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33 | utigp2vi | What vaccine candidates are being tested for Covid-19? | RAN translation and frameshifting as translational challenges at simple repeats of human neurodegenerative disorders Repeat-associated disorders caused by expansions of short sequences have been classified as coding and noncoding and are thought to be caused by protein gain-of-function and RNA gain-of-function mechanisms, respectively. The boundary between such classifications has recently been blurred by the discovery of repeat-associated non-AUG (RAN) translation reported in spinocerebellar ataxia type 8, myotonic dystrophy type 1, fragile X tremor/ataxia syndrome and C9ORF72 amyotrophic lateral sclerosis and frontotemporal dementia. This noncanonical translation requires no AUG start codon and can initiate in multiple frames of CAG, CGG and GGGGCC repeats of the sense and antisense strands of disease-relevant transcripts. RNA structures formed by the repeats have been suggested as possible triggers; however, the precise mechanism of the translation initiation remains elusive. Templates containing expansions of microsatellites have also been shown to challenge translation elongation, as frameshifting has been recognized across CAG repeats in spinocerebellar ataxia type 3 and Huntington's disease. Determining the critical requirements for RAN translation and frameshifting is essential to decipher the mechanisms that govern these processes. The contribution of unusual translation products to pathogenesis needs to be better understood. In this review, we present current knowledge regarding RAN translation and frameshifting and discuss the proposed mechanisms of translational challenges imposed by simple repeat expansions. |
21 | 714jbplw | what are the mortality rates overall and in specific populations | COVID-19: Clinical course and outcomes of 36 maintenance hemodialysis patients from a single center in Spain. SARS-CoV-2-pneumonia emerged in Wuhan, China in December 2019. Unfortunately, there is lack of evidence about the optimal management of novel coronavirus disease 2019 (COVID-19), even less in patients on maintenance hemodialysis (MHD) therapy than in the general population. In this retrospective observational single-center study we analyzed the clinical course and outcomes of all MHD patients hospitalized with COVID-19 from March 12(th) to April 10(th), 2020 as confirmed by real time polymerase chain reaction. Baseline features, clinical course, laboratory data, and different therapies were compared between survivors and non-survivors to identify risk factors associated with mortality. Among the 36 patients, 11 (30.5%) died and 7 could be discharged within the observation period. Clinical and radiological evolution during the first week of admission were predictive of mortality. Among the 36 patients, 18 had worsening of their clinical status, as defined by severe hypoxia with oxygen therapy requirements greater than 4 Liters/minute and radiological worsening. Significantly 11 out of those 18 patients (61.1%) died. None of the classical cardiovascular risk factors in the general population were associated with higher mortality. However, a longer time on hemodialysis (hazard ratio 1.008(95% confidence interval 1.001-1.015) per year), increased LDH levels (1.006(1.001-1.011), and lower lymphocyte count (0.996 (0.992-1.000) one week after clinical onset were all significantly associated with higher mortality risk. Thus, the mortality among hospitalized hemodialysis patients diagnosed with COVID-19 is high. Lymphopenia and increased LDH levels were associated with poor prognosis. |
19 | qm3mgl7x | what type of hand sanitizer is needed to destroy Covid-19? | Involving antimicrobial stewardship programs in COVID-19 response efforts: All hands on deck |
2 | q9ab1pji | how does the coronavirus respond to changes in the weather | Nexus between COVID-19, temperature and exchange rate in Wuhan City: New findings from Partial and Multiple Wavelet Coherence Abstract This study attempts to document the nexus between weather, covid-19 outbreak in Wuhan and the Chinese economy. We employ 24-h daily average temperature, daily new confirmed cases of a covid-19 in Wuhan, and RMB exchange rate to represent the weather, covid-19 outbreak, and Chinese economy, respectively. The methodology of Wavelet Transform Coherence (WTC), Partial Wavelet Coherence (PWC), and Multiple Wavelet Coherence (MWC) is used to analyze the daily data collected from 21st January 2020 to 31st March 2020. Results reveal significant coherence between series at different time-frequency combinations. Overall results show the insignificance of an increase in temperature to contain new covid-19 infections. The Renminbi exchange rate showed a negative coherence at specific time-frequency spots suggesting a negative but limited impact of the covid-19 outbreak in Wuhan on the Chinese export economy. Our results are contrary to many earlier studies, which show a significant impact of increased temperature in slowing down covid-19 spread. These results can have important implications for economic and containment policy making regarding the covid-19 outbreak. |
39 | hd5yvs5x | What is the mechanism of cytokine storm syndrome on the COVID-19? | Hydroxychloroquine treatment in COVID‐19: a descriptive observational analysis of 30 cases from a single center in Wuhan, China Hydroxychloroquine (HCQ) garnered scientific attention in early February following publication of reports showing in vitro activity of chloroquine (CQ) against COVID‐19. While studies are mixed on this topic, the therapeutic effect of HCQ or CQ still need more valid clinical evidence. In this descriptive observational study, we aimed to discuss the treatment response of HCQ in COVID‐19 infected patients and 30 cases were included. The demographic, treatment, laboratory parameters of C‐reactive protein (CRP) and interleukin‐6 (IL‐6) before and after HCQ therapy and clinical outcome in the 30 COVID‐19 patients were assessed. In order to evaluate the effect of mediation time point, we also divided these cases into two groups, patients began administrated with HCQ within 7 days hospital (defined as early delivery group) and 7 days after hospital (defined as later delivery group). We found that, the elevated IL‐6, a risk factor in severe patients were reduced to normal level after HCQ treatment. More importantly, patients treated with HCQ at the time of early hospital recovered faster than those who treated later or taken as second line choose for their obvious shorter hospitalization time. In summary, early use of HCQ was better than later use and the effect of IL‐6 and CRP level can not be ruled out. This article is protected by copyright. All rights reserved. |
20 | fkr6zat6 | are patients taking Angiotensin-converting enzyme inhibitors (ACE) at increased risk for COVID-19? | Susceptibility to mouse hepatitis virus strain 3 in BALB/cJ mice: failure of immune cell proliferation and interleukin 2 production. |
6 | qd3d3a78 | what types of rapid testing for Covid-19 have been developed? | Diagnostic methods and potential portable biosensors for coronavirus disease 2019 Timely detection and diagnosis are urgently needed to guide epidemiological measures, infection control, antiviral treatment, and vaccine research. In this review, biomarkers/indicators for diagnosis of coronavirus disease 2019 (COVID-19) or detection of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) in the environment are summarized and discussed. It is concluded that the detection methods targeting antibodies are not suitable for screening of early and asymptomatic cases since most patients had an antibody response at about 10 days after onset of symptoms. However, antibody detection methods can be combined with quantitative real-time reverse transcriptase-polymerase chain reaction (RT-qPCR) to significantly improve the sensitivity and specificity of diagnosis, and boost vaccine research. Fast, sensitive and accurate detection methods targeting antigens need to be developed urgently. Various specimens for diagnosis or detection are compared and analyzed. Among them, deep throat saliva and induced sputum are desired for RT-qPCR test or other early detection technologies. Chest computerized tomography (CT) scan, RT-qPCR, lateral flow immunochromatographic strip (LFICS) for diagnosis of COVID-19 are summarized and compared. Specially, potential electrochemical (EC) biosensor, surface enhanced Raman scattering (SERS)-based biosensor, field-effect transistor (FET)-based biosensor, surface plasmon resonance (SPR)-based biosensor and artificial intelligence (AI) assisted diagnosis of COVID-19 are emphasized. Finally, some commercialized portable detection device, current challenges and future directions are discussed. |
22 | nrdiqees | are cardiac complications likely in patients with COVID-19? | History of coronary heart disease increases the mortality rate of COVID-19 patients: a nested case-control study Background: China has experienced an outbreak of a novel human coronavirus (SARS-CoV-2) since December 2019, which quickly became a worldwide pandemic in early 2020. There is limited evidence on the mortality risk effect of pre-existing comorbidities for coronavirus disease 2019 (COVID-19), which has important implications for early treatment. Objective: Evaluate the risk of pre-existing comorbidities on COVID-19 mortality, and provide clinical suggestions accordingly. Method: This study used a nested case-control design. A total of 94 publicly reported deaths in locations outside of Hubei Province, China, between December 18th, 2019 and March 8th, 2020 were included as cases. Each case was matched with up to three controls, based on gender and age (94 cases and 181 controls). The inverse-probability-weighted Cox proportional hazard model was performed. Results: History of comorbidities significantly increased the death risk of COVID-19: one additional pre-existing comorbidity led to an estimated 40% higher risk of death (p<0.001). The estimated mortality risk in patients with CHD was three times of those without CHD (p<0.001). The estimated 30-day survival probability for a profile patient with pre-existing CHD (65-year-old female with no other comorbidities) was 0.53 (95% CI [0.34-0.82]), while it was 0.85 (95% CI [0.79-0.91]) for those without CHD. Older age was also associated with increased death risk: every 5-year increase in age was associated with a 20% increased risk of mortality (p<0.001). Conclusion: Extra care and early medical intervention are needed for patients with pre-existing comorbidities, especially CHD. |
5 | ocnxfgny | what drugs have been active against SARS-CoV or SARS-CoV-2 in animal studies? | Binding of SARS-CoV-2 and angiotensin-converting enzyme 2: clinical implications |
6 | rd0g5j55 | what types of rapid testing for Covid-19 have been developed? | Comparison of xTAG Respiratory Virus Panel and Verigene Respiratory Virus Plus for Detecting Influenza Virus and Respiratory Syncytial Virus BACKGROUND: Nucleic acid amplification tests have allowed simultaneous detection of multiple respiratory viruses. METHODS: We compared the results of a liquid bead array xTAG Respiratory Virus Panel (RVP; (Luminex Corporation, Toronto, Canada) and a solid microarray Verigene Respiratory Virus Plus (RV+; Nanosphere, Northbrook, IL) for the detection of influenza A virus (INF A), influenza B virus (INF B), and respiratory syncytial virus (RSV) in 170 respiratory specimens from hospitalized patients. RESULTS: Overall, xTAG RVP demonstrated sensitivities and specificities of 97.6 and 100% for INF A, 100 and 99.4% for INF B, and 100 and 100% for RSV, while the Verigene RV+ test sensitivities and specificities were 95.1 and 98.5%, 100.0 and 99.4%, and 97.1 and 100%, respectively. There were no significant differences in the area under the curves between the two assays for each virus (P = 0.364 for INF A, P = 1.000 for INF B, P = 0.317 for RSV). Comparing the results of two assays, discordant results were present mostly due to subtype assignments and identification of coinfections. The detection of viruses was not significantly different (P = 1.000) and the virus/subtype assignment showed good agreement with kappa coefficients of 0.908. CONCLUSION: The xTAG RVP and Verigene RV+ showed high sensitivities and specificities, and good overall agreement in detection and identification of INF and RSV. These assays can be used in clinical settings for a reliable detection of respiratory viruses found commonly in hospitalized patients. |
13 | n4v4n8d1 | what are the transmission routes of coronavirus? | Features, Evaluation and Treatment Coronavirus (COVID-19) According to the World Health Organization (WHO), viral diseases continue to emerge and represent a serious issue to public health In the last twenty years, several viral epidemics such as the severe acute respiratory syndrome coronavirus (SARS-CoV) in 2002 to 2003, and H1N1 influenza in 2009, have been recorded Most recently, the Middle East respiratory syndrome coronavirus (MERS-CoV) was first identified in Saudi Arabia in 2012 In a timeline that reaches the present day, an epidemic of cases with unexplained low respiratory infections detected in Wuhan, the largest metropolitan area in China's Hubei province, was first reported to the WHO Country Office in China, on December 31, 2019 Published literature can trace the beginning of symptomatic individuals back to the beginning of December 2019 As they were unable to identify the causative agent, these first cases were classified as "pneumonia of unknown etiology " The Chinese Center for Disease Control and Prevention (CDC) and local CDCs organized an intensive outbreak investigation program The etiology of this illness is now attributed to a novel virus belonging to the coronavirus (CoV) family, COVID-19 On February 11, 2020, the WHO Director-General, Dr Tedros Adhanom Ghebreyesus, announced that the disease caused by this new CoV was a "COVID-19," which is the acronym of "coronavirus disease 2019" In the past twenty years, two additional coronavirus epidemics have occurred SARS-CoV provoked a large-scale epidemic beginning in China and involving two dozen countries with approximately 8000 cases and 800 deaths, and the MERS-CoV that began in Saudi Arabia and has approximately 2,500 cases and 800 deaths and still causes as sporadic cases This new virus seems to be very contagious and has quickly spread globally In a meeting on January 30, 2020, per the International Health Regulations (IHR, 2005), the outbreak was declared by the WHO a Public Health Emergency of International Concern (PHEIC) as it had spread to 18 countries with four countries reporting human-to-human transmission An additional landmark occurred on February 26, 2020, as the first case of the disease, not imported from China, was recorded in the United States Initially, the new virus was called 2019-nCoV Subsequently, the task of experts of the International Committee on Taxonomy of Viruses (ICTV) termed it the SARS-CoV-2 virus as it is very similar to the one that caused the SARS outbreak (SARS-CoVs) The CoVs have become the major pathogens of emerging respiratory disease outbreaks They are a large family of single-stranded RNA viruses (+ssRNA) that can be isolated in different animal species For reasons yet to be explained, these viruses can cross species barriers and can cause, in humans, illness ranging from the common cold to more severe diseases such as MERS and SARS Interestingly, these latter viruses have probably originated from bats and then moving into other mammalian hosts — the Himalayan palm civet for SARS-CoV, and the dromedary camel for MERS-CoV — before jumping to humans The dynamics of SARS-Cov-2 are currently unknown, but there is speculation that it also has an animal origin The potential for these viruses to grow to become a pandemic worldwide seems to be a serious public health risk Concerning COVID-19, the WHO raised the threat to the CoV epidemic to the "very high" level, on February 28, 2020 Probably, the effects of the epidemic caused by the new CoV has yet to emerge as the situation is quickly evolving World governments are at work to establish countermeasures to stem possible devastating effects Health organizations coordinate information flows and issues directives and guidelines to best mitigate the impact of the threat At the same time, scientists around the world work tirelessly, and information about the transmission mechanisms, the clinical spectrum of disease, new diagnostics, and prevention and therapeutic strategies are rapidly developing Many uncertainties remain with regard to both the virus-host interac ion and the evolution of the epidemic, with specific reference to the times when the epidemic will reach its peak At the moment, the therapeutic strategies to deal with the infection are only supportive, and prevention aimed at reducing transmission in the community is our best weapon Aggressive isolation measures in China have led to a progressive reduction of cases in the last few days In Italy, in geographic regions of the north of the peninsula, political and health authorities are making incredible efforts to contain a shock wave that is severely testing the health system In the midst of the crisis, the authors have chosen to use the "Statpearls" platform because, within the PubMed scenario, it represents a unique tool that may allow them to make updates in real-time The aim, therefore, is to collect information and scientific evidence and to provide an overview of the topic that will be continuously updated |
