use age-related case fatality rates as a basis for estimating risk, and use previous data from risk of death during influenza outbreaks to estimate the additional risk associated with chemotherapy. We use data from randomised trials to estimate benefit across a range of curative and palliative settings, and address the balance of benefit against the risk of harm. We then use those data to estimate the impact on national chemotherapy delivery patterns. |
50 | 8lktpcda | what is known about an mRNA vaccine for the SARS-CoV-2 virus? | Design of a peptide-based subunit vaccine against novel coronavirus SARS-CoV-2 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. |
24 | unnrflmr | what kinds of complications related to COVID-19 are associated with diabetes | Broad-spectrum coronavirus antiviral drug discovery Introduction: The highly pathogenic coronaviruses severe acute respiratory syndrome coronavirus (SARS-CoV) and Middle East respiratory syndrome coronavirus (MERS-CoV) are lethal zoonotic viruses that have emerged into human populations these past 15 years. These coronaviruses are associated with novel respiratory syndromes that spread from person-to-person via close contact, resulting in high morbidity and mortality caused by the progression to Acute Respiratory Distress Syndrome (ARDS). Areas covered: The risks of re-emergence of SARS-CoV from bat reservoir hosts, the persistence of MERS-CoV circulation, and the potential for future emergence of novel coronaviruses indicate antiviral drug discovery will require activity against multiple coronaviruses. In this review, approaches that antagonize viral nonstructural proteins, neutralize structural proteins, or modulate essential host elements of viral infection with varying levels of efficacy in models of highly pathogenic coronavirus disease are discussed. Expert opinion: Treatment of SARS and MERS in outbreak settings has focused on therapeutics with general antiviral activity and good safety profiles rather than efficacy data provided by cellular, rodent, or nonhuman primate models of highly pathogenic coronavirus infection. Based on lessons learned from SARS and MERS outbreaks, lack of drugs capable of pan-coronavirus antiviral activity increases the vulnerability of public health systems to a highly pathogenic coronavirus pandemic. |
8 | 9032hh5c | how has lack of testing availability led to underreporting of true incidence of Covid-19? | Chinese and Italian COVID-19 outbreaks can be correctly described by a modified SIRD model The COVID-19 disease is rapidly spreading in whole globe, affecting millions of people and pushing governments to take drastic measures to contain the outbreaks. The understanding of the dynamics of the epidemic is of great interest for the governments and health authorities that are facing COVID-19 outbreaks. The scarce presence of epidemiologic data, due to the still ongoing outbreaks, makes prediction difficult and mainly based on heuristic (fitting) models. However, these models with non-physical based parameters, can only give limited insight in the evolution of the outbreaks. In this work a SIRD compartmental model was developed to describe and predict the evolution of the Chinese and Italian outbreaks. Exploiting the similarities of the measures taken by the governments to contain the virus and of the total population number of Hubei province and Italy, the model was tuned on the Chinese outbreak (almost extinguished) and by perturbation the Italian outbreak was describe and predicted. |
23 | 8yablc7b | what kinds of complications related to COVID-19 are associated with hypertension? | The Role of Other Bacteria, Fungi, and Viruses in Bronchiectasis Bronchiectasis, a heterogeneous disease, is characterized by a vicious cycle of airway infection and inflammation that results in structural damage to the airways and the surrounding lung parenchyma [1]. Many microorganisms have been associated with bronchiectasis, both as a complication of the anatomic abnormalities and possibly as a cause of the structural disease as well [2, 3]. Diverse polymicrobial communities are present in the airways of patients with bronchiectasis [4]. Studies using standard microbiologic culture techniques have demonstrated the presence of bacterial, fungal, and viral pathogens in the lungs of bronchiectasis patients both when the patient is clinically stable and when there is an exacerbation of disease [2, 5]. Newer molecular techniques have broadened our understanding of the microbiome in bronchiectasis patients [4, 6]. Pseudomonas aeruginosa has been repeatedly shown to be a problematic pathogen in patients with bronchiectasis and is associated with a worse prognosis [7, 8]. Multiple epidemiologic reports have shown that approximately 20–35% of patients worldwide with bronchiectasis are chronically infected with P. aeruginosa [2, 9, 10]. Several antibiotic trials have been published where the main target of therapy is Pseudomonas aeruginosa [11–17]. (See Chap. 10.1007/978-3-319-61452-6_11 for a full review of P. aeruginosa infections associated with bronchiectasis.) Another problematic group of pathogens, nontuberculous mycobacteria (NTM), is a common infecting organism in bronchiectasis, particularly in the United States and in parts of Asia [2, 18]. NTM infection is fully discussed in Chap. 10.1007/978-3-319-61452-6_13. In this chapter, we will review the role of bacterial pathogens other than P. aeruginosa and the impact of fungal and viral infections in bronchiectasis patients. (See Table 13.1.) |
41 | yxmqmetv | What are the impacts of COVID-19 among African-Americans that differ from the rest of the U.S. population? | Occupational Health Science in the Time of COVID-19: Now more than Ever Workers bear a heavy share of the burden of how countries contend with COVID-19; they face numerous serious threats to their occupational health ranging from those associated with direct exposure to the virus to those reflecting the conflicts between work and family demands. Ten experts were invited to comment on occupational health issues unique to their areas of expertise. The topics include work-family issues, occupational health issues faced by emergency medical personnel, the transition to telework, discrimination against Asian-Americans, work stressors, presenteeism, the need for supportive supervision, safety concerns, economic stressors, and reminders of death at work. Their comments describe the nature of the occupational health concerns created by COVID-19 and discuss both unanswered research questions and recommendations to help organizations reduce the impacts of COVID-19 on workers. |
5 | px1qsx8q | what drugs have been active against SARS-CoV or SARS-CoV-2 in animal studies? | Boceprevir, GC-376, and calpain inhibitors II, XII inhibit SARS-CoV-2 viral replication by targeting the viral main protease A new coronavirus SARS-CoV-2, also called novel coronavirus 2019 (2019-nCoV), started to circulate among humans around December 2019, and it is now widespread as a global pandemic. The disease caused by SARS-CoV-2 virus is called COVID-19, which is highly contagious and has an overall mortality rate of 6.35% as of May 26, 2020. There is no vaccine or antiviral available for SARS-CoV-2. In this study, we report our discovery of inhibitors targeting the SARS-CoV-2 main protease (M(pro)). Using the FRET-based enzymatic assay, several inhibitors including boceprevir, GC-376, and calpain inhibitors II, and XII were identified to have potent activity with single-digit to submicromolar IC(50) values in the enzymatic assay. The mechanism of action of the hits was further characterized using enzyme kinetic studies, thermal shift binding assays, and native mass spectrometry. Significantly, four compounds (boceprevir, GC-376, calpain inhibitors II and XII) inhibit SARS-CoV-2 viral replication in cell culture with EC(50) values ranging from 0.49 to 3.37 µM. Notably, boceprevir, calpain inhibitors II and XII represent novel chemotypes that are distinct from known substrate-based peptidomimetic M(pro) inhibitors. A complex crystal structure of SARS-CoV-2 M(pro) with GC-376, determined at 2.15 Å resolution with three protomers per asymmetric unit, revealed two unique binding configurations, shedding light on the molecular interactions and protein conformational flexibility underlying substrate and inhibitor binding by M(pro). Overall, the compounds identified herein provide promising starting points for the further development of SARS-CoV-2 therapeutics. |
31 | bzsc9289 | How does the coronavirus differ from seasonal flu? | Influenza A Virus Infections in Dromedary Camels, Nigeria and Ethiopia, 2015–2017 We examined nasal swabs and serum samples acquired from dromedary camels in Nigeria and Ethiopia during 2015–2017 for evidence of influenza virus infection. We detected antibodies against influenza A(H1N1) and A(H3N2) viruses and isolated an influenza A(H1N1)pdm09–like virus from a camel in Nigeria. Influenza surveillance in dromedary camels is needed. |
15 | br0oxhc3 | how long can the coronavirus live outside the body | Demyelination, and remyelination by Schwann cells and oligodendrocytes after kainate-induced neuronal depletion in the central nervous system Abstract Excitotoxins are thought to kill neurons while sparing afferent fibers and axons of passage. The validity of this classical conclusion has recently been questioned by the demonstration of axonal demyelination. In addition, axons are submitted to a profound alteration of their glial environment. This work was, therefore, undertaken to reassess axonoglial interactions over time after an excitotoxic lesion in the rat. Ultrastructural studies were carried out in the ventrobasal thalamus two days to 18 months after neuronal depletion by in situ injections of kainic acid. In some cases, lemniscal afferents were identified by using anterograde transport of wheatgerm agglutinin conjugated to horseradish peroxidase from the dorsal column nuclei. Two and four days after kainate injection, numerous dying axons displaying typical signs of Wallerian degeneration were observed in a neuropile characterized by the loss of neuronal somata and dendrites, an increase in number of microglia/macrophages and the disappearance of astrocytes. Ten and 12 days after kainate injection, degenerating axons were no longer observed although myelin degeneration of otherwise unaltered axons was ongoing with an accumulation of myelin remnants in the neuropile. At 16 and 20 days, the demyelination process was apparently complete and axons of different diameters were sometimes packed together. One and two months after kainate injection, the axonal environment changed again: remyelination of large-caliber axons occurred at the same time as reactive astrocytes, oligodendrocytes and numerous Schwann cells appeared in the tissue. Schwann cell processes surrounded aggregates of axons of diverse calibers, ensheathed small ones and myelinated larger ones. Axons were also remyelinated by oligodendrocytes. Horseradish peroxidase-labeled lemniscal afferents could be myelinated by either of the two cell types. After three months, the neuropile exhibited an increase in number of hypertrophied astrocytes and the progressive loss of any other cellular or axonal element. At this stage, remaining Schwann cells were surrounded by a glia limitans formed by astrocytic processes. These data indicate that although excitotoxins are sparing the axons, they are having a profound and complex effect on the axonal environment. Demyelination occurs over the first weeks, accompanying the loss of astrocytes and oligodendrocytes. Axonal ensheathment and remyelination takes place in a second period, associated with the reappearance of oligodendrocytes and recruitment of numerous Schwann cells, while reactive astrocytes appear in the tissue at a slightly later time. Over the following months, astrocytes occupy a greater proportion of the neuron-depleted territory and other elements decrease in number. These successive stages in alteration of axonoglial interactions seem to evolve in parallel to the changes in density and terminal morphology that we described earlier for myelinated afferent fibers to the excitotoxic lesion. |
