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7 | 7gfk554m | are there serological tests that detect antibodies to coronavirus? | SARS‐CoV‐2 Seroconversion in Humans: A Detailed Protocol for a Serological Assay, Antigen Production, and Test Setup In late 2019, cases of atypical pneumonia were detected in China. The etiological agent was quickly identified as a betacoronavirus (named SARS‐CoV‐2), which has since caused a pandemic. Several methods allowing for the specific detection of viral nucleic acids have been established, but these only allow detection of the virus during a short period of time, generally during acute infection. Serological assays are urgently needed to conduct serosurveys, to understand the antibody responses mounted in response to the virus, and to identify individuals who are potentially immune to re‐infection. Here we describe a detailed protocol for expression of antigens derived from the spike protein of SARS‐CoV‐2 that can serve as a substrate for immunological assays, as well as a two‐stage serological enzyme‐linked immunosorbent assay (ELISA). These assays can be used for research studies and for testing in clinical laboratories. © 2020 The Authors. Current Protocols in Microbiology published by Wiley Periodicals LLC. Basic Protocol 1: Mammalian cell transfection and protein purification Basic Protocol 2: A two‐stage ELISA for high‐throughput screening of human serum samples for antibodies binding to the spike protein of SARS‐CoV‐2 |
23 | 2eg3keqo | what kinds of complications related to COVID-19 are associated with hypertension? | Renin–angiotensin system inhibitors in the COVID-19 pandemic: consequences of antihypertensive drugs |
27 | nn1rgdw0 | what is known about those infected with Covid-19 but are asymptomatic? | Detection and isolation of asymptomatic individuals can make the difference in COVID-19 epidemic management Mathematical modeling of infectious diseases is a powerful tool for the design of management policies and a fundamental part of the arsenal currently deployed to deal with the COVID-19 pandemic. Here we present a compartmental model for the disease that can provide healthcare burden parameters allowing to infer possible containment and suppression strategies, explicitly including asymptomatic individuals. The main conclusion of our work is that efficient and timely detection and isolation of these asymptomatic individuals can have dramatic effects on the effective reproduction number and healthcare burden parameters. This intervention can provide a valuable tool complementary to other non-pharmaceutical interventions to contain the epidemic. |
38 | pruvl2l4 | What is the mechanism of inflammatory response and pathogenesis of COVID-19 cases? | The COVID-19 Pandemic during the Time of the Diabetes Pandemic: Likely Fraternal Twins? An altered immune response to pathogens has been suggested to explain increased susceptibility to infectious diseases in patients with diabetes. Recent evidence has documented several immunometabolic pathways in patients with diabetes directly related to the COVID-19 infection. This also seems to be the case for prediabetic subjects with proinflammatory insulin resistance syndrome accompanied with prothrombotic hyperinsulinemic and dysglycemic states. Patients with frank hyperglycemia, dysglycemia and/or hyperinsulinemia develop systemic immunometabolic inflammation with higher levels of circulating cytokines. This deleterious scenario has been proposed as the underlying mechanism enhancing a cytokine storm-like hyperinflammatory state in diabetics infected with severe COVID-19 triggering multi-organ failure. Compared with moderately affected COVID-19 patients, diabetes was found to be highly prevalent among severely affected patients suggesting that this non-communicable disease should be considered as a risk factor for adverse outcomes. The COVID-19 pandemic mirrors with the diabetes pandemic in many pathobiological aspects. Our interest is to emphasize the ties between the immunoinflammatory mechanisms that underlie the morbidity and lethality when COVID-19 meets diabetes. This review brings attention to two pathologies of highly complex, multifactorial, developmental and environmentally dependent manifestations of critical importance to human survival. Extreme caution should be taken with diabetics with suspected symptoms of COVID-19 infection. |
24 | as391ou8 | what kinds of complications related to COVID-19 are associated with diabetes | Early in the epidemic: impact of preprints on global discourse about COVID-19 transmissibility |
3 | lmmrnitr | will SARS-CoV2 infected people develop immunity? Is cross protection possible? | Partial unlock model for COVID-19 or similar pandemic averts medical and economic disaster Data as of March 29, 2020 show that the flattening strategy for COVID-19 in the U.S. is working so well that a clean removal of social distancing (aka unlock) at any time in 2020 will produce a renewed catastrophe, overloading the healthcare system. Leaving the economy locked down for a long time is its own catastrophe. An SIR-type model with clear parameters suitable for public information, and both tracking and predictive capabilities which learns disease spread characteristics rapidly as policy changes, suggests that a solution to the problem is a partial unlock. Case load can be managed so as not to exceed critical resources such as ventilators, yet allow enough people to get sick that herd immunity develops and a full unlock can be achieved in as little as five weeks from beginning of implementation. The partial unlock could be for example 3 full working days per week. Given that not all areas or individuals will respond, and travel and public gatherings are still unlikely, the partial unlock might be 5 full working days per week. The model can be regionalized easily, and by expediting the resolution of the pandemic in the U.S. medical equipment and volunteers, many of them with already acquired immunity, can be made available to other countries. |
47 | 4jgjw56d | what are the health outcomes for children who contract COVID-19? | Psychiatric Training During a Global Pandemic: How COVID-19 Has Affected Clinical Care, Teaching, and Trainee Well-Being. The COVID-19 pandemic has altered many aspects of personal and professional life, including how psychiatry is practiced and how trainees are taught. This Open Forum outlines the challenges faced by psychiatric training directors in adult as well as child and adolescent psychiatry in meeting the educational needs of trainees amid this international crisis. Prioritizing trainee protection and education as well as high-quality treatment for patients, the authors discuss effective communication strategies, rapid telepsychiatry expansion into clinical practice, curricular adjustments, and the importance of well-being. This Open Forum concludes with reflections and considerations for training directors as they prepare for subsequent stages of the COVID-19 pandemic. |
43 | 2nnq5uf0 | How has the COVID-19 pandemic impacted violence in society, including violent crimes? | Family violence and COVID-19: Increased vulnerability and reduced options for support |
27 | 6qsk6mij | what is known about those infected with Covid-19 but are asymptomatic? | Asymptomatic Middle East Respiratory Syndrome Coronavirus (MERS-CoV) infection: Extent and implications for infection control: A systematic review Abstract Background The Middle East Respiratory Syndrome Coronavirus (MERS-CoV) emerged in 2012 and attracted an international attention as the virus caused multiple healthcare associated outbreaks. There are reports of the role of asymptomatic individuals in the transmission of MERS-CoV, however, the exact role is not known. Method The MEDLINE/PubMed and Scopus databases were searched for relevant papers published till August 2018 describing asymptomatic MERS-CoV infection. Results A total of 10 papers were retrieved and included in the final analysis and review. The extent of asymptomatic MERS infection had increased with change in the policy of testing asymptomatic contacts. In early cases in April 2012–October 2013, 12.5% were asymptomatic among 144 PCR laboratory-confirmed MERS-CoV cases while in 2014 the proportion rose to 25.1% among 255 confirmed cases. The proportion of asymptomatic cases reported among pediatric confirmed MERS-CoV cases were higher (41.9%–81.8%). Overall, the detection rate of MERS infection among asymptomatic contacts was 1-3.9% in studies included in this review. Asymptomatic individuals were less likely to have underlying condition compared to fatal cases. Of particular interest is that most of the identified pediatric cases were asymptomatic with no clear explanation. Conclusions The proportion of asymptomatic MERS cases were detected with increasing frequency as the disease progressed overtime. Those patients were less likely to have comorbid disease and may contribute to the transmission of the virus. |
28 | vyayyk50 | what evidence is there for the value of hydroxychloroquine in treating Covid-19? | Effectiveness of glucocorticoid therapy in patients with severe coronavirus disease 2019: protocol of a randomized controlled trial BACKGROUND: At the end of 2019, a novel coronavirus outbreak emerged in Wuhan, China, and its causative organism has been subsequently designated the 2019 novel coronavirus (2019-nCoV). The effectiveness of adjunctive glucocorticoid therapy in the management of 2019-nCoV-infected patients with severe lower respiratory tract infections is not clear, and warrants further investigation. METHODS: The present study will be conducted as an open-labeled, randomized, controlled trial. We will enrol 48 subjects from Chongqing Public Health Medical Center. Each eligible subject will be assigned to an intervention group (methylprednisolone via intravenous injection at a dose of 1–2 mg/kg/day for 3 days) or a control group (no glucocorticoid use) randomly, at a 1:1 ratio. Subjects in both groups will be invited for 28 days of follow-up which will be scheduled at four consecutive visit points. We will use the clinical improvement rate as our primary endpoint. Secondary endpoints include the timing of clinical improvement after intervention, duration of mechanical ventilation, duration of hospitalization, overall incidence of adverse events, as well as rate of adverse events at each visit, and mortality at 2 and 4 weeks. DISCUSSION: The present coronavirus outbreak is the third serious global coronavirus outbreak in the past two decades. Oral and parenteral glucocorticoids have been used in the management of severe respiratory symptoms in coronavirus-infected patients in the past. However, there remains no definitive evidence in the literature for or against the utilization of systemic glucocorticoids in seriously ill patients with coronavirus-related severe respiratory disease, or indeed in other types of severe respiratory disease. In this study, we hope to discover evidence either supporting or opposing the systemic therapeutic administration of glucocorticoids in patients with severe coronavirus disease 2019. TRIAL REGISTRATION: ClinicalTrials.gov, ChiCTR2000029386, http://www.chictr.org.cn/showproj.aspx?proj=48777. |
25 | nlavfnpt | which biomarkers predict the severe clinical course of 2019-nCOV infection? | COVID-19 infection induces readily detectable morphological and inflammation-related phenotypic changes in peripheral blood monocytes, the severity of which correlate with patient outcome Background: Excessive monocyte/macrophage activation with the development of a cytokine storm and subsequent acute lung injury, leading to acute respiratory distress syndrome (ARDS) is a feared consequence of infection with COVID-19. The ability to recognize and potentially intervene early in those patients at greatest risk of developing this complication could be of great clinical utility. Methods: We performed detailed flow cytometric analysis of peripheral blood samples from 28 COVID-19 patients treated at Xian No.8 Hospital and the First Affiliated Hospital of Xian Jiaotong University in early 2020 in an attempt to identify factors that could help predict severity of disease and patient outcome. Findings: While we did not detect significant differences in the number of monocytes between patients with COVID-19 and normal healthy individuals,we did identify significant morphological and functional differences, which are more pronounced in patients requiring prolonged hospitalization and ICU admission. Patients with COVID-19 have larger than normal monocytes, easily identified on forward scatter, side scatter analysis by routine flow cytometry,with the presence of a distinct population of monocytes with high forward scatter (FSC-high). On more detailed analysis, these FSC-high monocytes are CD11b+, CD14+, CD16+, CD68+, CD80+, CD163+, CD206+ and secrete IL-6, IL-10 and TNF-alpha, consistent with an inflammatory phenotype. Conclusions: The detection and serial monitoring of this subset of inflammatory monocytes using flow cytometry could be of great help in guiding the prognostication and treatment of patients with COVID-19 and merits further evaluation. |
18 | 3vwi5myc | what are the best masks for preventing infection by Covid-19? | Perioperative Management of Patients Infected with the Novel Coronavirus: Recommendation from the Joint Task Force of the Chinese Society of Anesthesiology and the Chinese Association of Anesthesiologists The outbreak of the new Coronavirus disease, COVID-19, has been involved in 77,262 cases in China as well as in 27 other countries as of February 24, 2020. Because the virus is novel to human beings, and there is no vaccine yet available, every individual is susceptible and can become infected. Healthcare workers are at high risk, and unfortunately, more than 3,000 healthcare workers in China have been infected. Anesthesiologists are among healthcare workers who are at an even higher risk of becoming infected because of their close contact with infected patients and high potential of exposure to respiratory droplets or aerosol from their patients' airways. In order to provide healthcare workers with updated recommendations on the management of patients in the perioperative setting as well as for emergency airway management outside of the operating room, the two largest anesthesia societies, the Chinese Society of Anesthesiology (CSA) and the Chinese Association of Anesthesiologists (CAA) have formed a task force to produce the recommendations. The task force hopes to help healthcare workers, particularly anesthesiologists, optimize the care of their patients and protect patients, healthcare workers, and the public from becoming infected. The recommendations were created mainly based on the practice and experience of anesthesiologists who provide care to patients in China. Therefore, adoption of these recommendations outside of China must be done with caution, and the local environment, culture, uniqueness of the healthcare system, and patients' needs should be considered. The task force will continuously update the recommendations and incorporate new information in future versions. |
9 | 3qswmt52 | how has COVID-19 affected Canada | Paucity and disparity of publicly available sex-disaggregated data for the COVID-19 epidemic hamper evidence-based decision-making COVID-19 has joined the long list of human disorders with sexually dimorphic expression. Increased lethality in men was evident in the first large reports from ChinaCDC and WHO-China, and the gender gap appeared even wider in the early Italian outbreak. Newspapers and scientific journals alike have commented on this finding and the preexisting conditions, biological processes, and gender role behavior differences that may underlie it. However, as for other diseases, and in spite of years of advocating for the collection of raw epidemiological data and the analysis of clinical trial data sets by sex, very little appeared to be released about sex differences in characteristics of the epidemics beyond infection and death rates, such as severity of disease, comorbidities, rate of recovery, length of hospital stay, or number of tests for the SARS-CoV-2 coronavirus. These data are critical not only for scientists to understand the pathophysiology of disease, but also to inform decision-making by countries and healthcare systems on how to prioritize testing and best allocate scarce resources and relief funds. Systematic analysis of official websites for the 20 countries and 6 US states reporting the highest number of cases on March 21, 2020, revealed a wide disparity in sex-disaggregated data made available to the public and scholars. Only a handful of the countries reported cases by sex separately. None of the other characteristics, including fatality rates, were stratified by sex at the time. Beyond suboptimal sex disaggregation, our analysis found a paucity of usable raw data sets and a generalized lack of standardization of captured data, making comparisons difficult. A second round of data capture in April found more complete, but even more disparate, information. Our analysis revealed a wide range of sex ratios among confirmed cases, which changed over time. In countries where a male-biased sex ratio was initially reported, the reported proportion of women among cases dramatically increased in under 3 weeks. In contrast, men were consistently over-represented in severe cases, intensive care admissions, and deaths. We also show that the sex ratio varies with age, with a complex pattern, reproduced across the 6 countries for which data were found. Accurate, peer-reviewed, statistical analysis of harmonized, sex-disaggregated data for other characteristics of epidemics, such as availability of testing, suspected source of infection, or comorbidities will be critical to understand where the observed disparities come from and to generate evidence-based recommendations for decision-making by institutions and governments around the world. |