41 | 5c6nwrdo | What are the impacts of COVID-19 among African-Americans that differ from the rest of the U.S. population? | A culturally specific mental health and spirituality approach for African Americans facing the COVID-19 pandemic A series of 15-min videos were produced to provide resources to pastors in African-American communities to aid them in conveying accurate public and mental health information about COVID-19. Video presenters included trusted experts in public and mental health and pastors with considerable experience responding to the needs of the African-American community during the COVID-19 pandemic. Four culturally specific core themes to consider when providing care to African Americans who are at increased risk during the pandemic were identified: ritual disruption, negative reactions for not following public health guidelines, trauma, and culture and trust. (PsycInfo Database Record (c) 2020 APA, all rights reserved). |
24 | q6gbxghx | what kinds of complications related to COVID-19 are associated with diabetes | Post COVID-19 diabetes care—lessons and challenges |
36 | jmrg4oeb | What is the protein structure of the SARS-CoV-2 spike? | Mutations, Recombination and Insertion in the Evolution of 2019-nCoV The 2019 novel coronavirus (2019-nCoV or SARS-CoV-2) has spread more rapidly than any other betacoronavirus including SARS-CoV and MERS-CoV. However, the mechanisms responsible for infection and molecular evolution of this virus remained unclear. We collected and analyzed 120 genomic sequences of 2019-nCoV including 11 novel genomes from patients in China. Through comprehensive analysis of the available genome sequences of 2019-nCoV strains, we have tracked multiple inheritable SNPs and determined the evolution of 2019-nCoV relative to other coronaviruses. Systematic analysis of 120 genomic sequences of 2019-nCoV revealed co-circulation of two genetic subgroups with distinct SNPs markers, which can be used to trace the 2019-nCoV spreading pathways to different regions and countries. Although 2019-nCoV, human and bat SARS-CoV share high homologous in overall genome structures, they evolved into two distinct groups with different receptor entry specificities through potential recombination in the receptor binding regions. In addition, 2019-nCoV has a unique four amino acid insertion between S1 and S2 domains of the spike protein, which created a potential furin or TMPRSS2 cleavage site. Our studies provided comprehensive insights into the evolution and spread of the 2019-nCoV. Our results provided evidence suggesting that 2019-nCoV may increase its infectivity through the receptor binding domain recombination and a cleavage site insertion. Novel 2019-nCoV sequences revealed the evolution and specificity of betacoronavirus with possible mechanisms of enhanced infectivity. |
13 | skl42x2p | what are the transmission routes of coronavirus? | II. Sachverzeichnis |
38 | w1ulwscj | What is the mechanism of inflammatory response and pathogenesis of COVID-19 cases? | SARS-CoV-2, which induces COVID-19, causes kawasaki-like disease in children: role of pro-inflammatory and anti-inflammatory cytokines Acute severe respiratory syndrome coronavirus-2 (SARS-CoV-2) caused a global pandemic coronavirus disease 2019 (COVID-19). In humans, SARS-CoV-2 infection leads to acute respiratory distress syndrome which presents edema, hemorrhage, intra-alveolar fibrin deposition, and vascular changes characterized by thrombus formation, micro-angiopathy and thrombosis. These clinical signs are mediated by pro-inflammatory cytokines. In recent studies it has been noted that COVID-19 pandemic can affect patients of all ages, including children (even if less severely) who were initially thought to be immune. Kawasaki disease is an autoimmune acute febrile inflammatory condition, which primarily affects young children. The disease can present immunodeficiency with the inability of the immune system to fight inflammatory pathogens and leads to fever, rash, alterations of the mucous membranes, conjunctiva infection, pharyngeal erythema, adenopathy, and inflammation. In the COVID-19 period, virus infection aggravates the condition of Kawasaki disease, but it has also been noted that children affected by SARS-V-2 may develop a disease similar to Kawasaki's illness. However, it is uncertain whether the virus alone can give Kawasaki disease-like forms. As in COVID-19, Kawasaki disease and its similar forms are mediated by pro-inflammatory cytokines produced by innate immunity cells such as macrophages and mast cells (MCs). In light of the above, it is therefore pertinent to think that by blocking pro-inflammatory cytokines with new anti-inflammatory cytokines, such as IL-37 and IL-38, it is possible to alleviate the symptoms of the disease and have a new available therapeutic tool. However, since Kawasaki and Kawasaki-like diseases present immunodeficiency, treatment with anti-inflammatory/immunosuppressant molecules must be applied very carefully. |
39 | 6mhmnhlm | What is the mechanism of cytokine storm syndrome on the COVID-19? | [Exploration on scientific connotation of TCM syndromes and recommended prescriptions against COVID-19 based on TCMTP V2.0] Coronavirus disease 2019(COVID-19) has attracted great attentions from the whole world. Traditional Chinese medicine(TCM) has been widely used and shown satisfying efficacies in treating all stages of COVID-19. In this study, the molecular interaction networks of different stages of COVID-19(the early, severe, critical and recovery stage) were constructed using the links among symptoms-related genes collected from TCMIP V2.0(http://www.tcmip.cn/), an integrated pharmacology network-computing platform for TCM. Following the network topological feature calculation and functional enrichment analysis, we found that the molecular targets and pathways related with the "immune-inflammation system" were involved throughout all the stages of COVID-19. The severe stage and the critical period of COVID-19 were occupied by a large proportion of inflammatory factors and pathways, suggesting that there might be a cytokine storm in these periods, along with respiratory disorders, cardiopulmonary dysfunction, nervous system disorders, etc. Accordingly, the therapeutic targets and pathways hit by the recommended prescriptions against COVID-19 were also aimed to regulate the balance of immune-inflammation system, nutrient absorption and metabolism, abnormal energy metabolism, the cardio-pulmonary function, nerve system function, etc., which may be related to the therapeutic effects of these prescriptions in terms of several clinical symptoms, such as expiratory dyspnea, chest tightness and shortness of breath, abdominal distension and constipation, sweating and limb cold, dizziness, and irritability, etc. The above findings reflect the integrative actions of TCM characterizing by multiple-components, multiple-targets, multiple-pathways, and multiple-effects. This study systematically constructed the molecular networks of different TCM syndromes during the development and progression of COVID-19 and uncovered the biological basis for symptomatic treatment of TCM. Furthermore, our data revealed the pharmacological mechanisms and the scientific connotation of recommended prescriptions, which may provide supports for the prevention and treatment of COVID-19 using TCM. |
11 | y6hu31aa | what are the guidelines for triaging patients infected with coronavirus? | Development of a data-driven COVID-19 prognostication tool to inform triage and step-down care for hospitalised patients in Hong Kong: A population based cohort study Abstract Background: This is the first study on prognostication in an entire cohort of laboratory-confirmed COVID-19 patients in the city of Hong Kong. Prognostic tool is essential in the contingency response for the next wave of outbreak. This study aims to develop prognostic models to predict COVID-19 patients' clinical outcome on day 1 and day 5 of hospital admission. Methods: We did a retrospective analysis of a complete cohort of 1,037 COVID-19 laboratory-confirmed patients in Hong Kong as of 30 April 2020, who were admitted to 16 public hospitals with their data sourced from an integrated electronic health records system. It covered demographic information, chronic disease(s) history, presenting symptoms as well as the worst clinical condition status, biomarkers' readings and Ct value of PCR tests on Day-1 and Day-5 of admission. The study subjects were randomly split into training and testing datasets in a 8:2 ratio. Extreme Gradient Boosting (XGBoost) model was used to classify the training data into three disease severity groups on Day-1 and Day-5. Results: The 1,037 patients had a mean age of 37.8 (SD {+/-} 17.8), 53.8% of them were male. They were grouped under three disease outcome: 4.8% critical/serious, 46.8% stable and 48.4% satisfactory. Under the full models, 30 indicators on Day-1 and Day-5 were used to predict the patients' disease outcome and achieved an accuracy rate of 92.3% and 99.5%. With a trade-off between practical application and predictive accuracy, the full models were reduced into simpler models with seven common specific predictors, including the worst clinical condition status (4-level), age group, and five biomarkers, namely, CRP, LDH, platelet, neutrophil/lymphocyte ratio and albumin/globulin ratio. Day-1 model's accuracy rate, macro- and micro-averaged sensitivity and specificity were 91.3%, 84.9%-91.3% and 96.0%-95.7% respectively, as compared to 94.2%, 95.9%-94.2% and 97.8%-97.1% under Day-5 model. as compared to 94.2%, 95.0%-97.1% and 98.3%-98.6% under Day-5 model. Conclusions: Both Day-1 and Day-5 models can accurately predict the disease severity. Relevant clinical management could be planned according to the predicted patients' outcome. The model is transformed into a simple online calculator to provide convenient clinical reference tools at the point of care, with an aim to inform clinical decision on triage and step-down care. Keywords: COVID-19, prognostic, prediction, clinical outcome, disease severity, triage, step-down care |
15 | y7s6qt6j | how long can the coronavirus live outside the body | Drivers of airborne human-to-human pathogen transmission Airborne pathogens — either transmitted via aerosol or droplets — include a wide variety of highly infectious and dangerous microbes such as variola virus, measles virus, influenza A viruses, Mycobacterium tuberculosis, Streptococcus pneumoniae, and Bordetella pertussis. Emerging zoonotic pathogens, for example, MERS coronavirus, avian influenza viruses, Coxiella, and Francisella, would have pandemic potential were they to acquire efficient human-to-human transmissibility. Here, we synthesize insights from microbiological, medical, social, and economic sciences to provide known mechanisms of aerosolized transmissibility and identify knowledge gaps that limit emergency preparedness plans. In particular, we propose a framework of drivers facilitating human-to-human transmission with the airspace between individuals as an intermediate stage. The model is expected to enhance identification and risk assessment of novel pathogens. |
38 | f9000hjy | What is the mechanism of inflammatory response and pathogenesis of COVID-19 cases? | Complement, a target for therapy in inflammatory and degenerative diseases The complement system is a key innate immune defence against infection and an important driver of inflammation; however, these very properties can also cause harm. Inappropriate or uncontrolled activation of complement can cause local and/or systemic inflammation, tissue damage and disease. Complement provides numerous options for drug development as it is a proteolytic cascade that involves nine specific proteases, unique multimolecular activation and lytic complexes, an arsenal of natural inhibitors, and numerous receptors that bind to activation fragments. Drug design is facilitated by the increasingly detailed structural understanding of the molecules involved in the complement system. Only two anti-complement drugs are currently on the market, but many more are being developed for diseases that include infectious, inflammatory, degenerative, traumatic and neoplastic disorders. In this Review, we describe the history, current landscape and future directions for anti-complement therapies. SUPPLEMENTARY INFORMATION: The online version of this article (doi:10.1038/nrd4657) contains supplementary material, which is available to authorized users. |
5 | yth9hh5q | what drugs have been active against SARS-CoV or SARS-CoV-2 in animal studies? | Pharmacologic Treatments for Coronavirus Disease 2019 (COVID-19): A Review Importance: The pandemic of coronavirus disease 2019 (COVID-19) caused by the novel severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) presents an unprecedented challenge to identify effective drugs for prevention and treatment. Given the rapid pace of scientific discovery and clinical data generated by the large number of people rapidly infected by SARS-CoV-2, clinicians need accurate evidence regarding effective medical treatments for this infection. Observations: No proven effective therapies for this virus currently exist. The rapidly expanding knowledge regarding SARS-CoV-2 virology provides a significant number of potential drug targets. The most promising therapy is remdesivir. Remdesivir has potent in vitro activity against SARS-CoV-2, but it is not US Food and Drug Administration approved and currently is being tested in ongoing randomized trials. Oseltamivir has not been shown to have efficacy, and corticosteroids are currently not recommended. Current clinical evidence does not support stopping angiotensin-converting enzyme inhibitors or angiotensin receptor blockers in patients with COVID-19. Conclusions and Relevance: The COVID-19 pandemic represents the greatest global public health crisis of this generation and, potentially, since the pandemic influenza outbreak of 1918. The speed and volume of clinical trials launched to investigate potential therapies for COVID-19 highlight both the need and capability to produce high-quality evidence even in the middle of a pandemic. No therapies have been shown effective to date. |