3 | i5b0k41k | will SARS-CoV2 infected people develop immunity? Is cross protection possible? | Challenges in maintaining treatment services for people who use drugs during the COVID-19 pandemic The impact of COVID-19 across health services, including treatment services for people who use drugs, is emerging but likely to have a high impact. Treatment services for people who use drugs provide essential treatment services including opiate agonist treatment and needle syringe programmes alongside other important treatment programmes across all substance types including withdrawal and counselling services. Drug and alcohol hospital consultation-liaison clinicians support emergency departments and other services provided in hospital settings in efficiently managing patients who use drugs and present with other health problems. COVID-19 will impact on staff availability for work due to illness. Patients may require home isolation and quarantine periods. Ensuring ongoing supply of opiate treatment during these periods will require significant changes to how treatment is provided. The use of monthly depot buprenorphine as well as moving from a framework of supervised dosing will be required for patients on sublingual buprenorphine and methadone. Ensuring ready access to take-home naloxone for patients is crucial to reduce overdose risks. Delivery of methadone and buprenorphine to the homes of people with confirmed COVID-19 infections is likely to need to occur to support home isolation. People who use drugs are likely to be more vulnerable during the COVID-19 epidemic, due to poorer health literacy and stigma and discrimination towards this group. People who use drugs may prioritise drug use above other health concerns. Adequate supply of clean injecting equipment is important to prevent outbreaks of blood-borne viruses. Opiate users may misinterpret SARS-CoV2 symptoms as opiate withdrawal and manage this by using opioids. Ensuring people who use drugs have access to drug treatment as well as access to screening and testing for SARS-CoV2 where this is indicated is important. |
6 | zyrzfm40 | what types of rapid testing for Covid-19 have been developed? | Types of Assays for SARS-CoV-2 Testing: A Review. 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. |
23 | jyfcpsu6 | what kinds of complications related to COVID-19 are associated with hypertension? | [Hypertension, RAAS blockade and risk in COVID-19 patients]. 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. |
27 | p5bahejq | what is known about those infected with Covid-19 but are asymptomatic? | The Effects of Social Support on Sleep Quality of Medical Staff Treating Patients with Coronavirus Disease 2019 (COVID-19) in January and February 2020 in China BACKGROUND: Coronavirus disease 2019 (COVID-19), formerly known as severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) and 2019 novel coronavirus (2019-nCoV), was first identified in December 2019 in Wuhan City, China. Structural equation modeling (SEM) is a multivariate analysis method to determine the structural relationship between measured variables. This observational study aimed to use SEM to determine the effects of social support on sleep quality and function of medical staff who treated patients with COVID-19 in January and February 2020 in Wuhan, China. MATERIAL/METHODS: A one-month cross-sectional observational study included 180 medical staff who treated patients with COVID-19 infection. Levels of anxiety, self-efficacy, stress, sleep quality, and social support were measured using the and the Self-Rating Anxiety Scale (SAS), the General Self-Efficacy Scale (GSES), the Stanford Acute Stress Reaction (SASR) questionnaire, the Pittsburgh Sleep Quality Index (PSQI), and the Social Support Rate Scale (SSRS), respectively. Pearson's correlation analysis and SEM identified the interactions between these factors. RESULTS: Levels of social support for medical staff were significantly associated with self-efficacy and sleep quality and negatively associated with the degree of anxiety and stress. Levels of anxiety were significantly associated with the levels of stress, which negatively impacted self-efficacy and sleep quality. Anxiety, stress, and self-efficacy were mediating variables associated with social support and sleep quality. CONCLUSIONS: SEM showed that medical staff in China who were treating patients with COVID-19 infection during January and February 2020 had levels of anxiety, stress, and self-efficacy that were dependent on sleep quality and social support. |
29 | 69toerzi | 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? | Learning from the Past: Possible Urgent Prevention and Treatment Options for Severe Acute Respiratory Infections Caused by 2019‐nCoV With the current trajectory of the 2019‐nCoV outbreak unknown, public health and medicinal measures will both be needed to contain spreading of the virus and to optimize patient outcomes. Although little is known about the virus, an examination of the genome sequence shows strong homology with its better‐studied cousin, SARS‐CoV. The spike protein used for host cell infection shows key nonsynonymous mutations that might hamper the efficacy of previously developed therapeutics but remains a viable target for the development of biologics and macrocyclic peptides. Other key drug targets, including RNA‐dependent RNA polymerase and coronavirus main proteinase (3CLpro), share a strikingly high (>95 %) homology to SARS‐CoV. Herein, we suggest four potential drug candidates (an ACE2‐based peptide, remdesivir, 3CLpro‐1 and a novel vinylsulfone protease inhibitor) that could be used to treat patients suffering with the 2019‐nCoV. We also summarize previous efforts into drugging these targets and hope to help in the development of broad‐spectrum anti‐coronaviral agents for future epidemics. |
11 | 54o2p36a | what are the guidelines for triaging patients infected with coronavirus? | Lactate dehydrogenase, a Risk Factor of Severe COVID-19 Patients BACKGROUND The World Health Organization (WHO) has recently declared coronavirus disease 2019 (COVID-19) a public health emergency of global concern. Updated analysis of cases might help identify the characteristic and risk factors of the illness severity. METHODS We extracted data regarding 47 patients with confirmed COVID-19 from Renmin Hospital of Wuhan University between February 1 and February 18, 2020. The degree of severity of COVID-19 patients (severe vs. non-severe) was defined at the time of admission according to American Thoracic Society (ATS) guidelines for community-acquired pneumonia (CAP). RESULTS The median age was 64.91 years, 26 cases (55.31%) were male of which, and 70.83% were severe cases. Severe patients had higher APACHE II (9.92 vs 4.74) and SOFA (3.0 vs 1.0) scores on admission, as well as the higher PSI (86.13 vs 61.39), Curb-65 (1.14 vs 0.48) and CT semiquantitative scores (5.0 vs 2.0) when compared with non-severe patients. Among all univariable parameters, APACHE II, SOFA, lymphocytes, CRP, LDH, AST, cTnI, BNP, et al were significantly independent risk factors of COVID-19 severity. Among which, LDH was most positively related both with APACHE II (R = 0.682) and SOFA (R = 0.790) scores, as well as PSI (R = 0.465) and CT (R = 0.837) scores. To assess the diagnostic value of these selected parameters, LDH (0.9727) had maximum sensitivity (100.00%) and specificity (86.67%), with the cutoff value of 283. As a protective factor, lymphocyte counts less than 1.045 x 109 /L showed a good accuracy for identification of severe patients with AUC = 0.9845 (95%CI 0.959-1.01), the maximum specificity (91.30%) and sensitivity (95.24%). In addition, LDH was positively correlated with CRP, AST, BNP and cTnI, while negatively correlated with lymphocyte cells and its subsets, including CD3+, CD4+ and CD8+ T cells (P < 0.01). CONCLUSIONS This study showed that LDH coule be identified as a powerful predictive factor for early recognition of lung injury and severe COVID-19 cases. And importantly, lymphocyte counts, especially CD3+, CD4+, and CD8+ T cells in the peripheral blood of COVID-19 patients, which was relevant with serum LDH, were also dynamically correlated with the severity of the disease. FUNDING Key Project of Shanghai Municipal Health Bureau (2016ZB0202) |
32 | dtukacm7 | Does SARS-CoV-2 have any subtypes, and if so what are they? | Nanopore metagenomic sequencing of influenza virus directly from respiratory samples: diagnosis, drug resistance and nosocomial transmission Background: Influenza virus presents a significant challenge to public health by causing seasonal epidemics and occasional pandemics. Nanopore metagenomic sequencing has the potential to be deployed for near-patient testing, providing rapid diagnosis of infection, rationalising antimicrobial therapy, and supporting interventions for infection control. This study aimed to evaluate the applicability of this sequencing approach as a routine laboratory test for influenza in clinical settings. Methods: We conducted Nanopore metagenomic sequencing for 180 respiratory samples from a UK hospital during the 2018/19 influenza season, and compared results to routine molecular diagnostic testing. We investigated drug resistance, genetic diversity, and nosocomial transmission using influenza sequence data. Results: Metagenomic sequencing was 83% (75/90) sensitive and 93% (84/90) specific for detecting influenza A viruses compared with the diagnostic standard (Cepheid Xpress/BioFire FilmArray Respiratory Panel). We identified a H3N2 genome with the oseltamivir resistant S331R mutation in the NA protein, potentially associated with the emergence of a distinct intra-subtype reassortant. Whole genome phylogeny refuted suspicions of a transmission cluster in the infectious diseases ward, but identified two other clusters that likely reflected nosocomial transmission, associated with a predominant strain circulating in the community. We also detected a range of other potentially pathogenic viruses and bacteria from the metagenome. Conclusion: Nanopore metagenomic sequencing can detect the emergence of novel variants and drug resistance, providing timely insights into antimicrobial stewardship and vaccine design. Generation of full genomes can contribute to the investigation and management of nosocomial outbreaks. |
37 | 2cvp8wch | What is the result of phylogenetic analysis of SARS-CoV-2 genome sequence? | The first two cases of 2019-nCoV in Italy: Where they come from? A novel Coronavirus, 2019-nCoV, has been identified as the causal pathogen of an ongoing epidemic, with the first cases reported in Wuhan, China, last December 2019, and has since spread to other countries worldwide, included Europe and very recently Italy. In this short report, phylogenetic reconstruction was used to better understand the transmission dynamics of the virus from its first introduction in China focusing on the more recent evidence of infection in a couple of Chinese tourists arrived in Italy on 23rd January 2020 and labeled as Coronavirus Italian cases. A maximum clade credibility tree has been built using a dataset of 54 genome sequences of 2019-nCoV plus two closely related bat strains (SARS-like CoV) available in GenBank. Bayesian time-scaled phylogenetic analysis was implemented in BEAST 1.10.4. The Bayesian phylogenetic reconstruction showed that 2019-2020 nCoV firstly introduced in Wuhan on 25 November 2019, started epidemic transmission reaching many countries worldwide, including Europe and Italy where the two strains isolated dated back 19 January 2020, the same that the Chinese tourists arrived in Italy. Strains isolated outside China were intermixed with strains isolated in China as evidence of likely imported cases in Rome, Italy, and Europe, as well. In conclusion, this report suggests that further spread of 2019-nCoV epidemic was supported by human mobility and that quarantine of suspected or diagnosed cases is useful to prevent further transmission. Viral genome phylogenetic analysis represents a useful tool for the evaluation of transmission dynamics and preventive action. |
