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32 | sbswy7el | Does SARS-CoV-2 have any subtypes, and if so what are they? | SARS-CoV-2: Camazotz's Curse The world is currently face to face with a pandemic which is spreading rapidly across the globe caused by SARS-CoV-2, a strain of Coronaviruses (CoVs) belonging to subgenus Sarbecovirus of genus Betacoronavirus. World Health Organisation (WHO) on 11 Feb 20 named this disease caused by SARS-CoV-2 as Covid-19. This pandemic is spreading rapidly and more than 20,00,000 cases have occurred globally. The human Coronaviruses discovered in 1960s were considered potentially harmless endemic viruses with seasonal distribution before late 2002. The CoVs are found in a large number of domestic and wild animals and birds. The first pandemic caused by Coronavirus caused by SARS-CoV was recognized in the late 2002 in Guangdong Province and resulted in widespread morbidity and mortality. This was followed by MERS-CoV which began in 2012 in the Arabian peninsula with multiple outbreaks related to it in various parts of the globe. Various studies have suggested how these viruses made their entry from their natural reservoir bats via intermediate host like civets and camels in case of SARS-CoV and MERS-CoV respectively. The intermediate host of the SARS-CoV-2 still needs to be established. The SARS-CoV-2 has 96.2% similarity to the bat Severe Acute Respiratory Syndrome related-Coronavirus (SARSr-CoV RaTG13). SARS-CoV-2 has been found to be more distant in relation to SARS-CoV (79%) and MERS-CoV (50%). At the whole genome sequence level pangolin CoV and SARSr-CoV RaTG13 show 91.02% and 96.2% similarity with SARS-CoV-2 but the S1 subunit of spike protein of pangolin CoV is more closely related to SARS-CoV-2 than SARSr-CoV RaTG13. The genetic analysis of the currently circulating strains of the pandemic have shown 99.98-100% similarity in their genomes implying a recent shift to humans. The animal source of SARS-CoV-2 needs to be identified to implement control measures in the present pandemic. Also, how the virus moves interspecies will help predict and prevent future pandemics. |
25 | r0r1kvkp | which biomarkers predict the severe clinical course of 2019-nCOV infection? | Development and external validation of a prognostic multivariable model on admission for hospitalized patients with COVID-19 Background: COVID-19 pandemic has developed rapidly and the ability to stratify the most vulnerable patients is vital. However, routinely used severity scoring systems are often low on diagnosis, even in non-survivors. Therefore, clinical prediction models for mortality are urgently required. Methods: We developed and internally validated a multivariable logistic regression model to predict inpatient mortality in COVID-19 positive patients using data collected retrospectively from Tongji Hospital, Wuhan (299 patients). External validation was conducted using a retrospective cohort from Jinyintan Hospital, Wuhan (145 patients). Nine variables commonly measured in these acute settings were considered for model development, including age, biomarkers and comorbidities. Backwards stepwise selection and bootstrap resampling were used for model development and internal validation. We assessed discrimination via the C statistic, and calibration using calibration-in-the-large, calibration slopes and plots. Findings: The final model included age, lymphocyte count, lactate dehydrogenase and SpO2 as independent predictors of mortality. Discrimination of the model was excellent in both internal (c=0.89) and external (c=0.98) validation. Internal calibration was excellent (calibration slope=1). External validation showed some over-prediction of risk in low-risk individuals and under-prediction of risk in high-risk individuals prior to recalibration. Recalibration of the intercept and slope led to excellent performance of the model in independent data. Interpretation: COVID-19 is a new disease and behaves differently from common critical illnesses. This study provides a new prediction model to identify patients with lethal COVID-19. Its practical reliance on commonly available parameters should improve usage of limited healthcare resources and patient survival rate. |
8 | 6s22uhu9 | how has lack of testing availability led to underreporting of true incidence of Covid-19? | Smart Pooled sample Testing for COVID-19: A Possible Solution for Sparsity of Test Kits There is an exponential growth of COVID-19. The adaptation of preventive measures to limit the spread of infection among the people is the best solution to this health issue. The identification of infected cases and their isolation from healthy people is one of the most important preventive measures. In this regard, screening of the samples from a large number of people is needed which requires a lot of reagent kits for the detection of SARS-CoV-2. The use of smart pooled sample testing with the help of algorithms may be a quite useful strategy in the current prevailing scenario of the COVID-19 pandemic. With the help of this strategy, the optimum number of samples to be pooled for a single test may be determined based on the total positivity rate of the particular community. |
36 | vy7d2ocs | What is the protein structure of the SARS-CoV-2 spike? | Elucidation of Cellular Targets and Exploitation of the Receptor Binding Domain of SARS-CoV-2 for vaccine and monoclonal antibody synthesis The pandemic caused by novel severe acute respiratory syndrome coronavirus (SARS-CoV-2) has resulted in over 452,822 deaths in the first twenty days of June 2020 due to the coronavirus virus disease 2019 (COVID-19). The SARS-CoV-2 uses the host angiotensin-converting enzyme 2 (ACE2) receptor to gain entry inside the human cells where it replicates by using the cell protein synthesis mechanisms. The knowledge of the tissue distribution of ACE2 in human organs is therefore important to predict the clinical course of the COVID-19. Also important is the understanding of the viral receptor-binding domain (RBD) a region within the spike (S) proteins that enable the entry of the virus into the host cells to synthesize vaccine and monoclonal antibodies (mAbs). We performed an exhaustive search of human protein databases to establish the tissues that express ACE2 and performed an in-depth analysis like sequence alignments and homology modeling of the spike protein (S) of the SARS-CoV-2 to identify antigenic regions in the RBD that can be exploited to synthesize vaccine and mAbs. Our results show that ACE2 is widely expressed in human organs that may explain the pulmonary, systemic, and neurological deficits seen in COVID-19 patients. We show that though the S protein of the SARS-CoV-2 is a homolog of S protein of SARS-CoV-1, it has regions of dissimilarities in the RBD and transmembrane segments. We show peptide sequences in the RBD of SARS-CoV-2 that can bind to the MHC alleles and serve as effective epitopes for vaccine and mAbs synthesis. This article is protected by copyright. All rights reserved. |
23 | mjddkz95 | what kinds of complications related to COVID-19 are associated with hypertension? | Poverty, Health and Livelihoods Developing countries, especially those in the tropical regions of the world, are known for poverty and infectious diseases (ID). People in developing countries carry on their day-to-day living amongst these two challenges. Between the years 1940–2004, over 300 emerging human ID have been reported worldwide. Infectious diseases have resulted in high mortality and morbidity in developing countries. Affecting more than 1 billion of the world's population, neglected tropical diseases (NTD) are a group of infectious diseases that are endemic in the poorest regions of the world. Most of the affected populations live in rural areas with very minimal resources but at high risk of disease due to their livelihood. Non-communicable diseases are also on the increase in developing countries, further exacerbating public health challenges in these regions. With nearly 15 million people dying each year as a result of ID, most of them living in developing countries, there is need to find solutions to prevent and tackle infectious diseases in these communities. This book is devoted to infectious diseases and livelihoods in developing countries. |
44 | 4bltio08 | How much impact do masks have on preventing the spread of the COVID-19? | Lack of SARS Transmission among Public Hospital Workers, Vietnam The severe acute respiratory syndrome (SARS) outbreak in Vietnam was amplified by nosocomial spread within hospital A, but no transmission was reported in hospital B, the second of two designated SARS hospitals. Our study documents lack of SARS-associated coronavirus transmission to hospital B workers, despite variable infection control measures and the use of personal protective equipment. |
14 | rbw1vam9 | what evidence is there related to COVID-19 super spreaders | Coronavirus y atención primaria |
32 | efa09wfs | Does SARS-CoV-2 have any subtypes, and if so what are they? | Genotypic characterization of canine coronaviruses associated with fatal canine neonatal enteritis in the United States. Emerging canine coronavirus (CCoV) variants that are associated with systemic infections have been reported in the European Union; however, CCoV-associated disease in the United States is incompletely characterized. The purpose of this study was to correlate the clinicopathological findings and viral antigen distribution with the genotypic characteristics of CCoV in 11 puppies from nine premises in five states that were submitted for diagnostic investigation at Cornell University between 2008 and 2013. CCoV antigen was found in epithelial cells of small intestinal villi in all puppies and the colon in 2 of the 10 puppies where colon specimens were available. No evidence of systemic CCoV infection was found. Comparative sequence analyses of viral RNA extracted from intestinal tissues revealed CCoV-II genotype in 9 out of 11 puppies. Of the nine CCoV-IIs, five were subtyped as group IIa and one as IIb, while three CCoVs could not be subtyped. One of the CCoV-IIa variants was isolated in cell culture. Infection with CCoV alone was found in five puppies, of which two also had small intestinal intussusception. Concurrent infections with either parvovirus (n = 1), attaching-effacing Escherichia coli (n = 4), or protozoan parasites (n = 3) were found in the other six puppies. CCoV is an important differential diagnosis in outbreaks of severe enterocolitis among puppies between 4 days and 21 weeks of age that are housed at high population density. These findings will assist with the rapid laboratory diagnosis of enteritis in puppies and highlight the need for continued surveillance for CCoV variants and intestinal viral diseases of global significance. |
21 | svempphd | what are the mortality rates overall and in specific populations | Excess deaths in people with cardiovascular diseases during the COVID-19 pandemic. Background: Cardiovascular diseases(CVD) increase mortality risk from coronavirus infection(COVID-19), but there are concerns that the pandemic has affected supply and demand of acute cardiovascular care. We estimated excess mortality in specific CVDs, both direct, through infection, and indirect, through changes in healthcare. Methods: We used population-based electronic health records from 3,862,012 individuals in England to estimate pre- and post-COVID-19 mortality risk(direct effect) for people with incident and prevalent CVD. We incorporated: (i)pre-COVID-19 risk by age, sex and comorbidities, (ii)estimated population COVID-19 prevalence, and (iii)estimated relative impact of COVID-19 on mortality(relative risk, RR: 1.5, 2.0 and 3.0). For indirect effects, we analysed weekly mortality and emergency department data for England/Wales and monthly hospital data from England(n=2), China(n=5) and Italy(n=1) for CVD referral, diagnosis and treatment until 1 May 2020. Findings: CVD service activity decreased by 60-100% compared with pre-pandemic levels in eight hospitals across China, Italy and England during the pandemic. In China, activity remained below pre-COVID-19 levels for 2-3 months even after easing lockdown, and is still reduced in Italy and England. Mortality data suggest indirect effects on CVD will be delayed rather than contemporaneous(peak RR 1.4). For total CVD(incident and prevalent), at 10% population COVID-19 rate, we estimated direct impact of 31,205 and 62,410 excess deaths in England at RR 1.5 and 2.0 respectively, and indirect effect of 49932 to 99865 excess deaths. Interpretation: Supply and demand for CVD services have dramatically reduced across countries with potential for substantial, but avoidable, excess mortality during and after the COVID-19 pandemic. |
26 | 1c0i5q74 | what are the initial symptoms of Covid-19? | Association of infected probability of COVID-19 with ventilation rates in confined spaces: a Wells-Riley equation based investigation Background: A growing number of epidemiological cases are proving the possibility of airborne transmission of coronavirus disease 2019 (COVID-19). Ensuring adequate ventilation rate is essential to reduce the risk of infection in confined spaces. Methods: We obtained the quantum generation rate by a COVID-19 infector with a reproductive number based fitting approach, and then estimated the association between infected probability and ventilation rate with the Wells-Riley equation. Results: The estimated quantum generation rate of COVID-19 is 14-48 /h. To ensure infected probabolity less than 1%, ventilation rate lareger than common values (100-350 m3/h and 1200-4000 m3/h for 15 minutes and 3 hours exposure, respectively) is required. If both the infector and susceptibles wear masks, the ventilation rate ensuring less than 1% infected probability is reduced to 50-180 m3/h and 600-2000 m3/h correspondingly, which is easier to be achieved by normal ventilation mode applied in some typical scenarios, including offices, classrooms, buses and aircraft cabins. Interpretation: The risk of potential airborne transmission in confined spaces cannot be ignored. Strict preventive measures that have been widely adopted should be effective in reducing the risk of airborne transmitted infection. |
21 | a0ovwba0 | what are the mortality rates overall and in specific populations | Understanding the Outcomes of Supplementary Support Services in Palliative Care for Older People. A Scoping Review and Mapping Exercise. CONTEXT Supplementary support services in palliative care for older people are increasingly common, but with no recommended tools to measure outcomes, nor reviews synthesising anticipated outcomes. Common clinically focussed tools may be less appropriate. OBJECTIVE To identify stakeholder perceptions of key outcomes from supplementary palliative care support services, then map these onto outcome measurement tools to assess relevance and item redundancy. METHODS A scoping review using Arksey and O'Malley's design. EMBASE, CINAHL, MEDLINE and PSYCHinfo searched using terms relating to palliative care, qualitative research and supplementary support interventions. Papers imported into Endnote™, and Covidence™ used by two reviewers to assess against inclusion criteria. Included papers were imported into NVivo™, and thematically coded to identify key concepts underpinning outcomes. Each item within contender outcome measurement tools was assessed against each concept. RESULTS 60 included papers focused on advance care planning, guided conversations, and volunteer befriending services. Four concepts were identified: enriching relationships; greater autonomy and perceived control; knowing more; and improved mental health. Mapping concepts to contender tool items revealed issues of relevance and redundancy. Some tools had no redundant items, but mapped only to two of four outcome themes, others mapped to all concepts, but with many redundant questions. Tools such as ICECAP-SCM and McGill Quality of Life had high relevance and low redundancy. CONCLUSIONS Pertinent outcome concepts for these services and population are not well represented in commonly used outcome measurement tools, and this may have implications in appropriately measuring outcomes. This review and mapping method may have utility in fields where selecting appropriate outcome tools can be challenging. |
22 | y50ou7gg | are cardiac complications likely in patients with COVID-19? | Triage Considerations for Patients Referred for Structural Heart Disease Intervention During the Coronavirus Disease 2019 (COVID-19) Pandemic: An ACC /SCAI Consensus Statement. The COVID-19 pandemic has strained health care resources around the world causing many institutions to curtail or stop elective procedures. This has resulted in the inability to care for patients valvular and structural heart disease (SHD) in a timely fashion potentially placing these patients at increased risk for adverse cardiovascular complications including congestive heart failure and death. The effective triage of these patients has become challenging in the current environment as clinicians have had to weigh the risk of bringing susceptible patients into the hospital environment during the COVID-19 pandemic versus the risk of delaying a needed procedure. In this document, we suggest guidelines as to how to triage patients in need of SHD interventions and provide a framework of how to decide when it may be appropriate to proceed with intervention despite the ongoing pandemic. In particular, we address the triage of patients in need of trans-catheter aortic valve replacement and percutaneous mitral valve repair. We also address procedural issues and considerations for the function of structural heart disease teams during the COVID-19 pandemic. This article is protected by copyright. All rights reserved. |