42 | 2h3kz82b | Does Vitamin D impact COVID-19 prevention and treatment? | Neutrophil-to-lymphocyte ratio as an independent risk factor for mortality in hospitalized patients with COVID-19 Abstract Background Several studies have described the clinical characteristics of patients with novel coronavirus (SARS-CoV-2) infected pneumonia (COVID-19), indicating severe patients tended to have higher neutrophil to lymphocyte ratio (NLR). Whether baseline NLR could be an independent predictor of in-hospital death in Chinese COVID-19 patients remains to be investigated. Methods A cohort of patients with COVID-19 admitted to the Zhongnan Hospital of Wuhan University from January 1 to February 29 was retrospectively analyzed. The baseline data of laboratory examinations, including NLR, were collected. Univariate and multivariate logistic regression models were developed to assess the independent relationship between the baseline NLR and in-hospital all-cause death. A sensitivity analysis was performed by converting NLR from a continuous variable to a categorical variable according to tertile. Interaction and stratified analyses were conducted as well. Results 245 COVID-19 patients were included in the final analyses, and the in-hospital mortality was 13.47%. Multivariate analysis demonstrated that there was 8% higher risk of in-hospital mortality for each unit increase in NLR (Odds ratio [OR] = 1.08; 95% confidence interval [95% CI], 1.01 to 1.14; P = 0.0147). Compared with patients in the lowest tertile, the NLR of patients in the highest tertile had a 15.04-fold higher risk of death (OR = 16.04; 95% CI, 1.14 to 224.95; P = 0.0395) after adjustment for potential confounders. Notably, the fully adjusted OR for mortality was 1.10 in males for each unit increase of NLR (OR = 1.10; 95% CI, 1.02 to 1.19; P = 0.016). Conclusions NLR is an independent risk factor of the in-hospital mortality for COVID-19 patients especially for male. Assessment of NLR may help identify high risk individuals with COVID-19. |
38 | 86ex3gxt | What is the mechanism of inflammatory response and pathogenesis of COVID-19 cases? | Angiotensin-Converting Enzyme 2 and the Resolution of Inflammation: In Support of Continuation of Prescribed Angiotensin-Converting Enzyme Inhibitors and Angiotensin-Receptor Blockers |
22 | 8eh90ber | are cardiac complications likely in patients with COVID-19? | TH17 responses in cytokine storm of COVID-19: An emerging target of JAK2 inhibitor Fedratinib Abstract COVID-19 emerges as a pandemic disease with high mortality. Development of effective prevention and treatment is an urgent need. We reviewed TH17 responses in patients with SARS-CoV-2 and proposed an FDA approved JAK2 inhibitor Fedratinib for reducing mortality of patients with TH17 type immune profiles. |
7 | 5trqi9tp | are there serological tests that detect antibodies to coronavirus? | A systematic review of lopinavir therapy for SARS coronavirus and MERS coronavirus—A possible reference for coronavirus disease‐19 treatment option In the past few decades, coronaviruses have risen as a global threat to public health. Currently, the outbreak of coronavirus disease‐19 (COVID‐19) from Wuhan caused a worldwide panic. There are no specific antiviral therapies for COVID‐19. However, there are agents that were used during the severe acute respiratory syndrome (SARS) and Middle East respiratory syndrome (MERS) epidemics. We could learn from SARS and MERS. Lopinavir (LPV) is an effective agent that inhibits the protease activity of coronavirus. In this review, we discuss the literature on the efficacy of LPV in vitro and in vivo, especially in patients with SARS and MERS, so that we might clarify the potential for the use of LPV in patients with COVID‐19. |
3 | si7oucep | will SARS-CoV2 infected people develop immunity? Is cross protection possible? | Echoes of 2009 H1N1 Influenza Pandemic in the COVID Pandemic Abstract The severe acute respiratory syndrome–related coronavirus-2 (SARS-CoV2) pandemic that has engulfed the globe has had incredible effects on health care systems and economic activity. Social distancing and school closures have played a central role in public health efforts to counter the coronavirus disease 2019 (COVID)-19 pandemic. The most recent global pandemic prior to COVID-19 was the 2009 pandemic, hemagglutinin type 1 and neuraminidase type 1 (H1N1) influenza. The course of events in 2009 offer some rich lessons that could be applied to the current COVID-19 pandemic. This commentary highlights some of the most relevant points and a discussion of possible outcomes of the COVID-19 pandemic. © 2020 Elsevier Inc. |
47 | vdx1mmsh | what are the health outcomes for children who contract COVID-19? | COVID-19 pharmacologic treatments for children: research priorities and approach to pediatric studies Clinical trials of pharmacologic treatments of coronavirus disease 2019 (COVID-19) are being rapidly designed and implemented in adults. Children are often not considered during development of novel treatments for infectious diseases until very late. Although children appear to have a lower risk compared to adults of severe COVID-19 disease, a substantial number of children globally will benefit from pharmacologic treatments. It will be reasonable to extrapolate efficacy of most treatments from adult trials to children. Pediatric trials should focus on characterizing a treatment's pharmacokinetics, optimal dose and safety, across the age spectrum. These trials should use an adaptive design to efficiently add or remove arms in what will be a rapidly evolving treatment landscape, and should involve a large number of sites across the globe in a collaborative effort to facilitate efficient implementation. All stakeholders must commit to equitable access to any effective, safe treatment for children everywhere. |
13 | rike3ukb | what are the transmission routes of coronavirus? | Environmental contamination of the SARS-CoV-2 in healthcare premises: An urgent call for protection for healthcare workers Importance A large number of healthcare workers (HCWs) were infected by SARS-CoV-2 during the ongoing outbreak of COVID-19 in Wuhan, China. Hospitals are significant epicenters for the human-to-human transmission of the SARS-CoV-2 for HCWs, patients, and visitors. No data has been reported on the details of hospital environmental contamination status in the epicenter of Wuhan. Objective To investigate the extent to which SARS-CoV-2 contaminates healthcare settings, including to identify function zones of the hospital with the highest contamination levels and to identify the most contaminated objects, and personal protection equipment (PPE) in Wuhan, China. Design A field investigation was conducted to collect the surface swabs in various environments in the hospital and a laboratory experiment was conducted to examine the presence of the SARS-CoV-2 RNA. Setting Six hundred twenty-six surface samples were collected within the Zhongnan Medical Center in Wuhan, China in the mist of the COVID-19 outbreak between February 7 - February 27, 2020. Participants Dacron swabs were aseptically collected from the surfaces of 13 hospital function zones, five major objects, and three major personal protection equipment (PPE). The SARS-CoV-2 RNAs were detected by reverse transcription-PCR (RT-PCR). Main Outcomes and Measures SARS-CoV-2 RNAs Results The most contaminated zones were the intensive care unit specialized for taking care of novel coronavirus pneumonia (NCP) (31.9%), Obstetric Isolation Ward specialized for pregnant women with NCP (28.1%), and Isolation Ward for NCP (19.6%). We classified the 13 zones into four contamination levels. The most contaminated objects are self-service printers (20.0%), desktop/keyboard (16.8%), and doorknob (16.0%). Both hand sanitizer dispensers (20.3%) and gloves (15.4%) were most contaminated PPE. Conclusions and Relevance Many surfaces were contaminated with SARS-CoV-2 across the hospital in various patient care areas, commonly used objects, medical equipment, and PPE. The 13 hospital function zones were classified into four contamination levels. These findings emphasize the urgent need to ensure adequate environmental cleaning, strengthen infection prevention training, and improve infection prevention precautions among HCWs during the outbreak of COVID-19. The findings may have important implications for modifying and developing urgently needed policy to better protect healthcare workers during this ongoing pandemic of SARS-CoV-2. |
10 | 79m2t343 | has social distancing had an impact on slowing the spread of COVID-19? | Analyzing situational awareness through public opinion to predict adoption of social distancing amid pandemic COVID‐19 COVID‐19 pandemic has affected over 100 countries in a matter of weeks. People's response toward social distancing in the emerging pandemic is uncertain. In this study, we evaluated the influence of information (formal and informal) sources on situational awareness of the public for adopting health‐protective behaviors such as social distancing. For this purpose, a questionnaire‐based survey was conducted. The hypothesis proposed suggests that adoption of social distancing practices is an outcome of situational awareness which is achieved by the information sources. Results suggest that information sources, formal (P = .001) and informal (P = 0.007) were found to be significantly related to perceived understanding. Findings also indicate that social distancing is significantly influenced by situational awareness, P = .000. It can, therefore, be concluded that an increase in situational awareness in times of public health crisis using formal information sources can significantly increase the adoption of protective health behavior and in turn contain the spread of infectious diseases. |
28 | wkfamdv6 | what evidence is there for the value of hydroxychloroquine in treating Covid-19? | Potential of chloroquine and hydroxychloroquine to treat COVID-19 causes fears of shortages among people with systemic lupus erythematosus. |
34 | puu8wib8 | What are the longer-term complications of those who recover from COVID-19? | Endocrine and metabolic link to coronavirus infection Type 2 diabetes mellitus and hypertension are the most common comorbidities in patients with coronavirus infections. Emerging evidence demonstrates an important direct metabolic and endocrine mechanistic link to the viral disease process. Clinicians need to ensure early and thorough metabolic control for all patients affected by COVID-19. |
21 | iemjb7r9 | what are the mortality rates overall and in specific populations | A review of vaccine research and development: Human acute respiratory infections() Worldwide, acute respiratory infections (ARIs) constitute the leading cause of acute illnesses, being responsible for nearly 4 million deaths every year, mostly in young children and infants in developing countries. The main infectious agents responsible for ARIs include influenza virus, respiratory syncytial virus (RSV), parainfluenza virus type 3 (PIV-3), Streptococcus pneumoniae and Haemophilus influenzae. While effective vaccines against influenza, H. influenzae type b (Hib) and S. pneumoniae infections have been available for several years, no vaccine is available at present against illnesses caused by RSV, PIV-3, metapneumovirus or any of the three novel coronaviruses. In addition, the threat constituted by the multiple outbreaks of avian influenza during the last few years is urgently calling for the development of new influenza vaccines with broader spectrum of efficacy, which could provide immunity against an avian influenza virus pandemic. This article reviews the state of the art in vaccine R&D against ARIs and attempts to address these basic public health questions. |
50 | msjurww1 | what is known about an mRNA vaccine for the SARS-CoV-2 virus? | Does BCG protect against SARS-CoV-2 infection ?: elements of proof. Background : There are several factors explaining the difference in the spread of SARS-CoV-2 infection including the BCG vaccination. This fact is supported by the concept of beneficial non specific effect of this live vaccine associated to its interaction with the immune system. Our study aims to identify the correlation between the universal BCG vaccination policy and the mortality attributed to COVID-19. Methods : We conducted an epidemiological study in which we collected COVID-19 pandemic data of April 11th, 2020 from the web site worldometers.info . The exclusion criteria for our study were a number of inhabitants less than one million, low-income countries according to the World Bank classification, a total number of infection cases less than 500 and countries that have performed less than one hundred tests per million inhabitants. Results : Countries that never had universal BCG vaccination policy have a higher mortality (correlated to performed diagnostic tests) attributed to SARS-CoV-2 infection (p<0.001). We found that the year of introduction of vaccination influenced significantly the mortality. Countries that started immunization policy before 1960 had more favorable results (p=0.049). For countries that started the BCG vaccination after 1960, countries with current policies have lower mortality attributed to SARS-CoV-2 infection than countries that have stopped immunization (p=0.047). Conclusions : Countries that have a BCG vaccination policy have a lower mortality attributed to SARS-CoV-2 infection. The populations of countries that applied this immunization before 1960 are more protected even if this universal policy has been interrupted. |
27 | 3zyyjtkc | what is known about those infected with Covid-19 but are asymptomatic? | Covid-19: Nine in 10 pregnant women with infection when admitted for delivery are asymptomatic, small study finds |
49 | 5lhvix51 | do individuals who recover from COVID-19 show sufficient immune response, including antibody levels and T-cell mediated immunity, to prevent re-infection? | Reappearance of Effector T Cells Predicts Successful Recovery from COVID-19 Background: Elucidating the role of T cell responses in COVID-19 is of utmost importance to understand the clearance of SARS-CoV-2 infection. Methods: 90 individuals were enrolled in this study, 30 hospitalized COVID-19 patients and 60 age- and gender-matched healthy controls (HC). Using two comprehensive 11-color flow cytometric panels conforming to Good Laboratory Practice (GLP) and approved for clinical diagnostics, we longitudinally examined cell count differences in lymphocyte populations and T cell activation in COVID-19 patients. Findings: Absolute numbers of lymphocyte subsets were differentially decreased in COVID-19 patients according to clinical severity. In severe disease (SD) patients, all lymphocyte subsets were reduced, whilst in mild disease (MD) NK, NKT and {gamma}{delta} T cells were at the level of HC. Additionally, we provide evidence of T cell activation in MD but not SD, when compared to HC. Interestingly, follow up samples revealed a marked increase in effector T cells and memory subsets in convalescing but not in non-convalescing patients. Interpretation: Our data suggest that activation and expansion of innate and adaptive lymphocytes play a major role in COVID-19. Additionally, recovery is associated with formation of T cell memory as suggested by the missing formation of effector and central memory T cells in SD but not in MD. Our data imply that the presence of SARS-CoV-2 responsive T cells contributes to convalescence in MD. Thus, understanding the T cell-response in the context of clinical severity might serve as foundation to overcome the lack of effective anti-viral immune response in severely affected COVID-19 patients and can offer prognostic value as biomarker for disease outcome and control. |