19 | py6qu4tl | what type of hand sanitizer is needed to destroy Covid-19? | Teicoplanin potently blocks the cell entry of 2019-nCoV Since December 2019, the outbreak of a new coronavirus, named 2019-nCoV, has greatly threatened the public health in China and raised great concerns worldwide. No specific treatment for this infection is currently available. We previously reported that teicoplanin, a glycopeptide antibiotic which has routinely been used in the clinic to treat bacterial infection with low toxicity, significantly inhibits the invasion of cells by Ebola virus, SARS-CoV and MERS-CoV, via specifically inhibiting the activity of cathepsin L. Here, we tested the efficacy of teicoplanin against 2019-nCoV virus infection and found that teicoplanin potently prevents the entrance of 2019-nCoV-Spike-pseudoviruses into the cytoplasm, with an IC50 of 1.66 μM. Although the inhibitory effect upon the replication of wildtype viruses ex vivo and in vivo remains to be determined, our preliminary result indicates that the potential antiviral activity of teicoplanin could be applied for the treatment of 2019-nCoV virus infection. |
15 | bcdiq8xh | how long can the coronavirus live outside the body | Escape from Human Monoclonal Antibody Neutralization Affects In Vitro and In Vivo Fitness of Severe Acute Respiratory Syndrome Coronavirus BACKGROUND: Severe Acute Respiratory Syndrome (SARS) emerged as a human disease in 2002 and detailed phylogenetic analysis and epidemiological studies have suggested that the SARS-Coronavirus (SARS-CoV) originated from animals. The Spike (S) glycoprotein has been identified as a major target of protective immunity and contains at least three regions that are targeted by neutralizing antibodies in the S1 and S2 domains. We previously characterized a panel of neutralizing human monoclonal antibodies (MAbs) but the majority of epitopes recognized by the MAbs remained unknown. METHODS: In this study we generated neutralization escape mutants and studied the effect of these neutralization escape mutations on human and animal receptor usage as well as in vitro and in vivo fitness. RESULTS: Distinct but partially overlapping sets of amino acids were identified that are critical to the binding of MAbs with differential neutralization profiles. We also identified possible interactions between the S1 and S2 domains of the SARS-CoV S glycoprotein. Finally, we showed that escape from neutralization usually attenuates SARS-CoV infection. CONCLUSIONS: These data provide a mechanism to overcome neutralization escape by using broadly cross reactive cocktails of cross-neutralizing MAbs that recognize residues within the receptor binding domain, critical for virus replication and virulence. |
38 | 1xf2sxtv | What is the mechanism of inflammatory response and pathogenesis of COVID-19 cases? | The MERS-CoV receptor DPP4 as a candidate binding target of the SARS-CoV-2 spike SUMMARY The ongoing outbreak of the novel coronavirus pneumonia COVID-19 has caused great number of cases and deaths, but our understanding about the pathogen SARS-CoV-2 remains largely unclear. The attachment of the virus with the cell-surface receptor and a co-factor is the first step for the infection. Here, bioinformatics approaches combining human-virus protein interaction prediction and protein docking based on crystal structures have revealed the high affinity between human dipeptidyl peptidase 4 (DPP4) and the spike (S) receptor-binding domain of SARS-CoV-2. Intriguingly, the crucial binding residues of DPP4 are identical to those as bound to the MERS-CoV-S. Moreover, E484 insertion and adjacent substitutions should be most essential for this DPP4-binding ability acquirement of SARS-CoV-2-S compared with SARS-CoV-S. This potential utilization of DPP4 as a binding target for SARS-CoV-2 may offer novel insight into the viral pathogenesis, and help the surveillance and therapeutics strategy for meeting the challenge of COVID-19. |
34 | 5xcm23f2 | What are the longer-term complications of those who recover from COVID-19? | A case report of neonatal COVID-19 infection in China In December 2019, the 2019 novel coronavirus disease (COVID-19) caused by SARS-CoV-2 emerged in China and now has spread in many countries. Pregnant women are susceptible population of COVID-19 which are more likely to have complications and even progresse to severe illness. We report a case of neonatal COVID-19 infection in China with pharyngeal swabs tested positive by rRT-PCR assay 36 hours after birth. However, whether the case is a vertical transmission from mother to child remains to be confirmed. |
13 | bntjg90x | what are the transmission routes of coronavirus? | Anaesthetic managment and clinical outcomes of parturients with COVID-19: a multicentre, retrospective, propensity score matched cohort study Objective:To analyse the clinical features of COVID-19 parturients, and to compare anaesthetic regimen and clinical outcomes in parturients with or without COVID-19 undergoing cesarean delivery.Methods: Data were extracted from the electronic medical record of 3 medical institutions in Hubei Province, China, from June 1, 2019 to March 20, 2020 according to inclusion and exclusion criteria. After propensity score matching with demographics, the clinical and laboratory characteristics of parturients with or without COVID-19 were analysed. The anaesthetic regimen and clinical outcomes of themselves and their infants were compared in these two groups of parturients. Results: A total of 1,588 patients without SARS-CoV-2 infection undergoing cesarean delivery were retrospectively included. After achieving a balanced cohort through propensity score matching, 89 patients (COVID-19 group), who were diagnosed with COVID-19 by SARS-CoV-2 nucleic acid test and CT scan matched with 173 patients without COVID-19 (Control group). The SARS-CoV-2 infected parturients in the early stages of COVID-19 outbreak was much more than during the later stage. The main clinical characteristics of parturients with COVID-19 were fever (34.8%), cough (33.7%), an increased plasma CRP (52.8%) and a decreased lymphocyte counting (33.7%). A high rate of emergency and a high incidence of anaesthesia-related complications, such as pharyngalgia, multiple puncture, intraoperative hypotension, nausea, vomiting, vertigo and chills in the COVID-19 parturients. In addition, the parturients with COVID-19 had a long duration of operation and hospital stay, and an increased intraoperative oxytocin utilization and postoperative oxygen therapy. The newborns from the SARS-CoV-2 infected mothers, who received general anaesthesia, had a high risk of Apgar score [≤]8 at 1 and 5 minutes after delivery and a higher rate of neonatal intensive care unit (NICU) admission. Conclusions: Anaesthesia-related complications occur more frequently in the COVID-19 parturients and their newborns have a high risk of distress. |
15 | x9laa9uk | how long can the coronavirus live outside the body | Barriers of the Human Organism and Their Achilles' Heels The human body is covered by barriers separating it from the external and internal surroundings. The "milieu enterieur" has to be stabilised in spite of the variable external and internal conditions of toxic, osmotic, microbial and climatic environmental circumstances. This first line of barriers is composed of skin and mucous membranes of complicated structures. A second line of barrier system is present in our organisms. Certain organs have to be separated from the immune system and other parts of the body because of evolutionary reasons (eye-bulb and testicles) because of unique proteins "unknown" for the acquired immune system. The blood-brain barrier (BBB) is providing enhanced safety circumstances for the central nervous system. The second line of barriers is represented by the special properties of the capillary endothelial system. The maternal-fetal barrier is the most complex. At the maternal fetal interface two individuals of two different haplotypes has to be live 9 months separated by a very complicated dynamic barrier. The placenta is the organ, which is separating the maternal and fetal tissues. Similar to others the bidirectional transport of gasses, metabolites, cells, proteins, regulatory substances, are transported by active or passive transcellular and intercellular mechanisms. The fetal immune system develops immunotolerance to all maternal cells and antigens transferred transplacentally. The problem is to mitigate the maternal immune system to tolerate the paternal haplotype of the fetus. In the case of normal pregnancy a complex series of physiological modifications can solve the problem without harmful consequences to the mother and fetus. The outermost contact cells of trophoblasts express instead of HLA-class Ia and class II antigens non-variable HLA-C, HLA-E, HLA-F and HLA-G antigens. The first consequence of this is reduction of the activity of maternal natural killer cells and maternal dendritic cells; Progesteron, micro-RNA and mediators influence the development of T effector-cells. The production of soluble HLA-G(5 and 6) and IL-10 supports the differentiation of Th-2 CD4(+) helper cells, reducing the ability of maternal cells to kill fetal cells. Series of receptors and costimulators are expressed by the different lines of semi-allogenic trophoblast cells to bind HLA-G and mitigate maternal immune response; The maternal immunotolerance is further facilitated by the activation of CD4(+)CD25(bright)Foxp3(+) regulatory T (T(REG)) cells. Infections have to be prevented during pregnancy. The cells of placenta express 10 Toll-like receptors a group of pattern recognition receptors responsible for innate immunity. The interferon level is also higher in the placental tissues than in the somatic fetal or maternal cells. The complement system is also adapted to the requirements of the pregnancy and fetal damage is inhibited by the production of "assymmetric IgG antibodies" under hormonal and placental-regulation. These modifications prevent the activation of complement, cytotoxic activity, opsonising ability, antigen clearance and precipitating activity of the molecules. The Achilles' heels of the different barriers are regularly found by virus infections. Lamina cribrosa of the blood-brain barrier, optical nerve of the eyes, etc. the risk factors of the maternal-fetal barrier has been summarised in Table 1.1. |