23 | kjovtgua | what kinds of complications related to COVID-19 are associated with hypertension? | Rapid and accurate identification of COVID-19 infection through machine learning based on clinical available blood test results Since the sudden outbreak of coronavirus disease 2019 (COVID-19), it has rapidly evolved into a momentous global health concern. Due to the lack of constructive information on the pathogenesis of COVID-19 and specific treatment, it highlights the importance of early diagnosis and timely treatment. In this study, 11 key blood indices were extracted through random forest algorithm to build the final assistant discrimination tool from 49 clinical available blood test data which were derived by commercial blood test equipments. The method presented robust outcome to accurately identify COVID-19 from a variety of suspected patients with similar CT information or similar symptoms, with accuracy of 0.9795 and 0.9697 for the cross-validation set and test set, respectively. The tool also demonstrated its outstanding performance on an external validation set that was completely independent of the modeling process, with sensitivity, specificity, and overall accuracy of 0.9512, 0.9697, and 0.9595, respectively. Besides, 24 samples from overseas infected patients with COVID-19 were used to make an in-depth clinical assessment with accuracy of 0.9167. After multiple verification, the reliability and repeatability of the tool has been fully evaluated, and it has the potential to develop into an emerging technology to identify COVID-19 and lower the burden of global public health. The proposed tool is well-suited to carry out preliminary assessment of suspected patients and help them to get timely treatment and quarantine suggestion. The assistant tool is now available online at http://lishuyan.lzu.edu.cn/COVID2019_2/. |
2 | re9c3e0b | how does the coronavirus respond to changes in the weather | Chapter One Parasites of seabirds: A survey of effects and ecological implications Abstract Parasites are ubiquitous in the environment, and can cause negative effects in their host species. Importantly, seabirds can be long-lived and cross multiple continents within a single annual cycle, thus their exposure to parasites may be greater than other taxa. With changing climatic conditions expected to influence parasite distribution and abundance, understanding current level of infection, transmission pathways and population-level impacts are integral aspects for predicting ecosystem changes, and how climate change will affect seabird species. In particular, a range of micro- and macro-parasites can affect seabird species, including ticks, mites, helminths, viruses and bacteria in gulls, terns, skimmers, skuas, auks and selected phalaropes (Charadriiformes), tropicbirds (Phaethontiformes), penguins (Sphenisciformes), tubenoses (Procellariiformes), cormorants, frigatebirds, boobies, gannets (Suliformes), and pelicans (Pelecaniformes) and marine seaducks and loons (Anseriformes and Gaviiformes). We found that the seabird orders of Charadriiformes and Procellariiformes were most represented in the parasite-seabird literature. While negative effects were reported in seabirds associated with all the parasite groups, most effects have been studied in adults with less information known about how parasites may affect chicks and fledglings. We found studies most often reported on negative effects in seabird hosts during the breeding season, although this is also the time when most seabird research occurs. Many studies report that external factors such as condition of the host, pollution, and environmental conditions can influence the effects of parasites, thus cumulative effects likely play a large role in how parasites influence seabirds at both the individual and population level. With an increased understanding of parasite-host dynamics it is clear that major environmental changes, often those associated with human activities, can directly or indirectly affect the distribution, abundance, or virulence of parasites and pathogens. |
4 | 2n4du9mr | what causes death from Covid-19? | Recent advances of therapeutic targets and potential drugs of COVID-19 Since December 2019, numerous cases of coronavirus disease 2019 (COVID-19) caused by the infection of the novel coronavirus (2019-nCoV) have been confirmed in Wuhan, China. The outbreak of 2019-nCoV in China embodied a significant and urgent threat to global health. 2019-nCoV was a new, highly contagious coronavirus discovered following the outbreak of SARS coronavirus (SARS-CoV) and MERS coronavirus (MERS-CoV). The novel coronavirus can cause severe respiratory disease and even death. However, no specific therapeutic drugs have been developed clinically thus far. This article examines the potential of therapeutic drugs by assessing the structure of 2019-nCoV, its mechanism in invading host cells, and the anti-viral mechanism of the human autoimmune system. We also review the latest research regarding the progress of potential therapeutic drugs and provide references for new drug developments of COVID-19. |
49 | rcdoewwv | do individuals who recover from COVID-19 show sufficient immune response, including antibody levels and T-cell mediated immunity, to prevent re-infection? | The trinity of COVID-19: immunity, inflammation and intervention Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) is the causative agent of the ongoing coronavirus disease 2019 (COVID-19) pandemic. Alongside investigations into the virology of SARS-CoV-2, understanding the fundamental physiological and immunological processes underlying the clinical manifestations of COVID-19 is vital for the identification and rational design of effective therapies. Here, we provide an overview of the pathophysiology of SARS-CoV-2 infection. We describe the interaction of SARS-CoV-2 with the immune system and the subsequent contribution of dysfunctional immune responses to disease progression. From nascent reports describing SARS-CoV-2, we make inferences on the basis of the parallel pathophysiological and immunological features of the other human coronaviruses targeting the lower respiratory tract — severe acute respiratory syndrome coronavirus (SARS-CoV) and Middle East respiratory syndrome coronavirus (MERS-CoV). Finally, we highlight the implications of these approaches for potential therapeutic interventions that target viral infection and/or immunoregulation. |
4 | b9phy6iw | what causes death from Covid-19? | A crisis for elderly with mental disorders: Relapse of symptoms due to heightened anxiety due to COVID-19 |
11 | hypyxzk2 | what are the guidelines for triaging patients infected with coronavirus? | Geo temporal distribution of 1,688 Chinese healthcare workers infected with COVID-19 in severe conditions, a secondary data analysis Introduction The COVID 19 outbreak is posing an unprecedented challenge to healthcare workers. This study analyzes the geo temporal effects on disease severity for the 1,688 Chinese healthcare workers infected with COVID 19. Method Using the descriptive results recently reported by the Chinese CDC, we compare the percentage of infected healthcare workers in severe conditions over time and across three areas in China, and the fatality rate of infected healthcare workers with all the infected individuals in China aged 22 to 59 years. Results Among the infected Chinese healthcare workers whose symptoms onset appeared during the same ten day period, the percentage of those in severe conditions decreased statistical significantly from 19.7% (Jan 11 to 20) to 14.4% (Jan 21 to 31) to 8.7% (Feb 1 to 11). Across the country, there was also a significant difference in the disease severity among patients symptoms onset during the same period, with Wuhan being the most severe (17%), followed by Hubei Province (10.4%), and the rest of China (7.0%). The case fatality rate for the 1,688 infected Chinese healthcare workers was significantly lower than that for the 29,798 infected patients aged 20 to 59 years 0.3% (5/1,688) vs. 0.65% (193/29,798), respectively. Conclusion The disease severity improved considerably over a short period of time in China. The more severe conditions in Wuhan compared to the rest of the country may be attributable to the draconian lockdown. The clinical outcomes of infected Chinese healthcare workers may represent a more accurate estimation of the severity of COVID 19 for those who have access to quality healthcare. |
29 | flkjekyo | 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? | Knowledge‐based structural models of SARS‐CoV‐2 proteins and their complexes with potential drugs The World Health Organization (WHO) has declared the coronavirus disease 2019 (COVID‐19) caused by the novel coronavirus SARS‐CoV‐2 a pandemic. There is, however, no confirmed anti‐COVID‐19 therapeutic currently. In order to assist structure‐based discovery efforts for repurposing drugs against this disease, we constructed knowledge‐based models of SARS‐CoV‐2 proteins and compared the ligand molecules in the template structures with approved/experimental drugs and components of natural medicines. Our theoretical models suggest several drugs, such as carfilzomib, sinefungin, tecadenoson, and trabodenoson, that could be further investigated for their potential for treating COVID‐19. |
33 | ibe62quo | What vaccine candidates are being tested for Covid-19? | Extraordinary diseases require extraordinary solutions |
2 | ptizke03 | how does the coronavirus respond to changes in the weather | COVID-19: Disease, management, treatment, and social impact Abstract COVID-19 was originated from Wuhan city of Hubei Province in China in December 2019. Since then it has spread in more than 210 countries and territories. It is a viral disease due to the Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2) virus. The patients show flu-like symptoms with a dry cough, sore throat, high fever, and breathing problems. The disease due to SARS-CoV-2 was named as COVID-19. About 2.2 million people have been infected with more than 0.15 million deaths globally. The United States of America is the most affected country with the highest patients of about 0.7 million. Despite great efforts, there is no treatment of this disease. However, prevention and management are the best options. This article describes SARS-CoV-2, disease, prevention and management, treatment and social impact on society. It was analyzed that a combination of antiviral drugs with hydroxyl-chloroquine and azithromycin (with the consultation of a medical practitioner) may be the best option to treat the patients, depending on the patient's conditions and symptoms. However, Unani therapy may be useful along with allopathic treatment. It is urgently advised and requested that all the persons should follow the preventive measures, managements and quarantine strictly without any religious discrepancy otherwise the situation may be the worst. Also, there is an urgent requirement to educate our new generation for science and technology to fight against any such disaster in future; if any. There is no need to be panic and proper prevention and management are essential to combat this disease. This article may be useful to create awareness among the public, to prevent, manage and treat COVID-19. |
11 | bu2w2ox6 | what are the guidelines for triaging patients infected with coronavirus? | Gastrointestinal tract symptoms in coronavirus disease 2019: Analysis of clinical symptoms in adult patients Objective: To investigate the clinical presentation of coronavirus disease 2019 (COVID-19), particularly the incidence of gastrointestinal tract symptoms. Design: We enrolled adult COVID-19 patients from a mobile cabin hospital in Wuhan with a definitive diagnosis by SARS-CoV-2 nucleic acid testing. Face-to-face interviews were conducted in which the patient selected COVID-19-related symptoms and report the time of onset and duration of symptoms. Results: A total of 212 adults were enrolled in this study, of which 127 (59.9%) were females, mean age was 48.50 (range: 17-79) years, and mean disease course was 26.78 (3-60) days. Fever and cough were the most common and earliest clinical symptoms of COVID-19. Diarrhoea occurred in 43.8% (93/212) of patients, of which 86.0% (80/93) had mushy stools. Nausea and vomiting were also common (20.7%). Diarrhoea lasted for 4.00(2.00-8.85) days and mostly occurred 5.00(0.25-11.00) days after the emergence of the first symptoms. Multiple logistic regression analysis found that diarrhoea was significantly correlated with fatigue [OR2.900,95%CI (1.629-5.164), p<0.0001]. Conclusions: Gastrointestinal tract symptoms are common in COVID-19 and most occur during the middle stage of the disease and lasts for a short period of time. Clinicians need to pay greater attention to gastrointestinal tract symptoms of COVID-19. |
32 | blqzi69t | Does SARS-CoV-2 have any subtypes, and if so what are they? | Genome-wide variations of SARS-CoV-2 infer evolution relationship and transmission route In the epidemic evolution of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), the issues of mutation, origin, typing and the effect of mutation on molecular detection remain to be unrevealed. In order to identify the evolutionary relationship of SARS-CoV-2 and evaluate the detection efficiency of primers that are currently used in different countries, we retrieved genomic sequences of 373 SARS-CoV-2 strains from multiple databases and performed genome-wide variation analysis. According to the nucleotide C28144T variation, the SARS-CoV-2 can be divided into group A (117 strains) and group B (256 strains). The spike protein gene (S gene) coding region 1841 (total 23403) A1841G, formed a B1 subgroup (40 strains) in group B, of which 30 strains were from European and American countries in March (especially Washington, USA). These mutations are likely to be influenced by the environment or the immunization selection pressure of different populations. Although the mutation is not in the receptor binding region (RBD) and alkaline cleavage region, it may also affect the ability of transmission and pathogenicity; however, the significance is not yet clear. As the ratio of A / B strains in the epidemic months showed an increasing trend (0.35: 1 in January, 0.62: 1 in February and 0.76: 1 in March), it seems that the transmissibility of group A strains becomes stronger with time. Based on the variation of 11 nucleotide sites during the epidemic process, it is speculated that the Washington strain is more like an ancestor type, and the Wuhan strain is the offspring of the group A virus strain. By comparing the detection capabilities of primers in different countries, the SARS-CoV-2 nucleotide variation may only affect molecular detection of very few strains. The differences in the transmissibility, pathogenicity and clinical manifestations of different types of strains require further investigations. |
21 | nl3f4sqk | what are the mortality rates overall and in specific populations | Meta-analysis of Relation of Creatine kinase-MB to Risk of Mortality in Coronavirus Disease 2019 Patients Recently, several emerging papers have focused on the association of the creatine kinase-MB (CK-MB) levels with the risk of mortality in infected coronavirus disease 2019 (COVID-19) patients. However, the conclusions are inconsistent. In order to obtain a definitive conclusion on the association between the levels of CK-MB and the risk of mortality in COVID-19 patients, a quantitative meta-analysis was conducted on the basis of published data. Chinese National Knowledge Infrastructure, Web of Science and PubMed databases were extensively searched. Five studies performed in China were finally included in this meta-analysis. The overall results showed that higher levels of CK-MB were significantly associated with an increased risk of the mortality in COVID-19 infected patients (SMD 0.99; 95% CI 0.57 to 1.42; P < 0.001). In conclusion, the elevated CK-MB levels were a crucial characteristic of the mortality of COVID-19 patients. |
38 | n6qipu17 | What is the mechanism of inflammatory response and pathogenesis of COVID-19 cases? | Glial response during cuprizone-induced de- and remyelination in the CNS: lessons learned Although astrogliosis and microglia activation are characteristic features of multiple sclerosis (MS) and other central nervous system (CNS) lesions the exact functions of these events are not fully understood. Animal models help to understand the complex interplay between the different cell types of the CNS and uncover general mechanisms of damage and repair of myelin sheaths. The so called cuprizone model is a toxic model of demyelination in the CNS white and gray matter, which lacks an autoimmune component. Cuprizone induces apoptosis of mature oligodendrocytes that leads to a robust demyelination and profound activation of both astrocytes and microglia with regional heterogeneity between different white and gray matter regions. Although not suitable to study autoimmune mediated demyelination, this model is extremely helpful to elucidate basic cellular and molecular mechanisms during de- and particularly remyelination independently of interactions with peripheral immune cells. Phagocytosis and removal of damaged myelin seems to be one of the major roles of microglia in this model and it is well known that removal of myelin debris is a prerequisite of successful remyelination. Furthermore, microglia provide several signals that support remyelination. The role of astrocytes during de- and remyelination is not well defined. Both supportive and destructive functions have been suggested. Using the cuprizone model we could demonstrate that there is an important crosstalk between astrocytes and microglia. In this review we focus on the role of glial reactions and interaction in the cuprizone model. Advantages and limitations of as well as its potential therapeutic relevance for the human disease MS are critically discussed in comparison to other animal models. |
7 | 9khsgtz3 | are there serological tests that detect antibodies to coronavirus? | Performance Characteristics of Four High-Throughput Immunoassays for Detection of IgG Antibodies against SARS-CoV-2. The role of serologic testing for SARS-CoV-2, both in the clinical and public health settings, will continue to evolve as we gain increasing insight into our immune response to the virus. Here, we evaluated four high throughput serologic tests for detection of anti-SARS-CoV-2 IgG antibodies, including assays from Abbott Laboratories (Abbott Park, IL), Epitope Diagnostics Inc. (San Diego, CA), Euroimmun (Lubeck, Germany), and Ortho-Clinical Diagnostics (Rochester, NY), using a panel of serially collected serum samples (N=224) from 56 patients with confirmed COVID-19, healthy donor sera from 2018 and a cross-reactivity serum panel collected in early 2020. Sensitivity of the Abbott, Epitope, Euroimmun and Ortho-Clinical IgG assays in convalescent serum samples collected more than 14 days post symptom onset or initial positive RT-PCR result was 92.9% (78/84), 88.1% (74/84), 97.6% (82/84) and 98.8% (83/84), respectively. Among unique convalescent patients, sensitivity of the Abbott, Epitope, Euroimmun and Ortho-Clinical anti-SARS-CoV-2 IgG assays was 97.3% (36/37), 73% (27/37), 94.6% (35/37) and 97.3% (36/37), respectively. Overall assay specificity and positive predictive values based on a 5% prevalence rate are 99.6%/92.8%, 99.6%/90.6%, 98.0%/71.2% and 99.6%/92.5%, respectively, for the Abbott, Epitope, Euroimmun and Ortho-Clinical IgG assays. In conclusion, we show high sensitivity in convalescent sera and high specificity for the Abbott, Euroimmun and Ortho-Clinical anti-SARS-CoV-2 IgG assays. With the unprecedented influx of commercially available serologic tests for detection of antibodies against SARS-CoV-2, it remains imperative that laboratories thoroughly evaluate such assays for accuracy prior to implementation. |