11 | txt4jiy8 | what are the guidelines for triaging patients infected with coronavirus? | A Novel Triage Tool of Artificial Intelligence Assisted Diagnosis Aid System for Suspected COVID-19 pneumonia In Fever Clinics Currently, the prevention and control of COVID-19 outside Hubei province in China, and other countries has become more and more critically serious. We developed and validated a diagnosis aid model without CT images for early identification of suspected COVID-19 pneumonia (S-COVID-19-P) on admission in adult fever patients and made the validated model available via an online triage calculator. Patients admitted from Jan 14 to Feb 26, 2020 with the epidemiological history of exposure to COVID-19 were included [Model development (n = 132) and validation (n = 32)]. Candidate features included clinical symptoms, routine laboratory tests and other clinical information on admission. Features selection and model development were based on Lasso regression. The primary outcome is the development and validation of a diagnosis aid model for S-COVID-19-P early identification on admission. The development cohort contains 26 S-COVID-19-P and 7 confirmed COVID-19 pneumonia cases. The model performance in held-out testing set and validation cohort resulted in AUCs of 0.841 and 0.938, F-1 score of 0.571 and 0.667, recall of 1.000 and 1.000, specificity of 0.727 and 0.778, and the precision of 0.400 and 0.500. Based on this model, an optimized strategy for S-COVID-19-P early identification in fever clinics has also been designed. S-COVID-19-P could be identified early by a machine-learning model only used collected clinical information without CT images on admission in fever clinics with 100% recall score. The well performed and validated model has been deployed as an online triage tool, which is available at: https://intensivecare.shinyapps.io/COVID19/. |
6 | f085c7sz | what types of rapid testing for Covid-19 have been developed? | Utilization of the respiratory virus multiplex reverse transcription-polymerase chain reaction test for adult patients at a Korean tertiary care center BACKGROUND/AIMS: Respiratory viruses (RVs) are considered to be important respiratory pathogens in adult patients, and the multiplex reverse transcription-polymerase chain reaction (RT-PCR) test is used frequently in adult patients with respiratory infections. However, clinical data regarding utilization of the multiplex RT-PCR test for RVs are lacking. METHODS: We investigated the utilization of the multiplex RT-PCR test for RVs at Chung-Ang University Hospital in Seoul, Korea, between January 2012 and April 2013. RESULTS: During the study period, the multiplex RT-PCR test was performed for 291 adult patients. The test frequency was 4.9% of rapid influenza antigen detection tests and 0.8% of respiratory bacterial culture studies. A turnaround time of < 48 hours was observed in 25.9% of positive tests. Most of the tests were performed for admitted patients (97.9%) with a community-acquired infection (84.2%) during the flu season (82.5%). RVs were detected in 81 of 291 cases (27.8%). The RV positivity rates for community- and hospital-acquired infections did not differ (28.6% vs. 23.9%, p = 0.52). Of 166 patients with pneumonia, 44 (26.5%) had a viral infection. Among the patients with RV-associated pneumonia, an RV other than influenza was detected in 20 patients (45.4%). CONCLUSIONS: The multiplex RT-PCR test for RVs was infrequently performed at a tertiary care center, and the test results were often reported late. The test was most often performed for admitted adult patients with community-acquired infections during the flu season. The utilization of multiplex RT-PCR testing for RVs in current clinical practice should be improved. |
7 | 6kq92nlx | are there serological tests that detect antibodies to coronavirus? | Respiratory Barrier as a Safeguard and Regulator of Defense Against Influenza A Virus and Streptococcus pneumoniae The primary function of the respiratory system of gas exchange renders it vulnerable to environmental pathogens that circulate in the air. Physical and cellular barriers of the respiratory tract mucosal surface utilize a variety of strategies to obstruct microbe entry. Physical barrier defenses including the surface fluid replete with antimicrobials, neutralizing immunoglobulins, mucus, and the epithelial cell layer with rapidly beating cilia form a near impenetrable wall that separates the external environment from the internal soft tissue of the host. Resident leukocytes, primarily of the innate immune branch, also maintain airway integrity by constant surveillance and the maintenance of homeostasis through the release of cytokines and growth factors. Unfortunately, pathogens such as influenza virus and Streptococcus pneumoniae require hosts for their replication and dissemination, and prey on the respiratory tract as an ideal environment causing severe damage to the host during their invasion. In this review, we outline the host-pathogen interactions during influenza and post-influenza bacterial pneumonia with a focus on inter- and intra-cellular crosstalk important in pulmonary immune responses. |
18 | avzzo8ni | what are the best masks for preventing infection by Covid-19? | Respirators used by healthcare workers due to the COVID-19 outbreak increase end-tidal carbon dioxide and fractional inspired carbon dioxide pressure • As the requirement of personal protective equipment (PPE) has increased rapidly in a short time due to COVID-19, the compliance of the manufactured respirators with the standards seems to have been placed in the second plan. • Frequent use of PPE such as filtering facepiece respirators (FFRs) causes carbon dioxide re-breathing in healthcare workers during COVID-19 outbreak. • Even when resting, both expiratory and inspiratory carbon dioxide levels increase significantly with the use of PPE. • It should be kept in mind that healthcare workers may experience symptoms related to hypercapnia during their use of PPE. |
11 | gdzx3vlt | what are the guidelines for triaging patients infected with coronavirus? | Clinical characteristics of 182 pediatric COVID‐19 patients with different severities and allergic status BACKGROUND: The pandemic of coronavirus disease 2019 (COVID‐19) caused by severe acute respiratory syndrome coronavirus 2 (SARS‐CoV‐2) infection has made widespread impact recently. We aim to investigate the clinical characteristics of COVID‐19 children with different severities and allergic status. METHODS: Data extracted from the electronical medical records, including demographics, clinical manifestations, comorbidities, laboratory and immunological results and radiological images of 182 hospitalized COVID‐19 children were summarized and analyzed. RESULTS: The median age was 6 years old, ranging from 3 days to 15 years, and there were more boys (male‐female ratio about 2:1) within the studied 182 patients. Most of the children were infected by family members. Fever (43.4%) and dry cough (44.5%) were common symptoms, and gastrointestinal manifestations accounted for 11.0%, including diarrhea, abdominal discomfort and vomiting. 71.4% had abnormal chest computed tomography (CT) scan images, and typical signs of pneumonia were ground‐glass opacity and local patchy shadowing on admission. Laboratory results were mostly within normal ranges, and only a small ratio of lymphopenia (3.9%) and eosinopenia (29.5%) were observed. The majority (97.8%) of infected children were not severe, and 24 (13.2%) of them had asymptomatic infections. Compared to children without pneumonia(manifested as asymptomatic and acute upper respiratory infection), children with pneumonia were associated with higher percentages of the comorbidity history, symptoms of fever and cough, and increased levels of serum procalcitonin, alkaline phosphatase and serum interleukins (IL)‐2, IL‐4, IL‐6, IL‐10 and TNF‐α.There were no differences of treatments, duration of hospitalization, time from first positive to first negative nucleic acid testing and outcomes between children with mild pneumonia and without pneumonia. All the hospitalized COVID‐19 children had recovered except one death due to intussusception and sepsis. In 43 allergic children with COVID‐19, allergic rhinitis (83.7%) was the major disease, followed by drug allergy, atopic dermatitis, food allergy and asthma. Demographics and clinical features were not significantly different between allergic and non‐allergic groups. Allergic patients showed less increase in acute phase reactants, procalcitonin, D‐dimer and aspartate aminotransferase levels compared to all patients. Immunological profiles including circulating T, B and NK lymphocyte subsets, total immunoglobulin and complement levels and serum cytokines did not show any difference in allergic and pneumonia groups. Neither eosinophil counts nor serum total immunoglobulin E (IgE) levels showed a significant correlation with other immunological measures, such as other immunoglobulins, complements, lymphocyte subsets numbers and serum cytokine levels. CONCLUSION: Pediatric COVID‐19 patients tended to have a mild clinical course. Patients with pneumonia had higher proportion of fever and cough and increased inflammatory biomarkers than those without pneumonia. There was no difference between allergic and non‐allergic COVID‐19 children in disease incidence, clinical features, laboratory and immunological findings. Allergy was not a risk factor for developing and severity of SARS‐CoV‐2 infection and hardly influenced the disease course of COVID‐19 in children. |
32 | ot5pvtbl | Does SARS-CoV-2 have any subtypes, and if so what are they? | In vitro susceptibility of 10 clinical isolates of SARS coronavirus to selected antiviral compounds Abstract Effective antiviral agents are urgently needed to combat the possible return of severe acute respiratory syndrome (SARS). Commercial antiviral agents and pure chemical compounds extracted from traditional Chinese medicinal herbs were screened against 10 clinical isolates of SARS coronavirus by neutralisation tests with confirmation by plaque reduction assays. Interferon-beta-1a, leukocytic interferon-alpha, ribavirin, lopinavir, rimantadine, baicalin and glycyrrhizin showed antiviral activity. The two interferons were only active if the cell lines were pre-incubated with the drugs 16h before viral inoculation. Results were confirmed by plaque reduction assays. Antiviral activity varied with the use of different cell lines. Checkerboard assays for synergy were performed showing combinations of interferon beta-1a or leukocytic interferon-alpha with ribavirin are synergistic. Since the clinical and toxicity profiles of these agents are well known, they should be considered either singly or in combination for prophylaxis or treatment of SARS in randomised placebo controlled trials in future epidemics. |
12 | ehkht0mk | what are best practices in hospitals and at home in maintaining quarantine? | Factors influencing compliance with quarantine in Toronto during the 2003 SARS outbreak. The purpose of this study was to cull lessons from Toronto's experiences with large-scale quarantine during the outbreak of Severe Acute Respiratory Syndrome in early 2003. We focused on issues that affected the population's willingness to comply with quarantine. Information was acquired from interviews, telephone polling, and focus groups. Issues of quarantine legitimacy, criteria for quarantine, and the need to allow some quarantined healthcare workers to leave their homes to go to work were identified. Also important was the need to answer questions from people entering quarantine about the continuation of their wages, salaries, and other forms of income while they were not working, and about the means by which they would be supplied with groceries and other services necessary for daily living. The threat of enforcement had less effect on compliance than did the credibility of compliance-monitoring. Fighting boredom and other psychological stresses of quarantine, muting the forces of stigma against those in quarantine, and crafting and delivering effective and believable communications to a population of mixed cultures and languages also were critical. The need for officials to develop consistent quarantine policies, procedures, and public messages across jurisdictional boundaries was paramount. |
12 | kqntu6ej | what are best practices in hospitals and at home in maintaining quarantine? | Commentary on Ferguson, et al., "Impact of Non-pharmaceutical Interventions (NPIs) to Reduce COVID-19 Mortality and Healthcare Demand" A recent manuscript (Ferguson et al. in Impact of non-pharmaceutical interventions (NPIs) to reduce COVID-19 mortality and healthcare demand, Imperial College COVID-19 Response Team, London, 2020. https://www.imperial.ac.uk/media/imperial-college/medicine/sph/ide/gida-fellowships/Imperial-College-COVID19-NPI-modelling-16-03-2020.pdf) from Imperial College modelers examining ways to mitigate and control the spread of COVID-19 has attracted much attention. In this paper, we will discuss a coarse taxonomy of models and explore the context and significance of the Imperial College and other models in contributing to the analysis of COVID-19. |
22 | 7kidc16v | are cardiac complications likely in patients with COVID-19? | Novel coronavirus infection and pregnancy |
10 | nney9kuq | has social distancing had an impact on slowing the spread of COVID-19? | Public health interventions in India slowed the spread of COVID-19 epidemic dynamics Background The government of India implemented social distancing interventions to contain the COVID-19 epidemic. However, effects on epidemic dynamics are yet to be understood. Methods Rates of laboratory-confirmed COVID-19 infections per day and effective reproduction number (Rt) were estimated for 4 periods (Pre-lockdown and Lockdown Phases 1 to 3) according to nationally implemented phased interventions. Adoption of these interventions was estimated using Google mobility data. Estimates at the national level and for 12 Indian states most affected by COVID-19 are presented. Findings Daily case rates ranged from 0.03 to 30.05/10 million people across 4 discrete periods in India. From May 4-17, 2020, the National Capital Territory (NCT) of Delhi had the highest case rate (222/10 million people/day), whereas Kerala had the lowest (2.18/10 million/day). Average Rt was 1.99 (95% CI 1.93-2.06) for India; it ranged from 1.38 to 2.78, decreasing over time. Median mobility in India decreased in all contact domains, with the lowest being 21% in retail/recreation (95% CI 13-46%), except home which increased to 129% (95% CI 117-132%) compared to the 100% baseline value. Interpretation The Indian government imposed strict contact mitigation, followed by a phased relaxation, which slowed the spread of COVID-19 epidemic progression in India. The identified daily COVID-19 case rates and Rt will aid national and state governments in formulating ongoing COVID-19 containment plans. Furthermore, these findings may inform COVID-19 public health policy in developing countries with similar settings to India. Funding Non-funded. |
5 | 7cjm2yp0 | what drugs have been active against SARS-CoV or SARS-CoV-2 in animal studies? | Exploring the SARS-CoV-2 virus-host-drug interactome for drug repurposing Coronavirus Disease-2019 (COVID-19) is an infectious disease caused by the SARS-CoV-2 virus. It was first identified in Wuhan, China, and has since spread causing a global pandemic. Various studies have been performed to understand the molecular mechanisms of viral infection for predicting drug repurposing candidates. However, such information is spread across many publications and it is very time-consuming to access, integrate, explore, and exploit. We developed CoVex, the first interactive online platform for SARS-CoV-2 and SARS-CoV-1 host interactome exploration and drug (target) identification. CoVex integrates 1) experimentally validated virus-human protein interactions, 2) human protein-protein interactions and 3) drug-target interactions. The web interface allows user-friendly visual exploration of the virus-host interactome and implements systems medicine algorithms for network-based prediction of drugs. Thus, CoVex is an important resource, not only to understand the molecular mechanisms involved in SARS-CoV-2 and SARS-CoV-1 pathogenicity, but also in clinical research for the identification and prioritization of candidate therapeutics. We apply CoVex to investigate recent hypotheses on a systems biology level and to systematically explore the molecular mechanisms driving the virus life cycle. Furthermore, we extract and discuss drug repurposing candidates involved in these mechanisms. CoVex renders COVID-19 drug research systems-medicine-ready by giving the scientific community direct access to network medicine algorithms integrating virus-host-drug interactions. It is available at https://exbio.wzw.tum.de/covex/. |
39 | 1hfxju5f | What is the mechanism of cytokine storm syndrome on the COVID-19? | Use of anakinra in severe COVID-19: a case report Abstract Coronavirus Disease 19 is a global healthcare emergency with high lethality rate. Relevant inflammatory cytokine storm is associated with severity of disease and IL1 inhibition is a cornerstone treatment for hyperinflammatory diseases. We present here the case of a patient with critical COVID-19 successfully treated with IL-1 receptor antagonist (anakinra). |