16 | m8wggdc7 | how long does coronavirus remain stable on surfaces? | First reported nosocomial outbreak of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) in a pediatric dialysis unit BACKGROUND: Coronavirus disease 2019 (COVID-19) is a life-threatening respiratory condition caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) and was initially detected in China in December 2019. Currently, in Germany over 140,000 cases of COVID-19 are confirmed. Here we report a nosocomial outbreak of SARS-CoV-2 infections in the pediatric dialysis unit of the University Hospital of Münster (UHM). METHODS: Single-step real-time RT-PCR from nasopharyngeal swaps was used to diagnose the index patient and identify infected contacts. Epidemiological links were analyzed by patient interviews and chart reviews. In addition, each contact was assessed for exposure to the index case and monitored for clinical symptoms. Threshold cycle (Ct) values of all positive test results were compared between symptomatic and asymptomatic cases. RESULTS: Forty-eight cases were involved in this nosocomial outbreak. Nine contact cases developed laboratory confirmed COVID-19 infections. Two SARS-CoV-2 positive cases remained clinically asymptomatic. Eleven cases reported flu-like symptoms without positive results. Ct values were significantly lower in cases presenting typical COVID-19 symptoms, suggesting high viral shedding (p =0.007). CONCLUSION: Person-to-person transmission was at the heart of a hospital outbreak of SARS-CoV-2 between healthcare workers (HCWs) and patients in the pediatric dialysis unit at the UHM. Semi quantitative real-time RT-PCR results suggest that individuals with high viral load pose a risk to spread SARS-CoV-2 in the hospital setting. Our epidemiological observation highlights the need to develop strategies to trace and monitor SARS-CoV-2 infected HCWs in order to prevent COVID-19 outbreaks in the hospital setting. |
18 | 1warap0c | what are the best masks for preventing infection by Covid-19? | Protecting Surgical Teams During the COVID-19 Outbreak: A Narrative Review and Clinical Considerations |
19 | fjd0rsrf | what type of hand sanitizer is needed to destroy Covid-19? | Vagueness and Costs of the Pause on Gain-of-Function (GOF) Experiments on Pathogens with Pandemic Potential, Including Influenza Virus |
28 | u7j2gicv | what evidence is there for the value of hydroxychloroquine in treating Covid-19? | Advance of promising targets and agents against COVID-19 in China |
3 | hmeg2t9m | will SARS-CoV2 infected people develop immunity? Is cross protection possible? | Vaccine Development Against Middle East Respiratory Syndrome Various types of vaccines are under pre-clinical and clinical development to address the recent appearance of Middle East respiratory syndrome or MERS, an emerging infectious disease that has already caused over 600 deaths and remains a threat to world health. The causative agent for this respiratory disease is a member of the betacoronavirus genus, phylogenetically closely related to the SARS coronavirus that caused an international health emergency in 2002. With lessons learned from the outbreak of severe acute respiratory syndrome, and with undeniable technological advances, vaccine development against MERS was initially fast-paced and has produced several DNA and protein vaccine candidates with promising results during early pre-clinical testing. At least one vaccine candidate has even entered first-in-humans clinical trials now. With the number of MERS cases declining though and other infectious diseases attracting increased attention, the question remains, whether, similar to the situation after the SARS pandemic, vaccine development is halted or remains the priority it rightfully should. |
44 | 1kpw4ru0 | How much impact do masks have on preventing the spread of the COVID-19? | Coping with COVID-19: Exposure to COVID-19 and Negative Impact on Livelihood Predict Elevated Mental Health Problems in Chinese Adults The COVID-19 pandemic might lead to more mental health problems. However, few studies have examined sleep problems, depression, and posttraumatic symptoms among the general adult population during the COVID-19 outbreak, and little is known about coping behaviors. This survey was conducted online in China from February 1st to February 10th, 2020. Quota sampling was used to recruit 2993 Chinese citizens aged ≥18 years old. Mental health problems were assessed with the Post-Traumatic Stress Disorders (PTSD) Checklist for the Diagnostic and Statistical Manual of Mental Disorders, Fifth Edition (DSM-5), the Center for Epidemiological Studies Depression inventory, and the Pittsburgh Sleep Quality Index. Exposure to COVID-19 was measured with questions about residence at outbreak, personal exposure, media exposure, and impact on livelihood. General coping style was measured by the brief Coping Style Questionnaire (SCSQ). Respondents were also asked 12 additional questions about COVID-19 specific coping behaviors. Direct exposure to COVID-19 instead of the specific location of (temporary) residence within or outside the epicenter (Wuhan) of the pandemic seems important (standardized beta: 0.05, 95% confidence interval (CI): 0.02–0.09). Less mental health problems were also associated with less intense exposure through the media (standardized beta: −0.07, 95% CI: −0.10–−0.03). Perceived negative impact of the pandemic on livelihood showed a large effect size in predicting mental health problems (standardized beta: 0.15, 95% CI: 0.10–0.19). More use of cognitive and prosocial coping behaviors were associated with less mental health problems (standardized beta: −0.30, 95% CI: −0.34–−0.27). Our study suggests that the mental health consequences of the lockdown impact on livelihood should not be underestimated. Building on cognitive coping behaviors reappraisal or cognitive behavioral treatments may be most promising. |
35 | m8m4il3j | What new public datasets are available related to COVID-19? | COVID-19 Diagnostic and Management Protocol for Pediatric Patients This review aims to verify the main epidemiologic, clinical, laboratory-related, and therapeutic aspects of coronavirus disease 2019 (COVID-19) in critically ill pediatric patients. An extensive review of the medical literature on COVID-19 was performed, mainly focusing on the critical care of pediatric patients, considering expert opinions and recent reports related to this new disease. Experts from a large Brazilian public university analyzed all recently published material to produce a report aiming to standardize the care of critically ill children and adolescents. The report emphasizes on the clinical presentations of the disease and ventilatory support in pediatric patients with COVID-19. It establishes a flowchart to guide health practitioners on triaging critical cases. COVID-19 is essentially an unknown clinical condition for the majority of pediatric intensive care professionals. Guidelines developed by experts can help all practitioners standardize their attitudes and improve the treatment of COVID-19. |
42 | kmlvj6jk | Does Vitamin D impact COVID-19 prevention and treatment? | COVID-19 and addiction BACKGROUND AND AIMS: 2019-coronavirus disease (COVID-19) is causing insurmountable psychosocial impact on the whole mankind. Marginalized community, particularly those with substance use disorders (SUD), are particularly vulnerable to contract the infection and also likely to suffer from greater psychosocial burden. This article analyses the intricate bi-directional relationship between COVID-19 and addiction. METHODS: Pubmed and Google Scholar are searched with the following key terms- "COVID-19", "SARS-CoV2", "Pandemic", "Addiction", "Opioid", "Alcohol", "Smoking", "Addiction Psychiatry", "Deaddiction", "Substance use disorders", "Behavioral addiction". Few newspaper reports related to COVID-19 and addiction have also been added as per context. RESULTS: People with SUD are at greater risk of worse COVID-19 outcome. There is surge of addictive behaviors (both new and relapse) including behavioral addiction in this period. Withdrawal emergencies and death are also being increasingly reported. Addicted people are especially facing difficulties in accessing the healthcare services which are making them prone to procure drugs in illegal means. CONCLUSION: COVID-19 and addiction are the two pandemics which are on the verge of collision causing major public health threat. While every effort must be taken to make the public aware of deleterious effects of SUD on COVID-19 prognosis, the resumption of deaddiction services and easier accessibility of prescription drugs are needs of the hour. |
28 | d7dtflyd | what evidence is there for the value of hydroxychloroquine in treating Covid-19? | The Shifting Landscape of Genitourinary Oncology During the COVID-19 Pandemic and how Italian Oncologists Reacted: Results from a National Survey |
30 | yhhnzys5 | is remdesivir an effective treatment for COVID-19 | Perspectives: potential therapeutic options for SARS-CoV-2 patients based on feline infectious peritonitis strategies: central nervous system invasion and drug coverage |
11 | q2xjx56v | what are the guidelines for triaging patients infected with coronavirus? | "Daily Work in the Fever Clinics of Wuhan Union Hospital During the Novel Coronavirus Pneumonia Epidemic: A Special Spring Festival in Wuhan, China"Extracorporeal Membrane Oxygenation for Pediatric Patients With Coronavirus Disease 2019–Related Illness Objective: To describe current hospital guidelines and the opinions of extracorporeal membrane oxygenation leaders at U S children's hospitals concerning the use of extracorporeal membrane oxygenation for coronavirus disease 2019–positive pediatric patients Design: Confidential, self-administered questionnaire Setting: One hundred twenty-seven U S pediatric extracorporeal membrane oxygenation centers Subjects: Extracorporeal membrane oxygenation center program directors and coordinators Interventions: None Measurements and Main Results: In March 2020, a survey was sent to 127 pediatric extracorporeal membrane oxygenation centers asking them to report their current hospital extracorporeal membrane oxygenation guidelines for coronavirus disease 2019–positive patients Respondents were also asked their opinion on three ethical dilemmas including: prioritization of children over adults for extracorporeal membrane oxygenation use, institution of do-not-resuscitate orders, and the use of extracorporeal cardiopulmonary resuscitation for coronavirus disease 2019–positive patients Forty-seven extracorporeal membrane oxygenation centers had enacted guidelines including 46 (100%) that offer venovenous-extracorporeal membrane oxygenation and 42 (89%) that offer venoarterial-extracorporeal membrane oxygenation for coronavirus disease 2019–positive pediatric patients Forty-four centers (94%) stated that the indications for extracorporeal membrane oxygenation candidacy in coronavirus disease 2019 disease were similar to those used in other viral illnesses, such as respiratory syncytial virus or influenza Most program directors (98%) did not endorse that children hospitalized with coronavirus disease 2019 should be made do-not-resuscitate and had variable opinions on whether children should be given higher priority over adults when rationing extracorporeal membrane oxygenation Over half of program directors (60%) did not support the use of extracorporeal cardiopulmonary resuscitation for coronavirus disease 2019 Conclusions: The majority of pediatric extracorporeal membrane oxygenation centers have proactively established guidelines for the use of extracorporeal membrane oxygenation for coronavirus disease 2019–related illnesses Further work is needed to help guide the fair allocation of extracorporeal membrane oxygenation resources and to determine the appropriateness of extracorporeal cardiopulmonary resuscitation Drs MacGregor and Antiel are co-first authors Supplemental digital content is available for this article Direct URL citations appear in the printed text and are provided in the HTML and PDF versions of this article on the journal's website (http://journals lww com/pccmjournal) The authors have disclosed that they do not have any potential conflicts of interest For information regarding this article, E-mail: baddr@wustl edu ©2020The Society of Critical Care Medicine and the World Federation of Pediatric Intensive and Critical Care Societies |