20 | 4bripmvh | are patients taking Angiotensin-converting enzyme inhibitors (ACE) at increased risk for COVID-19? | In Vitro Reconstitution of SARS-Coronavirus mRNA Cap Methylation SARS-coronavirus (SARS-CoV) genome expression depends on the synthesis of a set of mRNAs, which presumably are capped at their 5′ end and direct the synthesis of all viral proteins in the infected cell. Sixteen viral non-structural proteins (nsp1 to nsp16) constitute an unusually large replicase complex, which includes two methyltransferases putatively involved in viral mRNA cap formation. The S-adenosyl-L-methionine (AdoMet)-dependent (guanine-N7)-methyltransferase (N7-MTase) activity was recently attributed to nsp14, whereas nsp16 has been predicted to be the AdoMet-dependent (nucleoside-2′O)-methyltransferase. Here, we have reconstituted complete SARS-CoV mRNA cap methylation in vitro. We show that mRNA cap methylation requires a third viral protein, nsp10, which acts as an essential trigger to complete RNA cap-1 formation. The obligate sequence of methylation events is initiated by nsp14, which first methylates capped RNA transcripts to generate cap-0 (7Me)GpppA-RNAs. The latter are then selectively 2′O-methylated by the 2′O-MTase nsp16 in complex with its activator nsp10 to give rise to cap-1 (7Me)GpppA(2′OMe)-RNAs. Furthermore, sensitive in vitro inhibition assays of both activities show that aurintricarboxylic acid, active in SARS-CoV infected cells, targets both MTases with IC(50) values in the micromolar range, providing a validated basis for anti-coronavirus drug design. |
17 | i4jy2wj6 | are there any clinical trials available for the coronavirus | Use of emerging oral anticoagulants in clinical practice: translating results from clinical trials to orthopedic and general surgical patient populations. OBJECTIVE A review of clinical data from oral anticoagulant studies in orthopedic/general surgery and extrapolation to actual clinical practice. SUMMARY BACKGROUND DATA In all surgical patients, there is a risk of postoperative venous thromboembolism (VTE). Parenteral unfractionated heparin, low-molecular-weight heparin, and fondaparinux are available for VTE prophylaxis. Vitamin K antagonists, the only available oral anticoagulants, are widely used in the United States for thromboprophylaxis in joint replacement surgery in spite of being associated with several disadvantages, limiting their effectiveness in the postoperative setting. The oral direct thrombin inhibitor ximelagatran, briefly approved outside the United States for thromboprophylaxis in orthopedic patients, was discontinued due to severe hepatotoxicity concerns. Recently, the oral factor Xa inhibitors rivaroxaban and apixaban have entered late phase development for VTE thromboprophylaxis and treatment and the oral direct thrombin inhibitor dabigatran has received marketing approval from the European Medicines Agency. METHODS Review of clinical studies of the oral anticoagulants in VTE prevention in orthopedic surgery and comparison with large observational registries. RESULTS : Results from Phase II/III studies suggest that new oral anticoagulants may provide an efficacious alternative in VTE prevention in orthopedic surgery. Furthermore, these new oral agents have, so far, shown a good overall safety profile, with no evidence of increased hepatotoxicity. However, comparison with large observational registries reveals differences between real-life patient populations, which make extrapolation of clinical trial data to actual clinical practice difficult. Differences in endpoint definitions also prevent indirect comparison of agents. Specific compliance and postmarketing safety issues (especially liver enzyme monitoring requirements) need to be clarified before these agents are widely accepted into routine clinical practice. CONCLUSIONS Although new oral anticoagulants appear promising, clinical trial results should be viewed with caution until they can be replicated in routine care settings across a broad spectrum of surgical patients. |
8 | zbzrxuoh | how has lack of testing availability led to underreporting of true incidence of Covid-19? | CT imaging and clinical course of asymptomatic cases with COVID-19 pneumonia at admission in Wuhan, China Abstract Purpose Aimed to characterize the CT imaging and clinical course of asymptomatic cases with COVID-19 pneumonia. Methods Asymptomatic cases with COVID-19 pneumonia confirmed by SARS-COV-2 nucleic acid testing in Renmin Hospital of Wuhan University were retrospectively enrolled. The characteristics of CT imaging and clinical feature were collected and analyzed. Results 58 asymptomatic cases with COVID-19 pneumonia admitted to our hospital between Jan 1, 2020 and Feb 23, 2020 were enrolled. All patients had history of exposure to SARS-CoV-2. On admission, patients had no symptoms and laboratory findings were normal. The predominant feature of CT findings in this cohort was ground glass opacity (GGO) (55, 94.8%) with peripheral (44, 75.9%) distribution, unilateral location (34, 58.6%) and mostly involving one or two lobes (38, 65.5%), often accompanied by characteristic signs. After short-term follow-up, 16 patients (27.6%) presented symptoms with lower lymphocyte count and higher CRP, mainly including fever, cough and fatigue. The evolution of lesions on CT imaging were observed in 10 patients (17.2%). The average days of hospitalization was19.80±10.82 days, and was significantly longer in progression patients (28.60±7.55 day). Conclusion CT imaging of asymptomatic cases with COVID-19 pneumonia has definite characteristics. Since asymptomatic infections as "covert transmitter", and some patients can progress rapidly in the short term. It is essential to pay attention to the surveillance of asymptomatic patients with COVID-19. CT scan has great value in screening and detecting patients with COVID-19 pneumonia, especially in the highly suspicious, asymptomatic cases with negative nucleic acid testing. |
40 | ttte21up | What are the observed mutations in the SARS-CoV-2 genome and how often do the mutations occur? | Investigating the genomic landscape of novel coronavirus (2019-nCoV) to identify non-synonymous mutations for use in diagnosis and drug design This study presents a comprehensive phylogenetic analysis of SARS-CoV2 isolates to understand discrete mutations that are occurring between patient samples. The analysis unravel various amino acid mutations in the viral proteins which may provide an explanation for varying treatment efficacies of different inhibitory drugs and a future direction towards a combinatorial treatment therapies based on the kind of mutation in the viral genome. |
32 | 9jdg7sot | Does SARS-CoV-2 have any subtypes, and if so what are they? | What settings have been linked to SARS-CoV-2 transmission clusters? Background: Concern about the health impact of novel coronavirus SARS-CoV-2 has resulted in widespread enforced reductions in people's movement ("lockdowns"). However, there are increasing concerns about the severe economic and wider societal consequences of these measures. Some countries have begun to lift some of the rules on physical distancing in a stepwise manner, with differences in what these "exit strategies" entail and their timeframes. The aim of this work was to inform such exit strategies by exploring the types of indoor and outdoor settings where transmission of SARS-CoV-2 has been reported to occur and result in clusters of cases. Identifying potential settings that result in transmission clusters allows these to be kept under close surveillance and/or to remain closed as part of strategies that aim to avoid a resurgence in transmission following the lifting of lockdown measures. Methods: We performed a systematic review of available literature and media reports to find settings reported in peer reviewed articles and media with these characteristics. These sources are curated and made available in an editable online database. Results: We found many examples of SARS-CoV-2 clusters linked to a wide range of mostly indoor settings. Few reports came from schools, many from households, and an increasing number were reported in hospitals and elderly care settings across Europe. Conclusions: We identified possible places that are linked to clusters of COVID-19 cases and could be closely monitored and/or remain closed in the first instance following the progressive removal of lockdown restrictions. However, in part due to the limits in surveillance capacities in many settings, the gathering of information such as cluster sizes and attack rates is limited in several ways: inherent recall bias, biased media reporting and missing data. |
49 | x39h7aat | do individuals who recover from COVID-19 show sufficient immune response, including antibody levels and T-cell mediated immunity, to prevent re-infection? | SARS-CoV-2: Virology, epidemiology, immunology and vaccine development This first International Alliance for Biological Standardization Covid-19 webinar brought together a broad range of international stakeholders, including academia, regulators, funders and industry, with a considerable delegation from low- and middle-income countries, to discuss the virology, epidemiology and immunology of, and the vaccine development for SARS-CoV-2. |
34 | nrj6ogr7 | What are the longer-term complications of those who recover from COVID-19? | Ethnicity and COVID-19: an urgent public health research priority |
23 | pxzr2j92 | what kinds of complications related to COVID-19 are associated with hypertension? | Expression of SARS-CoV-2 Receptor ACE2 and Coincident Host Response Signature Varies by Asthma Inflammatory Phenotype BACKGROUND: Over 300 million people carry a diagnosis of asthma with data to suggest they are at higher risk for infection or adverse outcomes from SARS-CoV-2. Asthma is remarkably heterogenous and it is currently unclear how patient intrinsic factors may relate to COVID-19. OBJECTIVE: Identify and characterize subsets of asthmatics at increased risk for SARS-CoV-2 infection. METHODS: Participants from 2 large asthma cohorts were stratified using clinically relevant parameters to identify factors related to ACE2 expression within bronchial epithelium. ACE-2 correlated gene signatures were used to interrogate publicly available databases to identify upstream signaling events and novel therapeutic targets. RESULTS: Stratifying by Type 2 inflammatory biomarkers, we identified subjects who demonstrated low peripheral blood eosinophils accompanied by increased expression of the SARS-CoV-2 receptor ACE2 in bronchial epithelium. Genes highly correlated with ACE2 overlapped with Type 1 and 2 interferon signatures, normally induced by viral infections. T cell recruitment and activation within bronchoalveolar lavage cells of ACE2-high subjects was reciprocally increased. These patients demonstrated characteristics corresponding to risk factors for severe COVID-19, including male sex, history of hypertension, low peripheral blood and elevated BAL lymphocytes. CONCLUSION: ACE2 expression is linked to upregulation of viral response genes in a subset of Type-2 low asthmatics with characteristics resembling known risk factors for severe COVID-19. Therapies targeting the interferon family and T cell activating factors may therefore be of benefit in a subset of patients. CLINICAL IMPLICATION: Type-2 low asthmatics may be at increased risk for adverse outcome from COVID-19 and deserve increased vigilance upon developing symptoms. |
49 | 1iio41wn | do individuals who recover from COVID-19 show sufficient immune response, including antibody levels and T-cell mediated immunity, to prevent re-infection? | Disruption of Adaptive Immunity Enhances Disease in SARS-CoV-2 Infected Syrian Hamsters Animal models recapitulating human COVID-19 disease, especially with severe disease, are urgently needed to understand pathogenesis and evaluate candidate vaccines and therapeutics. Here, we develop novel severe disease animal models for COVID-19 involving disruption of adaptive immunity in Syrian hamsters. Cyclophosphamide (CyP) immunosuppressed or RAG2 knockout (KO) hamsters were exposed to SARS-CoV-2 by the respiratory route. Both the CyP-treated and RAG2 KO hamsters developed clinical signs of disease that were more severe than in immunocompetent hamsters, notably weight loss, viral loads, and fatality (RAG2 KO only). Disease was prolonged in transiently immunosuppressed hamsters and uniformly lethal in RAG2 KO hamsters. We evaluated the protective efficacy of a neutralizing monoclonal antibody and found that pretreatment, even in immunosuppressed animals, limited infection. Our results suggest that functional B and/or T cells are not only important for the clearance of SARS-CoV-2, but also play an early role in protection from acute disease. One Sentence Summary An antibody targeting the spike protein of SARS-CoV-2 limits infection in immunosuppressed Syrian hamster models. |
17 | jvbehgb7 | are there any clinical trials available for the coronavirus | Dose prediction for repurposing nitazoxanide in SARS-CoV-2 treatment or chemoprophylaxis Background: Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) has been declared a global pandemic by the World Health Organisation and urgent treatment and prevention strategies are needed. Many clinical trials have been initiated with existing medications, but assessments of the expected plasma and lung exposures at the selected doses have not featured in the prioritisation process. Although no antiviral data is currently available for the major phenolic circulating metabolite of nitazoxanide (known as tizoxanide), the parent ester drug has been shown to exhibit in vitro activity against SARS-CoV-2. Nitazoxanide is an anthelmintic drug and its metabolite tizoxanide has been described to have broad antiviral activity against influenza and other coronaviruses. The present study used physiologically-based pharmacokinetic (PBPK) modelling to inform optimal doses of nitazoxanide capable of maintaining plasma and lung tizoxanide exposures above the reported nitazoxanide 90% effective concentration (EC90) against SARS-CoV-2. Methods: A whole-body PBPK model was constructed for oral administration of nitazoxanide and validated against available tizoxanide pharmacokinetic data for healthy individuals receiving single doses between 500 mg SARS-CoV-2 4000 mg with and without food. Additional validation against multiple-dose pharmacokinetic data when given with food was conducted. The validated model was then used to predict alternative doses expected to maintain tizoxanide plasma and lung concentrations over the reported nitazoxanide EC90 in >90% of the simulated population. Optimal design software PopDes was used to estimate an optimal sparse sampling strategy for future clinical trials. Results: The PBPK model was validated with AAFE values between 1.01 SARS-CoV-2 1.58 and a difference less than 2-fold between observed and simulated values for all the reported clinical doses. The model predicted optimal doses of 1200 mg QID, 1600 mg TID, 2900 mg BID in the fasted state and 700 mg QID, 900 mg TID and 1400 mg BID when given with food, to provide tizoxanide plasma and lung concentrations over the reported in vitro EC90 of nitazoxanide against SARS-CoV-2. For BID regimens an optimal sparse sampling strategy of 0.25, 1, 3 and 12h post dose was estimated. Conclusion: The PBPK model predicted that it was possible to achieve plasma and lung tizoxanide concentrations, using proven safe doses of nitazoxanide, that exceed the EC90 for SARS-CoV-2. The PBPK model describing tizoxanide plasma pharmacokinetics after oral administration of nitazoxanide was successfully validated against clinical data. This dose prediction assumes that the tizoxanide metabolite has activity against SARS-CoV-2 similar to that reported for nitazoxanide, as has been reported for other viruses. The model and the reported dosing strategies provide a rational basis for the design (optimising plasma and lung exposures) of future clinical trials of nitazoxanide in the treatment or prevention of SARS-CoV-2 infection. |