43 | 3zdj0x2w | How has the COVID-19 pandemic impacted violence in society, including violent crimes? | COVID-19 pandemic in France: health emergency experiences from the field AIM: This paper describes the situation regarding COVID-19 emergency in France as of early May 2020, the main policies to fight this virus, and the roles and responsibilities of nurses regarding their work at this time, as well as the challenges facing the profession. BACKGROUND: Europe continues to be affected by the COVID-19 pandemic. At the time of writing France was the fourth country with the highest number of detected cases and cumulative deaths. SOURCES OF EVIDENCE: Websites of the World Health Organization, French Government, French Agency of Public Health, French National Council of Nurses and ClinicalTrials.gov database, as well as the experiences of the authors. DISCUSSION: The history of the development of the pandemic in France helps explain the establishment of the state of health emergency and containment of the population. Many decisions made had undesirable repercussions, particularly in terms of intra-family violence, mental health disorders and the renunciation of care. Hospitals and primary care services, with significant investment by nurses, played a key role in the care of persons with and without COVID-19. CONCLUSION: France has suffered a very high toll in terms of COVID-19 morbidity and mortality, and effects on its people, health systems and health professionals, including nurses. IMPLICATIONS FOR NURSING PRACTICE: Nurses are recognized for their social usefulness in France. However, it is important to consider the collateral effects of this crisis on nurses and nursing and to integrate the health emergency nursing skills established during the pandemic into the standard field of nursing competence. IMPLICATIONS FOR NURSING POLICY: The nursing profession has expectations of a reflection on and revision of nursing skills as well as of its valorization in the French healthcare system, notably carried out by the French National Council Order of Nurses. |
35 | 18tn2v9q | What new public datasets are available related to COVID-19? | COVID-19 Chest CT Image Segmentation -- A Deep Convolutional Neural Network Solution A novel coronavirus disease 2019 (COVID-19) was detected and has spread rapidly across various countries around the world since the end of the year 2019, Computed Tomography (CT) images have been used as a crucial alternative to the time-consuming RT-PCR test. However, pure manual segmentation of CT images faces a serious challenge with the increase of suspected cases, resulting in urgent requirements for accurate and automatic segmentation of COVID-19 infections. Unfortunately, since the imaging characteristics of the COVID-19 infection are diverse and similar to the backgrounds, existing medical image segmentation methods cannot achieve satisfactory performance. In this work, we try to establish a new deep convolutional neural network tailored for segmenting the chest CT images with COVID-19 infections. We firstly maintain a large and new chest CT image dataset consisting of 165,667 annotated chest CT images from 861 patients with confirmed COVID-19. Inspired by the observation that the boundary of the infected lung can be enhanced by adjusting the global intensity, in the proposed deep CNN, we introduce a feature variation block which adaptively adjusts the global properties of the features for segmenting COVID-19 infection. The proposed FV block can enhance the capability of feature representation effectively and adaptively for diverse cases. We fuse features at different scales by proposing Progressive Atrous Spatial Pyramid Pooling to handle the sophisticated infection areas with diverse appearance and shapes. We conducted experiments on the data collected in China and Germany and show that the proposed deep CNN can produce impressive performance effectively. |
13 | xo8okcha | what are the transmission routes of coronavirus? | First cases of coronavirus disease 2019 (COVID-19) in France: surveillance, investigations and control measures, January 2020 A novel coronavirus (severe acute respiratory syndrome coronavirus 2, SARS-CoV-2) causing a cluster of respiratory infections (coronavirus disease 2019, COVID-19) in Wuhan, China, was identified on 7 January 2020. The epidemic quickly disseminated from Wuhan and as at 12 February 2020, 45,179 cases have been confirmed in 25 countries, including 1,116 deaths. Strengthened surveillance was implemented in France on 10 January 2020 in order to identify imported cases early and prevent secondary transmission. Three categories of risk exposure and follow-up procedure were defined for contacts. Three cases of COVID-19 were confirmed on 24 January, the first cases in Europe. Contact tracing was immediately initiated. Five contacts were evaluated as at low risk of exposure and 18 at moderate/high risk. As at 12 February 2020, two cases have been discharged and the third one remains symptomatic with a persistent cough, and no secondary transmission has been identified. Effective collaboration between all parties involved in the surveillance and response to emerging threats is required to detect imported cases early and to implement adequate control measures. |
19 | oc0edgd2 | what type of hand sanitizer is needed to destroy Covid-19? | 2019 Novel Coronavirus Disease (COVID-19): Paving the Road for Rapid Detection and Point-of-Care Diagnostics We believe a point-of-care (PoC) device for the rapid detection of the 2019 novel Coronavirus (SARS-CoV-2) is crucial and urgently needed. With this perspective, we give suggestions regarding a potential candidate for the rapid detection of the coronavirus disease 2019 (COVID-19), as well as factors for the preparedness and response to the outbreak of the COVID-19. |
28 | lq4awi0i | what evidence is there for the value of hydroxychloroquine in treating Covid-19? | The care of patients with Duchenne, Becker, and other muscular dystrophies in the COVID‐19 pandemic The coronavirus disease 2019 (COVID‐19) pandemic has resulted in the reorganization of health‐care settings affecting clinical care delivery to patients with Duchenne and Becker muscular dystrophy (DBMD) as well as other inherited muscular dystrophies. The magnitude of the impact of this public health emergency on the care of patients with DBMD is unclear as they are suspected of having an increased risk for severe manifestations of COVID‐19. In this article, the authors discuss their consensus recommendations pertaining to care of these patients during the pandemic. We address issues surrounding corticosteroid and exon‐skipping treatments, cardiac medications, hydroxychloroquine use, emergency/respiratory care, rehabilitation management, and the conduct of clinical trials. We highlight the importance of collaborative treatment decisions between the patient, family, and health‐care provider, considering any geographic or institution‐specific policies and precautions for COVID‐19. We advocate for continuing multidisciplinary care for these patients using telehealth. |
24 | ol2exczc | what kinds of complications related to COVID-19 are associated with diabetes | Characteristics of and Public Health Responses to the Coronavirus Disease 2019 Outbreak in China In December 2019, cases of unidentified pneumonia with a history of exposure in the Huanan Seafood Market were reported in Wuhan, Hubei Province. A novel coronavirus, SARS-CoV-2, was identified to be accountable for this disease. Human-to-human transmission is confirmed, and this disease (named COVID-19 by World Health Organization (WHO)) spread rapidly around the country and the world. As of 18 February 2020, the number of confirmed cases had reached 75,199 with 2009 fatalities. The COVID-19 resulted in a much lower case-fatality rate (about 2.67%) among the confirmed cases, compared with Severe Acute Respiratory Syndrome (SARS) and Middle East Respiratory Syndrome (MERS). Among the symptom composition of the 45 fatality cases collected from the released official reports, the top four are fever, cough, short of breath, and chest tightness/pain. The major comorbidities of the fatality cases include hypertension, diabetes, coronary heart disease, cerebral infarction, and chronic bronchitis. The source of the virus and the pathogenesis of this disease are still unconfirmed. No specific therapeutic drug has been found. The Chinese Government has initiated a level-1 public health response to prevent the spread of the disease. Meanwhile, it is also crucial to speed up the development of vaccines and drugs for treatment, which will enable us to defeat COVID-19 as soon as possible. |
3 | ne9xika4 | will SARS-CoV2 infected people develop immunity? Is cross protection possible? | The pathogenesis and alternative treatment of SARS-CoV2 |
12 | a2kill55 | what are best practices in hospitals and at home in maintaining quarantine? | COVID-19: Public Compliance with and Public Support for Stay-at-Home Mitigation Strategies Objectives: Governments worldwide have recommended unprecedented measures to mitigate the coronavirus disease 2019 (COVID-19) pandemic. As pressure mounts to scale back these measures, understanding public compliance with and priorities for COVID-19 mitigation is critical. The main aim of this study was to assess public compliance with and support for government-imposed stay-at-home orders in nations and cities with different COVID-19 infection and death rates. Design: In this cross-sectional study, questionnaires were administered to nationally representative respondents from April 2-8, 2020. Setting: Regions with different disease prevalence included two nations [the United States (US, high) and Australia (AU, low)] and two cities [New York (NY, high) and Los Angeles (LA, low)]. Participants: For adults 18 years or older residing in specified regions, eligible respondents were empaneled until representative quotas were reached for age, gender, and either race and ethnicity (US, NY, LA) or ancestry (AU), matching the 2010 US or 2016 AU census. Of 8718 eligible potential respondents, 5573 (response rate, 63.9%) completed surveys (US: 3010; NY: 507; LA: 525; AU: 1531). The median age was 47 years (range, 18-89); 3039 (54.5%) were female. Exposure: The prevalence of COVID-19 in each region (cumulative infections, deaths) as of April 8, 2020: US (458610, 15659), AU (5956, 45), NY (81803, 4571), LA (7530, 198). Main Outcomes Measures: Public compliance with and attitudes regarding government-imposed stay-at-home orders were evaluated and compared between regions. Results: Of 5573 total respondents, 4560 (81.8%) reported compliance with recommended quarantine or stay-at-home policies (range of samples, 75.5%-88.2%). Despite significant disruptions of social and work life, health, and behavior, 5022 respondents (90.1%) supported government-imposed stay-at-home orders (range of samples, 88.9%-93.1%). Of these, 90.8% believe orders should last at least three more weeks or until public health or government officials recommend, with such support spanning the political spectrum. Conclusions: Public compliance with stringent quarantine and stay-at-home policies was very high, in both highly-affected (US, NY) and minimally-affected regions (AU, LA). Despite extensive disruption of respondents′ lives, the vast majority supported continuation of long-term government-imposed stay-at-home orders. These findings have important implications for policymakers grappling with the decision as to when to lift restrictions. |
32 | t0owegm3 | Does SARS-CoV-2 have any subtypes, and if so what are they? | Genomic Sequencing of a SARS Coronavirus Isolate That Predated the Metropole Hotel Case Cluster in Hong Kong |
47 | sp28yiqr | what are the health outcomes for children who contract COVID-19? | What do differences in case fatality ratios between children and adults tell us about COVID-19? |
41 | i5fcedbo | What are the impacts of COVID-19 among African-Americans that differ from the rest of the U.S. population? | Scientific Abstracts |
44 | may2tf4u | How much impact do masks have on preventing the spread of the COVID-19? | Who should wear a face mask? Experts weigh in on Canada's COVID-19 response |
15 | ifpu2nyu | how long can the coronavirus live outside the body | Electrostatic Charged Nanofiber Filter for Filtering Airborne Novel Coronavirus (COVID-19) and Nano-aerosols Abstract The World Health Organization declared the novel coronavirus (COVID-19) outbreak as a pandemic on March 12, 2020. Within 3-1/2 months since outbreak in December 2019, over 1.3 million people have been infected across 206 countries with over 70,000 deaths. COVID-19 has a size of 60-140nm with mean size of the nano-aerosols, 100nm. The virus can be airborne by attaching to human secretion (fine particles, nasal/saliva droplets) of infected person or suspended fine particulates in air. While NIOSH has standardized N95 and N98 at 300nm, to-date there is no filter standards, nor special filter technologies, tailored for capturing airborne viruses and 100nm nano-aerosols. The latter also are present in high number concentration in atmospheric pollutants. This study addresses developing novel charged PVDF nanofiber filter technology to effectively capture the deadly airborne coronavirus with our target set at 100nm (nano-aerosol), and not 300nm. The virus and its attached particle were simulated by sodium chloride aerosols, 50-500nm, generated from sub-micron aerosol generator. PVDF nanofibers were produced with fiber diameters 84, 191, 349 and 525nm with excellent morphology. The fibers were subsequently charged by corona discharge. The amounts of charged fibers in a filter were increased to achieve high efficiency of 90% for the virus filter but the electrical interference between neighbouring fibers resulted in progressively marginal increase in efficiency and concurrently much higher pressure drop across the filter. The quality factor which measured the efficiency-to-pressure-drop kept decreasing. By redistributing the fibers in the filter into several modules, each separated by a permeable scrim material, the electrical interference was reduced, if not fully mitigated. Also, the additional scrim materials introduced macropores into the filter that further reduced the airflow resistance. With this approach, the quality factor can maintain relatively constant with increasing fiber amounts to achieve high filter efficiency. The optimal amounts of fiber in each module depended on the diameter of fibers in the module. Small fiber diameter that has already high performance required small amount of fibers per module. In contrast, large diameter fiber required more amounts of fiber per module to compensate for the poorer performance without incurring higher pressure drop. This approach was applied to develop four new nanofiber filters tailored for capturing 100nm airborne COVID-19 to achieve over 90% efficiency with pressure drop below 30Pa (3.1mm water). One filter developed meeting the 90% efficiency has ultralow pressure drop of only 18Pa (1.9mm water) while another filter meeting the 30Pa limit has high efficiency reaching 94%. These optimized filters based on rigorous engineering approach provide the badly needed technology for protecting the general public from the deadly airborne COVID-19 and other viruses, and nano-aerosols from air pollution which lead to chronic diseases. |
30 | htd7dmn9 | is remdesivir an effective treatment for COVID-19 | Hajj-associated viral respiratory infections: A systematic review Summary Respiratory tract infections (RTI) are the most common infections transmitted between Hajj pilgrims. The aim of this systematic review was to determine the prevalence of virus carriage potentially responsible for RTI among pilgrims before and after participating in the Hajj. A systematic search for relevant literature was conducted according to Preferred Reporting Items for Systematic Reviews and Meta-Analyses guidelines. 31 studies were identified. Severe Acute Respiratory Syndrome coronavirus and Middle East Respiratory Syndrome coronavirus (MERS) were never isolated in Hajj pilgrims. The viruses most commonly isolated from symptomatic patients during the Hajj by PCR were rhinovirus (5.9–48.8% prevalence), followed by influenza virus (4.5–13.9%) and non-MERS coronaviruses (2.7–13.2%) with most infections due to coronavirus 229E; other viruses were less frequently isolated. Several viruses including influenza A, rhinovirus, and non-MERS coronaviruses had low carriage rates among arriving pilgrims and a statistically significant increase in their carriage rate was observed, following participation in the Hajj. Further research is needed to assess the role of viruses in the pathogenesis of respiratory symptoms and their potential role in the severity of the symptoms. |
33 | txi5enyw | What vaccine candidates are being tested for Covid-19? | Conserved B and T cell epitopes prediction of ebola virus glycoprotein for vaccine development: An immuno-informatics approach Ebola virus (EBOV), a non-segmented single-stranded RNA virus, is often-most transmitted through body fluids like sweat, tears, saliva, and nasal secretions. Till date, there is no licensed vaccine of EBOV is available in the market; however, the world is increasingly vulnerable to this emerging threat. Hence, it is the need of time to develop a vaccine for EBOV to hinder its dissemination. The current study has been designed for identification and characterization of the potential B and T-cell epitopes using the Immuno-informatics tools, and it helped in finding the potent vaccine candidates against EBOV. Prediction, antigenicity and allergenicity testing of predicted B and T cells' epitopes was done as well to identify their potential as a vaccine candidate and to measure their safety level respectively. Among B-cell epitopes "WIPAGIGVTGVIIA" showed a high antigenicity score and it would play an important role in evoking the immune response. In T-cell epitopes, peptides "AIGLAWIPY" and "IRGFPRCRY" presented high antigenicity score, which binds to MHC class-I and MHC class-II alleles respectively. All predicted epitopes were analyzed and compared with already reported peptides carefully. Comparatively, Peptides predicted in the present study showed more immunogenicity score than already reported peptides, used as positive control, and are more immunogenic as compared to them. Peptides reported in the present study do not target only Zaire EBOV (ZEBOV), as in previous studies, but also other species, i.e. Tai Forest EBOV (TAFV), Sudan EBOV (SUDV), Bundibugyo EBOV (BDBV), and Reston EBOV (RESTV) and would bring the promising results as potent vaccine candidates. |