15 | hmy8fs3g | how long can the coronavirus live outside the body | A rapid advice guideline for the diagnosis and treatment of 2019 novel coronavirus (2019-nCoV) infected pneumonia (standard version) In December 2019, a new type viral pneumonia cases occurred in Wuhan, Hubei Province; and then named "2019 novel coronavirus (2019-nCoV)" by the World Health Organization (WHO) on 12 January 2020. For it is a never been experienced respiratory disease before and with infection ability widely and quickly, it attracted the world's attention but without treatment and control manual. For the request from frontline clinicians and public health professionals of 2019-nCoV infected pneumonia management, an evidence-based guideline urgently needs to be developed. Therefore, we drafted this guideline according to the rapid advice guidelines methodology and general rules of WHO guideline development; we also added the first-hand management data of Zhongnan Hospital of Wuhan University. This guideline includes the guideline methodology, epidemiological characteristics, disease screening and population prevention, diagnosis, treatment and control (including traditional Chinese Medicine), nosocomial infection prevention and control, and disease nursing of the 2019-nCoV. Moreover, we also provide a whole process of a successful treatment case of the severe 2019-nCoV infected pneumonia and experience and lessons of hospital rescue for 2019-nCoV infections. This rapid advice guideline is suitable for the first frontline doctors and nurses, managers of hospitals and healthcare sections, community residents, public health persons, relevant researchers, and all person who are interested in the 2019-nCoV. |
33 | p3zjxo1h | What vaccine candidates are being tested for Covid-19? | Determinants of COVID-19 Vaccine Acceptance in the U.S. Background:The COVID-19 pandemic continues to adversely affect the U.S., which leads globally in total cases and deaths. As COVID-19 vaccines are under development, public health officials and policymakers need to create strategic vaccine-acceptance messaging to effectively control the pandemic and prevent thousands of additional deaths. Methods: Using an online platform, we surveyed the U.S. adult population in May 2020 to understand risk perceptions about the COVID-19 pandemic, acceptance of a COVID-19 vaccine, and trust in sources of information. These factors were compared across basic demographics. Findings: Of the 672 participants surveyed, 450 (67%) said they would accept a COVID-19 vaccine if it is recommended for them. Males (72%), older adults ([≥]55 years; 78%), Asians (81%), and college and/or graduate degree holders (75%) were more likely to accept the vaccine. When comparing reported influenza vaccine uptake to reported acceptance of the COVID-19 vaccine: 1) participants who did not complete high school had a very low influenza vaccine uptake (10%), while 60% of the same group said they would accept the COVID-19 vaccine; 2) unemployed participants reported lower influenza uptake and lower COVID-19 vaccine acceptance when compared to those employed or retired; and, 3) black Americans reported lower influenza vaccine uptake and lower COVID-19 vaccine acceptance than nearly all other racial groups. Lastly, we identified geographic differences with Department of Health and Human Services regions 2 (New York) and 5 (Chicago) reporting less than 50 percent COVID-19 vaccine acceptance. Interpretation: Although our study found a 67% acceptance of a COVID-19 vaccine, there were noticeable demographic and geographical disparities in vaccine acceptance. Before a COVID-19 vaccine is introduced to the U.S., public health officials and policymakers must prioritize effective COVID-19 vaccine-acceptance messaging for all Americans, especially those who are most vulnerable. |
41 | 50zrnau8 | What are the impacts of COVID-19 among African-Americans that differ from the rest of the U.S. population? | The time scale of asymptomatic transmission affects estimates of epidemic potential in the COVID-19 outbreak The role of asymptomatic carriers in transmission poses challenges for control of the COVID-19 pandemic. Study of asymptomatic transmission and implications for surveillance and disease burden are ongoing, but there has been little study of the implications of asymptomatic transmission on dynamics of disease. We use a mathematical framework to evaluate expected effects of asymptomatic transmission on the basic reproduction number [Formula: see text] (i.e., the expected number of secondary cases generated by an average primary case in a fully susceptible population) and the fraction of new secondary cases attributable to asymptomatic individuals. If the generation-interval distribution of asymptomatic transmission differs from that of symptomatic transmission, then estimates of the basic reproduction number which do not explicitly account for asymptomatic cases may be systematically biased. Specifically, if asymptomatic cases have a shorter generation interval than symptomatic cases, [Formula: see text] will be over-estimated, and if they have a longer generation interval, [Formula: see text] will be under-estimated. Estimates of the realized proportion of asymptomatic transmission during the exponential phase also depend on asymptomatic generation intervals. Our analysis shows that understanding the temporal course of asymptomatic transmission can be important for assessing the importance of this route of transmission, and for disease dynamics. This provides an additional motivation for investigating both the importance and relative duration of asymptomatic transmission. |
18 | v5egtgdo | what are the best masks for preventing infection by Covid-19? | Clinical and Epidemiologic Characteristics of Spreaders of Middle East Respiratory Syndrome Coronavirus during the 2015 Outbreak in Korea Nosocomial transmission is an important characteristic of Middle East Respiratory Syndrome Coronavirus (MERS-CoV) infection. Risk factors for transmission of MERS-CoV in healthcare settings are not well defined. During the Korean outbreak in 2015, 186 patients had laboratory-confirmed MERS-CoV infection. Those suspected as a source of viral transmission were categorized into the spreader groups (super-spreader [n = 5] and usual-spreader [n = 10]) and compared to the non-spreader group (n = 171). Body temperature of ≥ 38.5°C (adjusted odds ratio [aOR], 5.54; 95% confidence interval [CI], 1.38–22.30; P = 0.016), pulmonary infiltration of ≥ 3 lung zones (aOR, 7.33; 95% CI, 1.93–27.79; P = 0.003), and a more nonisolated in-hospital days (aOR, 1.32 per 1 day; 95% CI, 1.09–1.60; P = 0.004) were significant risk factors in the spreader group. There was no different clinical factor between super-spreaders and usual-spreaders. Nonisolated in-hospital days was the only factor which tended to be higher in super-spreaders than usual-spreaders (Mean, 6.6 vs. 2.9 days; P = 0.061). Early active quarantine might help reducing the size of an outbreak. |
14 | 2558niqn | what evidence is there related to COVID-19 super spreaders | Complex dynamic behavior in a viral model with state feedback control strategies With the consideration of mechanism of prevention and control for the spread of viral diseases, in this paper, we propose two novel virus dynamics models where state feedback control strategies are introduced. The first model incorporates the density of infected cells (or free virus) as control threshold value; we analytically show the existence and orbit stability of positive periodic solution. Theoretical results imply that the density of infected cells (or free virus) can be controlled within an adequate level. The other model determines the control strategies by monitoring the density of uninfected cells when it reaches a risk threshold value. We analytically prove the existence and orbit stability of semi-trivial periodic solution, which show that the viral disease dies out. Numerical simulations are carried out to illustrate the main results. |
32 | l36f1gp7 | Does SARS-CoV-2 have any subtypes, and if so what are they? | Oral and Poster Manuscripts |
44 | 2x9rdzzb | How much impact do masks have on preventing the spread of the COVID-19? | Perceived Discrimination and Mental Distress Amid the COVID-19 Pandemic: Evidence From the Understanding America Study Introduction This study examines coronavirus disease 2019 (COVID-19) associated discrimination regardless of infection status. It evaluates the contribution of various risk factors (e.g., race/ethnicity, wearing a face mask) and the relationship with mental distress among U.S. adults in March and April 2020, when the pandemic escalated across the country. Methods Participants consisted of a probability-based, nationally representative sample of U.S. residents aged ≥18 years who completed COVID-19-related surveys online in March and April (n=3,665). Multivariable logistic regression was used to predict the probability of a person perceiving COVID-19 associated discrimination. Linear regression was used to analyze the association between discrimination and mental distress. Analyses were conducted in May 2020. Results Perception of COVID-19 associated discrimination increased from March (4%) to April (10%). Non-Hispanic blacks (absolute risk from 0.09 to 0.15 across months) and Asians (absolute risk from 0.11 to 0.17) were more likely to perceive discrimination than other racial/ethnic groups (absolute risk from 0.03 to 0.11). Individuals who wore face masks (absolute risk from 0.11 to 0.14) also perceived more discrimination compared with those who did not (absolute risk from 0.04 to 0.11). Perceiving discrimination was subsequently associated with increased mental distress (from 0.77 to 1.01 points on the 4-item Patient Health Questionnaire score). Conclusions Perception of COVID-19 associated discrimination was relatively low but increased with time. Perceived discrimination was associated with race/ethnicity and wearing face masks, and may contribute to greater mental distress during early stages of the pandemic. The long-term implications of this novel form of discrimination should be monitored. |
2 | ve8oz8td | how does the coronavirus respond to changes in the weather | Equine coronavirus: An emerging enteric virus of adult horses Equine coronavirus (ECoV) is an emerging virus associated clinically and epidemiologically with fever, depression, anorexia and less frequently colic and diarrhoea in adult horses. Sporadic cases and outbreaks have been reported with increased frequency since 2010 from Japan, the USA and more recently from Europe. A faeco‐oral transmission route is suspected and clinical or asymptomatic infected horses appear to be responsible for direct and indirect transmission of ECoV. A presumptive clinical diagnosis of ECoV infection may be suggested by clinical presentation, haematological abnormalities such as leucopenia due to lymphopenia and/or neutropenia. Confirmation of ECoV infection is provided by specific ECoV nucleic acid detection in faeces by quantitative PCR (qPCR) or demonstration of coronavirus antigen by immunohistochemistry or electron microscopy in intestinal biopsy material obtained ante or post mortem. The disease is generally self‐limiting and horses typically recover with symptomatic supportive care. Complications associated with disruption of the gastrointestinal barrier have been reported in some infected horses and include endotoxaemia, septicaemia and hyperammonaemia‐associated encephalopathy. Although specific immunoprophylactic measures have been shown to be effective in disease prevention for closely‐related coronaviruses such as bovine coronavirus (BCoV), such strategies have yet not been investigated for horses and disease prevention is limited to basic biosecurity protocols. This article reviews current knowledge concerning the aetiology, epidemiology, clinical signs, diagnosis, pathology, treatment and prevention of ECoV infection in adult horses. |