31 | t7c0drft | How does the coronavirus differ from seasonal flu? | Global COVID-19 transmission rate is influenced by precipitation seasonality and the speed of climate temperature warming The novel coronavirus disease 2019 (COVID-19) became a rapidly spreading worldwide epidemic; thus, it is a global priority to reduce the speed of the epidemic spreading. Several studies predicted that high temperature and humidity could reduce COVID-19 transmission. However, exceptions exist to this observation, further thorough examinations are thus needed for their confirmation. In this study, therefore, we used a global dataset of COVID-19 cases and global climate databases and comprehensively investigated how climate parameters could contribute to the growth rate of COVID-19 cases while statistically controlling for potential confounding effects using spatial analysis. We also confirmed that the growth rate decreased with the temperature; however, the growth rate was affected by precipitation seasonality and warming velocity rather than temperature. In particular, a lower growth rate was observed for a higher precipitation seasonality and lower warming velocity. These effects were independent of population density, human life quality, and travel restrictions. The results indicate that the temperature effect is less important compared to these intrinsic climate characteristics, which might thus be useful for explaining the exceptions. However, the contributions of the climate parameters to the growth rate were moderate; rather, the contribution of travel restrictions in each country was more significant. Although our findings are preliminary owing to data-analysis limitations, they may be helpful when predicting COVID-19 transmission. |
48 | lwgq7a6d | what are the benefits and risks of re-opening schools in the midst of the COVID-19 pandemic? | Decision-making on management of ms and nmosd patients during the COVID-19 pandemic: A latin american survey BACKGROUND: The emergence of COVID-19 and its vertiginous spreading speed represents a unique challenge to neurologists managing multiple sclerosis (MS) and neuromyelitis optica spectrum disorders (NMOSD). The need for data on the impact of the virus on these patients grows rapidly. There is an urgent necessity of sharing information to enable evidence-based decision making on the clinical management. There are no data on what physicians are doing on clinical practice in Latin American countries. AIM: to investigate current management opinion of Latin American MS and/or NMOSD expert neurologists based on their experience and recommendations. METHODS: we developed a voluntary web-based survey based on hypothetical situations that these patients may encounter, while taking into account the potential risk of developing severe COVID-19 infection. RESULTS: 60% of the experts had the possibility of monitoring their patients by telemedicine. Most neurologists postpone magnetic resonance. Laboratory blood tests delay is associated with the type of treatment. Platform therapies, dimethyl-fumarate and natalizumab are considered safe options to initiate in naive patients. CONCLUSION: decision-making about MS and NMOSD patients has become even more complex in order to adapt to the COVID-19 pandemic. Risks and benefits should be taken into consideration throughout the patient follow-up. |
32 | 3mpymd8a | Does SARS-CoV-2 have any subtypes, and if so what are they? | Emergence of novel coronavirus and progress toward treatment and vaccine In late December 2019, a group of patients was observed with pneumonia‐like symptoms that were linked with a wet market in Wuhan, China. The patients were found to have a novel coronavirus genetically related to a bat coronavirus that was termed SARS‐CoV‐2. The virus gradually spread worldwide and was declared a pandemic by WHO. Scientists have started trials on potential preventive and treatment options. Currently, there is no specific approved treatment for SARS‐CoV‐2, and various clinical trials are underway to explore better treatments. Some previously approved antiviral and other drugs have shown some in vitro activity. Here we summarize the fight against this novel coronavirus with particular focus on the different treatment options and clinical trials exploring treatment as well as work done toward development of vaccines. |
31 | 1whqwaan | How does the coronavirus differ from seasonal flu? | Influenza A H1N1 2009 (Swine Flu) and Pregnancy The Influenza A H1N1 pandemic (A H1N1) occurred between June 2009 and August 2010. Although the pandemic is now over, the virus has emerged as the predominant strain in the current seasonal influenza phase in the northern hemisphere. The A H1N1 influenza is a novel strain of the influenza A virus and is widely known as swine flu. The virus contains a mixture of genetic material from human, pig and bird flu virus. It is a new variety of flu which people have not had much immunity to. Much has been learnt from the Pandemic of 2009/2010 but the messages about vaccination and treatment seem to be taken slowly by the clinical profession. Most people affected by the virus, including pregnant women, suffer a mild viral illness, and make a full recovery. The median duration of illness is around seven days. This influenza typically affects the younger age group i.e. from the ages of 5–65 years. Current experience shows that the age group experiencing increased morbidity and mortality rates are in those under 65 years of age. Pregnant women, because of their altered immunity and physiological adaptations, are at higher risk of developing pulmonary complications, especially in the second and third trimesters. In the United Kingdom, twelve maternal deaths were reported to be associated with the H1N1 virus during the pandemic and clear avoidable factors were identified (Modder, Review of Maternal Deaths in the UK related to A H1N1 2009 influenza (CMACE). www.cmace.org.uk, 2010). The pregnancy outcomes were also poor for women who were affected by the virus with a fivefold increase in the perinatal mortality rate and threefold increase in the preterm delivery rate (Yates et al. Health Technol Assess 14(34):109–182, 2010). There continues to be a low uptake of the flu vaccine and commencement of antiviral treatment for pregnant women. |
35 | 12l3t9zh | What new public datasets are available related to COVID-19? | MaskIt: Masking for efficient utilization of incomplete public datasets for training deep learning models A major challenge in training deep learning models is the lack of high quality and complete datasets. In the paper, we present a masking approach for training deep learning models from a publicly available but incomplete dataset. For example, city of Hamburg, Germany maintains a list of trees along the roads, but this dataset does not contain any information about trees in private homes and parks. To train a deep learning model on such a dataset, we mask the street trees and aerial images with the road network. Road network used for creating the mask is downloaded from OpenStreetMap, and it marks the area where the training data is available. The mask is passed to the model as one of the inputs and it also coats the output. Our model learns to successfully predict trees only in the masked region with 78.4% accuracy. |
17 | lhzvq92z | are there any clinical trials available for the coronavirus | Sacubitril/valsartan in COVID-19 patients: the need for trials |
30 | l4ci8wr2 | is remdesivir an effective treatment for COVID-19 | Potent antiviral effect of protoporphyrin IX and verteporfin on SARS-CoV-2 infection The infection of SARS-CoV-2 has spread to more than 200 countries and regions and the numbers of infected people and deaths worldwide are expected to continue to rise. Current treatment of COVID-19 is limited and mostly supportive. At present, there is no specific therapeutics against SARS-CoV-2. In this study, we discovered that protoporphyrin IX and verteporfin, two FDA-approved drugs for treatment of human diseases, had significant antiviral effect against SARS-CoV-2, with EC50 values for the reduction of viral RNA at nanomolar concentrations. Both drugs completely inhibited the cytopathic effect (CPE) produced by SARS-CoV-2 infection at lower drug concentrations than that of remdesivir. The selection indices of protoporphyrin IX and verteporfin are 952.74 and 368.93, respectively, suggesting wide safety margins. Both drugs were able to prevent SARS-CoV-2 infection as well as suppress established SARS-CoV-2 infection. The compounds share a porphyrin ring structure. Molecular docking indicates that the compounds may interact with viral receptor ACE2 and could block the cell-cell fusion mediated by ACE2 and viral S protein. Our finding suggests that protoporphyrin IX and verteporfin might be potential antivirals against SARS-CoV-2 infection and also sheds new light on the development of a novel class of small compounds against SARS-CoV-2. |
23 | 3anst3os | what kinds of complications related to COVID-19 are associated with hypertension? | Assessing COVID-19 Risk, Vulnerability and Infection Prevalence in Communities Background: The spread of coronavirus in the United States with nearly one million confirmed cases and over 53,000 deaths has strained public health and health care systems. While many have focused on clinical outcomes, less attention has been paid to vulnerability and risk of infection. In this study, we developed a planning tool that examines factors that affect vulnerability to COVID-19. Methods: Across 46 variables, we defined five broad categories: 1) access to medical, 2) underlying health conditions, 3) environmental exposures, 4) vulnerability to natural disasters, and 5) sociodemographic, behavioral, and lifestyle factors. We also used reported rates for morbidity, hospitalization, and mortality in other regions to estimate risk at the county (Harris County) and census tract levels. Analysis: A principal component analysis was undertaken to reduce the dimensions. Then, to identify vulnerable census tracts, we conducted rank-based exceedance and K-means cluster analyses. Results: Our study showed a total of 722,357 (~17% of the County population) people, including 171,403 between the ages of 45-65 (~4% of County population), and 76,719 seniors (~2% of County population), are at a higher risk based on the aforementioned categories. The exceedance and K-means cluster analysis demonstrated that census tracts in the northeastern, eastern, southeastern and northwestern regions of the County are at highest risk. The results of age-based estimations of hospitalization rates showed the western part of the County might be in greater need of hospital beds. However, cross-referencing the vulnerability model with the estimation of potential hospitalized patients showed that part of the County has the least access to medical facilities. Conclusion: Policy makers can use this planning tool to identify neighborhoods at high risk for becoming hot spots; efficiently match community resources with needs, and ensure that the most vulnerable have access to equipment, personnel, and medical interventions. |
14 | g91f02gg | what evidence is there related to COVID-19 super spreaders | Evolving consensus on managing vitreo-retina and uvea practice in post-COVID-19 pandemic era. The COVID-19 pandemic has brought new challenges to the health care community. Many of the super-speciality practices are planning to re-open after the lockdown is lifted. However there is lot of apprehension in everyone's mind about conforming practices that would safeguard the patients, ophthalmologists, healthcare workers as well as taking adequate care of the equipment to minimize the damage. The aim of this article is to develop preferred practice patterns, by developing a consensus amongst the lead experts, that would help the institutes as well as individual vitreo-retina and uveitis experts to restart their practices with confidence. As the situation remains volatile, we would like to mention that these suggestions are evolving and likely to change as our understanding and experience gets better. Further, the suggestions are for routine patients as COVID-19 positive patients may be managed in designated hospitals as per local protocols. Also these suggestions have to be implemented keeping in compliance with local rules and regulations. |
8 | 6letcy57 | how has lack of testing availability led to underreporting of true incidence of Covid-19? | The value of mitigating epidemic peaks of COVID-19 for more effective public health responses |
26 | bu17n7zf | what are the initial symptoms of Covid-19? | COVID-19: what has been learned and to be learned about the novel coronavirus disease The outbreak of Coronavirus disease 2019 (COVID-19), caused by severe acute respiratory syndrome (SARS) coronavirus 2 (SARS-CoV-2), has thus far killed over 3,000 people and infected over 80,000 in China and elsewhere in the world, resulting in catastrophe for humans. Similar to its homologous virus, SARS-CoV, which caused SARS in thousands of people in 2003, SARS-CoV-2 might also be transmitted from the bats and causes similar symptoms through a similar mechanism. However, COVID-19 has lower severity and mortality than SARS but is much more transmissive and affects more elderly individuals than youth and more men than women. In response to the rapidly increasing number of publications on the emerging disease, this article attempts to provide a timely and comprehensive review of the swiftly developing research subject. We will cover the basics about the epidemiology, etiology, virology, diagnosis, treatment, prognosis, and prevention of the disease. Although many questions still require answers, we hope that this review helps in the understanding and eradication of the threatening disease. |
26 | m5h19hy6 | what are the initial symptoms of Covid-19? | Epidemiology, causes, clinical manifestation and diagnosis, prevention and control of coronavirus disease (COVID-19) during the early outbreak period: a scoping review BACKGROUND: The coronavirus disease (COVID-19) has been identified as the cause of an outbreak of respiratory illness in Wuhan, Hubei Province, China beginning in December 2019. As of 31 January 2020, this epidemic had spread to 19 countries with 11 791 confirmed cases, including 213 deaths. The World Health Organization has declared it a Public Health Emergency of International Concern. METHODS: A scoping review was conducted following the methodological framework suggested by Arksey and O'Malley. In this scoping review, 65 research articles published before 31 January 2020 were analyzed and discussed to better understand the epidemiology, causes, clinical diagnosis, prevention and control of this virus. The research domains, dates of publication, journal language, authors' affiliations, and methodological characteristics were included in the analysis. All the findings and statements in this review regarding the outbreak are based on published information as listed in the references. RESULTS: Most of the publications were written using the English language (89.2%). The largest proportion of published articles were related to causes (38.5%) and a majority (67.7%) were published by Chinese scholars. Research articles initially focused on causes, but over time there was an increase of the articles related to prevention and control. Studies thus far have shown that the virus' origination is in connection to a seafood market in Wuhan, but specific animal associations have not been confirmed. Reported symptoms include fever, cough, fatigue, pneumonia, headache, diarrhea, hemoptysis, and dyspnea. Preventive measures such as masks, hand hygiene practices, avoidance of public contact, case detection, contact tracing, and quarantines have been discussed as ways to reduce transmission. To date, no specific antiviral treatment has proven effective; hence, infected people primarily rely on symptomatic treatment and supportive care. CONCLUSIONS: There has been a rapid surge in research in response to the outbreak of COVID-19. During this early period, published research primarily explored the epidemiology, causes, clinical manifestation and diagnosis, as well as prevention and control of the novel coronavirus. Although these studies are relevant to control the current public emergency, more high-quality research is needed to provide valid and reliable ways to manage this kind of public health emergency in both the short- and long-term. |