49 | bej10xbf | do individuals who recover from COVID-19 show sufficient immune response, including antibody levels and T-cell mediated immunity, to prevent re-infection? | Specific Adoptive T-Cell Therapy for Viral and Fungal Infections Despite advances in anti-infective agents, viral and fungal infections after hematopoietic stem cell transplantation (HSCT) continue to cause life-threatening complications that limit the success of HSCT. Early adoptive T-cell immunotherapy studies showed that administration of allogeneic virus-specific cytotoxic T lymphocytes (vCTL) can prevent and control viral infections and reconstitute antiviral immunity to cytomegalovirus (CMV) and Epstein-Barr virus (EBV). Advances in immunobiology, in vitro culture technology, and current good manufacturing practice (cGMP) have provided opportunities for advancing adoptive cell therapy for viral infections: (1) T cells have been expanded targeting multiple pathogens; (2) vCTL production no longer requires viral infection or viral vector transduction of antigen-presenting cells (APCs); (3) the source of lymphocytes is no longer restricted to donors who are immune to the pathogens; (4) naive T cells have been redirected with chimeric antigen receptor T cells (CARTs) or armed with bispecific antibody-armed T cells (BATs) to mediate vCTL activity; (5) these technologies could be combined to targeted multiple viral or fungal pathogens; and (6) pathogen-specific T-cell products manufactured from third parties and banked for "off-the-shelf" use post-HSCT may soon become a reality. |
34 | y1afswkm | What are the longer-term complications of those who recover from COVID-19? | Identification of IgG antibody response to SARS-CoV-2 spike protein and its receptor binding domain does not predict rapid recovery from COVID-19 Diagnostic testing and evaluation of patient immunity against the novel severe acute respiratory syndrome (SARS) corona virus that emerged last year (SARS-CoV-2) are essential for health and economic crisis recovery of the world. It is suggested that potential acquired immunity against SARS-CoV-2 from prior exposure may be determined by detecting the presence of circulating IgG antibodies against viral antigens, such as the spike glycoprotein and its receptor binding domain (RBD). Testing our asymptomatic population for evidence of COVID-19 immunity would also offer valuable epidemiologic data to aid health care policies and health care management. Currently, there are over 100 antibody tests that are being used around the world without approval from the FDA or similar regulatory bodies, and they are mostly for rapid and qualitative assessment, with different degrees of error rates. ELISA-based testing for sensitive and rigorous quantitative assessment of SARS-CoV-2 antibodies can potentially offer mechanistic insights into the COVID-19 disease and aid communities uniquely challenged by limited financial resources and access to commercial testing products. Employing recombinant SARS-CoV-2 RBD and spike protein generated in the laboratory, we devised a quantitative ELISA for the detection of circulating serum antibodies. Serum from twenty SARS-CoV-2 RT-PCR confirmed COVID-19 hospitalized patients were used to detect circulating IgG titers against SARS-CoV-2 spike protein and RBD. Quantitative detection of IgG antibodies to the spike glycoprotein or the RBD in patient samples was not always associated with faster recovery, compared to patients with borderline antibody response to the RBD. One patient who did not develop antibodies to the RBD completely recovered from COVID-19. In surveying 99 healthy donor samples (procured between 2017-February 2020), we detected RBD antibodies in one donor from February 2020 collection with three others exhibiting antibodies to the spike protein but not the RBD. Collectively, our study suggests that more rigorous and quantitative analysis, employing large scale sample sets, is required to determine whether antibodies to SARS-CoV-2 spike protein or RBD is associated with protection from COVID-19 disease. It is also conceivable that humoral response to SARS-CoV-2 spike protein or RBD works in association with adaptive T cell response to determine clinical sequela and severity of COVID-19 disease. |
1 | cmaw7jcn | what is the origin of COVID-19 | Practical insights for paediatric otolaryngology surgical cases and performing microlaryngobronchoscopy during the COVID-19 pandemic Abstract Paediatric otolaryngology practice involves examining and operating in anatomical locations with high levels of aerosol generation and transmission of COVID-19 to treating clinicians, especially from the asymptomatic patient populations including children. During the COVID-19 pandemic all emergent otolaryngological conditions affecting the airway, oral, and nasal cavities should be managed medically where possible and any operating deferred. We present guidelines for operating on paediatric otolaryngological patients when necessary during the COVID-19 pandemic, and incorporate experience gathered during microlaryngobronchoscopy on a COVID-19 positive infant at our institution. |
5 | aexlwq79 | what drugs have been active against SARS-CoV or SARS-CoV-2 in animal studies? | Antiviral treatment of SARS-CoV-2-infected hamsters reveals a weak effect of favipiravir and a complete lack of effect for hydroxychloroquine SARS-CoV-2 rapidly spread around the globe after its emergence in Wuhan in December 2019. With no specific therapeutic and prophylactic options available, the virus was able to infect millions of people. To date, close to half a million patients succumbed to the viral disease, COVID-19. The high need for treatment options, together with the lack of small animal models of infection has led to clinical trials with repurposed drugs before any preclinical in vivo evidence attesting their efficacy was available. We used Syrian hamsters to establish a model to evaluate antiviral activity of small molecules in both an infection and a transmission setting. Upon intranasal infection, the animals developed high titers of SARS-CoV-2 in the lungs and pathology similar to that observed in mild COVID-19 patients. Treatment of SARS-CoV-2-infected hamsters with favipiravir or hydroxychloroquine (with and without azithromycin) resulted in respectively a mild or no reduction in viral RNA and infectious virus. Micro-CT scan analysis of the lungs showed no improvement compared to non-treated animals, which was confirmed by histopathology. In addition, both compounds did not prevent virus transmission through direct contact and thus failed as prophylactic treatments. By modelling the PK profile of hydroxychloroquine based on the trough plasma concentrations, we show that the total lung exposure to the drug was not the limiting factor. In conclusion, we here characterized a hamster infection and transmission model to be a robust model for studying in vivo efficacy of antiviral compounds. The information acquired using hydroxychloroquine and favipiravir in this model is of critical value to those designing (current and) future clinical trials. At this point, the data here presented on hydroxychloroquine either alone or combined with azithromycin (together with previously reported in vivo data in macaques and ferrets) provide no scientific basis for further use of the drug in humans. |
21 | vjpscyjf | what are the mortality rates overall and in specific populations | A demographic scaling model for estimating the total number of COVID-19 infections Understanding how widely COVID-19 has spread is critical for examining the pandemic's progression. Despite efforts to carefully monitor the pandemic, the number of confirmed cases may underestimate the total number of infections. We introduce a demographic scaling model to estimate COVID-19 infections using an broadly applicable approach that is based on minimal data requirements: COVID-19 related deaths, infection fatality rates (IFRs), and life tables. As many countries lack reliable estimates of age-specific IFRs, we scale IFRs between countries using remaining life expectancy as a marker to account for differences in age structures, health conditions, and medical services. Across 10 countries with most COVID-19 deaths as of May 13, 2020, the number of infections is estimated to be four [95% prediction interval: 2-11] times higher than the number of confirmed cases. Cross-country variation is high. The estimated number of infections is 1.4 million (six times the number of confirmed cases) for Italy; 3.1 million (2.2 times the number of confirmed cases) for the U.S.; and 1.8 times the number of confirmed cases for Germany, where testing has been comparatively extensive. Our prevalence estimates, however, are markedly lower than most others based on local seroprevalence studies. We introduce formulas for quantifying the bias that is required in our data on deaths in order to reproduce estimates published elsewhere. This bias analysis shows that either COVID-19 deaths are severely underestimated, by a factor of two or more; or alternatively, the seroprevalence based results are overestimates and not representative for the total population. |
40 | 3t75dbb7 | What are the observed mutations in the SARS-CoV-2 genome and how often do the mutations occur? | Combination attenuation offers strategy for live-attenuated coronavirus vaccines With an ongoing threat posed by circulating zoonotic strains, new strategies are required to prepare for the next emergent coronavirus (CoV). Previously, groups had targeted conserved coronavirus proteins as a strategy to generate live-attenuated vaccine strains against current and future CoVs. With this in mind, we explored whether manipulation of CoV NSP16, a conserved 2'O methyltransferase (MTase), could provide a broad attenuation platform against future emergent strains. Using the SARS-CoV mouse model, a NSP16 mutant vaccine was evaluated for protection from heterologous challenge, efficacy in the aging host, and potential for reversion to pathogenesis. Despite some success, concerns for virulence in the aged and potential for reversion makes targeting NSP16 alone an untenable approach. However, combining a 2'O MTase mutation with a previously described CoV fidelity mutant produced a vaccine strain capable of protection from heterologous virus challenge, efficacy in aged mice, and no evidence for reversion. Together, the results indicate that targeting the CoV 2'O MTase in parallel with other conserved attenuating mutations may provide a platform strategy for rapidly generating live-attenuated coronavirus vaccines. Significance Emergent coronaviruses remain a significant threat to global public health and rapid response vaccine platforms are needed to stem future outbreaks. However, failure of many previous CoV vaccine formulations has clearly highlighted the need to test efficacy under different conditions and especially in vulnerable populations like the aged and immune-compromised. This study illustrates that despite success in young models, the NSP16 mutant carries too much risk for pathogenesis and reversion in vulnerable models to be used as a stand-alone vaccine strategy. Importantly, the NSP16 mutation can be paired with other attenuating approaches to provide robust protection from heterologous challenge and in vulnerable populations. Coupled with increased safety and reduced pathogenesis, the study highlights the potential for NSP16 attenuation as a major component of future live-attenuated coronavirus vaccines. |
15 | 6anr4xdw | how long can the coronavirus live outside the body | Effects of temperature variation and humidity on the death of COVID-19 in Wuhan, China Abstract Meteorological parameters are the important factors influencing the infectious diseases such as severe acute respiratory syndrome (SARS) and influenza. This study aims to explore the association between Corona Virus Disease 2019 (COVID-19) deaths and weather parameters. In this study, we collected the daily death numbers of COVID-19, meteorological parameters and air pollutant data from 20 January 2020 to 29 February 2020 in Wuhan, China. Generalized additive model was applied to explore the effect of temperature, humidity and diurnal temperature range on the daily death counts of COVID-19. There were 2299 COVID-19 death counts in Wuhan during the study period. A positive association with COVID-19 daily death counts was observed for diurnal temperature range (r = 0.44), but negative association for relative humidity (r = −0.32). In addition, one unit increase in diurnal temperature range was only associated with a 2.92% (95% CI: 0.61%, 5.28%) increase in COVID-19 deaths in lag 3. However, both 1 unit increase of temperature and absolute humidity were related to the decreased COVID-19 death in lag 3 and lag 5, with the greatest decrease both in lag 3 [−7.50% (95% CI: −10.99%, −3.88%) and −11.41% (95% CI: −19.68%, −2.29%)]. In summary, this study suggests the temperature variation and humidity may also be important factors affecting the COVID-19 mortality. |
28 | ftrz24iu | what evidence is there for the value of hydroxychloroquine in treating Covid-19? | Driving forces for COVID-19 clinical trials using chloroquine: the need to choose the right research questions and outcomes |
35 | 0xqhpqm4 | What new public datasets are available related to COVID-19? | Serial interval in determining the estimation of reproduction number of the novel coronavirus disease (COVID-19) during the early outbreak ;Journal of Travel Medicine ;Oxford Academic Coronavirus disease 2019 (COVID-19), caused by the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), emerged in Wuhan, China in the end of 2019, and soon spread oversea A comprehensive and timely review summarized the scientific research in estimating the basic reproduction number (R0) released from 1 January to 7 February 2020 [1] During the early outbreak, when the key epidemiological features of COVID-19 were uncovered, the R0 estimation largely relied on the growth rate of the epidemic curve and the estimation of the serial interval (SI) Here, we demonstrated that an overlarge SI would lead to overestimation of R0 We adopted the growing process proposed in [2] deterministically with a population of 11 million in Wuhan, 1 case initially onset on 5 December 2019 and a fixed step at 1 day We consider two values of the mean serial interval (SI) that are SI at 4 6 days estimated based on 28 records of transmission chains [3], which was largely consistent with the SI estimate at 4 4 days based on 71 records [4];and SI at 8 days, which was closer to the SI of the severe acute respiratory syndrome (SARS, 8 4 days), SI of the Middle East respiratory syndrome (MERS, 7 6 days) As for demonstration that a larger SI could lead to overestimation in R0, we conducted the simulation with two schemes that are Scheme (I): R0 = 2, and SI = 4 6 days;and Scheme (II): R0 = 2, 3, 4 and 3 3 as summarized in [1], and SI = 8 days We also compared the simulation results with the previous estimates of the cumulative number of COVID-19 infection in Wuhan In Fig 1, the simulation results of the scheme (I) had almost the same growing trends as those of scheme (II) with R0 = 3 3 Although a higher R0 could force the epidemic curve increasing rapidly, a shorter SI could increase iteration of transmission generation, i e , transmission may occur shortly post infection According to the simple approximated formula that R0 = exp(γ∙SI), where γ was the exponential growth rate calculated from the incidence data directly, a longer SI would lead to a higher R0 estimate theoretically With a shorter SI at 4 6 days, which was supported by richer datasets in [3, 4], the R0 of COVID-19 could be lower than previous estimates based on longer SI By using the growth rate (γ) at 0 15 per day, the R0 was found at 2 0 with SI at 4 6 days, whereas 3 3 with SI at 8 days Although the effects of public health control were ignored in this analysis, our model could be Downloaded from https://academic oup com/jtm/advance-article-abstract/doi/10 1093/jtm/taaa033/5803291 by guest on 13 March 2020 4 extended by introducing an effective reproduction number accounting for the effectiveness of the control measures, and we remarked this modification would not affect the main conclusion Furthermore, as pointed out in [3], provided that the SI of COVID-19 might be shorter than its incubation period, pre-symptomatic transmission may occur shortly after being infected [5] This implies that a fraction of transmissions cannot be prevented solely through isolating the symptomatic cases, since the time when contact tracing is conducted, they may have already been infectious and generated secondary cases Therefore, the effectively quarantine of suspected (and probable) cases, as well as close contacts, and timely contact tracing were crucial in successful outbreak mitigation |