35 | v3euzmj8 | What new public datasets are available related to COVID-19? | Keep genome data freely accessible |
5 | u4bgqwlw | what drugs have been active against SARS-CoV or SARS-CoV-2 in animal studies? | Comparative computational analysis of SARS-CoV-2 nucleocapsid protein epitopes in taxonomically related coronaviruses Abstract Several research lines are currently ongoing to address the multitude of facets of the pandemic COVID-19. In line with the One-Health concept, extending the target of the studies to the animals which humans are continuously interacting with may favor a better understanding of the SARS-CoV-2 biology and pathogenetic mechanisms; thus, helping to adopt the most suitable containment measures. The last two decades have already faced severe manifestations of the coronavirus infection in both humans and animals, thus, circulating epitopes from previous outbreaks might confer partial protection from SARS-CoV-2 infections. In the present study, we provide an in-silico survey of the major nucleocapsid protein epitopes and compare them with the homologues of taxonomically-related coronaviruses with tropism for animal species that are closely inter-related with the human beings population all over the world. Protein sequence alignment provides evidence of high sequence homology for some of the investigated proteins. Moreover, structural epitope mapping by homology modelling revealed a potential immunogenic value also for specific sequences scoring a lower identity with SARS-CoV-2 nucleocapsid proteins. These evidence provide a molecular structural rationale for a potential role in conferring protection from SARS-CoV-2 infection and identifying potential candidates for the development of diagnostic tools and prophylactic-oriented strategies. |
7 | pbuevs5v | are there serological tests that detect antibodies to coronavirus? | A Review: Does Complement or the Contact System Have a Role in Protection or Pathogenesis of COVID-19? INTRODUCTION: COVID-19 presentation may include a profound increase in cytokines and associated pneumonia, rapidly progressing to acute respiratory distress syndrome (ARDS). This so-called cytokine storm often leads to refractory edema, respiratory arrest, and death. At present, anti-IL-6, antiviral therapy, convalescent plasma, hydroxychloroquine, and azithromycin among others are being investigated as potential treatments for COVID-19. As the disease etiology and precise therapeutic interventions are still not definitively defined, we wanted to review the roles that complement and the contact system may have in either the treatment or pathogenesis of the disease. METHODS: We searched the recent literature (PubMed) on complement and coronavirus; contact system and coronavirus; bradykinin and coronavirus; and angiotensin receptor and coronavirus. The manuscript complies with ethics guidelines and was deemed exempt from institutional review board approval according to Human Subjects Protection Office guidelines. RESULTS: Mouse models are available for the study of coronavirus and complement. Although complement is effective in protecting against many viruses, it does not seem to be protective against coronavirus. C3 knockout mice infected with SARS-CoV had less lung disease than wild-type mice, suggesting that complement may play a role in coronavirus pathogenesis. Some evidence suggests that the observed pulmonary edema may be bradykinin-induced and could be the reason that corticosteroids, antihistamines, and other traditional interventions for edema are not effective. Angiotensin-converting enzyme 2 (ACE2) is a co-receptor for SARS-CoV-2, and studies thus far have not concluded a benefit or risk associated with the use of either ACE-inhibitors or angiotensin receptor antagonists. SUMMARY: Activation of complement and the contact system, through generation of bradykinin, may play a role in the SARS-CoV-2-induced pulmonary edema, and our search suggests that further work is necessary to confirm our suspicions. |
40 | p4mhvogk | What are the observed mutations in the SARS-CoV-2 genome and how often do the mutations occur? | Mitochondrial mutations restricting spontaneous translational frameshift suppression in the yeast Saccharomyces cerevisiae The +1 frameshift mutation, M5631, which is located in the gene (oxi1) for cytochrome c oxidase II (COXII) of the yeast mitochondrial genome, is suppressed spontaneously to a remarkably high extent (20%–30%). The full-length wild-type COXII produced as a result of suppression allows the mutant strain to grow with a "leaky" phenotype on non-fermentable medium. In order to elucidate the factors and interactions involved in this translational suppression, the strain with the frameshift mutation was mutated by MnCl(2) treatment and a large number of mutants showing restriction of the suppression were isolated. Of 20 mutants exhibiting a strong, restricted, respiration-deficient (RD) phenotype, 6 were identified as having mutations in the mitochondrial genome. Furthermore, genetic analyses mapped one mutation to the vicinity of the gene for tRNA(Pro) and two others to a region of the tRNA cluster where two-thirds of all mitochondrial tRNA genes are encoded. The degree of restriction of the spontaneous frameshift suppression was characterized at the translational level by in vivo (35)S-labeling of the mitochondrial translational products and immunoblotting. These results showed that in some of these mutant strains the frameshift suppression product is synthesized to the same extent as in the leaky parent strain. It is suggested that more than one +1 frame-shifted product is made as a result of suppression in these strains: one is as functional as the wild-type COXII, the other(s) is (are) non-functional and prevent leaky growth on non-fermentable medium. A possible mechanism for this heterogenous frameshift suppression is discussed. |
15 | w0ezhrhv | how long can the coronavirus live outside the body | ABSL-4 Aerobiology Biosafety and Technology at the NIH/NIAID Integrated Research Facility at Fort Detrick The overall threat of a viral pathogen to human populations is largely determined by the modus operandi and velocity of the pathogen that is transmitted among humans. Microorganisms that can spread by aerosol are considered a more challenging enemy than those that require direct body-to-body contact for transmission, due to the potential for infection of numerous people rather than a single individual. Additionally, disease containment is much more difficult to achieve for aerosolized viral pathogens than for pathogens that spread solely via direct person-to-person contact. Thus, aerobiology has become an increasingly necessary component for studying viral pathogens that are naturally or intentionally transmitted by aerosol. The goal of studying aerosol viral pathogens is to improve public health preparedness and medical countermeasure development. Here, we provide a brief overview of the animal biosafety level 4 Aerobiology Core at the NIH/NIAID Integrated Research Facility at Fort Detrick, Maryland, USA. |
46 | 8uteqvl2 | what evidence is there for dexamethasone as a treatment for COVID-19? | Potential benefits and risks of omega-3 fatty acids supplementation to patients with COVID-19 Studies have shown that infection, excessive coagulation, cytokine storm, leukopenia, lymphopenia, hypoxemia and oxidative stress have also been observed in critically ill Severe Acute Respiratory Syndrome coronavirus 2 (SARS-CoV-2) patients in addition to the onset symptoms. There are still no approved drugs or vaccines. Dietary supplements could possibly improve the patient's recovery. Omega-3 fatty acids, specifically eicosapentaenoic acid (EPA) and docosahexaenoic acid (DHA), present an anti-inflammatory effect that could ameliorate some patients need for intensive care unit (ICU) admission. EPA and DHA replace arachidonic acid (ARA) in the phospholipid membranes. When oxidized by enzymes, EPA and DHA contribute to the synthesis of less inflammatory eicosanoids and specialized pro-resolving lipid mediators (SPMs), such as resolvins, maresins and protectins. This reduces inflammation. In contrast, some studies have reported that EPA and DHA can make cell membranes more susceptible to non-enzymatic oxidation mediated by reactive oxygen species, leading to the formation of potentially toxic oxidation products and increasing the oxidative stress. Although the inflammatory resolution improved by EPA and DHA could contribute to the recovery of patients infected with SARS-CoV-2, Omega-3 fatty acids supplementation cannot be recommended before randomized and controlled trials are carried out. |
25 | pnw7nnzh | which biomarkers predict the severe clinical course of 2019-nCOV infection? | Initial Clinical Impressions of the Critical Care of COVID-19 Patients in Seattle, New York City, and Chicago Since the first recognition of a cluster of novel respiratory viral infections in China in late December 2019, intensivists in the United States have watched with growing concern as infections with the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) virus―now named Coronavirus Disease of 2019 (COVID-19)―have spread to hospitals in the United States. Because COVID-19 is extremely transmissible and can progress to a severe form of respiratory failure, the potential to overwhelm available critical care resources is high and critical care management of COVID-19 patients has been thrust into the spotlight. COVID-19 arrived in the United States in January and, as anticipated, has dramatically increased the usage of critical care resources. Three of the hardest-hit cities have been Seattle, New York City, and Chicago with a combined total of over 14,000 cases as of March 23, 2020. In this special article, we describe initial clinical impressions of critical care of COVID-19 in these areas, with attention to clinical presentation, laboratory values, organ system effects, treatment strategies, and resource management. We highlight clinical observations that align with or differ from already published reports. These impressions represent only the early empiric experience of the authors and are not intended to serve as recommendations or guidelines for practice, but rather as a starting point for intensivists preparing to address COVID-19 when it arrives in their community. |
5 | e9uhe5z2 | what drugs have been active against SARS-CoV or SARS-CoV-2 in animal studies? | COVID-19 preclinical models: human angiotensin-converting enzyme 2 transgenic mice Coronavirus disease 2019 (COVID-19) is a declared pandemic that is spreading all over the world at a dreadfully fast rate. Severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2), the pathogen of COVID-19, infects the human body using angiotensin-converting enzyme 2 (ACE2) as a receptor identical to the severe acute respiratory syndrome (SARS) pandemic that occurred in 2002–2003. SARS-CoV-2 has a higher binding affinity to human ACE2 than to that of other species. Animal models that mimic the human disease are highly essential to develop therapeutics and vaccines against COVID-19. Here, we review transgenic mice that express human ACE2 in the airway and other epithelia and have shown to develop a rapidly lethal infection after intranasal inoculation with SARS-CoV, the pathogen of SARS. This literature review aims to present the importance of utilizing the human ACE2 transgenic mouse model to better understand the pathogenesis of COVID-19 and develop both therapeutics and vaccines. |