49 | 5ka9909n | do individuals who recover from COVID-19 show sufficient immune response, including antibody levels and T-cell mediated immunity, to prevent re-infection? | Lactate dehydrogenase-elevating virus: an ideal persistent virus? LDV contradicts all commonly held views about mechanisms of virus persistence, namely that persistence is primarily associated with noncytopathic viruses, or the selection of immune escape variants or other mutants, or a decrease in expression of certain viral proteins by infected cells, or replication in "immune-privileged sites", or a general suppression of the host immune system, etc. [1, 2, 5, 54, 77, 78]. LDV is a highly cytocidal virus that invariably establishes a life-long, viremic, persistence in mice, in spite of normal anti-viral immune responses. One secret of LDV's success in persistence is its specificity for a renewable, nonessential population of cells that is continuously regenerated, namely a subpopulation of macrophages. Since the continuous destruction of these cells is not associated with any obvious health effects, this macrophage population seems nonessential to the well-being of its host. The only function identified for this subpopulation of macrophages is clearance of the muscle type of LDH and some other enzymes [59, 67, 68]. Furthermore, the effects of LDV infection on the host immune system, namely the polyclonal activation of B cells and its associated production of autoantibodies, and the slight impairment of primary and secondary antibody responses also do not seem to be severe enough to cause any clinical consequences. But how does LDV replication in macrophages escape all host defenses? Persistence is not dependent on the seletion of immune escape variants or other mutants ([58] and Palmer, Even and Plagemann, unpublished results). Also, LDV replication is not restricted to immune-privileged sites [5]. LDV replication persists in the liver, lymphoidal tissues and testis [66]. Only the latter could be considered a site not readily accessible to immune surveillance. Most likely, resistance of LDV replication to antiviral immune responses is related to the unique structure of its envelope proteins and the production of large quantities of viral antigens. High titers of anti-LDV antibodies are generated in infected mice but they neutralize LDV infectivity only very inefficiently and, even though the antiviral antibodies are mainly of the IgG2a and IgG2b isotypes, they do not mediate complement lyses of virions [31]. Interaction of the antibodies and complement with the VP-3/VP-2 heterodimers in the viral envelope may be impeded by the exposure of only very short peptide segments of these proteins at the envelope surface and the presence of large oligosaccharide side chains. Furthermore, since LDV maturation is restricted to intracytoplasmic cisternae [59, 71], the question arises of whether any of the viral proteins are available on the surface of infected cells for ADCC. CTLs also fail to control LDV replication. Altough CTLs specific for N/VP-1 are rapidly generated, these have disappeared by 30 days p.i. [26]. The reasons for this loss are unknown, but high-dose clonal exhaustion [41, 51, 77, 78] is a reasonable possibility since, regardless of the infectious dose, large amounts of LDV proteins are present in all the lymphoidal tissues at the time of the induction of the CTL response. Furthermore, after exhaustion of CTLs in the periphery, continuous replication of LDV in the thymus [65] assures that the mice become permanently immunologically tolerant with respect to LDV antigen-specific CTLs as a result of negative selection in the thymus. LDV might be a primary example for the effectiveness of a permanent clonal CTL deletion in adult animals under natural conditions of infection. The presumed modes of transmission of LDV in nature and the events associated with its infection of mice are strikingly similar to those observed during the acute and asymptomatic phases of infection with human immunodeficiency virus (HIV) [24, 29, 74, 78]. These include: (1) primary inefficient transmission via sexual and transplacental routes but effective transmission via blood; (2) primary replication in renewable populations of lymphoidal cells with production of large amounts of virus after the initial infection of the host followed by persistent low level of viremia in spite of antiviral immune responses; (3) persistence, reflecting continuous rounds of productive, cytocidal infection of permissive cells [59, 74] and the rate of generation of permissive cells which may be the main factor in determining the level of virus production (in the case of HIV, the rate of activation of CD4(+) T cells to support a productive HIV replication might be the factor determining the rate of virus production and the progression of the disease); (4) rapid antibody formation but delayed production of neutralizing antibodies with limited neutralizing capacity; (5) rapid but transient generation of virus-specific CTLs; and (6) accumulation of large amounts of virus in newly formed germinal centers in the spleen and lymph nodes concomitant with an initiation of a permanent polyclonal activation of B cells resulting in an elevation of plasma IgG2a. The events described under points 2–6 might be generally associated with natural viremic persistent virus infections. Such persistent viruses, by necessity, have evolved properties that allow them to escape all host defenses and control of their infection by immunological processes is, therefore, difficult, if not impossible. Prevention of infection and chemotherapy may be the only approaches available to combat such virus infections. |
15 | o2la1jpm | how long can the coronavirus live outside the body | Potential challenges of employing a formal environmental scanning approach in hospitality organizations Most previous studies on environmental scanning (ES) in the field of hospitality management suggest that hospitality organizations establish formal systematic ES procedures and have a freestanding ES unit to identify opportunities and threats in their external environment. However, some serious criticisms have been raised in the field of strategic management against the employment of such a formal and systematic approach to ES. These opposing views have rarely been discussed in the hospitality management literature. The aim of this paper, therefore, is to bring these views to the fore in the process of reviewing previous research into ES, and to discuss the major challenges involved for hospitality organizations in employing such a formal approach to ES. The discussion throughout this paper reveals that ES is essential for every organization; however, it is even more complex and difficult to accomplish than portrayed in most previous studies in the hospitality management field. The paper identifies and discusses major challenges and problems in employing a form ES approach in hospitality organizations. It also provides recommendations about how ES activities can best be carried out in complex and dynamic environments. |
6 | xl2u8asv | what types of rapid testing for Covid-19 have been developed? | A rapid point of care immunoswab assay for SARS-CoV detection The emergence of severe acute respiratory syndrome (SARS) resulted in several outbreaks worldwide. Early tests for diagnosis were not always conclusive in identifying a SARS suspected patient. Nucleocapsid protein (NP) is the most predominant virus derived structural protein which is shed in high amounts in serum and nasopharyngeal aspirate during the first week of infection. As part of such efforts, a simple, easy to use immunoswab method was developed by generating a panel of monoclonal antibodies (MAbs), Bispecific MAbs and chicken polyclonal IgY antibody against the SARS-CoV nucleocapsid protein (NP). Employing the MAb-based immunoswab, an NP concentration of 200 pg/mL in saline and pig nasopharyngeal aspirate, and 500 pg/mL in rabbit serum were detected. BsMAb-based immunoswabs detected an NP concentration of 20 pg/mL in saline, 500 pg/mL in rabbit serum and 20–200 pg/mL in pig nasopharyngeal aspirate. Polyclonal IgY-based immunoswabs detected an NP concentration of 10 pg/mL in pig nasopharyngeal aspirate providing the most sensitive SARS point of care assay. Results show that the robust immunoswab method of detecting SARS-CoV NP antigen can be developed into an easy and effective way of identifying SARS suspected individuals during a future SARS epidemic, thereby reducing and containing the transmission. The key feature of this simple immunoswab diagnostic assay is its ability to detect the presence of the SARS-CoV antigen within 45–60 min with the availability of the body fluid samples. |
14 | j4q7pcfa | what evidence is there related to COVID-19 super spreaders | Coupling dynamics of epidemic spreading and information diffusion on complex networks Abstract The interaction between disease and disease information on complex networks has facilitated an interdisciplinary research area. When a disease begins to spread in the population, the corresponding information would also be transmitted among individuals, which in turn influence the spreading pattern of the disease. In this paper, firstly, we analyze the propagation of two representative diseases (H7N9 and Dengue fever) in the real-world population and their corresponding information on Internet, suggesting the high correlation of the two-type dynamical processes. Secondly, inspired by empirical analyses, we propose a nonlinear model to further interpret the coupling effect based on the SIS (Susceptible-Infected-Susceptible) model. Both simulation results and theoretical analysis show that a high prevalence of epidemic will lead to a slow information decay, consequently resulting in a high infected level, which shall in turn prevent the epidemic spreading. Finally, further theoretical analysis demonstrates that a multi-outbreak phenomenon emerges via the effect of coupling dynamics, which finds good agreement with empirical results. This work may shed light on the in-depth understanding of the interplay between the dynamics of epidemic spreading and information diffusion. |
8 | 944pn0k9 | how has lack of testing availability led to underreporting of true incidence of Covid-19? | Evolving Epidemiology and Impact of Non-pharmaceutical Interventions on the Outbreak of Coronavirus Disease 2019 in Wuhan, China BACKGROUND We described the epidemiological features of the coronavirus disease 2019 (Covid-19) outbreak, and evaluated the impact of non-pharmaceutical interventions on the epidemic in Wuhan, China. METHODS Individual-level data on 25,961 laboratory-confirmed Covid-19 cases reported through February 18, 2020 were extracted from the municipal Notifiable Disease Report System. Based on key events and interventions, we divided the epidemic into four periods: before January 11, January 11-22, January 23 - February 1, and February 2-18. We compared epidemiological characteristics across periods and different demographic groups. We developed a susceptible-exposed-infectious-recovered model to study the epidemic and evaluate the impact of interventions. RESULTS The median age of the cases was 57 years and 50.3% were women. The attack rate peaked in the third period and substantially declined afterwards across geographic regions, sex and age groups, except for children (age <20) whose attack rate continued to increase. Healthcare workers and elderly people had higher attack rates and severity risk increased with age. The effective reproductive number dropped from 3.86 (95% credible interval 3.74 to 3.97) before interventions to 0.32 (0.28 to 0.37) post interventions. The interventions were estimated to prevent 94.5% (93.7 to 95.2%) infections till February 18. We found that at least 59% of infected cases were unascertained in Wuhan, potentially including asymptomatic and mild-symptomatic cases. CONCLUSIONS Considerable countermeasures have effectively controlled the Covid-19 outbreak in Wuhan. Special efforts are needed to protect vulnerable populations, including healthcare workers, elderly and children. Estimation of unascertained cases has important implications on continuing surveillance and interventions. |
31 | fbwpw3jc | How does the coronavirus differ from seasonal flu? | Visualising the expansion and spread of coronavirus disease 2019 by cartograms Coronavirus disease 2019 (COVID-19) has emerged as a growing focus of global attention and a critical factor in public-health decision making. Towards fighting the COVID-19 outbreak, countries worldwide and international organisations have taken various actions, including promoting the transparency of and public access to disease data. In such public communications, maps have played an important role in that a map is worth a thousand words. Most of these have taken the form of a choropleth map. Here, we propose employing cartograms to visualise both the expansion and spread of COVID-19. We designed a combination of six circular cartograms containing the data of confirmed cases every 48 hours from 24 January to 3 February 2020. Such a design conveys both spatial and temporal information more intuitively and efficiently, so it can be expected to facilitate better public participation in the fight against COVID-19. |
11 | tgm90lbp | what are the guidelines for triaging patients infected with coronavirus? | Endocrine surgery in the Coronavirus disease 2019 pandemic: Surgical Triage Guidelines BACKGROUND: In the face of the COVID‐19 pandemic, cancer care has had to adapt rapidly given the Centers for Disease Control and Prevention and the American College of Surgeons (ACS) issuing recommendations to postpone nonurgent surgeries. METHODS: An institutional multidisciplinary group of Head and Neck Surgical Oncology, Surgical Endocrinology, and Medical Endocrinology devised Surgical Triaging Guidelines for Endocrine Surgery during COVID‐19, aligned with phases of care published by the ACS. RESULTS: Phases of care with examples of corresponding endocrine cases are outlined. Most cases can be safely postponed with active surveillance, including most differentiated and medullary thyroid cancers. During the most acute phase, all endocrine surgeries are deferred, except thyroid tumors requiring acute airway management. CONCLUSIONS: These guidelines provide context for endocrine surgery within the spectrum of surgical oncology, with the goal of optimal individualized multidisciplinary patient care and the expectation of significant resource diversion to care for patients with COVID‐19. |
27 | myqli11j | what is known about those infected with Covid-19 but are asymptomatic? | The Novel Coronavirus, 2019-nCoV, is Highly Contagious and More Infectious Than Initially Estimated The novel coronavirus (2019-nCoV) is a recently emerged human pathogen that has spread widely since January 2020. Initially, the basic reproductive number, R0, was estimated to be 2.2 to 2.7. Here we provide a new estimate of this quantity. We collected extensive individual case reports and estimated key epidemiology parameters, including the incubation period. Integrating these estimates and high-resolution real-time human travel and infection data with mathematical models, we estimated that the number of infected individuals during early epidemic double every 2.4 days, and the R0 value is likely to be between 4.7 and 6.6. We further show that quarantine and contact tracing of symptomatic individuals alone may not be effective and early, strong control measures are needed to stop transmission of the virus. |
12 | v3gww4iv | what are best practices in hospitals and at home in maintaining quarantine? | Transmission of corona virus disease 2019 during the incubation period may lead to a quarantine loophole Background: The ongoing outbreak of novel corona virus disease 2019 (COVID-19) in Wuhan, China, is arousing international concern. This study evaluated whether and when the infected but asymptomatic cases during the incubation period could infect others. Methods: We collected data on demographic characteristics, exposure history, and symptom onset day of the confirmed cases, which had been announced by the Chinese local authorities. We evaluated the potential of transmission during the incubation period in 50 infection clusters, including 124 cases. All the secondary cases had a history of contact with their first-generation cases prior to symptom onset. Results: The estimated mean incubation period for COVID-19 was 4.9 days (95% confidence interval [CI], 4.4 to 5.4) days, ranging from 0.8 to 11.1 days (2.5th to 97.5th percentile). The observed mean and standard deviation (SD) of serial interval was 4.1±3.3 days, with the 2.5th and 97.5th percentiles at -1 and 13 days. The infectious curve showed that in 73.0% of the secondary cases, their date of getting infected was before symptom onset of the first-generation cases, particularly in the last three days of the incubation period. Conclusions: The results indicated the transmission of COVID-9 occurs among close contacts during the incubation period, which may lead to a quarantine loophole. Strong and effective countermeasures should be implemented to prevent or mitigate asymptomatic transmission during the incubation period in populations at high risk. |
26 | 9jb3w0zu | what are the initial symptoms of Covid-19? | A new threat from an old enemy: Re-emergence of coronavirus (Review) The new outbreak of coronavirus from December 2019 has brought attention to an old viral enemy and has raised concerns as to the ability of current protection measures and the healthcare system to handle such a threat. It has been known since the 1960s that coronaviruses can cause respiratory infections in humans; however, their epidemic potential was understood only during the past two decades. In the present review, we address current knowledge on coronaviruses from a short history to epidemiology, pathogenesis, clinical manifestation of the disease, as well as treatment and prevention strategies. Although a great amount of research and efforts have been made worldwide to prevent further outbreaks of coronavirus-associated disease, the spread and lethality of the 2019 outbreak (COVID-19) is proving to be higher than previous epidemics on account of international travel density and immune naivety of the population. Only strong, joint and coordinated efforts of worldwide healthcare systems, researchers, and pharmaceutical companies and receptive national leaders will succeed in suppressing an outbreak of this scale. |
22 | 99ttewb5 | are cardiac complications likely in patients with COVID-19? | Livestock infectious diseases and zoonoses. Infectious diseases of livestock are a major threat to global animal health and welfare and their effective control is crucial for agronomic health, for safeguarding and securing national and international food supplies and for alleviating rural poverty in developing countries. Some devastating livestock diseases are endemic in many parts of the world and threats from old and new pathogens continue to emerge, with changes to global climate, agricultural practices and demography presenting conditions that are especially favourable for the spread of arthropod-borne diseases into new geographical areas. Zoonotic infections that are transmissible either directly or indirectly between animals and humans are on the increase and pose significant additional threats to human health and the current pandemic status of new influenza A (H1N1) is a topical example of the challenge presented by zoonotic viruses. In this article, we provide a brief overview of some of the issues relating to infectious diseases of livestock, which will be discussed in more detail in the papers that follow. |