36 | hsa107za | What is the protein structure of the SARS-CoV-2 spike? | Crystal structure of NL63 respiratory coronavirus receptor-binding domain complexed with its human receptor. NL63 coronavirus (NL63-CoV), a prevalent human respiratory virus, is the only group I coronavirus known to use angiotensin-converting enzyme 2 (ACE2) as its receptor. Incidentally, ACE2 is also used by group II SARS coronavirus (SARS-CoV). We investigated how different groups of coronaviruses recognize the same receptor, whereas homologous group I coronaviruses recognize different receptors. We determined the crystal structure of NL63-CoV spike protein receptor-binding domain (RBD) complexed with human ACE2. NL63-CoV RBD has a novel beta-sandwich core structure consisting of 2 layers of beta-sheets, presenting 3 discontinuous receptor-binding motifs (RBMs) to bind ACE2. NL63-CoV and SARS-CoV have no structural homology in RBD cores or RBMs; yet the 2 viruses recognize common ACE2 regions, largely because of a "virus-binding hotspot" on ACE2. Among group I coronaviruses, RBD cores are conserved but RBMs are variable, explaining how these viruses recognize different receptors. These results provide a structural basis for understanding viral evolution and virus-receptor interactions. |
9 | w048fg2b | how has COVID-19 affected Canada | Questions concerning the New Haven Coronavirus |
43 | uhef4yut | How has the COVID-19 pandemic impacted violence in society, including violent crimes? | Intimate partner violence in Greece: a study of 664 consecutive forensic clinical examinations BACKGROUND: Intimate partner violence (IPV) is a well-known phenomenon, which affects mostly women. While IPV victims may attend emergency departments (EDs) seeking medical care, not all of them will make an allegation against their abusers. OBJECTIVE: The aim of this study was to examine the prevalence and the characteristics of the victims, who had made an allegation about the violent incident and had been examined by a forensic pathologist for judicial purposes, and had attended EDs seeking medical care, before the forensic examination. METHODS: We reviewed the archives of clinical examinations that were conducted at the Department of Forensic Medicine and Toxicology of National and Kapodistrian University of Athens during a 5-year period (2012-16). RESULTS: Six hundred sixty-four clinical examinations were conducted at our Department for IPV allegations. According to our findings, women were more likely to seek medical care than men. Victims who have attended EDs were more likely to have sustained injuries located at least on the head or on the lower limbs. CONCLUSION: The majority of IPV victims in the broader region of Attica (Greece) were women, usually married, and aged between 30 and 49 years old. Despite the fact that the majority of IPV incidents are not reported to police, every person who is engaged in the process of dealing with IPV victims has to be educated and adequately informed about this phenomenon, its implications and the possible ways to deal with it. Furthermore, victims need to be educated and informed adequately in waiting rooms of EDs. |
24 | yi6ugew9 | what kinds of complications related to COVID-19 are associated with diabetes | Clinical characteristics and outcomes of COVID-19 hospitalized patients with diabetes in the United Kingdom: A retrospective single centre study AIM: To describe the clinical characteristics and outcomes of hospitalized COVID-19 patients with diabetes. METHODS: A retrospective cross-sectional study was conducted among patients admitted to the William Harvey Hospital in England between March 10th and May10th, 2020 with a laboratory-confirmed severe acute respiratory syndrome-coronavirus-2 (SARS-CoV-2), known as COVID-19. Variation in characteristics, length of stay in hospital, diabetes status, duration of diabetes, control of diabetes, comorbidities and outcomes were examined. RESULTS: There were 232 COVID-19 presentations. Mean (standard deviation (SD), range) age was 70.5 (±15.7, 30-101) years, 62.5% were male, and 37.5% were having diabetes. There were 43.4% males and 27.6 females, p = 0.016, with diabetes admitted to our hospital due to COVID-19. Patients with diabetes were more likely to have longer length of stay (LOS) in hospital, 14.4 (SD ± 9.6) days, compared to the patients without diabetes, 9.8 (SD ± 17.1) days, p < 0.0001. Patients with diabetic ketoacidosis (DKA) were more likely to survive (87.1%) compared to patients without DKA (50.6%), p = 0.046. CONCLUSION: Males were more likely to be admitted to hospital with COVID-19 illness than females. Hospitalized COVID-19 patients with diabetes had a longer LOS in hospital than patients without diabetes. Older age COVID-19 patients with diabetes and patients without DKA were less likely to survive compared to younger patients and patients with DKA, respectively. Further studies with large sample size are needed. |
37 | r3mm13mf | What is the result of phylogenetic analysis of SARS-CoV-2 genome sequence? | Structural analysis of the putative SARS-CoV-2 primase complex We report the crystal structure of the SARS-CoV-2 putative primase composed of the nsp7 and nsp8 proteins. We observed a dimer of dimers (2:2 nsp7-nsp8) in the crystallographic asymmetric unit. The structure revealed a fold with a helical core of the heterotetramer formed by both nsp7 and nsp8 that is flanked with two symmetry-related nsp8 β-sheet subdomains. It was also revealed that two hydrophobic interfaces one of approx. 1340 Å(2) connects the nsp7 to nsp8 and a second one of approx. 950 Å(2) connects the dimers and form the observed heterotetramer. Interestingly, analysis of the surface electrostatic potential revealed a putative RNA binding site that is formed only within the heterotetramer. |
42 | 9itdow8a | Does Vitamin D impact COVID-19 prevention and treatment? | Does vitamin D status impact mortality from SARS-CoV-2 infection? |
29 | 3pxo0j42 | 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? | Repurposing of clinically approved drugs for treatment of coronavirus disease 2019 in a 2019-novel coronavirus-related coronavirus model BACKGROUND: Medicines for the treatment of 2019-novel coronavirus (2019-nCoV) infections are urgently needed. However, drug screening using live 2019-nCoV requires high-level biosafety facilities, which imposes an obstacle for those institutions without such facilities or 2019-nCoV. This study aims to repurpose the clinically approved drugs for the treatment of coronavirus disease 2019 (COVID-19) in a 2019-nCoV-related coronavirus model. METHODS: A 2019-nCoV-related pangolin coronavirus GX_P2V/pangolin/2017/Guangxi was described. Whether GX_P2V uses angiotensin-converting enzyme 2 (ACE2) as the cell receptor was investigated by using small interfering RNA (siRNA)-mediated silencing of ACE2. The pangolin coronavirus model was used to identify drug candidates for treating 2019-nCoV infection. Two libraries of 2406 clinically approved drugs were screened for their ability to inhibit cytopathic effects on Vero E6 cells by GX_P2V infection. The anti-viral activities and anti-viral mechanisms of potential drugs were further investigated. Viral yields of RNAs and infectious particles were quantified by quantitative real-time polymerase chain reaction (qRT-PCR) and plaque assay, respectively. RESULTS: The spike protein of coronavirus GX_P2V shares 92.2% amino acid identity with that of 2019-nCoV isolate Wuhan-hu-1, and uses ACE2 as the receptor for infection just like 2019-nCoV. Three drugs, including cepharanthine (CEP), selamectin, and mefloquine hydrochloride, exhibited complete inhibition of cytopathic effects in cell culture at 10 µmol/L. CEP demonstrated the most potent inhibition of GX_P2V infection, with a concentration for 50% of maximal effect [EC50] of 0.98 µmol/L. The viral RNA yield in cells treated with 10 µmol/L CEP was 15,393-fold lower than in cells without CEP treatment ([6.48 ±â€Š0.02] × 10vs. 1.00 ±â€Š0.12, t = 150.38, P < 0.001) at 72 h post-infection (p.i.). Plaque assays found no production of live viruses in media containing 10 µmol/L CEP at 48 h p.i. Furthermore, we found CEP had potent anti-viral activities against both viral entry (0.46 ±â€Š0.12, vs.1.00 ±â€Š0.37, t = 2.42, P < 0.05) and viral replication ([6.18 ±â€Š0.95] × 10vs. 1.00 ±â€Š0.43, t = 3.98, P < 0.05). CONCLUSIONS: Our pangolin coronavirus GX_P2V is a workable model for 2019-nCoV research. CEP, selamectin, and mefloquine hydrochloride are potential drugs for treating 2019-nCoV infection. Our results strongly suggest that CEP is a wide-spectrum inhibitor of pan-betacoronavirus, and further study of CEP for treatment of 2019-nCoV infection is warranted. |
22 | 67dna02j | are cardiac complications likely in patients with COVID-19? | COVID-19: A United Kingdom National Health Service cardiology perspective. |
40 | icp5iuwb | What are the observed mutations in the SARS-CoV-2 genome and how often do the mutations occur? | Low serum 25-hydroxyvitamin D levels are associated with increased risk of viral coinfections in wheezing children |
13 | 4zb3dfja | what are the transmission routes of coronavirus? | Operationalizing COVID-19 testing: Who, what, when, where, why, and how The authors review the rationale behind and approaches to testing for COVID-19, the quality of currently available tests, the role of data analytics in strategizing testing, and using the electronic medical record and other programs designed to steward COVID-19 testing and follow-up of patients. |
24 | i74h7kzl | what kinds of complications related to COVID-19 are associated with diabetes | Metabolic disorders and storage diseases Primary metabolic disorders and storage diseases are caused by endogenous factors, usually a gene mutation. Since the congenital defect is predominantly or exclusively located in the liver, the resulting diseases also become manifest in this organ. |
49 | itu39mln | do individuals who recover from COVID-19 show sufficient immune response, including antibody levels and T-cell mediated immunity, to prevent re-infection? | Long-Term Persistence of Robust Antibody and Cytotoxic T Cell Responses in Recovered Patients Infected with SARS Coronavirus Most of the individuals infected with SARS coronavirus (SARS-CoV) spontaneously recovered without clinical intervention. However, the immunological correlates associated with patients' recovery are currently unknown. In this report, we have sequentially monitored 30 recovered patients over a two-year period to characterize temporal changes in SARS-CoV-specific antibody responses as well as cytotoxic T cell (CTL) responses. We have found persistence of robust antibody and CTL responses in all of the study subjects throughout the study period, with a moderate decline one year after the onset of symptoms. We have also identified two potential major CTL epitopes in N proteins based on ELISPOT analysis of pooled peptides. However, despite the potent immune responses and clinical recovery, peripheral lymphocyte counts in the recovered patients have not yet been restored to normal levels. In summary, our study has, for the first time, characterized the temporal and dynamic changes of humoral and CTL responses in the natural history of SARS-recovered individuals, and strongly supports the notion that high and sustainable levels of immune responses correlate strongly with the disease outcome. Our findings have direct implications for future design and development of effective therapeutic agents and vaccines against SARS-CoV infection. |
45 | 5jbppzck | How has the COVID-19 pandemic impacted mental health? | Depression, anxiety, and stress and socio-demographic correlates among general Indian public during COVID-19 BACKGROUND: The severe outbreak of COVID-19 has affected the mental health of Indians. AIM: The objective of this article was to find the prevalence rates of depression, anxiety and stress and their socio-demographic correlates among Indian population during the lockdown to contain the spread of COVID-19. METHODS: A cross-sectional survey was conducted using an electronic questionnaire. A total of 354 participants were recruited through convenience sampling. Depression, anxiety and stress were measured using Depression Anxiety Stress Scale (DASS-21), a 21-item self-reported questionnaire. RESULTS: In total, 25%, 28% and 11.6% of the participants were moderate to extremely severely depressed, anxious and stressed, respectively. Binary logistic regressions indicated employment status (odds ratio (OR) = 1.91; 95% confidence interval (CI): 1.072-3.418) and binge drinking (OR = 2.03; 95% CI: 1.045-3.945) were significantly associated with depressive symptoms; gender (OR = 2.17; 95% CI: 1.317-3.589), employment status (OR = 1.77; 95% CI: 1.002-3.141) and binge drinking (OR = 2.62; 95% CI: 1.361-5.048) were significantly associated with anxiety symptoms; and binge drinking (OR = 3.42; 95% CI: 1.544-7.583) was significantly associated with stress symptoms. CONCLUSION: Depression, anxiety and stress among Indian population during the lockdown were prevalent. Along with other measures to contain the spread of COVID-19, mental health of citizens needs the urgent attention of the Indian government and mental health experts. Further large-scale studies should be conducted on different professions and communities such as health care professionals and migrant workers and incorporate other mental health indicators. |
41 | 8jyby4xo | What are the impacts of COVID-19 among African-Americans that differ from the rest of the U.S. population? | COVID-19 in people living with diabetes: An international consensus The COVID-19 pandemic has added an enormous toll to the existing challenge of diabetes care world-wide. A large proportion of patients with COVID-19 requiring hospitalization and/or succumbing to the disease have had diabetes and other chronic conditions as underlying risk factors. In particular, individuals belonging to racial/ethnic minorities in the U.S. and other countries have been significantly and disproportionately impacted. Multiple and complex socioeconomic factors have long played a role in increasing the risk for diabetes and now for COVID-19. Since the pandemic began, the global healthcare community has accumulated invaluable clinical experience on providing diabetes care in the setting of COVID-19. In addition, understanding of the pathophysiological mechanisms that link these two diseases is being developed. The current clinical management of diabetes is a work in progress, requiring a shift in patient-provider interaction beyond the walls of clinics and hospitals: the use of tele-medicine when feasible, innovative patient education programs, strategies to ensure medication and glucose testing availability and affordability, as well as numerous ideas on how to improve meal plans and physical activity. Notably, this worldwide experience offers us the possibility to not only prepare better for future disasters but also transform diabetes care beyond the COVID-19 era. |
34 | dumf55yg | What are the longer-term complications of those who recover from COVID-19? | Analysis of 92 deceased patients with COVID-19 OBJECTIVE: This retrospective study aimed to analysis the clinical characteristics and complications in death cases with novel coronavirus disease-19 (COVID-19). METHOD: We collected the medical records of 92 patients with COVID-19 in Renmin Hospital of Wuhan University who died during January 6th to February 25th, 2020, summarized the clinical characteristics of complications. RESULTS: There were 91 death cases who developed different complications including acute respiratory distress syndrome (ARDS) (73/91), myocardial injury (31/91), liver injury (15/91), renal insufficiency (14/91), multiple organ dysfunction syndrome (MODS) (14/91) and pneumothorax (1/91). Among these patients, 83 patients had at least one complication. While 1 patient who died of recurrent gastrointestinal bleeding was not directly linked to COVID-19. CONCLUSION: The main complications of deceased patients with COVID-19 were ARDS, myocardial injury, liver injury, renal insufficiency and MODS. This article is protected by copyright. All rights reserved. |
18 | k5nfy43y | what are the best masks for preventing infection by Covid-19? | Messaging Mask Wearing During the COVID-19 Crisis: Ideological Differences As the U.S. Government works to slow the spread of the novel coronavirus, messaging is important in getting individuals to comply with public health recommendations, especially as the response from the public seems to be polarized along partisan and ideological lines. Using a recent Centers for Disease Control recommendation of wearing facemasks, I use Regulatory Focus Theory to predict that conservatives will be more responsive to messages related to promotion, while liberals are more responsive to messages related to prevention. Using a pre-registered experimental design, I find no evidence that prevention messages influence attitudes toward mask wearing. Promotion messages, however, cause conservatives to become less supportive of mask wearing, in contrast to theoretical predictions. These findings suggest that, related to messaging about mask wearing, strong ideological differences do not emerge related to the focus of the message. |
11 | vsinwqnr | what are the guidelines for triaging patients infected with coronavirus? | Intensive care management of coronavirus disease 2019 (COVID-19): challenges and recommendations Summary As coronavirus disease 2019 (COVID-19) spreads across the world, the intensive care unit (ICU) community must prepare for the challenges associated with this pandemic. Streamlining of workflows for rapid diagnosis and isolation, clinical management, and infection prevention will matter not only to patients with COVID-19, but also to health-care workers and other patients who are at risk from nosocomial transmission. Management of acute respiratory failure and haemodynamics is key. ICU practitioners, hospital administrators, governments, and policy makers must prepare for a substantial increase in critical care bed capacity, with a focus not just on infrastructure and supplies, but also on staff management. Critical care triage to allow the rationing of scarce ICU resources might be needed. Researchers must address unanswered questions, including the role of repurposed and experimental therapies. Collaboration at the local, regional, national, and international level offers the best chance of survival for the critically ill. |