13 | dw0qsl4s | what are the transmission routes of coronavirus? | Amino acid changes in the spike protein of feline coronavirus correlate with systemic spread of virus from the intestine and not with feline infectious peritonitis Recent evidence suggests that a mutation in the spike protein gene of feline coronavirus (FCoV), which results in an amino acid change from methionine to leucine at position 1058, may be associated with feline infectious peritonitis (FIP). Tissue and faecal samples collected post mortem from cats diagnosed with or without FIP were subjected to RNA extraction and quantitative reverse-transcriptase polymerase chain reaction (qRT-PCR) to detect FCoV RNA. In cats with FIP, 95% of tissue, and 81% of faecal samples were PCR-positive, as opposed to 22% of tissue, and 60% of faecal samples in cats without FIP. Relative FCoV copy numbers were significantly higher in the cats with FIP, both in tissues (P < 0.001) and faeces (P = 0.02). PCR-positive samples underwent pyrosequencing encompassing position 1058 of the FCoV spike protein. This identified a methionine codon at position 1058, consistent with the shedding of an enteric form of FCoV, in 77% of the faecal samples from cats with FIP, and in 100% of the samples from cats without FIP. In contrast, 91% of the tissue samples from cats with FIP and 89% from cats without FIP had a leucine codon at position 1058, consistent with a systemic form of FCoV. These results suggest that the methionine to leucine substitution at position 1058 in the FCoV spike protein is indicative of systemic spread of FCoV from the intestine, rather than a virus with the potential to cause FIP. |
20 | g9fnq1rk | are patients taking Angiotensin-converting enzyme inhibitors (ACE) at increased risk for COVID-19? | Pneumopathies dites atypiques à coronavirus Résumé La nouvelle pneumopathie, appelée pneumonie atypique, revêt dans 20 % de cas l'aspect d'une forme grave (severe acute respiratory syndrome, SARS). C'est parmi ces cas que l'on trouve surtout les 5 % de mortalité. C'est le diagnostic et le traitement tardif qui entraînent ces formes sévères. Il faut donc traiter tôt en se fondant sur le tableau clinique, la notion de contage, l'identification du virus. ribavirine et corticoïdes en sont les éléments principaux. Abstract A new respiratory illness, designated as atypical pneumonia, produces in 20% of the cases a much more serious disease termed severe acute respiratory syndrome (SARS), which can be fatal in 5% of the cases. Delayed diagnosis and treatment are the underlying causes for the development of SARS. Measures for the management of the disease should be taken swiftly, based on clinical symptoms, definite contact and isolation of the virus. Current treatment of SARS involves antiviral agents, such as ribavirin, and corticosteroids. |
19 | kbd2h4l0 | what type of hand sanitizer is needed to destroy Covid-19? | The potential role of IL-6 in monitoring severe case of coronavirus disease 2019 Abstract. Background: The outbreak of coronavirus disease 2019 (COVID-19) in Wuhan City, China spreads rapidly since December, 2019. Most patients show mild symptoms, but some of them develop into severe disease. There is currently no specific medication. The purpose of this study is to to explore changes of markers in peripheral blood of severe COVID-19 patients, which may be of value in disease monitoring. Methods Clinical data of patients with nonsevere and severe type COVID-19 diagnosed by laboratory test in our institution were collected. The relationship between peripheral blood cells and cytokines, clinical manifestation and outcome was analyzed. Results A total of 69 severe type COVID-19 patients were included. On admission, the median age of severe cases was 56-year old, with 52.17% female patient. The most common symptoms were fever (79.72%), cough (63.77%), shortness of breath (57.97%) and fatigue (50.72%). Diarrhea is less common. The most common comorbidity is hypertension. Upon admission, the proportion of bilateral pulmonary involvement and interstitial abnormalities evidenced by chest computed tomography (CT) imaging in severe cases was 60.87% and 27.54%, respectively. Compared with patients with nonsevere disease, those with severe disease showed obvious lymphocytopenia. Elevated level of lactate dehydrogenase (LDH), C-reactive protein (CRP), ferritin and D-dimer was found in most cases. Two patients (2.9%) needed transfer to the intensive care unit. Baseline immunological parameters and most of the inflammatory parameters were basically within the normal range. However, baseline interleukin-6 (IL-6) was significantly increased in severe type, which was closely related to the maximal body temperature during hospitalization and to CT findings. Baseline IL-6 was also significantly related to the increase of baseline level of CRP, LDH, ferritin and D-dimer. The increase of baseline IL-6 level suggests that it may positively correlate with the severity of COVID-19. Among the 30 severe type patients whose IL-6 was assessed before and after treatment, significant decrease in IL-6 and improved CT assessment was found in 25 patients after treatment. Whereas the IL-6 level was further increased in 3 cases, which was closely related to disease progression. It is suggested that IL-6 may be used as a marker for disease monitoring in severe COVID-19 patients. Conclusions On admission, the baseline level of IL-6, CRP, LDH and ferritin was closely related to the severity of COVID-19, and the elevated IL-6 was significantly related to the clinical manifestation of severe type patients. The decrease of IL-6 was closely related to treatment effectiveness, while the increase of IL-6 indicated disease exacerbation. Collectively, the dynamic change of IL-6 level can be used as a marker for disease monitoring in patients with severe COVID-19. |
32 | oc1u46p9 | Does SARS-CoV-2 have any subtypes, and if so what are they? | Sampling considerations for detecting genetic diversity of influenza viruses in the DoD Global Respiratory Pathogen Surveillance Program. The Department of Defense (DoD) Global Respiratory Pathogen Surveillance Program annually monitors the genetic diversity of influenza viruses circulating in DoD beneficiary populations. This program relies on a global network of partners across the DoD to submit respiratory specimens throughout the influenza season. In previous seasons, representative specimens for sequencing were chosen because of cost and time restrictions associated with reliance on Sanger-based sequencing technology. The effect of this specimen prioritization for sequencing has not been previously examined in the respiratory surveillance program. Here, specimen prioritization was simulated by iteratively subsetting sequencing data sets from 1 October 2013 through 15 March 2017 to determine how prioritizing affects common metrics of genetic diversity. Prioritization of specimens did not meaningfully affect calculations of average influenza genetic diversity within seasons or subtypes. Because of the high genetic diversity of influenza, prioritizing resulted in fewer unique viruses and less accurate measures of geographic relationships although it still provided relevant estimates. Given the advent of cost-effective next-generation sequencing approaches, all programs should carefully consider how best to prioritize influenza sequencing to recover meaningful information on the evolutionary dynamics of the virus. |
34 | geixma05 | What are the longer-term complications of those who recover from COVID-19? | 62(ND) ASMS Conference on Mass Spectrometry and Allied Topics |
8 | b1iyr42n | how has lack of testing availability led to underreporting of true incidence of Covid-19? | Structural, glycosylation and antigenic variation between 2019 novel coronavirus (2019-nCoV) and SARS coronavirus (SARS-CoV) The emergence of 2019 novel coronavirus (2019-nCoV) is of global concern and might have emerged from RNA recombination among existing coronaviruses. CoV spike (S) protein which is crucial for receptor binding, membrane fusion via conformational changes, internalization of the virus, host tissue tropism and comprises crucial targets for vaccine development, remain largely uncharacterized. Therefore, the present study has been planned to determine the sequence variation, structural and antigenic divergence of S glycoprotein which may be helpful for the management of 2019-nCoV infection. The sequences of spike glycoprotein of 2019-nCoV and SARS coronavirus (SARS-CoV) were used for the comparison. The sequence variations were determined using EMBOSS Needle pairwise sequence alignment tools. The variation in glycosylation sites was predicted by NetNGlyc 1.0 and validated by N-GlyDE server. Antigenicity was predicted by NetCTL 1.2 and validated by IEDB Analysis Resource server. The structural divergence was determined by using SuperPose Version 1.0 based on cryo-EM structure of the SARS coronavirus spike glycoprotein. Our data suggests that 2019-nCoV is newly spilled coronavirus into humans in China is closely related to SARS-CoV, which has only 12.8% of difference with SARS-CoV in S protein and has 83.9% similarity in minimal receptor-binding domain with SARS-CoV. Addition of a novel glycosylation sites were observed in 2019-nCoV. In addition, antigenic analysis proposes that great antigenic differences exist between both the viral strains, but some of the epitopes were found to be similar between both the S proteins. In spite of the variation in S protein amino acid composition, we found no significant difference in their structures. Collectively, for the first time our results exhibit the emergence of human 2019-nCoV is closely related to predecessor SARS-CoV and provide the evidence that 2019-nCoV uses various novel glycosylation sites as SARS-CoV and may have a potential to become pandemic owing its antigenic discrepancy. Further, demonstration of novel Cytotoxic T lymphocyte epitopes may impart opportunities for the development of peptide based vaccine for the prevention of 2019-nCoV. |
23 | 9y35ykzf | what kinds of complications related to COVID-19 are associated with hypertension? | Cardiomyopathy |
49 | ve51wy5p | do individuals who recover from COVID-19 show sufficient immune response, including antibody levels and T-cell mediated immunity, to prevent re-infection? | ACE2 and TMPRSS2 variants and expression as candidates to sex and country differences in COVID-19 severity in Italy Orthopaedic Guidelines for the COVID-19 Post-Outbreak Period: Experience from Wuhan, People's Republic of China As the outbreak of coronavirus disease 2019 (COVID-19) progresses, prognostic markers for early identification of high-risk individuals are an urgent medical need Italy has one of the highest numbers of SARS-CoV-2-related deaths and one of the highest mortality rates Worldwide, a more severe course of COVID-19 is associated with older age, comorbidities, and male sex Hence, we searched for possible genetic components of COVID-19 severity among Italians by looking at expression levels and variants in ACE2 and TMPRSS2 genes, crucial for viral infection Exome and SNP-array data from a large Italian cohort were used to compare the rare-variants burden and polymorphisms frequency with Europeans and East Asians Moreover, we looked into gene expression databases to check for sex-unbalanced expression While we found no significant evidence that ACE2 is associated with disease severity/sex bias, TMPRSS2 levels and genetic variants proved to be possible candidate disease modulators, prompting for rapid experimental validations on large patient cohorts Currently, the coronavirus disease 2019 (COVID-19) crisis has rapidly spread worldwide As the earliest outbreak area of the pandemic, Wuhan, People's Republic of China, is gradually recovering to its normal state under the effective control of government authorities Outpatient services in major hospitals are now being restored An accumulation of asymptomatic infections is a potential risk for medical personnel, especially when there is crowding in hospitals As the biggest center for orthopaedic patients in Wuhan, our orthopaedic outpatient department admits >300 patients per day Optimal guidelines on how to handle this huge number of patients during the post-outbreak stage of the COVID-19 pandemic, particularly with regard to potential asymptomatic infection, are urgently needed for orthopaedic surgeons We have developed and proposed applicable guidelines to fill this knowledge gap, including the necessary protective strategies for medical personnel in orthopaedic outpatient and inpatient wards as well as during surgery We also have provided mental health recommendations for health-care workers To the best of our knowledge, these guidelines are the first of their kind for orthopaedic surgeons who are slowly reestablishing medical activity following the pandemic |
3 | fw4pmaoc | will SARS-CoV2 infected people develop immunity? Is cross protection possible? | Evidence of the Recombinant Origin and Ongoing Mutations in Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2) The recent global outbreak of viral pneumonia designated as Coronavirus Disease 2019 (COVID-19) by coronavirus (SARS-CoV-2) has threatened global public health and urged to investigate its source. Whole genome analysis of SARS-CoV-2 revealed ~96% genomic similarity with bat CoV (RaTG13) and clustered together in phylogenetic tree. Furthermore, RaTGl3 also showed 97.43% spike protein similarity with SARS-CoV-2 suggesting that RaTGl3 is the closest strain. However, RBD and key amino acid residues supposed to be crucial for human-to-human and cross-species transmission are homologues between SARS-CoV-2 and pangolin CoVs. These results from our analysis suggest that SARS-CoV-2 is a recombinant virus of bat and pangolin CoVs. Moreover, this study also reports mutations in coding regions of 125 SARS-CoV-2 genomes signifying its aptitude for evolution. In short, our findings propose that homologous recombination has been occurred between bat and pangolin CoVs that triggered cross-species transmission and emergence of SARS-CoV-2, and, during the ongoing outbreak, SARS-CoV-2 is still evolving for its adaptability. |
24 | cusk2t80 | what kinds of complications related to COVID-19 are associated with diabetes | Epidemiological, demographic, and clinical characteristics of 47 cases of Middle East respiratory syndrome coronavirus disease from Saudi Arabia: a descriptive study Summary Background Middle East respiratory syndrome (MERS) is a new human disease caused by a novel coronavirus (CoV). Clinical data on MERS-CoV infections are scarce. We report epidemiological, demographic, clinical, and laboratory characteristics of 47 cases of MERS-CoV infections, identify knowledge gaps, and define research priorities. Methods We abstracted and analysed epidemiological, demographic, clinical, and laboratory data from confirmed cases of sporadic, household, community, and health-care-associated MERS-CoV infections reported from Saudi Arabia between Sept 1, 2012, and June 15, 2013. Cases were confirmed as having MERS-CoV by real-time RT-PCR. Findings 47 individuals (46 adults, one child) with laboratory-confirmed MERS-CoV disease were identified; 36 (77%) were male (male:female ratio 3·3:1). 28 patients died, a 60% case-fatality rate. The case-fatality rate rose with increasing age. Only two of the 47 cases were previously healthy; most patients (45 [96%]) had underlying comorbid medical disorders, including diabetes (32 [68%]), hypertension (16 [34%]), chronic cardiac disease (13 [28%]), and chronic renal disease (23 [49%]). Common symptoms at presentation were fever (46 [98%]), fever with chills or rigors (41 [87%]), cough (39 [83%]), shortness of breath (34 [72%]), and myalgia (15 [32%]). Gastrointestinal symptoms were also frequent, including diarrhoea (12 [26%]), vomiting (ten [21%]), and abdominal pain (eight [17%]). All patients had abnormal findings on chest radiography, ranging from subtle to extensive unilateral and bilateral abnormalities. Laboratory analyses showed raised concentrations of lactate dehydrogenase (23 [49%]) and aspartate aminotransferase (seven [15%]) and thrombocytopenia (17 [36%]) and lymphopenia (16 [34%]). Interpretation Disease caused by MERS-CoV presents with a wide range of clinical manifestations and is associated with substantial mortality in admitted patients who have medical comorbidities. Major gaps in our knowledge of the epidemiology, community prevalence, and clinical spectrum of infection and disease need urgent definition. Funding None. |