11 | 7kxtntj2 | what are the guidelines for triaging patients infected with coronavirus? | Spinal anaesthesia for patients with coronavirus disease 2019 and possible transmission rates in anaesthetists: retrospective, single-centre, observational cohort study BACKGROUND: The safety of performing spinal anaesthesia for both patients and anaesthetists alike in the presence of active infection with the novel coronavirus disease 2019 (COVID-19) is unclear. Here, we report the clinical characteristics and outcomes for both patients with COVID-19 and the anaesthetists who provided their spinal anaesthesia. METHODS: Forty-nine patients with radiologically confirmed COVID-19 for Caesarean section or lower-limb surgery undergoing spinal anaesthesia in Zhongnan Hospital, Wuhan, China participated in this retrospective study. Clinical characteristics and perioperative outcomes were recorded. For anaesthesiologists exposed to patients with COVID-19 by providing spinal anaesthesia, the level of personal protective equipment (PPE) used, clinical outcomes (pulmonary CT scans), and confirmed COVID-19 transmission rates (polymerase chain reaction [PCR]) were reviewed. RESULTS: Forty-nine patients with COVID-19 requiring supplementary oxygen before surgery had spinal anaesthesia (ropivacaine 0.75%), chiefly for Caesarean section (45/49 [91%]). Spinal anaesthesia was not associated with cardiorespiratory compromise intraoperatively. No patients subsequently developed severe pneumonia. Of 44 anaesthetists, 37 (84.1%) provided spinal anaesthesia using Level 3 PPE. Coronavirus disease 2019 infection was subsequently confirmed by PCR in 5/44 (11.4%) anaesthetists. One (2.7%) of 37 anaesthetists who wore Level 3 PPE developed PCR-confirmed COVID-19 compared with 4/7 (57.1%) anaesthetists who had Level 1 protection in the operating theatre (relative risk reduction: 95.3% [95% confidence intervals: 63.7–99.4]; P<0.01). CONCLUSIONS: Spinal anaesthesia was delivered safely in patients with active COVID-19 infection, the majority of whom had Caesarean sections. Level 3 PPE appears to reduce the risk of transmission to anaesthetists who are exposed to mildly symptomatic surgical patients. |
28 | coryaz2s | what evidence is there for the value of hydroxychloroquine in treating Covid-19? | Broad spectrum antiviral remdesivir inhibits human endemic and zoonotic deltacoronaviruses with a highly divergent RNA dependent RNA polymerase Abstract The genetically diverse Orthocoronavirinae (CoV) family is prone to cross species transmission and disease emergence in both humans and livestock. Viruses similar to known epidemic strains circulating in wild and domestic animals further increase the probability of emergence in the future. Currently, there are no approved therapeutics for any human CoV presenting a clear unmet medical need. Remdesivir (RDV, GS-5734) is a monophosphoramidate prodrug of an adenosine analog with potent activity against an array of RNA virus families including Filoviridae, Paramyxoviridae, Pneumoviridae, and Orthocoronavirinae, through the targeting of the viral RNA dependent RNA polymerase (RdRp). We developed multiple assays to further define the breadth of RDV antiviral activity against the CoV family. Here, we show potent antiviral activity of RDV against endemic human CoVs OC43 (HCoV-OC43) and 229E (HCoV-229E) with submicromolar EC50 values. Of known CoVs, the members of the deltacoronavirus genus have the most divergent RdRp as compared to SARS- and MERS-CoV and both avian and porcine members harbor a native residue in the RdRp that confers resistance in beta-CoVs. Nevertheless, RDV is highly efficacious against porcine deltacoronavirus (PDCoV). These data further extend the known breadth and antiviral activity of RDV to include both contemporary human and highly divergent zoonotic CoV and potentially enhance our ability to fight future emerging CoV. |
37 | my16g91c | What is the result of phylogenetic analysis of SARS-CoV-2 genome sequence? | Severe acute respiratory syndrome (SARS)—paradigm of an emerging viral infection Abstract An acute and often severe respiratory illness emerged in southern China in late 2002 and rapidly spread to different areas of the Far East as well as several countries around the globe. When the outbreak of this apparently novel infectious disease termed severe acute respiratory syndrome (SARS) came to an end in July 2003, it had caused over 8000 probable cases worldwide and more than 700 deaths. Starting in March 2003, the World Health Organization (WHO) organised an unprecedented international effort by leading laboratories working together to find the causative agent. Little more than one week later, three research groups from this WHO-coordinated network simultaneously found evidence of a hitherto unknown coronavirus in SARS patients, using different approaches. After Koch's postulates had been fulfilled, WHO officially declared on 16 April 2003 that this virus never before seen in humans is the cause of SARS. Ever since, progress around SARS-associated coronavirus (SARS-CoV) has been swift. Within weeks of the first isolate being obtained, its complete genome was sequenced. Diagnostic tests based on the detection of SARS-CoV RNA were developed and made available freely and widely; nevertheless the SARS case definition still remains based on clinical and epidemiological criteria. The agent's environmental stability, methods suitable for inactivation and disinfection, and potential antiviral compounds have been studied, and development of vaccines and immunotherapeutics is ongoing. Despite its grave consequences in humanitarian, political and economic terms, SARS may serve as an example of how much can be achieved through a well-coordinated international approach, combining the latest technological advances of molecular virology with more "traditional" techniques carried out to an excellent standard. |
44 | q4jn5h00 | How much impact do masks have on preventing the spread of the COVID-19? | COVID-19 Deaths: Which Explanatory Variables Matter the Most? As Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2) spreads around the World, many questions about the disease are being answered; however, many more remain poorly understood. Although the situation is rapidly evolving, with datasets being continually corrected or updated, it is crucial to understand what factors may be driving transmission through different populations. While studies are beginning to highlight specific parameters that may be playing a role, few have attempted to thoroughly estimate the relative importance of these disparate variables that likely include: climate, population demographics, and imposed state interventions. In this report, we compiled a database of more than 28 potentially explanatory variables for each of the 50 U.S. states through early May 2020. Using a combination of traditional statistical and modern machine learning approaches, we identified those variables that were the most statistically significant, and, those that were the most important. These variables were chosen to be fiduciaries of a range of possible drivers for COVID-19 deaths in the USA. We found that population-weighted density (PWD), some "stay at home" metrics, monthly temperature and precipitation, race/ethnicity, and chronic low respiratory death rate, were all statistically significant. Of these, PWD and mobility metrics dominated. This suggests that the biggest impact on COVID-19 deaths was, at least initially, a function of where you lived, and not what you did. However, clearly, increasing social distancing has the net effect of (at least temporarily) reducing the effective PWD. Our results strongly support the idea that the loosening of "lock-down" orders should be tailored to the local PWD. In contrast to these variables, while still statistically significant, race/ethnicity, health, and climate effects could only account for a few percent of the variability in deaths. Where associations were anticipated but were not found, we discuss how limitations in the parameters chosen may mask a contribution that might otherwise be present. |
11 | c7gklo23 | what are the guidelines for triaging patients infected with coronavirus? | Essential care of critical illness must not be forgotten in the COVID-19 pandemic |
32 | xy7w8hbz | Does SARS-CoV-2 have any subtypes, and if so what are they? | Characterization of the receptor-binding domain (RBD) of 2019 novel coronavirus: implication for development of RBD protein as a viral attachment inhibitor and vaccine The outbreak of Coronavirus Disease 2019 (COVID-19) has posed a serious threat to global public health, calling for the development of safe and effective prophylactics and therapeutics against infection of its causative agent, severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), also known as 2019 novel coronavirus (2019-nCoV). The CoV spike (S) protein plays the most important roles in viral attachment, fusion and entry, and serves as a target for development of antibodies, entry inhibitors and vaccines. Here, we identified the receptor-binding domain (RBD) in SARS-CoV-2 S protein and found that the RBD protein bound strongly to human and bat angiotensin-converting enzyme 2 (ACE2) receptors. SARS-CoV-2 RBD exhibited significantly higher binding affinity to ACE2 receptor than SARS-CoV RBD and could block the binding and, hence, attachment of SARS-CoV-2 RBD and SARS-CoV RBD to ACE2-expressing cells, thus inhibiting their infection to host cells. SARS-CoV RBD-specific antibodies could cross-react with SARS-CoV-2 RBD protein, and SARS-CoV RBD-induced antisera could cross-neutralize SARS-CoV-2, suggesting the potential to develop SARS-CoV RBD-based vaccines for prevention of SARS-CoV-2 and SARS-CoV infection. |
38 | 64in4bei | What is the mechanism of inflammatory response and pathogenesis of COVID-19 cases? | Coronavirus Disease 2019 (COVID-19) and Cardiac Injury. |
21 | 7qpleke5 | what are the mortality rates overall and in specific populations | Racial Inequalities in Mortality from Coronavirus: The Tip of the Iceberg |
37 | ahifxfhn | What is the result of phylogenetic analysis of SARS-CoV-2 genome sequence? | Sequence analysis of the S1 glycoprotein gene of infectious bronchitis viruses: identification of a novel phylogenetic group in Korea Twelve Korean infectious bronchitis viruses (IBVs) were isolated in the field from chickens suspected of being carriers of infectious bronchitis between 2001 and 2003. The S1 glycoprotein genes of these IBV isolates were amplified by reverse transcriptase-polymerase chain reaction (RT-PCR) and analyzed by restriction fragment length polymorphism (RFLP) analysis. These Korean IBV isolates were classified into three groups according to their RFLP patterns obtained using the restriction enzyme HaeIII. Half of the twelve isolates were similar to the KM91 RFLP pattern, which is a common pattern in Korea. Three more isolates were related to the Arkansas strain pattern, but with some unique variations. The other three viruses showed variant RFLP patterns. For a comparison with the published sequences for non-Korean IBV strains, amplified PCR products from the twelve isolates were cloned and sequenced. The Korean IBV field isolates had 71.2-99.7% nucleotide sequence homology with each other and 45.9-80.7% nucleotide sequence homology with non-Korean IBV strains. With respect to the deduced amino acid sequence, the Korean IBV isolates had 71.5-99.3% similarity with each other and 44.9-80.3% similarity with non-Korean IBV strains. Phylogenetic tree analysis revealed that some of the IBV isolates appear to belong to a new group, different from the non-Korean IBV strains or from previously isolated Korean IBV strains. Specifically, the new Korean IBV isolates K10217-03, K3-3 and K1255-03 represented a separate group. These findings suggest that the Korean IBVs appear to be continuously evolving. |