25 | uqls3p01 | which biomarkers predict the severe clinical course of 2019-nCOV infection? | Genomic variance of the 2019-nCoV coronavirus There is rising global concern for the recently emerged novel Coronavirus (2019-nCov). Full genomic sequences have been released by the worldwide scientific community in the last few weeks in order to understand the evolutionary origin and molecular characteristics of this virus. Taking advantage of all the genomic information currently available, we constructed a phylogenetic tree including also representatives of other coronaviridae, such as Bat coronavirus (BCoV) and SARS. We confirm high sequence similarity (>99%) between all sequenced 2019-nCoVs genomes available, with the closest BCoV sequence sharing 96.2% sequence identity, confirming the notion of a zoonotic origin of 2019-nCoV. Despite the low heterogeneity of the 2019-nCoV genomes, we could identify at least two hyper-variable genomic hotspots, one of which is responsible for a Serine/Leucine variation in the viral ORF8-encoded protein. Finally, we perform a full proteomic comparison with other coronaviridae, identifying key aminoacidic differences to be considered for antiviral strategies deriving from previous anti-coronavirus approaches. |
33 | 96rup00o | What vaccine candidates are being tested for Covid-19? | Interactions of Pathogens with the Host Abstract Infection occurs when a microbe enters a normally nonsterile tissue and may cause an infectious disease with signs and symptoms or a subclinical infection. Infections that are not cleared by the host are characterized as persistent. The agent in nonreplicating or latent infection may begin to grow again or to reactivate. Growth of a microorganism such as normal bacterial flora on a normally nonsterile body surface such as the colonic mucosa in the absence of disease is called colonization. Some infectious agents known as pathogens routinely cause disease; others known as opportunistic cause disease only in persons with altered host defenses, such as acquired immunodeficiency syndrome. The location where a pathogen normally resides is the reservoir, such as naturally infected animals. The mechanism by which the pathogen moves from the reservoir into the patient is known as transmission such as by drinking contaminated water. The portals of entry are mucosal, respiratory, gastrointestinal, genitourinary, and cutaneous. A pathogen may replicate at the portal of entry and cause disease by secreting a toxin or enter the body and spread via the lymphatic or blood vessels, nerves, urinary tract, respiratory tract, cerebrospinal fluid, over mesothelial surfaces, or to the fetus transplacentally. Many infectious agents target a particular organ where they replicate and cause damage, for example, hepatitis, myocarditis, and meningoencephalitis. |
30 | aeuy92bx | is remdesivir an effective treatment for COVID-19 | Potent neutralization of 2019 novel coronavirus by recombinant ACE2-Ig 2019-nCoV, which is a novel coronavirus emerged in Wuhan, China, at the end of 2019, has caused at least infected 11,844 as of Feb 1, 2020. However, there is no specific antiviral treatment or vaccine currently. Very recently report had suggested that novel CoV would use the same cell entry receptor, ACE2, as the SARS-CoV. In this report, we generated a novel recombinant protein by connecting the extracellular domain of human ACE2 to the Fc region of the human immunoglobulin IgG1. An ACE2 mutant with low catalytic activity was also used in the study. The fusion proteins were then characterized. Both fusion proteins has high affinity binding to the receptor-binding domain (RBD) of SARS-CoV and 2019-nCoV and exerted desired pharmacological properties. Moreover, fusion proteins potently neutralized SARS-CoV and 2019-nCoV in vitro. As these fusion proteins exhibit cross-reactivity against coronaviruses, they could have potential applications for diagnosis, prophylaxis, and treatment of 2019-nCoV. |
35 | cmfo60z0 | What new public datasets are available related to COVID-19? | Interferon-Induced Transmembrane Protein (IFITM3) Is Upregulated Explicitly in SARS-CoV-2 Infected Lung Epithelial Cells Current guidelines for COVID-19 management recommend the utilization of various repurposed drugs. Despite ongoing research toward the development of a vaccine against SARS-CoV-2, such a vaccine will not be available in time to contribute to the containment of the ongoing pandemic. Therefore, there is an urgent need to develop a framework for the rapid identification of novel targets for diagnostic and therapeutic interventions. We analyzed publicly available transcriptomic datasets of SARS-CoV infected humans and mammals to identify consistent differentially expressed genes then validated in SARS-CoV-2 infected epithelial cells transcriptomic datasets. Comprehensive toxicogenomic analysis of the identified genes to identify possible interactions with clinically proven drugs was carried out. We identified IFITM3 as an early upregulated gene, and valproic acid was found to enhance its mRNA expression as well as induce its antiviral action. These findings indicate that analysis of publicly available transcriptomic and toxicogenomic data represents a rapid approach for the identification of novel targets and molecules that can modify the action of such targets during the early phases of emerging infections like COVID-19. |
15 | ua0luq11 | how long can the coronavirus live outside the body | How Should the Rehabilitation Community Prepare for 2019-nCoV? Abstract With the 2019-nCoV pandemic spreading quickly in USA and the world, it is urgent that the rehabilitation community quickly understands the epidemiology of the virus and what we can and must do to face this microbial adversary at the early stages of this likely long global pandemic. The 2019-nCoV is a novel virus so the majority of world's population does not have prior immunity to it. It is more infectious and fatal than seasonal influenza, and definitive treatment and a vaccine are months away. Our arsenal against it are currently mainly social distancing and infection control measures. |
12 | qdap5cxo | what are best practices in hospitals and at home in maintaining quarantine? | SARS in Singapore--key lessons from an epidemic. The rapid containment of the Singapore severe acute respiratory syndrome (SARS) outbreak in 2003 involved the introduction of several stringent control measures. These measures had a profound impact on the healthcare system and community, and were associated with significant disruptions to normal life, business and social intercourse. An assessment of the relative effectiveness of the various control measures is critical in preparing for future outbreaks of a similar nature. The very "wide-net" surveillance, isolation and quarantine policy adopted was effective in ensuring progressively earlier isolation of probable SARS cases. However, it resulted in nearly 8000 contacts being put on home quarantine and 4300 on telephone surveillance, with 58 individuals eventually being diagnosed with probable SARS. A key challenge is to develop very rapid and highly sensitive tests for SARS infection, which would substantially reduce the numbers of individuals that need to be quarantined without decreasing the effectiveness of the measure. Daily temperature monitoring of all healthcare workers (HCWs) in hospitals was useful for early identification of HCWs with SARS. However, daily temperature screening of children in schools failed to pick up any SARS cases. Similarly, temperature screening at the airport and other points of entry did not yield any SARS cases. Nevertheless, the latter 2 measures probably helped to reassure the public that schools and the community were safe during the SARS outbreak. Strong political leadership and effective command, control and coordination of responses were critical factors for the containment of the outbreak. |
10 | ue2sp06r | has social distancing had an impact on slowing the spread of COVID-19? | Protecting the psychological health of children through effective communication about COVID-19 |
27 | uptfhv4h | what is known about those infected with Covid-19 but are asymptomatic? | Handling and Processing of Blood Specimens from Patients with COVID‐19 for Safe Studies on Cell Phenotype and Cytokine Storm The pandemic caused by severe acute respiratory syndrome coronavirus 2 heavily involves all those working in a laboratory. Samples from known infected patients or donors who are considered healthy can arrive, and a colleague might be asymptomatic but able to transmit the virus. Working in a clinical laboratory is posing several safety challenges. Few years ago, International Society for Advancement of Cytometry published guidelines to safely analyze and sort human samples that were revised in these days. We describe the procedures that we have been following since the first patient appeared in Italy, which have only slightly modified our standard one, being all human samples associated with risks. © 2020 International Society for Advancement of Cytometry |
44 | pn11rt09 | How much impact do masks have on preventing the spread of the COVID-19? | Knowledge, Attitudes, and Practices Toward COVID-19 in a Saudi Arabian Population: A Cross-Sectional Study Background Preventative measures are necessary to control a pandemic such as coronavirus disease 2019 (COVID-19), and different platforms to communicate guidelines have varying levels of effectiveness. Objective At the time of this study, there were no published studies investigating knowledge, attitudes, and practices related to COVID-19 within the Saudi population. Therefore, this study aims to address this gap in current knowledge and provide baseline data to the government and other health associations for preventive measurements for future outbreaks. Methods This study was conducted among the Saudi population using an online questionnaire. The questionnaire assessed the awareness of the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) incubation period, the known symptoms of COVID-19, the mode of transmission of SARS-CoV-2, and infection control measures for prevention. Results The study included 6000 participants. Most respondents (84.93%) of the population reported awareness of the virus, 78.78% reported a belief that the virus leads to death, 89.47% reported a belief that 14 days is the incubation period, and 93.73% were aware of the possibility of asymptomatic carriers. Conclusions The Saudi population is aware of the attitudes and practices of prevention as well as the mode of transmission. The efforts by the Ministry of Health were effective in increasing awareness among the Saudi population toward COVID-19. |
19 | 8kf2tguf | what type of hand sanitizer is needed to destroy Covid-19? | Effective health communication – a key factor in fighting the COVID-19 pandemic |
19 | 9rn8kzst | what type of hand sanitizer is needed to destroy Covid-19? | 15 Cleaning and decontamination of the healthcare environment Abstract: Evidence is accumulating for the role of cleaning in controlling hospital infections. Hospital pathogens such as meticillin-resistant Staphylococcus aureus (MRSA), vancomycin-resistant enterococci (VRE), norovirus, multi-resistant Gram-negative bacilli and Clostridium difficile persist in the healthcare environment for considerable lengths of time. Cleaning with both detergent and disinfectant-based regimens help control these pathogens in both routine and outbreak situations. The most important transmission risk comes from organisms on frequently handled items because hand contact with a contaminated site could deliver a pathogen to a patient. Cleaning practices should be tailored to clinical risk, near-patient areas and hand-touch-sites and scientifically evaluated for all surfaces and equipment in today's hospitals. |
5 | tedurmyb | what drugs have been active against SARS-CoV or SARS-CoV-2 in animal studies? | Coalition: Advocacy for prospective clinical trials to test the post-exposure potential of hydroxychloroquine against COVID-19 Abstract Our coalition of public health experts, doctors, and scientists worldwide want to draw attention to the need for high-quality evaluation protocols of the potential beneficial effect of hydroxychloroquine (HCQ) as a post-exposure drug for exposed people, meaning people with close contact with positive tested patients, including home and medical caregivers. We have reviewed the mechanisms of antiviral effect of HCQ, the risk-benefit ratio taking into consideration the PK/PD of HCQ and the thresholds of efficacy. We have studied its use as an antimalarial, an antiviral, and an immunomodulating drug and concluded that the use of HCQ at does matching that of the standard treatment of Systemic Lupus erythematous, which has proven safety and efficacy in terms of HCQ blood and tissue concentration adapted to bodyweight (2,3), at 6 mg/kg/day 1 (loading dose) followed by 5 mg/kg/day, with a maximum limit of 600 mg/day in all cases should swiftly be clinically evaluated as a post-exposure drug for exposed people. |
3 | 7p8mw6e6 | will SARS-CoV2 infected people develop immunity? Is cross protection possible? | Antiviral B cell and T cell immunity in the lungs Respiratory viruses are frequent causes of repeated common colds, bronchitis and pneumonia, which often occur unpredictably as epidemics and pandemics. Despite those decimating effects on health and decades of intensive research, treatments remain largely supportive. The only commonly available vaccines are against influenza virus, and even these need improvement. The lung shares some features with other mucosal sites, but preservation of its especially delicate anatomical structures necessitates a fine balance of pro- and anti-inflammatory responses; well-timed, appropriately placed and tightly regulated T cell and B cell responses are essential for protection from infection and limitation of symptoms, whereas poorly regulated inflammation contributes to tissue damage and disease. Recent advances in understanding adaptive immunity should facilitate vaccine development and reduce the global effect of respiratory viruses. |
13 | 7i52vltp | what are the transmission routes of coronavirus? | Preliminary identification of potential vaccine targets for the COVID-19 coronavirus (SARS-CoV-2) based on SARS-CoV immunological studies The beginning of 2020 has seen the emergence of COVID-19 outbreak caused by a novel coronavirus, Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2). There is an imminent need to better understand this new virus and to develop ways to control its spread. In this study, we sought to gain insights for vaccine design against SARS-CoV-2 by considering the high genetic similarity between SARS-CoV-2 and SARS-CoV, which caused the outbreak in 2003, and leveraging existing immunological studies of SARS-CoV. By screening the experimentally-determined SARS-CoV-derived B cell and T cell epitopes in the immunogenic structural proteins of SARS-CoV, we identified a set of B cell and T cell epitopes derived from the spike (S) and nucleocapsid (N) proteins that map identically to SARS-CoV-2 proteins. As no mutation has been observed in these identified epitopes among the available SARS-CoV-2 sequences (as of 9 February 2020), immune targeting of these epitopes may potentially offer protection against this novel virus. For the T cell epitopes, we performed a population coverage analysis of the associated MHC alleles and proposed a set of epitopes that is estimated to provide broad coverage globally, as well as in China. Our findings provide a screened set of epitopes that can help guide experimental efforts towards the development of vaccines against SARS-CoV-2. |
29 | ogiicyik | 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? | Eltrombopag is a potential target for drug intervention in SARS-CoV-2 spike protein The COVID-19 pandemic, caused by the severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2), is a current global threat for which there is an urgent need to search for an effective therapy. The transmembrane spike (S) glycoprotein of SARS-CoV-2 directly binds to the host angiotensin-converting enzyme 2 (ACE2) and mediates viral entrance, which is therefore considered as a promising drug target. Considering that new drug development is a time-consuming process, drug repositioning may facilitate rapid drug discovery dealing with sudden infectious diseases. Here, we compared the differences between the virtual structural proteins of SARS-CoV-2 and SARS-CoV, and selected a pocket mainly localizing in the fusion cores of S2 domain for drug screening. A virtual drug design algorithm screened the Food and Drug Administration-approved drug library of 1234 compounds, and 13 top scored compounds were obtained through manual screening. Through in vitro molecular interaction experiments, eltrombopag was further verified to possess a high binding affinity to S protein plus human ACE2 and could potentially affect the stability of the ACE2-S protein complex. Hence, it is worth further exploring eltrombopag as a potential drug for the treatment of SARS-CoV-2 infection. |
7 | w1p50t4p | are there serological tests that detect antibodies to coronavirus? | More prevalent, less deadly? Bayesian inference of the COVID19 Infection Fatality Ratio from mortality data We use an established semi-mechanistic Bayesian hierarchical model of the COVID-19 pandemic, driven by European mortality data, to estimate the prevalence of immunity. We allow the infection-fatality ratio (IFR) to vary, adapt the model's priors to better reflect emerging information, and re-evaluate the model fitting in the light of current mortality data. The results indicate that the IFR of COVID-19 may be an order of magnitude smaller than the current consensus, with the corollary that the virus is more prevalent than currently believed. These results emerge from a simple model and ought to be treated with caution. They emphasise the value of rapid community-scale antibody testing when this becomes available. |
13 | cfwtyud2 | what are the transmission routes of coronavirus? | [Consideration and prevention for the aerosol transmission of 2019 novel coronavirus] Novel coronavirus pneumonia broke out from Wuhan, and spreading to the whole nation and world since Dec, 2019. It is now the critical stage to fight against the virus. Previous epidemiological investigations and animal experiments suggest aerosol could perform as virus transmitter. Based on the clinical observation, the possibility of aerosol transmission of 2019 novel coronavirus has aroused a lot of attention. This study focuses on the feature of aerosol transmission, and the pathogens involved in. We analyzed the possibility of aerosol transmission for the novel coronavirus. Relevant strategies to prevent novel coronavirus pneumonia are established, serving as references to the medical personnel and general public during their work or daily life. ( Chin J Ophthalmol, 2020, 56: ). |