19 | r87am6k4 | what type of hand sanitizer is needed to destroy Covid-19? | Effects of Audio-Visual Stimulation on Hand Hygiene Compliance among Family and Non-Family Visitors of Pediatric Wards: A Quasi-Experimental Pre-post Intervention Study Abstract Purpose This study aimed to identify the differences in interventional effects on hand hygiene compliance (HHC) among families and visitors in pediatric wards. Design & methods A total of 2787 family and non-family visitors entering through the glass sliding door of 6 pediatric wards at a university children's hospital were observed for 4 h, respectively, before and after interventions between April 27 and May 20, 2018. In the first intervention, a visual stimulus emphasized the location of the hand sanitizer. In the second intervention, an additional auditory stimulus transmitted a cue through a motion sensor speaker. Results During the preliminary observation, the HHC rates of family and non-family visitors were 0.0% and 1.5%, respectively; after the visual stimulus, they were 0.6% and 5.4%, and after the audio-visual stimulus, 1.8% and 8.2%. There was a significant increase in the overall HHC with the visual (OR, 5.22; 95% CI, 1.76–20.90) and audio-visual (OR, 8.67; 95% CI, 3.08–33.70) stimuli (Fisher's exact test, p < .05). Conclusions The HHC of family and non-family visitors entering pediatric wards was very low and the audio-visual stimulus was found to be more effective than was the visual stimulus alone. Practice implications To reduce healthcare-associated infection, pediatric wards must actively implement effective interventions. Using audio-visual stimulation to increase HHC among visitors will provide advantages. Follow-up research should examine the current state of HHC among visitors in various locations and conditions. |
21 | ipoj13va | what are the mortality rates overall and in specific populations | Alisporivir inhibits MERS- and SARS-coronavirus replication in cell culture, but not SARS-coronavirus infection in a mouse model Abstract Currently, there is no registered treatment for infections with emerging zoonotic coronaviruses like SARS- and MERS-coronavirus. We here report that in cultured cells low-micromolar concentrations of alisporivir, a non-immunosuppressive cyclosporin A-analog, inhibit the replication of four different coronaviruses, including MERS- and SARS-coronavirus. Ribavirin was found to further potentiate the antiviral effect of alisporivir in these cell culture-based infection models, but this combination treatment was unable to improve the outcome of SARS-CoV infection in a mouse model. Nevertheless, our data provide a basis to further explore the potential of Cyp inhibitors as host-directed, broad-spectrum inhibitors of coronavirus replication. |
46 | 32ozud9i | what evidence is there for dexamethasone as a treatment for COVID-19? | The effect of intraoperative administration of dexamethasone for PONV prophylaxis on perioperative blood glucose level in obese and normal weight children. BACKGROUND The incidence of postoperative nausea and vomiting (PONV) can be reduced by dexamethasone. Single-dose administration may cause elevated blood glucose levels in obese adults. No data are available for children. OBJECTIVE The aim was to evaluate perioperative blood glucose changes related to body weight in children who received dexamethasone. PATIENTS AND METHODS This prospective observational study included 62 children. All patients received total intravenous anesthesia and a single dose of dexamethasone (0.15 mg/kg, maximum 8 mg). Blood glucose levels were measured up to 6 h. Standard deviation scores (SDS) were calculated using age- and gender-specific body mass index (BMI) percentiles, p<0.05. RESULTS A total of 62 children (11.5±2.9 years, median SDS 0.43, 29% overweight/obese) were included. Blood glucose levels increased from 5.52±0.52 to 6.74±0.84 mmol/L 6 h after dexamethasone without correlation to the BMI-SDS. CONCLUSIONS This study showed an increase of perioperative blood glucose (normoglycemic ranges) after single dose of dexamethasone, but no BMI-dependent effect was observed in children. Therefore, low-dose dexamethasone may be used in obese children for PONV prophylaxis. |
35 | ntx2c04x | What new public datasets are available related to COVID-19? | Covid-19: Pandemonium in our time While pandemonium has come to mean wild and noisy disorder, the reference here is to John Milton's epic poem Paradise Lost and the upheaval following Lucifer's banishment from Heaven and his construction of Pandæmonium as his hub. Today's avalanche of conflicting news on how to deal with the coronavirus disease 2019 (Covid-19) brings to mind the Trinity nuclear bomb test with Enrico Fermi estimating its strength by releasing small pieces of paper into the air and measuring their displacement by the shock wave. Fermi's result, in fact not far from the true value, emphasised his ability to make good approximations with few or no actual data. The current wave of Covid-19 presents just this kind of situation as it engulfs the world from ground zero in Wuhan, China. Much information is indeed missing, but datasets that might lead to useful ideas on how to handle this pandemic are steadily accumulating. |
14 | hfgmmuy6 | what evidence is there related to COVID-19 super spreaders | Severe Middle East Respiratory Syndrome (MERS) Pneumonia Abstract Middle East Respiratory Syndrome (MERS) is a viral respiratory infection, which ranges from asymptomatic infection to severe pneumonia and multiorgan failure, caused by a novel coronavirus named Middle East Respiratory Syndrome Coronavirus (MERS-CoV). Majority of cases have been reported from Saudi Arabia. MERS cases occur as sporadic cases or as clusters or hospital outbreaks. Dromedary camels are thought to be a host for MERS-CoV. Direct contact with dromedary camels within 14days prior to infection was identified as an independent risk factor for MERS. Diagnosis of MERS is based on a positive real-time reverse transcriptase polymerase chain reaction (rRT-PCR), obtained from a respiratory specimen. The mainstay of management of MERS-CoV infection is supportive care. There is no specific antiviral therapy for MERS-CoV infection at present, although several modalities of treatment options have been examined or are under investigation. |
40 | j3h80aui | What are the observed mutations in the SARS-CoV-2 genome and how often do the mutations occur? | Conservation and Variability of Dengue Virus Proteins: Implications for Vaccine Design BACKGROUND: Genetic variation and rapid evolution are hallmarks of RNA viruses, the result of high mutation rates in RNA replication and selection of mutants that enhance viral adaptation, including the escape from host immune responses. Variability is uneven across the genome because mutations resulting in a deleterious effect on viral fitness are restricted. RNA viruses are thus marked by protein sites permissive to multiple mutations and sites critical to viral structure-function that are evolutionarily robust and highly conserved. Identification and characterization of the historical dynamics of the conserved sites have relevance to multiple applications, including potential targets for diagnosis, and prophylactic and therapeutic purposes. METHODOLOGY/PRINCIPAL FINDINGS: We describe a large-scale identification and analysis of evolutionarily highly conserved amino acid sequences of the entire dengue virus (DENV) proteome, with a focus on sequences of 9 amino acids or more, and thus immune-relevant as potential T-cell determinants. DENV protein sequence data were collected from the NCBI Entrez protein database in 2005 (9,512 sequences) and again in 2007 (12,404 sequences). Forty-four (44) sequences (pan-DENV sequences), mainly those of nonstructural proteins and representing ∼15% of the DENV polyprotein length, were identical in 80% or more of all recorded DENV sequences. Of these 44 sequences, 34 (∼77%) were present in ≥95% of sequences of each DENV type, and 27 (∼61%) were conserved in other Flaviviruses. The frequencies of variants of the pan-DENV sequences were low (0 to ∼5%), as compared to variant frequencies of ∼60 to ∼85% in the non pan-DENV sequence regions. We further showed that the majority of the conserved sequences were immunologically relevant: 34 contained numerous predicted human leukocyte antigen (HLA) supertype-restricted peptide sequences, and 26 contained T-cell determinants identified by studies with HLA-transgenic mice and/or reported to be immunogenic in humans. CONCLUSIONS/SIGNIFICANCE: Forty-four (44) pan-DENV sequences of at least 9 amino acids were highly conserved and identical in 80% or more of all recorded DENV sequences, and the majority were found to be immune-relevant by their correspondence to known or putative HLA-restricted T-cell determinants. The conservation of these sequences through the entire recorded DENV genetic history supports their possible value for diagnosis, prophylactic and/or therapeutic applications. The combination of bioinformatics and experimental approaches applied herein provides a framework for large-scale and systematic analysis of conserved and variable sequences of other pathogens, in particular, for rapidly mutating viruses, such as influenza A virus and HIV. |
43 | iotj0jwd | How has the COVID-19 pandemic impacted violence in society, including violent crimes? | The bedford-stuyvesant healthy homes initiative: A comprehensive approach to residential hazard assessment and control |
12 | 7g9xx5lg | what are best practices in hospitals and at home in maintaining quarantine? | Deep thought of COVID-19 based on Diamond Princess's quarantine and home quarantine Not Available. |
10 | 3f7olev8 | has social distancing had an impact on slowing the spread of COVID-19? | Timing of non-pharmaceutical interventions to mitigate COVID-19 transmission and their effects on mobility: A cross-country analysis Non-pharmaceutical interventions (NPIs) that encourage physical distancing can decrease and delay the transmission of COVID-19. They have been implemented globally during the pandemic, however, the specific NPIs implemented and the timing of interventions has varied widely. We validated two published datasets on the implementation of NPIs globally. The health and socioeconomic factors associated with delay in implementation of NPIs was analyzed using fractional logit and probit models, and beta regression models. The probability of timely NPI implementation by a country was analyzed using a probit model. The effects of these interventions on mobility changes using Google social mobility reports, were analyzed with propensity score matching methods. Three NPIs were analyzed: national school closure, national lockdown, and global travel ban. Countries with higher incomes, larger populations, and better health preparedness measures had greater delays in implementation. Countries with greater population density, more democratic political systems, lower case detection capacity, and later arrival of first cases were more likely to implement NPIs. Implementation of lockdowns significantly reduced physical mobility. Mobility was further reduced when lockdowns were enforced with curfews or fines, or were more strictly defined. National school closures did not significantly change mobility. The implementation of NPIs is a global public good during pandemics, and the international community needs to address constraints and design incentives so countries implement NPIs in a timely manner. Further analysis is needed on the effect of NPI variations on mobility and transmission, and their associated costs. |
19 | k8k5kg4z | what type of hand sanitizer is needed to destroy Covid-19? | Possibility of Disinfection of SARS-CoV-2 (COVID-19) in Human Respiratory Tract by Controlled Ethanol Vapor Inhalation Viruses such as SARS-CoV-2 and Influenza are lipophilic, enveloped viruses, and are relatively easy to inactivate by exposure to alcohols. The envelope mainly consists of the lipid bilayer, taken from the host cells at assembly/budding stage of the viral life cycle. Therefore the constitution of the lipid bilayer should be common in all SARS, MERS and influenza viruses, even after mutations, and thus these closely-related viruses will be disinfected by exposure to ethanol with the same concentration. Existing experimental data indicate that an ethanol concentration of 30~40 v/v% is sufficient to inactivate Influenza-A viruses in solution[1,2,3]. The author suggests that it may be possible to use alcoholic beverages of 16~20 v/v% concentration for this disinfection process, such as Whisky (1:1 hot water dilution) or Japanese Sake, because they are readily available and safe (non-toxic). By inhaling the alcohol vapor at 50~60$^\circ$C (122~140$^\circ$F) through the nose for one or two minutes, it will condense on surfaces inside the respiratory tract; mainly in the nasal cavity. The alcohol concentration will be intensified to ~36 v/v% by this process, which is enough to disinfect the corona virus on the mucous membrane. This method also provides more moisture into respiratory tract, and helps to clean the inside of the nasal cavity by stimulating blowing of the nose, and also makes the mucous escalator work actively so that the self-clearing mechanism in the trachea will remove viruses faster. An alternative prompt method is also discussed. We use 40 v/v% whisky or similar alcohol, dripping on a gauze, inhale the vapor slowly at room temperature. This method works well for the front part of the nasal cavity. This is suitable for clinical workers, because they may need to use prompt preventative measures at any time. |
21 | jfe8neec | what are the mortality rates overall and in specific populations | SARS – CoV -2: reasons of epidemiology of severe ill disease cases and therapeutic approach using trivalent vaccine (tetanus, diphtheria and Bordetella pertussis) Abstract The novel coronavirus COVID-19 follows transmission route and clinical presentation of all community-acquired coronaviruses. Instead, the rate of transmission is significative higher, with a faster spread of the virus responsible of the worldwide outbreak and a significative higher mortality rate due to the development of a severe lung injury. Most noteworthy is the distribution of death rate among age groups. Children and younger people are almost protected from severe clinical presentation. Possible explanation of this phenomenon could be the ability of past vaccinations (especially tetanic, diphtheria toxoids and inactivated bacteria as pertussis) to stimulate immune system and to generate a scattered immunity against non-self antigens in transit, as coronaviruses and other community-circulating viruses and make immune system readier to develop specific immunity against COVID-19. The first support to this hypothesis is the distribution of mortality rate during historical pandemics ("Spanish flu" 1918, "Asian flu" 1956 and "the Hong Kong flu" 1968) among age groups before and after the introduction of vaccines. The immunological support to the hypothesis derives from recent studies about immunotherapy for malignancies, which propose the use of oncolytic vaccines combined with toxoids in order to exploit CD4+ memory T cell recall in supporting the ongoing anti-tumour response. According to this hypothesis vaccine formulations (tetanus, diphtheria, Bordetella pertussis) could be re-administrate after the first contact with Covid-19, better before the development of respiratory severe illness and of course before full-blown ARDS (Acute Respiratory Distress Syndrome). The CD4+ memory exploiting could help immune system to recall immunity of already know antigens against coronaviruses, avoiding or limiting "lung crash" until virus specific immunity develops and making it faster and prolonged. Finally, this administration could be helpful not only in already infected patients, but also before infection. In fact, people could have an immune system more ready when the contact with the COVID-19 will occur. |