15 | u7tz6xzz | how long can the coronavirus live outside the body | COVID-19 Outbreak: An Overview BACKGROUND: In late December 2019, Chinese health authorities reported an outbreak of pneumonia of unknown origin in Wuhan, Hubei Province. SUMMARY: A few days later, the genome of a novel coronavirus was released (http://virological.org/t/novel-2019-coronavirus-genome/319; Wuhan-Hu-1, GenBank accession No. MN908947) and made publicly available to the scientific community. This novel coronavirus was provisionally named 2019-nCoV, now SARS-CoV-2 according to the Coronavirus Study Group of the International Committee on Taxonomy of Viruses. SARS-CoV-2 belongs to the Coronaviridae family, Betacoronavirus genus, subgenus Sarbecovirus. Since its discovery, the virus has spread globally, causing thousands of deaths and having an enormous impact on our health systems and economies. In this review, we summarize the current knowledge about the epidemiology, phylogenesis, homology modeling, and molecular diagnostics of SARS-CoV-2. KEY MESSAGES: Phylogenetic analysis is essential to understand viral evolution, whereas homology modeling is important for vaccine strategies and therapies. Highly sensitive and specific diagnostic assays are key to case identification, contact tracing, identification of the animal source, and implementation of control measures. |
30 | bz3i0q7a | is remdesivir an effective treatment for COVID-19 | Data Monitoring for the Chinese Clinical Trials of Remdesivir in Treating Patients with COVID-19 During the Pandemic Crisis Two phase-III, double-blind, randomized clinical trials of remdesivir plus SOC (standard of care) versus placebo plus SOC have been conducted in Wuhan hospitals by Chinese investigators during the urgent COVID-19 epidemic [ClincalTrials.gov NCT04257656 and NCT04252664]. These trials have been highly anticipated worldwide. We expect investigators of the trials will soon report the clinical and laboratory findings from the medical perspective. This manuscript provides documentary style information on the process of monitoring key data and making recommendations to the sponsor and investigators based on analytical insights when dealing with the emergent situation from the statistical viewpoint. Having monitored data sequentially from 237 patients, we comment on the strength and weakness of the study design and suggest the treatment effect of remdesivir on severe COVID-19 cases. Our experience with using the Dynamic Data Monitoring (DDM) tool has demonstrated its efficiency and reliability in supporting DSMB's instantaneous review of essential data during the emergent situation. DDM, when used properly by disciplined statisticians, has shown its capability of exploring the trial data flexibly and, in the meantime, protecting the trial's scientific integrity. |
47 | o90k48vy | what are the health outcomes for children who contract COVID-19? | Characteristics of Hospitalized Pediatric COVID-19 Cases - Chicago, Illinois, March - April 2020. BACKGROUND To date, no report on COVID-19 pediatric patients in a large urban center with data on underlying comorbidities and co-infection for hospitalized cases has been published. METHODS Case series of Chicago COVID-19 patients aged 0-17 years reported to Chicago Department of Public Health (CDPH) from 3/5/20-4/8/20. Enhanced case investigation performed. Chi-square and Wilcoxon two-sample tests to compare characteristics among hospitalized and non-hospitalized cases. RESULTS During March 5-April 8, 2020, 6369 lab-confirmed cases of COVID-19 were reported to CDPH; 64 (1.0%) were among children 0-17 years. Ten patients (16%) were hospitalized, seven (70%) required intensive care (ICU); median length of hospitalization 4 days (range: 1-14). Reported fever and dyspnea were significantly higher in hospitalized patients compared to non-hospitalized patients (9/10 vs. 28/54, p = 0.04 and 7/10 vs. 10/54, p = 0.002, respectively). Hospitalized patients were significantly younger than non-hospitalized patients (median, 3.5 years vs. 12 years; p = 0.03) and all either had an underlying comorbidity or co-infection. Among the 34 unique households with multiple laboratory-confirmed infections, median number of laboratory-confirmed infections was 2 (range: 2-5), and 31 (91%) households had at least one COVID-19 infected adult. For 15 households with available data to assess transmission, 11 (73%) were adult-to-child, 2 (13%) child-to-child, and 2 (13%) child-to-adult. CONCLUSIONS Enhanced case investigation of hospitalized patients revealed that underlying comorbidities and co-infection might have contributed to severe disease. Given frequency of household transmission, healthcare providers should consider alternative dispositional planning for affected families of children living with comorbidities. |
43 | i5b0k41k | How has the COVID-19 pandemic impacted violence in society, including violent crimes? | Challenges in maintaining treatment services for people who use drugs during the COVID-19 pandemic The impact of COVID-19 across health services, including treatment services for people who use drugs, is emerging but likely to have a high impact. Treatment services for people who use drugs provide essential treatment services including opiate agonist treatment and needle syringe programmes alongside other important treatment programmes across all substance types including withdrawal and counselling services. Drug and alcohol hospital consultation-liaison clinicians support emergency departments and other services provided in hospital settings in efficiently managing patients who use drugs and present with other health problems. COVID-19 will impact on staff availability for work due to illness. Patients may require home isolation and quarantine periods. Ensuring ongoing supply of opiate treatment during these periods will require significant changes to how treatment is provided. The use of monthly depot buprenorphine as well as moving from a framework of supervised dosing will be required for patients on sublingual buprenorphine and methadone. Ensuring ready access to take-home naloxone for patients is crucial to reduce overdose risks. Delivery of methadone and buprenorphine to the homes of people with confirmed COVID-19 infections is likely to need to occur to support home isolation. People who use drugs are likely to be more vulnerable during the COVID-19 epidemic, due to poorer health literacy and stigma and discrimination towards this group. People who use drugs may prioritise drug use above other health concerns. Adequate supply of clean injecting equipment is important to prevent outbreaks of blood-borne viruses. Opiate users may misinterpret SARS-CoV2 symptoms as opiate withdrawal and manage this by using opioids. Ensuring people who use drugs have access to drug treatment as well as access to screening and testing for SARS-CoV2 where this is indicated is important. |
25 | rcxctwhv | which biomarkers predict the severe clinical course of 2019-nCOV infection? | Cardiovascular disease as a biomarker for an increased risk of COVID-19 infection and related poor prognosis |
49 | 0002xs6a | do individuals who recover from COVID-19 show sufficient immune response, including antibody levels and T-cell mediated immunity, to prevent re-infection? | The Father-Daughter Dinner Dance: A Waltz With Ethics and COVID-19 Commentary on "The Father-Daughter Dinner Dance: A Waltz With Ethics and COVID-19" |
36 | bzvaqu08 | What is the protein structure of the SARS-CoV-2 spike? | Structural and Functional Basis of SARS-CoV-2 Entry by Using Human ACE2 The recent emergence of a novel coronavirus (SARS-CoV-2) in China has caused significant public health concerns. Recently, ACE2 was reported as an entry receptor for SARS-CoV-2. In this study, we present the crystal structure of the C-terminal domain of SARS-CoV-2 (SARS-CoV-2-CTD) spike (S) protein in complex with human ACE2 (hACE2), which reveals a hACE2-binding mode similar overall to that observed for SARS-CoV. However, atomic details at the binding interface demonstrate that key residue substitutions in SARS-CoV-2-CTD slightly strengthen the interaction and lead to higher affinity for receptor binding than SARS-RBD. Additionally, a panel of murine monoclonal antibodies (mAbs) and polyclonal antibodies (pAbs) against SARS-CoV-S1/receptor-binding domain (RBD) were unable to interact with the SARS-CoV-2 S protein, indicating notable differences in antigenicity between SARS-CoV and SARS-CoV-2. These findings shed light on the viral pathogenesis and provide important structural information regarding development of therapeutic countermeasures against the emerging virus. |
12 | favf1hh3 | what are best practices in hospitals and at home in maintaining quarantine? | Medical Ethics in Disasters Disasters frequently create demands that outstrip available existing medical and societal resources. This may be particularly problematic for giving medical care, because disasters may destroy the infrastructures necessary to both provide patients care and keep new health problems from emerging. Disaster may, for example, not only strike care providers and hospital facilities directly; they may decimate communities' capacities to provide food to the population and carry out critical waste disposal services. All these effects may be most important to policymakers and care providers deciding triage priorities during disasters. Referring to just these two examples, food and waste disposal services, for instance, care providers should treat first not only other care providers, who can, then, take care of others, but food preparers and waste disposal personnel, likewise, to save the most lives. These two examples are just a few among many that warrant priority for this same reason. |
25 | m95bmi9t | which biomarkers predict the severe clinical course of 2019-nCOV infection? | Potential Rapid Diagnostics, Vaccine and Therapeutics for 2019 Novel Coronavirus (2019-nCoV): A Systematic Review 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. |
15 | tya0rvxk | how long can the coronavirus live outside the body | Gastrointestinal Disease in Exotic Small Mammals Abstract Exotic small mammal medicine is a relatively new specialty area within veterinary medicine. Ferrets, rabbits, and rodents have long been used as animal models in human medical research investigations, resulting in a body of basic anatomic and physiologic information that can be used by veterinarians treating these species. Unfortunately, there is a paucity of veterinary articles that describe clinical presentation, diagnosis, and treatment options of gastrointestinal (GI) disease as it affects exotic small mammals. Although there is little reference material relating to exotic small mammal GI disease, patients are commonly presented to veterinary hospitals with digestive tract disorders. This article provides the latest information available for GI disease in ferrets (Helicobacter mustelae gastritis, inflammatory bowel disease [IBD], GI lymphoma, systemic coronavirus, coccidiosis, and liver disease), rabbits (GI motility disorders, liver lobe torsion, astrovirus, and coccidiosis), guinea pigs (gastric dilatation volvulus [GDV]), rats (Taenia taeniaeformis), and hamsters (Clostridium difficile). Both noninfectious diseases and emerging infectious diseases are reviewed as well as the most up-to-date diagnostics and treatment options. |
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