1 | hq4jb2wy | what is the origin of COVID-19 | Subunit Vaccines Against Emerging Pathogenic Human Coronaviruses Seven coronaviruses (CoVs) have been isolated from humans so far. Among them, three emerging pathogenic CoVs, including severe acute respiratory syndrome coronavirus (SARS-CoV), Middle East respiratory syndrome coronavirus (MERS-CoV), and a newly identified CoV (2019-nCoV), once caused or continue to cause severe infections in humans, posing significant threats to global public health. SARS-CoV infection in humans (with about 10% case fatality rate) was first reported from China in 2002, while MERS-CoV infection in humans (with about 34.4% case fatality rate) was first reported from Saudi Arabia in June 2012. 2019-nCoV was first reported from China in December 2019, and is currently infecting more than 70000 people (with about 2.7% case fatality rate). Both SARS-CoV and MERS-CoV are zoonotic viruses, using bats as their natural reservoirs, and then transmitting through intermediate hosts, leading to human infections. Nevertheless, the intermediate host for 2019-nCoV is still under investigation and the vaccines against this new CoV have not been available. Although a variety of vaccines have been developed against infections of SARS-CoV and MERS-CoV, none of them has been approved for use in humans. In this review, we have described the structure and function of key proteins of emerging human CoVs, overviewed the current vaccine types to be developed against SARS-CoV and MERS-CoV, and summarized recent advances in subunit vaccines against these two pathogenic human CoVs. These subunit vaccines are introduced on the basis of full-length spike (S) protein, receptor-binding domain (RBD), non-RBD S protein fragments, and non-S structural proteins, and the potential factors affecting these subunit vaccines are also illustrated. Overall, this review will be helpful for rapid design and development of vaccines against the new 2019-nCoV and any future CoVs with pandemic potential. This review was written for the topic of Antivirals for Emerging Viruses: Vaccines and Therapeutics in the Virology section of Frontiers in Microbiology. |
46 | 87uhx3pt | what evidence is there for dexamethasone as a treatment for COVID-19? | Rethinking the role of hydroxychloroquine in the treatment of COVID-19 There are currently no proven or approved treatments for coronavirus disease 2019 (COVID-19). Early anecdotal reports and limited in vitro data led to the significant uptake of hydroxychloroquine (HCQ), and to lesser extent chloroquine (CQ), for many patients with this disease. As an increasing number of patients with COVID-19 are treated with these agents and more evidence accumulates, there continues to be no high-quality clinical data showing a clear benefit of these agents for this disease. Moreover, these agents have the potential to cause harm, including a broad range of adverse events including serious cardiac side effects when combined with other agents. In addition, the known and potent immunomodulatory effects of these agents which support their use in the treatment of auto-immune conditions, and provided a component in the original rationale for their use in patients with COVID-19, may, in fact, undermine their utility in the context of the treatment of this respiratory viral infection. Specifically, the impact of HCQ on cytokine production and suppression of antigen presentation may have immunologic consequences that hamper innate and adaptive antiviral immune responses for patients with COVID-19. Similarly, the reported in vitro inhibition of viral proliferation is largely derived from the blockade of viral fusion that initiates infection rather than the direct inhibition of viral replication as seen with nucleoside/tide analogs in other viral infections. Given these facts and the growing uncertainty about these agents for the treatment of COVID-19, it is clear that at the very least thoughtful planning and data collection from randomized clinical trials are needed to understand what if any role these agents may have in this disease. In this article, we review the datasets that support or detract from the use of these agents for the treatment of COVID-19 and render a data informed opinion that they should only be used with caution and in the context of carefully thought out clinical trials, or on a case-by-case basis after rigorous consideration of the risks and benefits of this therapeutic approach. |
18 | isbq1fqt | what are the best masks for preventing infection by Covid-19? | Diarrhea during COVID-19 infection: pathogenesis, epidemiology, prevention and management Abstract Background and aims The severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2 / COVID-19) pandemic is a worldwide emergency. An increasing number of diarrhea cases is reported. Here we investigate the epidemiology, clinical presentation, molecular mechanisms, management, and prevention of SARS-CoV-2 associated diarrhea. Methods We searched on PubMed, EMBASE, and Web of Science up to March 2020 to identify studies documenting diarrhea and mechansism of intestinal inflammation in patients with confirmed diagnosis of SARS-CoV-2 infection. Results Clinical studies show an incidence rate of diarrhea ranging from 2% to 50% of cases. It may precede or trail respiratory symptoms. A pooled analysis revealed an overall percentage of diarrhea onset of 10.4%. SARS-CoV uses the the angiotensin-converting enzyme 2 (ACE2) and the serine protease TMPRSS2 for S protein priming. ACE2 and TMPRSS2 are not only expressed in lung, but also in the small intestinal epithelia. ACE2 is expressed furthermore in the upper esophagus, liver, and colon. SARS-CoV-2 binding affinity to ACE2 is significantly higher (10-20 times) compared with SARS-CoV. Several reports indicate viral RNA shedding in stool detectable longer time period than in nasopharyngeal swabs. Current treatment is supportive, but several options appear promising and are the subject of investigation. Conclusion Diarrhea is a frequent presenting symptom in patients infected with SARS-CoV-2. Increasing evidence indicates possible fecal oral transmission, indicating the need for a rapid and effective modification of the screening and diagnostic algorithms. The optimal methods to prevent, manage, and treat diarrhea in COVID-19 infected patients are subjects of intensive research. |
21 | y6w3wfvk | what are the mortality rates overall and in specific populations | Spatial Disparities in Coronavirus Incidence and Mortality in the United States: An Ecological Analysis as of May 2020 PURPOSE: This ecological analysis investigates the spatial patterns of the COVID-19 epidemic in the United States in relation to socioeconomic variables that characterize US counties. METHODS: Data on confirmed cases and deaths from COVID-19 for 2,814 US counties were obtained from Johns Hopkins University. We used Geographic Information Systems (GIS) to map the spatial aspects of this pandemic and investigate the disparities between metropolitan and nonmetropolitan communities. Multiple regression models were used to explore the contextual risk factors of infections and death across US counties. We included population density, percent of population aged 65+, percent population in poverty, percent minority population, and percent of the uninsured as independent variables. A state-level measure of the percent of the population that has been tested for COVID-19 was used to control for the impact of testing. FINDINGS: The impact of COVID-19 in the United States has been extremely uneven. Although densely populated large cities and their surrounding metropolitan areas are hotspots of the pandemic, it is counterintuitive that incidence and mortality rates in some small cities and nonmetropolitan counties approximate those in epicenters such as New York City. Regression analyses support the hypotheses of positive correlations between COVID-19 incidence and mortality rates and socioeconomic factors including population density, proportions of elderly residents, poverty, and percent population tested. CONCLUSIONS: Knowledge about the spatial aspects of the COVID-19 epidemic and its socioeconomic correlates can inform first responders and government efforts. Directives for social distancing and to "shelter-in-place" should continue to stem the spread of COVID-19. |
46 | dsklkntt | what evidence is there for dexamethasone as a treatment for COVID-19? | Off-Label Real World Experience Using Tocilizumab for Patients Hospitalized with COVID-19 Disease in a Regional Community Health System: A Case-Control Study Objective: To determine if Tocilizumab treatment in patients hospitalized with laboratory confirmed SARS-CoV-2 infection and subsequent COVID-19 disease provides short-term survival benefit. Design: Case-control, observational study that includes an observation period from arrival to discharge or inpatient death. Both Cox proportional hazards and average treatment effects models were used to determine survival and treatment benefits. Setting: Three Cone Health acute care hospitals including one COVID dedicated facility. Patients: Patients admitted with confirmed SARS-CoV-2 from March 16, 2020 through April 22, 2020. Exposure: Tocilizumab dosed at either 400 mg fixed dose or 8 mg/kg weight-based dose with maximum single dose of 800mg. Measurements and Main Results: Overall, 86 patients were admitted during the observation period with confirmed COVID-19 disease. Of these, 21 received Tocilizumab during the hospital stay. Both the Cox model and treatment effects models showed short-term survival benefit. There was an associated 75% reduction in the risk of inpatient death when treated (HR 0.25; 95% CI 0.07-0.90) in the Cox model. This association was confirmed in the treatment effects model where we found a 52.7% reduced risk of dying while hospitalized compared to those not treated (RR 0.472; 95% CI 0.449-0.497). In both models, we show short-term survival benefit in patients with severe COVID-19 illness. |
13 | raelqb6j | what are the transmission routes of coronavirus? | Multinational modeling of SARS-CoV-2 spreading dynamics: Insights on the heterogeneity of COVID-19 transmission and its potential healthcare burden Background: Modelling and projections of COVID-19 using a single set of transmission parameters can be an elaborated because the application of different levels of containment measures at different stages of the worldwide COVID-19 outbreak. Methods: We developed a piecewise fitting SEIR methodology to fit the progress of the COVID-19 that can be applied on any of the 185 countries listed in John Hopkins Coronavirus Resource Center. The contagious contact rate, the rate of removal and the initially exposed population were obtained at three different stages of the pandemic for a set of 18 countries, and globally for the total number of cases worldwide. The active number of infections and the removed populations were fitted simultaneously to validate the SEIR model against the available time series reports on the number of confirmed infections, recoveries and deaths. We evaluate the effect of a reduction of contagious contact rate on the level of burden put on local healthcare infrastructure considering different levels of intervention. As a guideline for future public health interventions, we also estimated the maximum number of future cases and its potential peak date. Findings: We project that the peak in the number of infections worldwide will take place after the third quarter of 2020 with a decline rate that might extend beyond 2020. For 12 out of the 18 countries analyzed, we observe that, following the trend at the date of this study, the number of severe infections will surpass their healthcare capacity. For a 90% reduction scenario of the contagious contact rate, four out of the 18 countries analyzed will undergo a significant delay in the peak of infection, extending the course of the epidemic further than our simulation window (365 days). Interpretation: We identify three stages for the COVID-19 transmission dynamics, which suggest that it is highly heterogeneous between countries and its contagious contact rate, is currently affected by both local responses of the public health interventions and to the population's adherence to the measures. Funding: No funding received. |
40 | j9u63w6z | What are the observed mutations in the SARS-CoV-2 genome and how often do the mutations occur? | The potential of putative zinc-binding motifs of haemagglutinin A (HA) protein for categorization and prediction of pathogenicity of H5 subtypes of avian influenza virus In the present study, we used the potential of bioinformatics and computational analysis to predict the existence and biological relevance of zinc finger (ZF) motifs in heamagglutinin A (HA) protein of Avian Influenza (AI) virus. Sequence data of Avian Influenza (AI) virus were retrieved from accessible databases (GenBank, GISAID, IRD) and analyzed for the existence, as well as functional prediction of the putative zinc finger or ''zinc-binding'' motif(s) of HA protein. It is hypothesized that the ZF motif(s) in HA of AI can be used as a ''novel'' biomarker for categorization of the virus and/or its virulence. As a model for analysis, we used the H5 subtypes of highly pathogenic, non-pathogenic and low pathogenic avian influenza (HPAI, NPAI and LPAI) of H5N1 and H5N2 of avian and human origin. Interestingly, our method of characterization using the zinc-finger agrees with the existing classification in distinguishing between highly pathogenic and non-pathogenic or low pathogenic subtypes. The new method also clearly distinguished between low and non-pathogenic strains of H5N2 and H5N1 which are indistinguishable by the existing method that utilizes the sequence of amino acids of the proteolytic cleavage site for pathogenicity. It is hypothesized that zinc through the activities of zinc-binding proteins modulates the virulence property of the viral subtypes. Our observation further revealed that only the HA protein among the eight encoded proteins of influenza virus contain high numbers of Cys-His residues. It is expected that the information gathered from the analysis of the data will be useful to generate more research hypotheses/designs that will give further insight towards the identification and control of avian influenza virus through the molecular manipulation of zinc finger motifs present in viral HA protein. |
11 | s2bnrvm8 | what are the guidelines for triaging patients infected with coronavirus? | COVID-19 Infection in a Patient with End-Stage Kidney Disease Since December 2019, the epidemic of coronavirus disease 2019 (COVID-19) has spread very rapidly in China and worldwide. In this article, we report on a 75-year-old man infected with 2019 novel coronavirus who has end-stage kidney disease (ESKD). COVID-19 patients with ESKD need isolation dialysis, but most of them cannot be handled in time due to limited continuous renal replacement therapy (CRRT) machines. CRRT provided benefits for this patient by removing potentially damaging toxins and stabilizing his metabolic and hemodynamic status. With the control of uremia and fluid status, this patient ended up with an uneventful post-CRRT course, absence of clinical symptoms, and negative PCR tests. Greater efforts are needed to decrease the mortality of COVID-19-infected ESKD patients. |
38 | 3g06zxmx | What is the mechanism of inflammatory response and pathogenesis of COVID-19 cases? | COVID-19: Pathogenesis, cytokine storm and therapeutic potential of interferons ABSTRACT The outbreak of the novel SARS-CoV-2 (severe acute respiratory syndrome coronavirus 2) responsible for coronavirus disease 2019 (COVID-19) has developed into a major health hazard across the globe. The rapid escalation of the COVID-19 and the considerable associated illness leading to death has transformed it into a critical global public health issue. The current clinical investigation in patients with COVID-19 has showed strong upregulation of cytokine and interferon production after critical infection with SARS-CoV2- induced pneumonia. The current research suggests that few groups of patients with COVID-19 might have a cytokine storm syndrome. Thus, identification and treatment of hyperinflammation using existing, approved therapies with proven safety profiles to address the immediate need to reduce the rising mortality. To date, no specific therapeutic drug or vaccine has been discovered to treat this COVID-19. Intensive research is in progress to identify a promising drug therapy. Hence, several options were proposed to control this fast-emerging pandemic, including antiviral drugs, vaccines, small-molecules, monoclonal antibodies, oligonucleotides, peptides, and interferons (IFNs). |
38 | pjotppso | What is the mechanism of inflammatory response and pathogenesis of COVID-19 cases? | Vitamin intervention for cytokine storm in the patients with coronavirus disease 2019 |
12 | rk3d6se9 | what are best practices in hospitals and at home in maintaining quarantine? | Establishing and managing a quarantine and isolation centre in COVID-19 pandemic The novel coronavirus disease (COVID-19) is a recent pandemic which has spread to over 200 countries of the world since its outbreak. As of 21st April, 2020, more than 2.3 million confirmed cases have been reported. The World Health Organization (WHO) has issued a strategic preparedness response plan for countries at risk. This is based on the knowledge of previous epidemics and experience shared by Chinese health authorities. There is special emphasis on strict 'quarantine and isolation' of suspected/diagnosed cases. Pakistan is a developing country with a weak healthcare system. Pakistan Armed Forces have always provided services to the countrymen during natural and man-made disasters. During this pandemic the largest rehabilitation institute in the country was converted into a 130-bed dedicated isolation and quarantine facility for the COVID-19 patients. We will share our experience of establishing and managing this quarantine and isolation facility and highlight the achievements and out-of-the-box solutions applicable for low resource countries like Pakistan. |