28 | 9sdlm4jf | what evidence is there for the value of hydroxychloroquine in treating Covid-19? | Risks of Hydroxychloroquine use for COVID-19 prophylaxis |
43 | hw9o9n01 | How has the COVID-19 pandemic impacted violence in society, including violent crimes? | Effects of the COVID-19 pandemic on mental well-being amongst individuals in society- A letter to the editor on "The Socio-Economic Implications of the Coronavirus and COVID-19 Pandemic: A Review" |
12 | o72unm3q | what are best practices in hospitals and at home in maintaining quarantine? | COVID-19 and mental health: A review of the existing literature Abstract The COVID-19 pandemic is a major health crisis affecting several nations, with over 720,000 cases and 33,000 confirmed deaths reported to date. Such widespread outbreaks are associated with adverse mental health consequences. Keeping this in mind, existing literature on the COVID-19 outbreak pertinent to mental health was retrieved via a literature search of the PubMed database. Published articles were classified according to their overall themes and summarized. Preliminary evidence suggests that symptoms of anxiety and depression (16–28%) and self-reported stress (8%) are common psychological reactions to the COVID-19 pandemic, and may be associated with disturbed sleep. A number of individual and structural variables moderate this risk. In planning services for such populations, both the needs of the concerned people and the necessary preventive guidelines must be taken into account. The available literature has emerged from only a few of the affected countries, and may not reflect the experience of persons living in other parts of the world. In conclusion, subsyndromal mental health problems are a common response to the COVID-19 pandemic. There is a need for more representative research from other affected countries, particularly in vulnerable populations. |
2 | 95zjnp77 | how does the coronavirus respond to changes in the weather | The Role of Viral Population Diversity in Adaptation of Bovine Coronavirus to New Host Environments The high mutation rate of RNA viruses enables a diverse genetic population of viral genotypes to exist within a single infected host. In-host genetic diversity could better position the virus population to respond and adapt to a diverse array of selective pressures such as host-switching events. Multiple new coronaviruses, including SARS, have been identified in human samples just within the last ten years, demonstrating the potential of coronaviruses as emergent human pathogens. Deep sequencing was used to characterize genomic changes in coronavirus quasispecies during simulated host-switching. Three bovine nasal samples infected with bovine coronavirus were used to infect human and bovine macrophage and lung cell lines. The virus reproduced relatively well in macrophages, but the lung cell lines were not infected efficiently enough to allow passage of non lab-adapted samples. Approximately 12 kb of the genome was amplified before and after passage and sequenced at average coverages of nearly 950×(454 sequencing) and 38,000×(Illumina). The consensus sequence of many of the passaged samples had a 12 nucleotide insert in the consensus sequence of the spike gene, and multiple point mutations were associated with the presence of the insert. Deep sequencing revealed that the insert was present but very rare in the unpassaged samples and could quickly shift to dominate the population when placed in a different environment. The insert coded for three arginine residues, occurred in a region associated with fusion entry into host cells, and may allow infection of new cell types via heparin sulfate binding. Analysis of the deep sequencing data indicated that two distinct genotypes circulated at different frequency levels in each sample, and support the hypothesis that the mutations present in passaged strains were "selected" from a pre-existing pool rather than through de novo mutation and subsequent population fixation. |
27 | 1ix7mtxd | what is known about those infected with Covid-19 but are asymptomatic? | Asymptomatic Patients with Novel Coronavirus Disease (COVID-19) |
31 | 7eqpb7ge | How does the coronavirus differ from seasonal flu? | Adenovirus-Based Vectors for the Development of Prophylactic and Therapeutic Vaccines Emerging and reemerging infectious diseases as well as cancer pose great global health impacts on the society. Vaccines have emerged as effective treatments to prevent or reduce the burdens of already developed diseases. This is achieved by means of activating various components of the immune system to generate systemic inflammatory reactions targeting infectious agents or diseased cells for control/elimination. DNA virus-based genetic vaccines gained significant attention in the past decades owing to the development of DNA manipulation technologies, which allowed engineering of recombinant viral vectors encoding sequences for foreign antigens or their immunogenic epitopes as well as various immunomodulatory molecules. Despite tremendous progress in the past 50 years, many hurdles still remain for achieving the full clinical potential of viral-vectored vaccines. This chapter will present the evolution of vaccines from "live" or "attenuated" first-generation agents to recombinant DNA and viral-vectored vaccines. Particular emphasis will be given to human adenovirus (Ad) for the development of prophylactic and therapeutic vaccines. Ad biological properties related to vaccine development will be highlighted along with their advantages and potential hurdles to be overcome. In particular, we will discuss (1) genetic modifications in the Ad capsid protein to reduce the intrinsic viral immunogenicity, (2) antigen capsid incorporation for effective presentation of foreign antigens to the immune system, (3) modification of the hexon and fiber capsid proteins for Ad liver de-targeting and selective retargeting to cancer cells, (4) Ad-based vaccines carrying "arming" transgenes with immunostimulatory functions as immune adjuvants, and (5) oncolytic Ad vectors as a new therapeutic approach against cancer. Finally, the combination of adenoviral vectors with other non-adenoviral vector systems, the prime/boost strategy of immunization, clinical trials involving Ad-based vaccines, and the perspectives for the field development will be discussed. |
2 | vy0vcom2 | how does the coronavirus respond to changes in the weather | Syndromic surveillance insights from a symptom assessment app before and during COVID-19 measures in Germany and the United Kingdom: results from repeated cross-sectional analyses Background: Unprecedented lockdown measures have been introduced in countries across the world to mitigate the spread and consequences of COVID-19. While attention has focused on the effects of these measures on epidemiological indicators relating directly to the infection, there is increased recognition of their broader health implications. However, assessing these implications in real time is a challenge, due to limitations of existing syndromic surveillance data and tools. Objective: To explore the added value of mobile phone app-based symptom assessment tools as real time health insight providers to inform public health policy makers. Methods: A comparative and descriptive analysis of the proportion of all self-reported symptoms entered by users during an Ada assessment in Germany and the United Kingdom (UK) was conducted between two periods: before and after the implementation of Phase One COVID-19 measures. Additional analyses were performed to explore the association between symptom trends and seasonality, and symptom trends and weather. Differences in the proportion of unique symptoms between the periods were analyzed using Pearson's Chi-squared test and reported as Log2 Fold Changes (Log2 FC). Results: Between 48,300-54,900 symptomatic users reported 140,500-170,400 symptoms during the Baseline and Measures periods in Germany. Between 34,200-37,400 symptomatic users in the UK reported 112,100-131,900 symptoms during the Baseline and Measures periods. The majority of symptomatic users were female (Germany 68,600/103,200, 66.52%; UK 51,200/71,600, 72.74%). The majority (Germany 68,500/100,000, 68.45%; UK 50,900/68,800, 73.91%) were aged between 10 and 29 years, and about a quarter (Germany 26,200/100,000, 26.15%; UK 14,900/68,800, 21.65%) were between 30-59 years. 103 symptoms were reported either more or less frequently (with statistically significant differences) during the Measures as compared to the Baseline period, and 34 of these were found in both countries. The following mental health symptoms (Log2 FC, P-value) were reported less often during the Measures period: inability to manage constant stress and demands at work (-1.07, P<.001), memory difficulty (-0.56, P<.001), depressed mood (-0.42, P<.001), and impaired concentration (-0.46, P<.001). Diminished sense of taste (2.26, P<.001) and hyposmia (2.20, P<.001) were reported more frequently during the Measures period. None of the 34 symptoms were found to be different between the same dates in 2019. Fourteen of the 34 symptoms had statistically significant associations with weather variables. Conclusions: Symptom assessment apps have an important role to play in facilitating improved understanding of the implications of public health policies such as COVID-19 lockdown measures. Not only do they provide the means to complement and cross-validate hypotheses based on data collected through more traditional channels, they can also generate novel insights through a real-time syndromic surveillance system. |
28 | rlxrn3ap | what evidence is there for the value of hydroxychloroquine in treating Covid-19? | QT Interval Prolongation and Torsade De Pointes in Patients with COVID-19 treated with Hydroxychloroquine/Azithromycin BACKGROUND: There is no known effective therapy for patients with COVID-19. Initial reports suggesting the potential benefit of Hydroxychloroquine/Azithromycin (HY/AZ) have resulted in massive adoption of this combination worldwide. However, while the true efficacy of this regimen is unknown, initial reports have raised concerns regarding the potential risk of QT prolongation and induction of torsade de pointes (TdP). OBJECTIVE: to assess the change in QTc interval and arrhythmic events in patients with COVID-19 treated with HY/AZ METHODS: This is a retrospective study of 251 patients from two centers, diagnosed with COVID-19 and treated with HY/AZ. We reviewed ECG tracings from baseline and until 3 days after completion of therapy to determine the progression of QTc and incidence of arrhythmia and mortality. RESULTS: QTc prolonged in parallel with increasing drug exposure and incompletely shortened after its completion. Extreme new QTc prolongation to > 500 ms, a known marker of high risk for TdP had developed in 23% of patients. One patient developed polymorphic ventricular tachycardia (VT) suspected as TdP, requiring emergent cardioversion. Seven patients required premature termination of therapy. The baseline QTc of patients exhibiting extreme QTc prolongation was normal. CONCLUSION: The combination of HY/AZ significantly prolongs the QTc in patients with COVID-19. This prolongation may be responsible for life threating arrhythmia in the form of TdP. This risk mandates careful consideration of HY/AZ therapy in lights of its unproven efficacy. Strict QTc monitoring should be performed if the regimen is given. |
17 | bhn2simp | are there any clinical trials available for the coronavirus | Umbilical cord blood therapy to prevent progression of COVID-19 related pneumonia: a structured summary of a study protocol for a pilot randomised controlled trial OBJECTIVES: Objective: To undertake a pilot, feasibility RCT of umbilical cord blood derived cell therapy for treatment of adult patients infected with SARS-CoV-2 virus related moderate-to-severe pneumonia to prevent progression to severe ARDS. Hypothesis: Expanded cord blood derived cell therapy will be feasible, well tolerated and show potential efficacy in the treatment of acute COVID-19 related moderate to severe pneumonia in adult patients because of their powerful anti-inflammatory and immunomodulatory properties. TRIAL DESIGN: Pilot, parallel design randomised controlled trial. PARTICIPANTS: The trial will recruit 24 hospitalised patients with confirmed SARS-CoV-2 infection and pneumonia from July to December 2020 at Monash Medical Centre in Melbourne, Australia. INTERVENTION AND COMPARATOR: Intervention: Intravenous injection of expanded umbilical cord blood cells at a dose of 5 million cells/kg (maximum dose - 500 million cells). Cell infusion will occur over 30-60 minutes through a peripheral intravenous cannula. Standard supportive care will continue as needed. Comparator: Standard supportive care. MAIN OUTCOMES: Safety and tolerability of cell administration within first 24 hours of administration; clinical improvement on a seven-category clinical improvement ordinal scale. RANDOMISATION: Randomisation will be done using computer generated allocation to intervention/ control groups in a 1:1 ratio (in blocks of 6) using sealed opaque envelopes. BLINDING (MASKING): This will be an unblinded study, given that it is the first study using expanded cord blood cells in COVID-19 patients. There will be no placebo infusion. NUMBERS TO BE RANDOMISED (SAMPLE SIZE): Twelve participants in each group. Total n=24. TRIAL STATUS: CBC-19 protocol v2, dated 23(rd) April 2020. Recruitment has not started yet. Estimated recruitment timeline is between 1st July – 31st December 2020. TRIAL REGISTRATION: Australian New Zealand Clinical Trials Registry, ACTRN12620000478910, registered 16th April 2020. FULL PROTOCOL: The full protocol is attached as an additional file, accessible from the Trials website (Additional file 1). In the interest in expediting dissemination of this material, the familiar formatting has been eliminated; this Letter serves as a summary of the key elements of the full protocol. |
13 | 3p4pcke8 | what are the transmission routes of coronavirus? | Individual risk management strategy and potential therapeutic options for the COVID-19 pandemic It is an ugly fact that a significant amount of the world's population will contract SARS-CoV-II infection with the current spreading. While a specific treatment is not yet coming soon, individual risk assessment and management strategies are crucial. The individual preventive and protective measures drive the personal risk of getting the disease. Among the virus-contracted hosts, their different metabolic status, as determined by their diet, nutrition, age, sex, medical conditions, lifestyle, and environmental factors, govern the personal fate toward different clinical severity of COVID-19, from asymptomatic, mild, moderate, to death. The careful individual assessment for the possible dietary, nutritional, medical, lifestyle, and environmental risks, together with the proper relevant risk management strategies, is the sensible way to deal with the pandemic of SARS-CoV-II. |