23 | mxyxwkhx | what kinds of complications related to COVID-19 are associated with hypertension? | Replicative homeostasis II: Influence of polymerase fidelity on RNA virus quasispecies biology: Implications for immune recognition, viral autoimmunity and other "virus receptor" diseases Much of the worlds' population is in active or imminent danger from established infectious pathogens, while sporadic and pandemic infections by these and emerging agents threaten everyone. RNA polymerases (RNA(pol)) generate enormous genetic and consequent antigenic heterogeneity permitting both viruses and cellular pathogens to evade host defences. Thus, RNA(pol )causes more morbidity and premature mortality than any other molecule. The extraordinary genetic heterogeneity defining viral quasispecies results from RNA(pol )infidelity causing rapid cumulative genomic RNA mutation a process that, if uncontrolled, would cause catastrophic loss of sequence integrity and inexorable quasispecies extinction. Selective replication and replicative homeostasis, an epicyclical regulatory mechanism dynamically linking RNApol fidelity and processivity with quasispecies phenotypic diversity, modulating polymerase fidelity and, hence, controlling quasispecies behaviour, prevents this happening and also mediates immune escape. Perhaps more importantly, ineluctable generation of broad phenotypic diversity after viral RNA is translated to protein quasispecies suggests a mechanism of disease that specifically targets, and functionally disrupts, the host cell surface molecules – including hormone, lipid, cell signalling or neurotransmitter receptors – that viruses co-opt for cell entry. This mechanism – "Viral Receptor Disease (VRD)" – may explain so-called "viral autoimmunity", some classical autoimmune disorders and other diseases, including type II diabetes mellitus, and some forms of obesity. Viral receptor disease is a unifying hypothesis that may also explain some diseases with well-established, but multi-factorial and apparently unrelated aetiologies – like coronary artery and other vascular diseases – in addition to diseases like schizophrenia that are poorly understood and lack plausible, coherent, pathogenic explanations. |
8 | 2seyiz3b | how has lack of testing availability led to underreporting of true incidence of Covid-19? | Neonatal Pertussis, an Under-Recognized Health Burden and Rationale for Maternal Immunization: A Systematic Review of South and South-East Asian Countries Pertussis is an under-recognized cause of neonatal morbidity and mortality. To review information on the epidemiology and disease burden of neonatal pertussis in South and Southeast Asian countries, a systematic literature review of three bibliographic databases was undertaken. Peer-reviewed original studies on neonatal pertussis epidemiology and burden published since 2000, with a geographical scope limited to South and Southeast Asian countries, were included. Data were systematically extracted based on parameters defined a priori. Our findings show that the burden of neonatal pertussis and its complications is substantial. An increase in the number of pertussis cases has been noted since early 2000, ranging from 61 to 92.9% in infants 0–3 months old. The most common symptoms an infant is likely to present with are cough with or without paroxysms, cyanosis, apnea, tachypnea, difficulty in breathing and leukocytosis. In addition, it can lead to hospitalization (length of stay: 5–7 days), complications (e.g., pneumonia, seizures) and mortality ranging from 5.6 to 14.7%. Other observations indicate that diagnosis is challenging because of non-specific clinical symptoms. Specifically, for obstetricians and gynecologists, the information available for making informed decisions on the prevention of neonatal pertussis is unreliable. Maternal immunization against pertussis during late stages of pregnancy has proven to be efficacious and well tolerated. A high burden of neonatal pertussis, as well as its complications, is observed in South and Southeast Asian countries. There is a need to intensify efforts to protect this vulnerable population with maternal vaccination. Funding: GlaxoSmithKline Biologicals SA Plain Language Summary: Plain language summary available for this article. Please see Fig. 1 and the following link: https://doi.org/10.6084/m9.figshare.7951187. |
9 | by4aefjc | how has COVID-19 affected Canada | Connecting BCG Vaccination and COVID-19: Additional Data The reasons for a wide variation in severity of coronavirus disease 2019 (COVID-19) across the affected countries of the world are not known. Two recent studies have suggested a link between the BCG vaccination policy and the morbidity and mortality due to COVID-19. In the present study we compared the impact of COVID-19 in terms of case fatality rates (CFR) between countries with high disease burden and those with BCG revaccination policies presuming that revaccination practices would have provided added protection to the population against severe COVID-19. We found a significant difference in the CFR between the two groups of countries. Our data further supports the view that universal BCG vaccination has a protective effect on the course of COVID-19 probably preventing progression to severe disease and death. Clinical trials of BCG vaccine are urgently needed to establish its beneficial role in COVID-19 as suggested by the epidemiological data, especially in countries without a universal BCG vaccination policy. Keywords: COVID-19, BCG vaccination, case fatality ratio, mortality, low resource countries |
32 | gc3iq0wp | Does SARS-CoV-2 have any subtypes, and if so what are they? | Comparative review of respiratory diseases caused by coronaviruses and influenza A viruses during epidemic season Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) continues to sweep the world, causing infection of millions and death of hundreds of thousands. The respiratory disease that it caused, COVID-19 (stands for coronavirus disease in 2019), has similar clinical symptoms with other two CoV diseases, severe acute respiratory syndrome and Middle East respiratory syndrome (SARS and MERS), of which causative viruses are SARS-CoV and MERS-CoV, respectively. These three CoVs resulting diseases also share many clinical symptoms with other respiratory diseases caused by influenza A viruses (IAVs). Since both CoVs and IAVs are general pathogens responsible for seasonal cold, in the next few months, during the changing of seasons, clinicians and public heath may have to distinguish COVID-19 pneumonia from other kinds of viral pneumonia. This is a discussion and comparison of the virus structures, transmission characteristics, clinical symptoms, diagnosis, pathological changes, treatment and prevention of the two kinds of viruses, CoVs and IAVs. It hopes to provide information for practitioners in the medical field during the epidemic season. |
43 | 7c72n11m | How has the COVID-19 pandemic impacted violence in society, including violent crimes? | The effects of misleading media reports about COVID-19 on Chinese tourists' mental health: a perspective article The novel coronavirus (COVID-19) has been declared apublic health emergency of international concern by the World Health Organization. This pandemic has since saturated the headlines of major international media channels that disseminate information to global citizens. However, some media coverage of COVID-19 has negatively influenced Chinese travellers' mental health due to the outbreak having been labelled "Chinese virus pandemonium." Key world leaders have also parroted such sensationalism; for example, President Donald Trump called COVID-19 the "Chinese virus". This discriminatory labelling has resulted in violent attacks on Chinese international travellers and students. This perspective article explores how misleading and discriminatory media reports may affect the mental well-being of ethnically Chinese travellers during the global COVID-19 pandemic. |
27 | vxl2flbn | what is known about those infected with Covid-19 but are asymptomatic? | Asymptomatic COVID-19 Infection in a Child with Nasal Foreign Body Abstract While children, particularly infants, are susceptible to severe and critical COVID-19 disease, over 55% of pediatric cases are present in asymptomatic or mildly symptomatic children. Aerosolized SARS-CoV-2 viral particles remain viable for up to 3 hours, raising concern about risk to healthcare workers during aerosol generating procedures (APGs) in the airway and nasopharynx. Herein we describe the first case of a nasal foreign body in an asymptomatic child with SARS-CoV-2 infection. We discuss management of this child and highlight the importance of considering asymptomatic infection and preoperative testing when planning procedures of the airway in the COVID-19 era. |
17 | 0vecbxny | are there any clinical trials available for the coronavirus | Impact of viral epidemic outbreaks on mental health of healthcare workers: a rapid systematic review Objectives: To examine the impact of providing healthcare during or after health emergencies caused by viral epidemic outbreaks on healthcare workers (HCWs) mental health, and to assess the available evidence base regarding interventions to reduce such impact. Design: Systematic rapid review and meta-analysis. Data sources: MEDLINE, Embase, and PsycINFO, searched up to 23 March 2020. Method: We selected observational and experimental studies examining the impact on mental health of epidemic outbreaks on HCWs. Titles and abstracts were screened by one reviewer, and full texts were evaluated by two reviewers independently. We extracted study characteristics, symptoms, prevalence of mental health problems, risk factors, mental health interventions, and its impact. We assessed risk of bias for each individual study. We conducted a narrative and tabulated synthesis of the results. We pooled data using random-effects meta-analyses to estimate the prevalence of specific mental health problems. We followed the GRADE approach to assess the certainty in the evidence. Results: We included 61 studies (56 examining impact on mental health and five about interventions to reduce such impact). Most were conducted in Asia (59%), examined the impact of the SARS epidemic (69%), and took place in the hospital setting (79%). The pooled prevalence was higher for anxiety (45%, 95% CI 21 to 69%; 6 studies, 3,373 participants), followed by depression (38%, 95% CI 15 to 60%; 7 studies, 3,636 participants), acute stress disorder (31%, 95% CI 0 to 82%, 3 studies , 2,587 participants), burnout (29%, 95% CI 25 to 32%; 3 studies; 1,168 participants) and post-traumatic stress disorder (19%, 95% CI 11 to 26%, 10 studies, 3,121 participants). Based on 37 studies, we identified a broad number of risk factors for these conditions, including sociodemographic: younger age and female gender; social factors: lack of social support, social rejection or isolation, stigmatization; and occupational: working in a high risk environment (frontline staff), specific occupational roles (e.g., nurse), and lower levels of specialized training, preparedness and job experience. Two out of five interventions identified were educational aimed to prevent mental health problems by increasing HCWs resilience. These interventions showed positive effects in confidence in support and training, pandemic self-efficacy and interpersonal problems solving (very low certainty). One multifaceted intervention (based on training and organisational changes) targeted at hospital nurses during the SARS epidemic produced statistically significant improvements in anxiety, depression, and sleep quality (very low certainty). The impact of the two remaining interventions (multifaceted and based on psychotherapy provision) was unreported. Conclusion: The prevalence of anxiety, depression, acute and post-traumatic stress disorder, and burnout, was high both during and after the outbreaks. These problems not only have a long-lasting effect on the mental health of HCWs, but also hinder the urgent response to the current COVID-19 pandemic, by jeopardising attention and decision-making. Governments and healthcare authorities should take urgent actions to protect the mental health of HCWs. In light of the limited evidence regarding the impact of interventions to tackle mental health problems in HCWs, the risk factors identified in this study represent important targets for future interventions. |
7 | 83n6zx29 | are there serological tests that detect antibodies to coronavirus? | Immunization |
5 | epcel2ez | what drugs have been active against SARS-CoV or SARS-CoV-2 in animal studies? | The epidemic of 2019-novel-coronavirus (2019-nCoV) pneumonia and insights for emerging infectious diseases in the future Abstract At the end of December 2019, a novel coronavirus, 2019-nCoV, caused an outbreak of pneumonia spreading from Wuhan, Hubei province, to the whole country of China, which has posed great threats to public health and attracted enormous attention around the world. To date, there are no clinically approved vaccines or antiviral drugs available for these human coronavirus infections. Intensive research on the novel emerging human infectious coronaviruses is urgently needed to elucidate their route of transmission and pathogenic mechanisms, and to identify potential drug targets, which would promote the development of effective preventive and therapeutic countermeasures. Herein, we describe the epidemic and etiological characteristics of 2019-nCoV, discuss its essential biological features, including tropism and receptor usage, summarize approaches for disease prevention and treatment, and speculate on the transmission route of 2019-nCoV. |
21 | l352l3yk | what are the mortality rates overall and in specific populations | Practical Strategies Against the Novel Coronavirus and COVID-19—the Imminent Global Threat The last month of 2019 harbingered the emergence of a viral outbreak that is now a major public threat globally. COVID-19 was first diagnosed and confirmed in a couple of cases with unknown pneumonia; the patients lived in, or travelled to, Wuhan, the capital of China's Hubei province. People now face a complex challenge that deserves urgent intervention by all involved in medical healthcare globally. Conventional antiviral therapies or vaccines are the most referred means of tackling the virus, but we think establishing these ideal management strategies is presently far-fetched. In-house isolation or quarantine of suspected cases to keep hospital admissions manageable and prevent in-hospital spread of the virus, and promoting general awareness about transmission routes are the practical strategies used to tackle the spread of COVID-19. Cases with weakened or compromised immune systems—for example, elderly individuals, young children, and those with pre-existing conditions such as diabetes, cancer, hypertension, and chronic respiratory diseases—are particularly more susceptible to COVID-19. Hopefully, cumulative data using whole-genome sequencing of the SARS-CoV-2 genome in parallel with mathematical modeling will help the molecular biologists to understand unknown features of the pathogenesis and epidemiology of COVID-19. |
39 | nr7d1zor | What is the mechanism of cytokine storm syndrome on the COVID-19? | Serum protein profiling reveals a landscape of inflammation and immune signaling in early-stage COVID-19 infection Coronavirus disease 2019 (COVID-19) is a highly contagious infection and threating the human lives in the world. The elevation of cytokines in blood is crucial to induce cytokine storm and immunosuppression in the transition of severity in COVID-19 patients. However, the comprehensive changes of serum proteins in COVID-19 patients throughout the SARS-CoV-2 infection is unknown. In this work, we developed a high-density antibody microarray and performed an in-depth proteomics analysis of serum samples collected from early COVID-19 (n=15) and influenza (n=13) patients. We identified a large set of differentially expressed proteins (n=125) that participate in a landscape of inflammation and immune signaling related to the SARS-CoV-2 infection. Furthermore, the significant correlations of neutrophil and lymphocyte with the CCL2 and CXCL10 mediated cytokine signaling pathways was identified. These information are valuable for the understanding of COVID-19 pathogenesis, identification of biomarkers and development of the optimal anti-inflammation therapy. |
27 | j9525ohh | what is known about those infected with Covid-19 but are asymptomatic? | China's fight against COVID-19: What we have done and what we should do next? Background: On 12 March, the World Health Organization Director-General declared that "the threat of a global pandemic has become a reality", and the disease caused by the novel coronavirus, known as COVID-19, has become a global concern. Chinese efforts in curbing the virus have widely been recognized. Even the WHO has lauded the efforts of the Chinese government and advised the world to learn from China in fighting the disease. Since the outbreak of COVID-19, to curb the spread of the epidemic, the Chinese government has implemented unprecedented prevention interventions at the nationwide level. Currently, the outbreak in Wuhan is changing in a positive direction and has been effectively controlled. However, it is not clear what these measures were and how these measures changed to curb the outbreak of COVID-19 quickly. This study explored the characteristics and identified that China's control strategies have changed the epidemiological curve of rapidly rising new confirmed cases of COVID-19. This study also seeks to expand the experiences and lessons from this outbreak. Methods: We collected public health interventions measures from Jan 20, 2020, to 5 March 2020, and data from COVID-19 daily newly confirmed cases and daily cumulates cases to compare the control effects and changing trends. We performed a retrospective description of these intervention strategies from three stages. Besides, from the perspective of public health, the experiences and lessons exposed by this outbreak were roughly summarized. Results: These non-pharmacology interventions measures adopted by the Chinese government by the instruction and spirit of President Xi Jinping were timely and efficient. Conclusions: The present study was conducted to comprehensively analyze from a social epidemiology context. The results confirmed that these radical interventions taken by the Chinese government were effective, ambitious, and agile. However, we must be aware that the epidemic situation in Wuhan is still challenging. Keywords: China; COVID-19; intervention measures; change features, lessons |