14 | 127c5bve | what evidence is there related to COVID-19 super spreaders | Decoding the evolution and transmissions of the novel pneumonia coronavirus (SARS-CoV-2 / HCoV-19) using whole genomic data The outbreak of COVID-19 started in mid-December 2019 in Wuhan, China. Up to 29 February 2020, SARS-CoV-2 (HCoV-19 / 2019-nCoV) had infected more than 85 000 people in the world. In this study, we used 93 complete genomes of SARS-CoV-2 from the GISAID EpiFlu(TM) database to investigate the evolution and human-to-human transmissions of SARS-CoV-2 in the first two months of the outbreak. We constructed haplotypes of the SARS-CoV-2 genomes, performed phylogenomic analyses and estimated the potential population size changes of the virus. The date of population expansion was calculated based on the expansion parameter tau (τ) using the formula t=τ/2u. A total of 120 substitution sites with 119 codons, including 79 non-synonymous and 40 synonymous substitutions, were found in eight coding-regions in the SARS-CoV-2 genomes. Forty non-synonymous substitutions are potentially associated with virus adaptation. No combinations were detected. The 58 haplotypes (31 found in samples from China and 31 from outside China) were identified in 93 viral genomes under study and could be classified into five groups. By applying the reported bat coronavirus genome (bat-RaTG13-CoV) as the outgroup, we found that haplotypes H13 and H38 might be considered as ancestral haplotypes, and later H1 was derived from the intermediate haplotype H3. The population size of the SARS-CoV-2 was estimated to have undergone a recent expansion on 06 January 2020, and an early expansion on 08 December 2019. Furthermore, phyloepidemiologic approaches have recovered specific directions of human-to-human transmissions and the potential sources for international infected cases. |
10 | ihijerw1 | has social distancing had an impact on slowing the spread of COVID-19? | Trading Privacy for the Greater Social Good: How Did America React During COVID-19? Digital contact tracing and analysis of social distancing from smartphone location data are two prime examples of non-therapeutic interventions used in many countries to mitigate the impact of the COVID-19 pandemic. While many understand the importance of trading personal privacy for the public good, others have been alarmed at the potential for surveillance via measures enabled through location tracking on smartphones. In our research, we analyzed massive yet atomic individual-level location data containing over 22 billion records from ten Blue (Democratic) and ten Red (Republican) cities in the U.S., based on which we present, herein, some of the first evidence of how Americans responded to the increasing concerns that government authorities, the private sector, and public health experts might use individual-level location data to track the COVID-19 spread. First, we found a significant decreasing trend of mobile-app location-sharing opt-out. Whereas areas with more Democrats were more privacy-concerned than areas with more Republicans before the advent of the COVID-19 pandemic, there was a significant decrease in the overall opt-out rates after COVID-19, and this effect was more salient among Democratic than Republican cities. Second, people who practiced social distancing (i.e., those who traveled less and interacted with fewer close contacts during the pandemic) were also less likely to opt-out, whereas the converse was true for people who practiced less social-distancing. This relationship also was more salient among Democratic than Republican cities. Third, high-income populations and males, compared with low-income populations and females, were more privacy-conscientious and more likely to opt-out of location tracking. |
14 | rnnz0gjc | what evidence is there related to COVID-19 super spreaders | SARS unanswered questions |
43 | gp0ajkt8 | How has the COVID-19 pandemic impacted violence in society, including violent crimes? | [Gender violence and other factors associated with emotional distress in female users of public health services in Mexico]. OBJECTIVE To identify and describe the factors associated with emotional distress in a national sample of women users of public health services in Mexico, such a Secretaria de Salud (SSA), Instituto Mexicano del Seguro Social (IMSS), Instituto de Seguridad y Servicios Sociales de los Trabajadores del Estado (ISSSTE). MATERIAL AND METHODS This research study was conducted using the database of the National Survey of Violence against Women that consisted of the responses of a total of 26 042 female users of health care services provided by the Mexican government health agencies. The Personal Health Scale (ESP per its initials in Spanish) was used to assess emotional distress. To measure violence a 19-item scale which explores different types of violence as well as severity was used. The relationship between emotional distress and gender violence was determined through a binary logistic regression model, as were economic status and demographic variables. RESULTS One of the most important findings of this study is the high prevalence of emotional distress (15.3%) among women seeking health care services from the public sector and the relationship of such emotional distress with the experience of marital physical, psychological, and sexual violence. Factors associated with emotional distress among female users of health care services were age (26 and older); activity (laborer); working hours (71 hours a week or more); alcohol intake (greater intake); abuse during childhood (frequency and types of abuse); severity of marital violence (severe violence); socioeconomic status (very low SES); and type of dwelling (urban). CONCLUSIONS The principal predictor of emotional distress was intimate partner abuse, especially in severe expression. The next predictor was violence in childhood. Taking into consideration these predictors it is recommended to use screening instruments to identify emotional distress and gender violence in health setting. It is important to design and implement attention and reference programs in public health services for women suffering from emotional distress and gender violence. |
8 | j4b2534p | how has lack of testing availability led to underreporting of true incidence of Covid-19? | Risk of hospitalization and death from COVID-19 infection in patients with chronic plaque psoriasis receiving a biological treatment and renal transplanted recipients in maintenance immunosuppressive treatment |
1 | sh7lrdou | what is the origin of COVID-19 | The epidemiology and pathogenesis of coronavirus disease (COVID-19) outbreak Coronavirus disease (COVID-19) is caused by SARS-COV2 and represents the causative agent of a potentially fatal disease that is of great global public health concern. Based on the large number of infected people that were exposed to the wet animal market in Wuhan City, China, it is suggested that this is likely the zoonotic origin of COVID-19. Person-to-person transmission of COVID-19 infection led to the isolation of patients that were subsequently administered a variety of treatments. Extensive measures to reduce person-to-person transmission of COVID-19 have been implemented to control the current outbreak. Special attention and efforts to protect or reduce transmission should be applied in susceptible populations including children, health care providers, and elderly people. In this review, we highlights the symptoms, epidemiology, transmission, pathogenesis, phylogenetic analysis and future directions to control the spread of this fatal disease. |
14 | jhxov1gu | what evidence is there related to COVID-19 super spreaders | Stability of the spreading in small-world network with predictive controller Abstract In this Letter, we apply the predictive control strategy to suppress the propagation of diseases or viruses in small-world network. The stability of small-world spreading model with predictive controller is investigated. The sufficient and necessary stability condition is given, which is closely related to the controller parameters and small-world rewiring probability p. Our simulations discover a phenomenon that, with the fixed predictive controller parameters, the spreading dynamics become more and more stable when p decreases from a larger value to a smaller one, and the suitable controller parameters can effectively suppress the spreading behaviors even when p varies within the whole spectrum, and the unsuitable controller parameters can lead to oscillation when p lies within a certain range. |
40 | 06vlesc7 | What are the observed mutations in the SARS-CoV-2 genome and how often do the mutations occur? | Mutations in Influenza A Virus Neuraminidase and Hemagglutinin Confer Resistance against a Broadly Neutralizing Hemagglutinin Stem Antibody. Influenza A virus (IAV), a major cause of human morbidity and mortality, continuously evolves in response to selective pressures. Stem-directed, broadly neutralizing antibodies (sBnAbs) targeting the influenza virus hemagglutinin (HA) are a promising therapeutic strategy, but neutralization escape mutants can develop. We used an integrated approach combining viral passaging, deep sequencing, and protein structural analyses to define escape mutations and mechanisms of neutralization escape in vitro for the F10 sBnAb. IAV was propagated with escalating concentrations of F10 over serial passages in cultured cells to select for escape mutations. Viral sequence analysis revealed three mutations in HA and one in neuraminidase (NA). Introduction of these specific mutations into IAV through reverse genetics confirmed their roles in resistance to F10. Structural analyses revealed that the selected HA mutations (S123G, N460S, and N203V) are away from the F10 epitope but may indirectly impact influenza virus receptor binding, endosomal fusion, or budding. The NA mutation E329K, which was previously identified to be associated with antibody escape, affects the active site of NA, highlighting the importance of the balance between HA and NA function for viral survival. Thus, whole-genome population sequencing enables the identification of viral resistance mutations responding to antibody-induced selective pressure.IMPORTANCE Influenza A virus is a public health threat for which currently available vaccines are not always effective. Broadly neutralizing antibodies that bind to the highly conserved stem region of the influenza virus hemagglutinin (HA) can neutralize many influenza virus strains. To understand how influenza virus can become resistant or escape such antibodies, we propagated influenza A virus in vitro with escalating concentrations of antibody and analyzed viral populations by whole-genome sequencing. We identified HA mutations near and distal to the antibody binding epitope that conferred resistance to antibody neutralization. Additionally, we identified a neuraminidase (NA) mutation that allowed the virus to grow in the presence of high concentrations of the antibody. Virus carrying dual mutations in HA and NA also grew under high antibody concentrations. We show that NA mutations mediate the escape of neutralization by antibodies against HA, highlighting the importance of a balance between HA and NA for optimal virus function. |
29 | rg76nlee | 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? | Resistance to anti-influenza agents |
30 | kjovtgua | is remdesivir an effective treatment for COVID-19 | Rapid and accurate identification of COVID-19 infection through machine learning based on clinical available blood test results Since the sudden outbreak of coronavirus disease 2019 (COVID-19), it has rapidly evolved into a momentous global health concern. Due to the lack of constructive information on the pathogenesis of COVID-19 and specific treatment, it highlights the importance of early diagnosis and timely treatment. In this study, 11 key blood indices were extracted through random forest algorithm to build the final assistant discrimination tool from 49 clinical available blood test data which were derived by commercial blood test equipments. The method presented robust outcome to accurately identify COVID-19 from a variety of suspected patients with similar CT information or similar symptoms, with accuracy of 0.9795 and 0.9697 for the cross-validation set and test set, respectively. The tool also demonstrated its outstanding performance on an external validation set that was completely independent of the modeling process, with sensitivity, specificity, and overall accuracy of 0.9512, 0.9697, and 0.9595, respectively. Besides, 24 samples from overseas infected patients with COVID-19 were used to make an in-depth clinical assessment with accuracy of 0.9167. After multiple verification, the reliability and repeatability of the tool has been fully evaluated, and it has the potential to develop into an emerging technology to identify COVID-19 and lower the burden of global public health. The proposed tool is well-suited to carry out preliminary assessment of suspected patients and help them to get timely treatment and quarantine suggestion. The assistant tool is now available online at http://lishuyan.lzu.edu.cn/COVID2019_2/. |
3 | s7klkqka | will SARS-CoV2 infected people develop immunity? Is cross protection possible? | Porcine Coronaviruses Transmissible gastroenteritis virus (TGEV), porcine epidemic diarrhoea virus (PEDV), and porcine deltacoronavirus (PDCoV) are enteropathogenic coronaviruses (CoVs) of swine. TGEV appearance in 1946 preceded identification of PEDV (1971) and PDCoV (2009) that are considered as emerging CoVs. A spike deletion mutant of TGEV associated with respiratory tract infection in piglets appeared in 1984 in pigs in Belgium and was designated porcine respiratory coronavirus (PRCV). PRCV is considered non-pathogenic because the infection is very mild or subclinical. Since PRCV emergence and rapid spread, most pigs have become immune to both PRCV and TGEV, which has significantly reduced the clinical and economic importance of TGEV. In contrast, PDCoV and PEDV are currently expanding their geographic distribution, and there are reports on the circulation of TGEV-PEDV recombinants that cause a disease clinically indistinguishable from that associated with the parent viruses. TGEV, PEDV and PDCoV cause acute gastroenteritis in pigs (most severe in neonatal piglets) and matches in their clinical signs and pathogenesis. Necrosis of the infected intestinal epithelial cells causes villous atrophy and malabsorptive diarrhoea. Profuse diarrhoea frequently combined with vomiting results in dehydration, which can lead to the death of piglets. Strong immune responses following natural infection protect against subsequent homologous challenge; however, these viruses display no cross-protection. Adoption of advance biosecurity measures and effective vaccines control and prevent the occurrence of diseases due to these porcine-associated CoVs. Recombination and reversion to virulence are the risks associated with generally highly effective attenuated vaccines necessitating further research on alternative vaccines to ensure their safe application in the field. |
12 | 2g4m0dy7 | what are best practices in hospitals and at home in maintaining quarantine? | Reducing the Impact of the Next Influenza Pandemic Using Household-Based Public Health Interventions BACKGROUND: The outbreak of highly pathogenic H5N1 influenza in domestic poultry and wild birds has caused global concern over the possible evolution of a novel human strain [1]. If such a strain emerges, and is not controlled at source [2,3], a pandemic is likely to result. Health policy in most countries will then be focused on reducing morbidity and mortality. METHODS AND FINDINGS: We estimate the expected reduction in primary attack rates for different household-based interventions using a mathematical model of influenza transmission within and between households. We show that, for lower transmissibility strains [2,4], the combination of household-based quarantine, isolation of cases outside the household, and targeted prophylactic use of anti-virals will be highly effective and likely feasible across a range of plausible transmission scenarios. For example, for a basic reproductive number (the average number of people infected by a typically infectious individual in an otherwise susceptible population) of 1.8, assuming only 50% compliance, this combination could reduce the infection (symptomatic) attack rate from 74% (49%) to 40% (27%), requiring peak quarantine and isolation levels of 6.2% and 0.8% of the population, respectively, and an overall anti-viral stockpile of 3.9 doses per member of the population. Although contact tracing may be additionally effective, the resources required make it impractical in most scenarios. CONCLUSIONS: National influenza pandemic preparedness plans currently focus on reducing the impact associated with a constant attack rate, rather than on reducing transmission. Our findings suggest that the additional benefits and resource requirements of household-based interventions in reducing average levels of transmission should also be considered, even when expected levels of compliance are only moderate. |
4 | 3ueg2i6w | what causes death from Covid-19? | Transmission Dynamics of COVID-19 and Impact on Public Health Policy In this work we construct a mathematical model for the transmission and spread of coronavirus disease 2019 or COVID-19. Our model features delay terms to account for (a) the time lapse or latency period between contracting the disease and displaying symptoms, and (b) the time lag in testing patients for the virus due to the limited numbers of testing facilities currently available. We find that the delay introduces a significant disparity between the actual and reported time-trajectories of cases in a particular region. Specifically, the reported case histories lag the actual histories by a few days. Hence, to minimize the spread of the disease, lockdowns and similarly drastic social isolation measures need to be imposed some time before the reported figures are approaching their peak values. We then account for the social reality that lockdowns can only be of a limited duration in view of practical considerations. We find that the most effective interval for imposing such a limited-time lockdown is one where the midpoint of the lockdown period coincides with the actual peak of the spread of the disease in the absence of the lockdown. We further show that the true effectivity of imposing a lockdown may be misrepresented and grossly underestimated by the reported case trajectories in the days following the action. |