5 | tph5n7ak | what drugs have been active against SARS-CoV or SARS-CoV-2 in animal studies? | Reversal of the Progression of Fatal Coronavirus Infection in Cats by a Broad-Spectrum Coronavirus Protease Inhibitor Coronaviruses infect animals and humans causing a wide range of diseases. The diversity of coronaviruses in many mammalian species is contributed by relatively high mutation and recombination rates during replication. This dynamic nature of coronaviruses may facilitate cross-species transmission and shifts in tissue or cell tropism in a host, resulting in substantial change in virulence. Feline enteric coronavirus (FECV) causes inapparent or mild enteritis in cats, but a highly fatal disease, called feline infectious peritonitis (FIP), can arise through mutation of FECV to FIP virus (FIPV). The pathogenesis of FIP is intimately associated with immune responses and involves depletion of T cells, features shared by some other coronaviruses like Severe Acute Respiratory Syndrome Coronavirus. The increasing risks of highly virulent coronavirus infections in humans or animals call for effective antiviral drugs, but no such measures are yet available. Previously, we have reported the inhibitors that target 3C-like protease (3CLpro) with broad-spectrum activity against important human and animal coronaviruses. Here, we evaluated the therapeutic efficacy of our 3CLpro inhibitor in laboratory cats with FIP. Experimental FIP is 100% fatal once certain clinical and laboratory signs become apparent. We found that antiviral treatment led to full recovery of cats when treatment was started at a stage of disease that would be otherwise fatal if left untreated. Antiviral treatment was associated with a rapid improvement in fever, ascites, lymphopenia and gross signs of illness and cats returned to normal health within 20 days or less of treatment. Significant reduction in viral titers was also observed in cats. These results indicate that continuous virus replication is required for progression of immune-mediated inflammatory disease of FIP. These findings may provide important insights into devising therapeutic strategies and selection of antiviral compounds for further development for important coronaviruses in animals and humans. |
17 | di23na30 | are there any clinical trials available for the coronavirus | Review and methodological analysis of trials currently testing treatment and prevention options for the novel coronavirus disease (COVID-19) globally. Background: As novel coronavirus disease (COVID-19) cases continue to steeply rise globally within an unprecedented short period of time, solid evidence from large randomised controlled trials is still lacking. Currently, numerous trials testing potential treatment and preventative options are undertaken globally. Objectives: We summarised all currently registered clinical trials examining treatment and prevention options for COVID-19 pneumonia. Additionally, we evaluated the quality of the retrieved interventional studies. Data sources: The ClinicalTrials.gov, the Chinese Clinical Trial Registry and the European Union Clinical Trials Register were systematically searched. Study eligibility criteria: Registered clinical trials examining treatment and/or prevention options for COVID-19 were included. No language, country or study design restrictions were applied. Withdrawn, cancelled studies and trials not reporting therapeutic or preventative strategies for COVID-19 were excluded. Participants and interventions: No restrictions in terms of participants' age and medical background or type of intervention were enforced. Methods: The registries were searched using the term "coronavirus" or "COVID-19" from their inception until 26th March 2020. Additional manual search of the registries was also performed. Eligible studies were summarised and tabulated. Interventional trials were methodologically analysed, excluding expanded access studies and trials testing Traditional Chinese Medicine. Results: In total, 309 trials evaluating therapeutic management options, 23 studies assessing preventive strategies and 3 studies examining both were retrieved. Interventional treatment studies were mostly randomised (n=150, 76%) and open-label (n=73, 37%) with a median number of planned inclusions of 90 (IQR 40-200). Major categories of interventions that are currently being investigated are discussed. Conclusion: Numerous clinical trials have been registered since the onset of the COVID-19 pandemic. Summarised data on these trials will assist physicians and researchers to promote patient care and guide future research efforts for COVID-19 pandemic containment. However, up to the end of March, 2020, significant information concerning reported trials was lacking. |
43 | 6hum16ve | How has the COVID-19 pandemic impacted violence in society, including violent crimes? | Conducting clinical trials in heart failure during (and after) the COVID-19 pandemic: an Expert Consensus Position Paper from the Heart Failure Association (HFA) of the European Society of Cardiology (ESC) The coronavirus disease 2019 (COVID-19) pandemic, caused by the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), has important implications for the safety of participants in clinical trials and the research staff caring for them and, consequently, for the trials themselves. Patients with heart failure may be at greater risk of infection with COVID-19 and the consequences might also be more serious, but they are also at risk of adverse outcomes if their clinical care is compromised. As physicians and clinical trialists, it is our responsibility to ensure safe and effective care is delivered to trial participants without affecting the integrity of the trial. The social contract with our patients demands no less. Many regulatory authorities from different world regions have issued guidance statements regarding the conduct of clinical trials during this COVID-19 crisis. However, international trials may benefit from expert guidance from a global panel of experts to supplement local advice and regulations, thereby enhancing the safety of participants and the integrity of the trial. Accordingly, the Heart Failure Association of the European Society of Cardiology on 21 and 22 March 2020 conducted web-based meetings with expert clinical trialists in Europe, North America, South America, Australia, and Asia. The main objectives of this Expert Position Paper are to highlight the challenges that this pandemic poses for the conduct of clinical trials in heart failure and to offer advice on how they might be overcome, with some practical examples. While this panel of experts are focused on heart failure clinical trials, these discussions and recommendations may apply to clinical trials in other therapeutic areas. |
22 | g9qlo3xh | are cardiac complications likely in patients with COVID-19? | Association of cardiac biomarkers and comorbidities with increased mortality, severity, and cardiac injury in COVID‐19 patients: A meta‐regression and Decision tree analysis BACKGROUND: Coronavirus disease‐2019 (COVID‐19) has a deleterious effect on several systems, including the cardiovascular system. We aim to systematically explore the association of COVID‐19 severity and mortality rate with the history of cardiovascular diseases and/or other comorbidities and cardiac injury laboratory markers. METHODS: The standardized mean difference (SMD) or odds ratio (OR) and 95% confidence intervals (CI) were applied to estimate pooled results from the 56 studies. The prognostic performance of cardiac markers for predicting adverse outcomes and to select the best cutoff threshold was estimated by ROC curve analysis. Decision tree analysis by combining cardiac markers with demographic and clinical features was applied to predict mortality and severity in COVID‐19 patients. RESULTS: A meta‐analysis of 17,794 patients showed patients with high cardiac troponin I (OR=5.22, 95%CI=3.73‐7.31, p<0.001) and AST levels (OR=3.64, 95%CI=2.84‐4.66, p<0.001) were more likely to develop adverse outcomes. High troponin I >13.75 ng/L combined with either advanced age >60 years or elevated AST level >27.72 U/L was the best model to predict poor outcomes. CONCLUSIONS: COVID‐19 severity and mortality are complicated by myocardial injury. Assessment of cardiac injury biomarkers may improve the identification of those patients at the highest risk and potentially lead to improved therapeutic approaches. This article is protected by copyright. All rights reserved. |
22 | z17n61m3 | are cardiac complications likely in patients with COVID-19? | How Hot Will it Get? |
31 | of9t5i10 | How does the coronavirus differ from seasonal flu? | Use of Toll-Like Receptor 3 Agonists Against Respiratory Viral Infections Respiratory RNA viruses are constantly evolving, thus requiring development of additional prophylactic and therapeutic strategies. Harnessing the innate immune system to non-specifically respond to viral infection has the advantage of being able to circumvent viral mutations that render the virus resistant to a particular therapeutic agent. Viruses are recognized by various cellular receptors, including Toll-like receptor (TLR) 3 which recognizes double-stranded (ds)RNA produced during the viral replication cycle. TLR3 agonists include synthetic dsRNA such as poly (IC), poly (ICLC) and poly (AU). These agents have been evaluated and found to be effective against a number of viral agents. One major limitation has been the toxicity associated with administration of these drugs. Significant time and effort have been spent to develop alternatives/modifications that will minimize these adverse effects. This review will focus on the TLR3 agonist, poly (IC)/(ICLC) with respect to its use in treatment/prevention of respiratory viral infections. |
13 | c4ld6qdw | what are the transmission routes of coronavirus? | [Challenges and countermeasures on Chinese malaria elimination programme during the coronavirus disease 2019 (COVID-19) outbreak]. Since the end of 2019, the coronavirus disease 2019 (COVID-19) has been extensively epidemic in China, which not only seriously threatens the safety and health of Chinese people, but also challenges the management of other infectious diseases. Currently, there are still approximately three thousand malaria cases imported into China every year. If the diagnosis and treatment of malaria cases as well as the investigation and response of the epidemic foci are not carried out timely, it may endanger patients'lives and cause the possible of secondary transmission, which threatens the achievements of malaria elimination in China. Due to the extensive spread and high transmission ability of the COVID-19, there is a possibility of virus infections among malaria cases during the medical care-seeking behaviors and among healthcare professionals during clinical diagnosis and treatment, sample collection and testing and epidemiological surveys. This paper analyzes the challenges of the COVID-19 for Chinese malaria elimination programme, and proposes the countermeasures in response to the COVID-19 outbreak, so as to provide the reference for healthcare professionals. |
20 | 0ojayw16 | are patients taking Angiotensin-converting enzyme inhibitors (ACE) at increased risk for COVID-19? | May patients receiving 5-alpha-reductase inhibitors be in higher risk of COVID-19 complications ? Abstract COVID-19 pandemic is a major challenge for global and national healthcare providers. Number of new cases is continuously increasing with an emerging trend showing worse prognosis in males in comparison to females. Based on this observation, our proposed hypothesis is that 5-alpha-reductase inhibitors, that are commonly used for BPH treatment, may be one of the factors contributing to poorer prognosis in males. Background With increasing number of COVID-19 cases, an evident sex- dependent difference in disease outcomes can be observed. Based on published studies with short term follow-up, males have 65% higher mortality rate (1). The question remains, whether long term observational studies will confirm improved recovery in females. |
31 | 56lhovmz | How does the coronavirus differ from seasonal flu? | Rapid diagnostic testing for seasonal influenza: an evidence-based review and comparison with unaided clinical diagnosis. BACKGROUND Worldwide, seasonal influenza imposes a considerable health and economic burden. Clinical diagnosis of influenza-like illness (ILI) is complicated by non-specific symptomatology. Rapid flu tests (RFTs) impact treatment decisions and may improve patient care; yet, recommendations for RFT use are broad, and the performance of unaided clinical diagnosis relative to RFTs is unclear. OBJECTIVES To determine age-stratified, overall sensitivities and specificities of the widely studied RFT, QuickVue® (Quidel Corporation, San Diego, CA), and clinical diagnosis of ILI by meta-analysis and to seek factors associated with poorer clinical diagnostic discrimination. METHODS A systematic literature review was conducted using article selection criteria identifying studies indexed in PubMed/MEDLINE, the Cochrane Library, and other pertinent sources of studies reporting sensitivity, specificity, and effects of RFTs and clinical diagnosis on decision-making for patients with ILI. RESULTS QuickVue's® diagnostic specificity exceeds that of unaided clinical diagnosis by 29-31%. False-positive results occur approximately 8.2 times more frequently by unaided clinical diagnosis than by the RFT alone. These findings were unaffected by seasonal variations in disease prevalence. RFTs reduce diagnostic testing, antibiotic use, and emergency department utilization while increasing antiviral prescription rates. No systematic relationship between the broadness of clinical diagnostic criteria for influenza and diagnostic performance was observed across studies included in this review. CONCLUSIONS Use of RFTs improves seasonal influenza diagnostic specificity above that based on unaided clinical diagnosis irrespective of the broadness of clinical diagnostic criteria, and affects clinical decision-making. These results provide an improved framework upon which to diagnose influenza, design future RFT studies, and modify existing recommendations for improved ILI patient management. |
6 | 5s03f0pp | what types of rapid testing for Covid-19 have been developed? | Pooled RNA extraction and PCR assay for efficient SARS-CoV-2 detection Testing for active SARS-CoV-2 infection is a fundamental tool in public health measures taken to control the COVID-19 pandemic. Due to the overwhelming use of SARS-CoV-2 RT-PCR tests worldwide, availability of test kits has become a major bottleneck. Here we demonstrate the reliability and efficiency of two simple pooling strategies that can increase testing capacity about 5-fold to 7.5-fold, in populations with a low infection rate. We have implemented the method in a routine clinical diagnosis setting, and already tested 2,168 individuals for SARS-CoV-2 using 311 RNA extraction and RT-PCR kits. |
17 | 6vxj083j | are there any clinical trials available for the coronavirus | Virus detection and its association with symptoms during influenza‐like illness in a sample of healthy adults enrolled in a randomised controlled vaccine trial Background Viral respiratory infections are associated with significant morbidity and mortality. Many new aetiological agents have been described recently. Objectives We looked for respiratory viruses in a population‐based sample of healthy adults with influenza‐like illness (ILI). We investigated host and spatio‐temporal associations with virus isolation and host, spatio‐temporal and virus associations with self‐reported symptoms. Patients/Methods We recruited 586 participants experiencing 651 illness episodes from a population of healthy adults enrolled in an influenza vaccine effectiveness trial. At ILI assessment visits, a respiratory swab was collected and tested for viruses using a combination of polymerase chain reaction (PCR) assays. Participants also completed a questionnaire detailing their clinical course in 336 episodes. Results Of 643 samples analysed, a virus was identified in 44%. Half were picornaviruses, with influenza and coronaviruses the next most common. Individuals with influenza were significantly less likely to have been immunised than the reference (virus negative) population (OR = 0·52 (0·31, 0·87) P = 0·01). The mean symptom score (95% CI) reported by individuals with influenza was significantly higher than in all other episodes [Influenza: 10·2 (9·4, 10·9); Other: 7·4 (7·2, 7·7); Difference (95% CI): 2·5 (1·5, 3·5); P < 0·001]. In an analysis restricted to influenza‐positive cases, the symptom score was not attenuated by vaccination. Conclusions Our findings indicate that a greater number of symptoms are displayed by individuals presenting with influenza confirmed ILI compared with other agents that cause ILI. While influenza vaccination reduced the probability of influenza virus detection, symptom score for influenza‐positive ILI was not attenuated. |
40 | xlf2ezm3 | What are the observed mutations in the SARS-CoV-2 genome and how often do the mutations occur? | Antibody cocktail to SARS-CoV-2 spike protein prevents rapid mutational escape seen with individual antibodies Antibodies targeting the spike protein of SARS-CoV-2 present a promising approach to combat the COVID19 pandemic; however, concerns remain that mutations can yield antibody resistance. We investigate the development of resistance against four antibodies to the spike protein that potently neutralize SARS-CoV-2, individually as well as when combined into cocktails. These antibodies remain effective against spike variants that have arisen in the human population. However, novel spike mutants rapidly appeared following in vitro passaging in the presence of individual antibodies, resulting in loss of neutralization; such escape also occurred with combinations of antibodies binding diverse but overlapping regions of the spike protein. Importantly, escape mutants were not generated following treatment with a non-competing antibody cocktail. |
4 | z7t0s7xb | what causes death from Covid-19? | Early evidence of pronounced brain involvement in fatal COVID-19 outcomes |
29 | og92zxnf | 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? | Use of the informational spectrum methodology for rapid biological analysis of the novel coronavirus 2019-nCoV: prediction of potential receptor, natural reservoir, tropism and therapeutic/vaccine target. A novel coronavirus recently identified in Wuhan, China (2019-nCoV) has expanded the number of highly pathogenic coronaviruses affecting humans. The 2019-nCoV represents a potential epidemic or pandemic threat, which requires a quick response for preparedness against this infection. The present report uses the informational spectrum methodology to identify the possible origin and natural host of the new virus, as well as putative therapeutic and vaccine targets. The performed in silico analysis indicates that the newly emerging 2019-nCoV is closely related to severe acute respiratory syndrome (SARS)-CoV and, to a lesser degree, Middle East respiratory syndrome (MERS)-CoV. Moreover, the well-known SARS-CoV receptor (ACE2) might be a putative receptor for the novel virus as well. Additional results indicated that civets and poultry are potential candidates for the natural reservoir of the 2019-nCoV, and that domain 288-330 of S1 protein from the 2019-nCoV represents promising therapeutic and/or vaccine target. |
31 | h4s25x7x | How does the coronavirus differ from seasonal flu? | Clinical trials: management of investigational products during the coronavirus (COVID-19) pandemic Disclaimer: In an effort to expedite the publication of articles related to the COVID-19 pandemic, AJHP is posting these manuscripts online as soon as possible after acceptance. Accepted manuscripts have been peer-reviewed and copyedited, but are posted online before technical formatting and author proofing. These manuscripts are not the final version of record and will be replaced with the final article (formatted per AJHP style and proofed by the authors) at a later time. |
9 | vahd59z8 | how has COVID-19 affected Canada | COVID-19 in Italy: Ageism and Decision-Making in a Pandemic |
36 | dtax0yti | What is the protein structure of the SARS-CoV-2 spike? | Host cell proteases: critical determinants of coronavirus tropism and pathogenesis Coronaviruses are a large group of enveloped, single-stranded positive-sense RNA viruses that infect a wide range of avian and mammalian species, including humans. The emergence of deadly human coronaviruses, severe acute respiratory syndrome coronavirus (SARS-CoV), and Middle East respiratory syndrome coronavirus (MERS-CoV) have bolstered research in these viral and often zoonotic pathogens. While coronavirus cell and tissue tropism, host range, and pathogenesis are initially controlled by interactions between the spike envelope glycoprotein and host cell receptor, it is becoming increasingly apparent that proteolytic activation of spike by host cell proteases also plays a critical role. Coronavirus spike proteins are the main determinant of entry as they possess both receptor binding and fusion functions. Whereas binding to the host cell receptor is an essential first step in establishing infection, the proteolytic activation step is often critical for the fusion function of spike, as it allows for controlled release of the fusion peptide into target cellular membranes. Coronaviruses have evolved multiple strategies for proteolytic activation of spike, and a large number of host proteases have been shown to proteolytically process the spike protein. These include, but are not limited to, endosomal cathepsins, cell surface transmembrane protease/serine (TMPRSS) proteases, furin, and trypsin. This review focuses on the diversity of strategies coronaviruses have evolved to proteolytically activate their fusion protein during spike protein biosynthesis and the critical entry step of their life cycle, and highlights important findings on how proteolytic activation of coronavirus spike influences tissue and cell tropism, host range and pathogenicity. |
3 | 6ngxo8ff | will SARS-CoV2 infected people develop immunity? Is cross protection possible? | Controlled, double-blind, randomized trial to assess the efficacy and safety of hydroxychloroquine chemoprophylaxis in SARS CoV2 infection in healthcare personnel in the hospital setting: A structured summary of a study protocol for a randomised controlled trial BACKGROUND: SARS-CoV-2 infection presents a high transmission in the group of health professionals in Spain (12-15% infected). Currently there is no accepted chemoprophylaxis but hydroxychloroquine (HDQ) is known to inhibit the coronavirus in vitro. Our hypothesis is that oral administration of hydroxychloroquine to healthcare professionals can reduce the incidence and prevalence of infection as well as its severity in this group. METHODS: Design: Prospective, single center, double blind, randomised, controlled trial (RCT). Participants: Adult health-care professionals (18-65 years) working in areas of high exposure and high risk of transmission of SARS-COV-2 (COVID areas, Intensive Care Unit –ICUs-, Emergency, Anesthesia and all those performing aerosol-generating procedures) will be included. Exclusion criteria include previous infection with SARS CoV2 (positive SARS-CoV-2 PCR or IgG serology), pregnancy or lactation, any contraindication to hydroxychloroquine or evidence of unstable or clinically significant systemic disease. INTERVENTIONS: Patients will be randomized (1:1) to receive once-daily oral Hydroxychloroquine 200mg for two months (HC group) or placebo (P group) in addition to the protective measures appropriate to the level of exposure established by the hospital. A serological evaluation will be carried out every 15 days with PCR in case of seroconversion, symptoms or risk exposure. Primary outcome is the percentage of subjects presenting infection (seroconversion and/or PCR +ve) by the SARS-Cov-2 virus during the observation period. Additionally, both the percentage of subjects in each group presenting Pneumonia with severity criteria (Curb 65 ≥2) and that of subjects requiring admission to ICU will be determined. DISCUSSION: While awaiting a vaccine, hygiene measures, social distancing and personal protective equipment are the only primary prophylaxis measures against SARS-CoV-2, but they have not been sufficient to protect our healthcare professionals. Some evidence of the in vitro efficacy of hydroxychloroquine against this virus is known, along with some clinical data that would support the study of this drug in the chemoprophylaxis of infection. However, there are still no data from controlled clinical trials in this regard. If our hypothesis is confirmed, hydroxychloroquine can help professionals fight this infection with more guarantees. PARTICIPANTS: This is a single-center study that will be carried out at the Marqués de Valdecilla University Hospital. 450 health professionals working at the Hospital Universitario Marqués de Valdecilla in areas of high exposure and high risk of transmission of SARS COV2 (COVID hospital areas, Intensive Care Unit, Emergency, Anesthesia and all those performing aerosol-generating procedures) will be included. Inclusion criteria: 1) Health professionals aged between 18 and 65 years (inclusive) at the time of the first screening visit; 2) They must provide signed written informed consent and agree to comply with the study protocol; 3) Active work in high exposure areas during the last two weeks and during the following weeks. Exclusion criteria: 1) Previous infection with SARS CoV2 (positive coronavirus PCR or positive serology with SARS Cov2 negative PCR and absence of symptoms); 2) Current treatment with hydroxychloroquine or chloroquine; 3) Hypersensitivity, allergy or any contraindication for taking hydroxychloroquine, in the technical sheet; 4) Previous or current treatment with tamoxifen or raloxifene; 5) Previous eye disease, especially maculopathy; 6) Known heart failure (Grade III to IV of the New York Heart Association classification) or prolonged QTc; 7) Any type of cancer (except basal cell) in the last 5 years; 6) Refusal to give informed consent; 8) Evidence of any other unstable or clinically significant untreated immune, endocrine, hematological, gastrointestinal, neurological, neoplastic or psychiatric illness; 9) Antibodies positive for the human immunodeficiency virus; 10) Significant kidney or liver disease; 11) Pregnancy or lactation. INTERVENTION AND COMPARATOR: 1. Intervention: (n = 225): One 200 mg hydroxychloroquine sulfate coated tablet once daily for two months. 2. Comparator (control group) (n = 225): One hydroxychloroquine placebo tablet (identical to that of the drug) once daily for two months. MAIN OUTCOMES: number and percentage of healthcare personnel presenting symptomatic and asymptomatic infection (see "Diagnosis of SARS CoV2 infection" below) by the SARS-Cov2 virus during the study observation period (8 weeks) in both treatment arms; number and percentage of healthcare personnel in each group presenting with Pneumonia with severity criteria (Curb 65 ≥2) and number and percentage of healthcare personnel requiring admission to the Intensive Care Unit (ICU) in both treatment arms. DIAGNOSIS OF SARS COV2 INFECTION: Determination of IgA, IgM and IgG type antibodies against SARS-CoV-2 using the Anti-SARS-CoV-2 ELISA kit (EUROIMMUN Medizinische Labordiagnostika AG, Germany) every two weeks. In cases of seroconversion, a SARS-CoV-2 PCR will be performed to rule out / confirm an active infection (RT-PCR in One Step: RT performed with mastermix (Takara) and IDT probes, following protocol published and validated by the CDC Evaluation of COVID-19 in case of SARS-CoV-2 infection RANDOMISATION: Participants will be allocated to intervention and comparator groups according to a balanced randomization scheme (1: 1). The assignment will be made through a computer-generated numeric sequence for all participants BLINDING (MASKING): Both participants and investigators responsible for recruiting and monitoring participants will be blind to the assigned arm. NUMBERS TO BE RANDOMISED (SAMPLE SIZE): Taking into account the current high prevalence of infection in healthcare personnel in Spain (up to 15%), to detect a difference equal to or greater than 8% in the percentage estimates through a two-tailed 95% CI, with a statistical power of 80% and a dropout rate of 5%, a total of 450 participants will need to be included (250 in each arm). TRIAL STATUS: The protocol approved by the health authorities in Spain (Spanish Agency for Medicines and Health Products "AEMPS") and the Ethics and Research Committee of Cantabria (CEIm Cantabria) corresponds to version 1.1 of April 2, 2020. Currently, recruitment has not yet started, with the start scheduled for the second week of May 2020. TRIAL REGISTRATION: Eudra CT number: 2020-001704-42 (Registered on 29 March 2020) FULL PROTOCOL: The full protocol is attached as an additional file, accessible from the Trials website (Additional file 1). In the interest in expediting dissemination of this material, the familiar formatting has been eliminated; this Letter serves as a summary of the key elements of the full protocol. The study protocol has been reported in accordance with the Standard Protocol Items: Recommendations for Clinical Interventional Trials (SPIRIT) guidelines (Additional file 2). |
39 | xf4sofyc | What is the mechanism of cytokine storm syndrome on the COVID-19? | Epigenetic dysregulation of ACE2 and interferon-regulated genes might suggest increased COVID-19 susceptibility and severity in lupus patients Abstract Infection caused by SARS-CoV-2 can result in severe respiratory complications and death. Patients with a compromised immune system are expected to be more susceptible to a severe disease course. In this report we suggest that patients with systemic lupus erythematous might be especially prone to severe COVID-19 independent of their immunosuppressed state from lupus treatment. Specifically, we provide evidence in lupus to suggest hypomethylation and overexpression of ACE2, which is located on the X chromosome and encodes a functional receptor for the SARS-CoV-2 spike glycoprotein. Oxidative stress induced by viral infections exacerbates the DNA methylation defect in lupus, possibly resulting in further ACE2 hypomethylation and enhanced viremia. In addition, demethylation of interferon-regulated genes, NFκB, and key cytokine genes in lupus patients might exacerbate the immune response to SARS-CoV-2 and increase the likelihood of cytokine storm. These arguments suggest that inherent epigenetic dysregulation in lupus might facilitate viral entry, viremia, and an excessive immune response to SARS-CoV-2. Further, maintaining disease remission in lupus patients is critical to prevent a vicious cycle of demethylation and increased oxidative stress, which will exacerbate susceptibility to SARS-CoV-2 infection during the current pandemic. Epigenetic control of the ACE2 gene might be a target for prevention and therapy in COVID-19. |
32 | leiuve0f | Does SARS-CoV-2 have any subtypes, and if so what are they? | Isolation of active peptides from plant hydrolysates that promote Vero cells growth in stirred cultures |
36 | sdtovjl6 | What is the protein structure of the SARS-CoV-2 spike? | Recombinant viral proteins for use in diagnostic ELISAs to detect virus infection ELISAs provide a valuable tool in the detection and diagnosis of virus infection. The ability to produce recombinant viral proteins will ensure that future ELISAs are safe, specific and rapid. This latter point being the most crucial advantage in that even if a virus cannot be cultured, provided gene sequence is available, it is possible to rapidly respond to emerging viruses and new viral strains of existing pathogens. Indeed, ELISAs based on peptides (corresponding to epitopes) also hold great promise, as in this case no cloning or expression of a recombinant protein is required. Both recombinant protein and peptide based systems lend themselves to large scale production and purification. These approaches can also be used to distinguish recombinant vaccines from parental or wild type viruses. |
37 | gmk4qo4i | What is the result of phylogenetic analysis of SARS-CoV-2 genome sequence? | The UCSC SARS-CoV-2 Genome Browser Background Researchers are generating molecular data pertaining to the SARS-CoV-2 RNA genome and its proteins at an unprecedented rate during the COVID-19 pandemic. As a result, there is a critical need for rapid and continuously updated access to the latest molecular data in a format in which all data can be quickly cross-referenced and compared. We adapted our genome browser visualization tool to the viral genome for this purpose. Molecular data, curated from published studies or from database submissions, are mapped to the viral genome and grouped together into "annotation tracks" where they can be visualized along the linear map of the viral genome sequence and programmatically downloaded in standard format for analysis. Results The UCSC Genome Browser for SARS-CoV-2 (https://genome.ucsc.edu/covid19.html) provides continuously updated access to the mutations in the many thousands of SARS-CoV-2 genomes deposited in GISAID and the international nucleotide sequencing databases, displayed alongside phylogenetic trees. These data are augmented with alignments of bat, pangolin, and other animal and human coronavirus genomes, including per-base evolutionary rate analysis. All available annotations are cross-referenced on the virus genome, including those from major databases (PDB, RFAM, IEDB, UniProt) as well as up-to-date individual results from preprints. Annotated data include predicted and validated immune epitopes, promising antibodies, RT-PCR and sequencing primers, CRISPR guides (from research, diagnostics, vaccines, and therapies), and points of interaction between human and viral genes. As a community resource, any user can add manual annotations which are quality checked and shared publicly on the browser the next day. Conclusions We invite all investigators to contribute additional data and annotations to this resource to accelerate research and development activities globally. Contact us at [email protected] with data suggestions or requests for support for adding data. Rapid sharing of data will accelerate SARS-CoV-2 research, especially when researchers take time to integrate their data with those from other labs on a widely-used community browser platform with standardized machine-readable data formats, such as the SARS-CoV-2 Genome Browser. |
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