39 | hmh4s3w4 | What is the mechanism of cytokine storm syndrome on the COVID-19? | Social Media as a Sensor of Air Quality and Public Response in China BACKGROUND: Recent studies have demonstrated the utility of social media data sources for a wide range of public health goals, including disease surveillance, mental health trends, and health perceptions and sentiment. Most such research has focused on English-language social media for the task of disease surveillance. OBJECTIVE: We investigated the value of Chinese social media for monitoring air quality trends and related public perceptions and response. The goal was to determine if this data is suitable for learning actionable information about pollution levels and public response. METHODS: We mined a collection of 93 million messages from Sina Weibo, China's largest microblogging service. We experimented with different filters to identify messages relevant to air quality, based on keyword matching and topic modeling. We evaluated the reliability of the data filters by comparing message volume per city to air particle pollution rates obtained from the Chinese government for 74 cities. Additionally, we performed a qualitative study of the content of pollution-related messages by coding a sample of 170 messages for relevance to air quality, and whether the message included details such as a reactive behavior or a health concern. RESULTS: The volume of pollution-related messages is highly correlated with particle pollution levels, with Pearson correlation values up to .718 (n=74, P<.001). Our qualitative results found that 67.1% (114/170) of messages were relevant to air quality and of those, 78.9% (90/114) were a firsthand report. Of firsthand reports, 28% (32/90) indicated a reactive behavior and 19% (17/90) expressed a health concern. Additionally, 3 messages of 170 requested that action be taken to improve quality. CONCLUSIONS: We have found quantitatively that message volume in Sina Weibo is indicative of true particle pollution levels, and we have found qualitatively that messages contain rich details including perceptions, behaviors, and self-reported health effects. Social media data can augment existing air pollution surveillance data, especially perception and health-related data that traditionally requires expensive surveys or interviews. |
18 | i19v85o9 | what are the best masks for preventing infection by Covid-19? | Protecting Labor and Delivery Personnel from COVID-19 during the Second Stage of Labor The novel coronavirus disease 2019 (COVID-19) is spreading fast and is affecting the clinical workers at much higher risk than the general population. Little is known about COVID-19 effect on pregnant women; however, the emerging evidence suggests they may be at high risk of asymptomatic disease. In light of projected shortage of personal protective equipment (PPE), there is an aggressive attempt at conservation. In obstetrics, the guidelines on PPE use are controversial and differ among hospitals, globally, as well as nationally. The centers for disease control and prevention (CDC) recommend using N95 respirators, which are respirators that offer a higher level of protection instead of a facemask for when performing or present for an aerosol-generating procedures (AGP). However, the second stage of labor is not considered an AGP. The second stage of labor can last up to 4 hours. During that time, labor and delivery personnel is in close contact to patients, who are exerting extreme effort during and frequently blow out their breath, cough, shout, and vomit, all of which put the health care team at risk, considering that COVID-19 transmission occurs through aerosol generated by coughing and sneezing. The CDC and the American College of Obstetricians and Gynecologists (ACOG) do not provide clarification on the use of N95 during the second stage. We recommend that labor and delivery personnel have the utmost caution and be granted the protection they need to protect themselves and other patients. This includes providing labor and delivery personnel full PPE including N95 for the second stage of labor. This is critical to ensure the adequate protection for health care workers and to prevent spread to other health care workers and patients. Key Points: Second stage of labor exposes providers to aerosol. COVID-19 risk during second stage of labor is high. N95 should be used during second stage of labor. |
15 | 7jfy66ve | how long can the coronavirus live outside the body | Robot assisted surgery during the COVID-19 pandemic, especially for gynecological cancer: a statement of the Society of European Robotic Gynaecological Surgery (SERGS) All surgery performed in an epicenter of the coronavirus disease 2019 (COVID-19) pandemic, irrespective of the known or suspected severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) status of the patient, should be regarded as high risk and protection of the surgical team at the bedside should be at the highest level. Robot assisted surgery (RAS) may help to reduce hospital stay for patients that urgently need complex-oncological-surgery, thus making room for COVID-19 patients. In comparison to open or conventional laparoscopic surgery, RAS potentially reduces not only contamination with body fluids and surgical gasses of the surgical area but also the number of directly exposed medical staff. A prerequisite is that general surgical precautions under COVID-19 circumstances must be taken, with the addition of prevention of gas leakage: • Use highest protection level III for bedside assistant, but level II for console surgeon. • Reduce the number of staff at the operation room. • Ensure safe and effective gas evacuation. • Reduce the intra-abdominal pressure to 8 mmHg or below. • Minimize electrocautery power and avoid use of ultrasonic sealing devices. • Surgeons should avoid contact outside theater (both in and out of the hospital). |
21 | na3o33b0 | what are the mortality rates overall and in specific populations | IMMUNOLOGY OF THE CAT |
4 | qvhwypjt | what causes death from Covid-19? | Clinical characteristics of 25 death cases with COVID-19: a retrospective review of medical records in a single medical center, Wuhan, China Abstract Objectives This study aims to summarize the clinical characteristics of death cases with COVID-19 and to identify critically ill patients of COVID-19 early and reduce their mortality. Methods The clinical records, laboratory findings and radiological assessments included chest X-ray or computed tomography were extracted from electronic medical records of 25 died patients with COVID-19 in Renmin Hospital of Wuhan University from Jan 14 to Feb 13, 2020. Two experienced clinicians reviewed and abstracted the data. Results The age and underlying diseases (hypertension, diabetes, etc.) were the most important risk factors for death of COVID-19 pneumonia. Bacterial infections may play an important role in promoting the death of patients. Malnutrition was common to severe patients. Multiple organ dysfunction can be observed, the most common organ damage was lung, followed by heart, kidney and liver. The rising of neutrophils, SAA, PCT, CRP, cTnI, D-dimer, LDH and lactate levels can be used as indicators of disease progression, as well as the decline of lymphocytes counts. Conclusions The clinical characteristics of 25 death cases with COVID-19 we summarized, which would be helpful to identify critically ill patients of COVID-19 early and reduce their mortality. |
26 | 5dontosm | what are the initial symptoms of Covid-19? | Comparative Analysis of Early-Stage Clinical Features Between COVID-19 and Influenza A H1N1 Virus Pneumonia Introduction: Influenza virus pneumonia and COVID-19 are two different types of respiratory viral pneumonia but with very similar clinical manifestations. The aim of the present study was to help clinicians gain a better understanding about differences between Influenza virus pneumonia and COVID-19 by comparative analysis of the early-stage clinical features. Methods: Clinical data of patients with confirmed diagnosis of COVID-19 and influenza A pneumonia identified in our hospital were collected and analyzed retrospectively to identify the clinical features that could differentiate between the two types of viral pneumonia. Results: The two types of viral pneumonia mainly affected adults, especially people over 50 years, with no gender difference between them. Fever, cough, sputum and muscle soreness were the most common symptoms of COVID-19. Some patients with COVID-19 may also exhibit digestive tract symptoms. Elevation of C-reactive protein (CRP) was a more common phenomenon in patients with COVID-19 than that in patients with influenza A H1N1 virus pneumonia. In addition, eosinophil count was decreased and the monocyte percentage was increased in COVID-19 patients. The grid-form shadow was a typical presentation of COVID-19 on the lung CT image, and the disease usually progressed quickly within a week. Conclusion: Influenza pneumonia and COVID-19 are two different types of respiratory viral pneumonia with very similar clinical manifestations. The percentage of monocytes is increased and the eosinophil count is decreased in COVID-19. Glass-ground density exudation shadow located peripherally is the typical sign of COVID-19 on the lung CT image, and the shadow often with grid-form sign. These features may not be typically observed in patients with influenza pneumonia. Chest CT scan combined with nucleic acid detection is an effective and accurate method for diagnosing COVID-19. Blood routine test has a limited diagnostic value in differentiating the two forms of pneumonia. |
36 | 88iu8n5h | What is the protein structure of the SARS-CoV-2 spike? | Structural modeling of 2019-novel coronavirus (nCoV) spike protein reveals a proteolytically-sensitive activation loop as a distinguishing feature compared to SARS-CoV and related SARS-like coronaviruses. The 2019 novel coronavirus (2019-nCoV) is currently causing a widespread outbreak centered on Hubei province, China and is a major public health concern. Taxonomically 2019-nCoV is closely related to SARS-CoV and SARS-related bat coronaviruses, and it appears to share a common receptor with SARS-CoV (ACE-2). Here, we perform structural modeling of the 2019-nCoV spike glycoprotein. Our data provide support for the similar receptor utilization between 2019-nCoV and SARS-CoV, despite a relatively low amino acid similarity in the receptor binding module. Compared to SARS-CoV, we identify an extended structural loop containing basic amino acids at the interface of the receptor binding (S1) and fusion (S2) domains, which we predict to be proteolytically-sensitive. We suggest this loop confers fusion activation and entry properties more in line with MERS-CoV and other coronaviruses, and that the presence of this structural loop in 2019-nCoV may affect virus stability and transmission. |
41 | wimsktta | What are the impacts of COVID-19 among African-Americans that differ from the rest of the U.S. population? | Loop mediated isothermal amplification (LAMP) assays as a rapid diagnostic for COVID-19 Abstract Recently, a novel coronavirus (SARS-CoV-2; coronavirus disease 2019, COVID-19) has emerged, rapidly spreading and severely straining the capacity of the global health community. Many nations are employing combinations of containment and mitigation strategies, where early diagnosis of COVID-19 is vital in controlling illness progression and limiting viral spread within the population. Thus, rapid and accurate methods of early detection are vital to contain COVID-19 and prevent further spread and predicted subsequent infectious waves of viral recurrence in future. Immediately after its initial characterization, Chinese and American Centers for Disease Control and Prevention (CDCs) rapidly employed molecular assays for detection of COVID-19, mostly employing real-time polymerase chain reaction (RT-PCR) methods. However, such methods require specific expensive items of equipment and highly trained analysts, requiring upwards of 4-8 hours to process. These requirements coupled with associated financial pressures may prevent effective deployment of such diagnostic tests. Loop mediated isothermal amplification(LAMP) is method of nucleic acid amplification which exhibits increased sensitivity and specificity are significantly rapid, and do not require expensive reagents or instruments, which aids in cost reduction for coronavirus detection. Studies have shown the successful application of LAMP assays in various forms to detect coronavirus RNA in patient samples, demonstrating that 1-10 copies of viral RNA template per reaction are sufficient for successful detection, ∼100-fold more sensitive than conventional RT-PCR methods. Importantly, studies have also now demonstrated the effectiveness of LAMP methodology in the detection of SARS-CoV-2 RNA at significantly low levels, particularly following numerous improvements to LAMP assay protocols. We hypothesise that recent advancements in enhanced LAMP protocols assay perhaps represent the best chance for a rapid and robust assay for field diagnosis of COVID-19, without the requirement of specialized equipment and highly trained professionals to interpret results. Herein, we present our arguments with a view to disseminate such findings, to assist the combat of this virus that is proving so devastating. We hope that this strategy could be applied rapidly, and confirmed for viability with clinical samples, before being rolled out for mass-diagnostic testing in these current times. |
14 | x82yaoxc | what evidence is there related to COVID-19 super spreaders | The COVID-19 pandemic: is our medicine still evidence-based? There is no randomized controlled trial that demonstrated the efficacy of antiviral therapy against COVID-19 yet. However, physicians are prescribing different drugs to a large part of COVID-19 population in the hope they will cure them. This does not reflect the evidence-based medicine approach. What we need is more evidence-based knowledge about what routine care practices we should to apply to ameliorate symptoms of patients and fight COVID-19 pathology. |
27 | hqech99b | what is known about those infected with Covid-19 but are asymptomatic? | Clinicopathological characteristics of 8697 patients with COVID-19 in China: a meta-analysis OBJECTIVE: Our study aims to present a summary of the clinicopathological characteristics of patients affected by the coronavirus disease 2019 (COVID-19) that can be used as a reference for further research and clinical decisions. DESIGN: Studies were included in the meta-analysis if they had cohort, case–control or case series designs and provided sufficient details on clinical symptoms, laboratory outcomes and asymptomatic patients. SETTING: PubMed, Embase, Chinese Biomedical Literature Database, Wanfang, China Science and Technology Journal Database and China National Knowledge Infrastructure databases were electronically searched to identify related studies published between 1 January 2020 and 16 March 2020. Three reviewers independently examined the literature, extracted relevant data and assessed the risk of publication bias before including the studies in the meta-analysis. PARTICIPANTS: The confirmed cases of COVID-19. RESULTS: A total of 55 unique retrospective studies involving 8697 patients with COVID-19 were identified. Meta-analysis showed that a higher proportion of infected patients were male (53.3%), and the two major symptoms observed were fever (78.4%) and cough (58.3%). Other common symptoms included fatigue (34%), myalgia (21.9%), expectoration (23.7%), anorexia (22.9%), chest tightness (22.9%) and dyspnoea (20.6%). Minor symptoms included nausea and vomiting (6.6%), diarrhoea (8.2%), headache (11.3%), pharyngalgia (11.6%), shivering (15.2%) and rhinorrhea (7.3%). About 5.4% of the patients were asymptomatic. Most patients showed normal leucocyte counts (64.7%) and elevated C reactive protein levels (65.9%). Lymphopaenia was observed in about 47.6% of the infected patients, along with abnormal levels of myocardial enzymes (49.4%) and liver function (26.4%). Other findings included leucopenia (23.5%), elevated D-dimer (20.4%), elevated erythrocyte sedimentation rate (20.4%), leucocytosis (9.9%), elevated procalcitonin (16.7%) and abnormal renal function (10.9%). CONCLUSIONS: The most commonly experienced symptoms of patients with COVID-19 were fever and cough. Myalgia, anorexia, chest tightness and dyspnoea were found in some patients. A relatively small percentage of patients were asymptomatic and could act as carriers of the disease. Most patients showed normal leucocyte counts, elevated levels of C reactive protein and lymphopaenia, confirming the viral origin of the disease. |
50 | gysf0vbv | what is known about an mRNA vaccine for the SARS-CoV-2 virus? | Vaccines to prevent severe acute respiratory syndrome coronavirus-induced disease An important effort has been performed after the emergence of severe acute respiratory syndrome (SARS) epidemic in 2003 to diagnose and prevent virus spreading. Several types of vaccines have been developed including inactivated viruses, subunit vaccines, virus-like particles (VLPs), DNA vaccines, heterologous expression systems, and vaccines derived from SARS-CoV genome by reverse genetics. This review describes several aspects essential to develop SARS-CoV vaccines, such as the correlates of protection, virus serotypes, vaccination side effects, and bio-safeguards that can be engineered into recombinant vaccine approaches based on the SARS-CoV genome. The production of effective and safe vaccines to prevent SARS has led to the development of promising vaccine candidates, in contrast to the design of vaccines for other coronaviruses, that in general has been less successful. After preclinical trials in animal models, efficacy and safety evaluation of the most promising vaccine candidates described has to be performed in humans. |
31 | 6w37btqf | How does the coronavirus differ from seasonal flu? | Cross-Country Age Disparities in COVID-19 Cases with Hospitalization, ICU Usage, and Morbidity In this paper, we examine cross-country differences, in terms of the age distribution of symptomatic cases, hospitalizations, intensive care unit (ICU) cases, and fatalities due to the novel COVID-19. By calculating conditional probabilities, we bridge country-level incidence data gathered from different countries and attribute the variability in data to country demographics. We then provide case, hospitalization, ICU, and fatality estimates for a comprehensive list of countries using the existing data from a variety of countries. |
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