25 | mzpkyo8w | which biomarkers predict the severe clinical course of 2019-nCOV infection? | Improving vaccine-induced immunity: Can Baseline Predict Outcome? Abstract Immune signatures measured at baseline and immediately prior to vaccination, may predict the immune response to vaccination. Such pre-vaccine assessment might allow not only population-based, but also more personalized vaccination strategies ('precision vaccination'). If baseline immune signatures are predictive, the underlying mechanism they reflect may also determine vaccination outcome. Thus, baseline signatures might contribute to identifying interventional targets to be modulated prior to vaccination in order to improve vaccination responses. This concept has the potential to transform vaccination strategies and usher in a new approach to improve global health. |
19 | 5kffoext | what type of hand sanitizer is needed to destroy Covid-19? | Evaluation of the Antiviral Potential of Halogenated Dihydrorugosaflavonoids and Molecular Modeling with nsP3 Protein of Chikungunya Virus (CHIKV) [Image: see text] Antiviral therapy is crucial for the circumvention of viral epidemics. The unavailability of a specific antiviral drug against the chikungunya virus (CHIKV) disease has created an alarming situation to identify or develop potent chemical molecules for remedial management of CHIKV. In the present investigation, in silico studies of dihydrorugosaflavonoid derivatives (5a–f) with non-structural protein-3 (nsP3) were carried out. nsP3 replication protein has recently been considered as a possible antiviral target in which crucial inhibitors fit into the adenosine-binding pocket of the macrodomain. The 4′-halogenated dihydrorugosaflavonoids displayed intrinsic binding with the nsp3 macrodomain (PDB ID: 3GPO) of CHIKV. Compounds 5c and 5d showed docking scores of −7.54 and −6.86 kcal mol(–1), respectively. Various in vitro assays were performed to confirm their (5a–f) antiviral potential against CHIKV. The non-cytotoxic dose was determined by 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide assay and was found to be <100 μM. The compounds 5c and 5d showed their inhibitory potential for CHIKV, which was determined through cytopathic effect assay and plaque reduction assay, which show inhibition up to 95 and 92% for 70 μM concentration of the compounds, respectively. The quantitative real-time polymerase chain reaction assay result confirmed the ability of 5c and 5d to reduce the viral RNA level at 70 μM concentration of compounds to nearly 95 and 93% concentration, respectively, in cells with CHIKV infection. Further, the CHIKV-inhibitory capacity of these compounds was corroborated by execution of immunofluorescence assay. The executed work will be meaningful for the future research of studied dihydrorugosaflavonoids against prime antiviral entrants, leading to remedial management to preclude CHIKV infection. |
26 | 662pfa61 | what are the initial symptoms of Covid-19? | Nelfinavir inhibits replication of severe acute respiratory syndrome coronavirus 2 in vitro In December 2019, severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) emerged in Wuhan, Hubei Province, China. No specific treatment has been established against coronavirus disease-2019 (COVID-19) so far. Therefore, it is urgently needed to identify effective antiviral agents for the treatment of this disease, and several approved drugs such as lopinavir have been evaluated. Here, we report that nelfinavir, an HIV-1 protease inhibitor, potently inhibits replication of SARS-CoV-2. The effective concentrations for 50% and 90% inhibition (EC50 and EC90) of nelfinavir were 1.13 µM and 1.76 µM respectively, the lowest of the nine HIV-1 protease inhibitors including lopinavir. The trough and peak serum concentrations of nelfinavir were three to six times higher than EC50 of this drug. These results suggest that nelfinavir is a potential candidate drug for the treatment of COVID-19 and should be assessed in patients with COVID-19. |
3 | smjgnkr3 | will SARS-CoV2 infected people develop immunity? Is cross protection possible? | Managing Cutaneous Immune-Mediated Diseases During the COVID-19 Pandemic Coronavirus disease 2019 (COVID-19) is a clinical syndrome caused by a novel coronavirus called severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). COVID-19 has spread rapidly worldwide and has been shown to have a wide spectrum of severity. COVID-19 has become a public health emergency of relevant international concern, and it was declared a pandemic by the World Health Organization on 11 March, 2020. SARS-CoV-2 infection in severe cases involves the host response as an important contributor to the disease process and tissue damage, mainly due to dysregulated and excessive innate immune responses. The primary immune response leads to viral clearance in the majority of cases. However, in a subgroup of patients, the secondary immune response may be exaggerated, leading to inflammatory-induced lung injury and other complications including pneumonitis, acute respiratory distress syndrome, respiratory failure, shock, organ failure, and potentially death. Several cutaneous immune-mediated diseases, including psoriasis, atopic dermatitis, and hidradenitis suppurativa, are therapeutically managed with biologic and non-biologic immunosuppressive and immunomodulatory drugs. The outbreak of COVID-19 affects the management of these chronic conditions, not only for those who are already receiving treatment but also for those who are about to start a new treatment to control their disease. In this article, the management of cutaneous immune-mediated diseases during the COVID-19 pandemic is discussed. |
27 | s0wmll4q | what is known about those infected with Covid-19 but are asymptomatic? | Cryo-EM structure of infectious bronchitis coronavirus spike protein reveals structural and functional evolution of coronavirus spike proteins As cell-invading molecular machinery, coronavirus spike proteins pose an evolutionary conundrum due to their high divergence. In this study, we determined the cryo-EM structure of avian infectious bronchitis coronavirus (IBV) spike protein from the γ-genus. The trimeric IBV spike ectodomain contains three receptor-binding S1 heads and a trimeric membrane-fusion S2 stalk. While IBV S2 is structurally similar to those from the other genera, IBV S1 possesses structural features that are unique to different other genera, thereby bridging these diverse spikes into an evolutionary spectrum. Specifically, among different genera, the two domains of S1, the N-terminal domain (S1-NTD) and C-terminal domain (S1-CTD), diverge from simpler tertiary structures and quaternary packing to more complex ones, leading to different functions of the spikes in receptor usage and membrane fusion. Based on the above structural and functional comparisons, we propose that the evolutionary spectrum of coronavirus spikes follows the order of α-, δ-, γ-, and β-genus. This study has provided insight into the evolutionary relationships among coronavirus spikes and deepened our understanding of their structural and functional diversity. |
21 | y5y4dbm1 | what are the mortality rates overall and in specific populations | Evaluating the virucidal efficacy of hydrogen peroxide vapour Summary Background Surface contamination has been implicated in the transmission of certain viruses, and surface disinfection can be an effective measure to interrupt the spread of these agents. Aim To evaluate the in-vitro efficacy of hydrogen peroxide vapour (HPV), a vapour-phase disinfection method, for the inactivation of a number of structurally distinct viruses of importance in the healthcare, veterinary and public sectors. The viruses studied were: feline calicivirus (FCV, a norovirus surrogate); human adenovirus type 1; transmissible gastroenteritis coronavirus of pigs (TGEV, a severe acute respiratory syndrome coronavirus [SARS-CoV] surrogate); avian influenza virus (AIV); and swine influenza virus (SwIV). Methods The viruses were dried on stainless steel discs in 20- or 40-μL aliquots and exposed to HPV produced by a Clarus L generator (Bioquell, Horsham, PA, USA) in a 0.2-m3 environmental chamber. Three vaporized volumes of hydrogen peroxide were tested in triplicate for each virus: 25, 27 and 33mL. Findings No viable viruses were identified after HPV exposure at any of the vaporized volumes tested. HPV was virucidal (>4-log reduction) against FCV, adenovirus, TGEV and AIV at the lowest vaporized volume tested (25mL). For SwIV, due to low virus titre on the control discs, >3.8-log reduction was shown for the 25-mL vaporized volume and >4-log reduction was shown for the 27-mL and 33-mL vaporized volumes. Conclusion HPV was virucidal for structurally distinct viruses dried on surfaces, suggesting that HPV can be considered for the disinfection of virus-contaminated surfaces. |
13 | ssnvr6nj | what are the transmission routes of coronavirus? | Identification of New Respiratory Viruses in the New Millennium The rapid advancement of molecular tools in the past 15 years has allowed for the retrospective discovery of several new respiratory viruses as well as the characterization of novel emergent strains. The inability to characterize the etiological origins of respiratory conditions, particularly in children, led several researchers to pursue the discovery of the underlying etiology of disease. In 2001, this led to the discovery of human metapneumovirus (hMPV) and soon following that the outbreak of Severe Acute Respiratory Syndrome coronavirus (SARS-CoV) promoted an increased interest in coronavirology and the latter discovery of human coronavirus (HCoV) NL63 and HCoV-HKU1. Human bocavirus, with its four separate lineages, discovered in 2005, has been linked to acute respiratory tract infections and gastrointestinal complications. Middle East Respiratory Syndrome coronavirus (MERS-CoV) represents the most recent outbreak of a completely novel respiratory virus, which occurred in Saudi Arabia in 2012 and presents a significant threat to human health. This review will detail the most current clinical and epidemiological findings to all respiratory viruses discovered since 2001. |
4 | tpic8ddl | what causes death from Covid-19? | Convalescent plasma or hyperimmune immunoglobulin for people with COVID-19: a rapid review. BACKGROUND Convalescent plasma and hyperimmune immunoglobulin may reduce mortality in patients with respiratory virus diseases, and are currently being investigated in trials as a potential therapy for coronavirus disease 2019 (COVID-19). A thorough understanding of the current body of evidence regarding the benefits and risks is required. OBJECTIVES: To assess whether convalescent plasma or hyperimmune immunoglobulin transfusion is effective and safe in the treatment of people with COVID-19. SEARCH METHODS The protocol was pre-published with the Center for Open Science and can be accessed here: osf.io/dwf53 We searched the World Health Organization (WHO) COVID-19 Global Research Database, MEDLINE, Embase, Cochrane COVID-19 Study Register, Centers for Disease Control and Prevention COVID-19 Research Article Database and trials registries to identify ongoing studies and results of completed studies on 23 April 2020 for case-series, cohort, prospectively planned, and randomised controlled trials (RCTs). SELECTION CRITERIA We followed standard Cochrane methodology and performed all steps regarding study selection in duplicate by two independent review authors (in contrast to the recommendations of the Cochrane Rapid Reviews Methods Group). We included studies evaluating convalescent plasma or hyperimmune immunoglobulin for people with COVID-19, irrespective of disease severity, age, gender or ethnicity. We excluded studies including populations with other coronavirus diseases (severe acute respiratory syndrome (SARS) or Middle East respiratory syndrome (MERS)) and studies evaluating standard immunoglobulins. DATA COLLECTION AND ANALYSIS We followed recommendations of the Cochrane Rapid Reviews Methods Group regarding data extraction and assessment. To assess bias in included studies, we used the assessment criteria tool for observational studies, provided by Cochrane Childhood Cancer. We rated the certainty of evidence using the GRADE approach for the following outcomes: all-cause mortality at hospital discharge, improvement of clinical symptoms (7, 15, and 30 days after transfusion), grade 3 and 4 adverse events, and serious adverse events. MAIN RESULTS: We included eight studies (seven case-series, one prospectively planned, single-arm intervention study) with 32 participants, and identified a further 48 ongoing studies evaluating convalescent plasma (47 studies) or hyperimmune immunoglobulin (one study), of which 22 are randomised. Overall risk of bias of the eight included studies was high, due to: study design; small number of participants; poor reporting within studies; and varied type of participants with different severities of disease, comorbidities, and types of previous or concurrent treatments, including antivirals, antifungals or antibiotics, corticosteroids, hydroxychloroquine and respiratory support. We rated all outcomes as very low certainty, and we were unable to summarise numerical data in any meaningful way. As we identified case-series studies only, we reported results narratively. Effectiveness of convalescent plasma for people with COVID-19 The following reported outcomes could all be related to the underlying natural history of the disease or other concomitant treatment, rather than convalescent plasma. All-cause mortality at hospital discharge All studies reported mortality. All participants were alive at the end of the reporting period, but not all participants had been discharged from hospital by the end of the study (15 participants discharged, 6 still hospitalised, 11 unclear). Follow-up ranged from 3 days to 37 days post-transfusion. We do not know whether convalescent plasma therapy affects mortality (very low-certainty evidence). Improvement of clinical symptoms (assessed by respiratory support) Six studies, including 28 participants, reported the level of respiratory support required; most participants required respiratory support at baseline. All studies reported improvement in clinical symptoms in at least some participants. We do not know whether convalescent plasma improves clinical symptoms (very low-certainty evidence). Time to discharge from hospital Six studies reported time to discharge from hospital for at least some participants, which ranged from four to 35 days after convalescent plasma therapy. Admission on the intensive care unit (ICU) Six studies included patients who were critically ill. At final follow-up the majority of these patients were no longer on the ICU or no longer required mechanical ventilation. Length of stay on the ICU Only one study (1 participant) reported length of stay on the ICU. The individual was discharged from the ICU 11 days after plasma transfusion. Safety of convalescent plasma for people with COVID-19 Grade 3 or 4 adverse events The studies did not report the grade of adverse events after convalescent plasma transfusion. Two studies reported data relating to participants who had experienced adverse events, that were presumably grade 3 or 4. One case study reported a participant who had moderate fever (38.9 °C). Another study (3 participants) reported a case of severe anaphylactic shock. Four studies reported the absence of moderate or severe adverse events (19 participants). We are very uncertain whether or not convalescent plasma therapy affects the risk of moderate to severe adverse events (very low-certainty evidence). Serious adverse events One study (3 participants) reported one serious adverse event. As described above, this individual had severe anaphylactic shock after receiving convalescent plasma. Six studies reported that no serious adverse events occurred. We are very uncertain whether or not convalescent plasma therapy affects the risk of serious adverse events (very low-certainty evidence). AUTHORS' CONCLUSIONS: We identified eight studies (seven case-series and one prospectively planned single-arm intervention study) with a total of 32 participants (range 1 to 10). Most studies assessed the risks of the intervention; reporting two adverse events (potentially grade 3 or 4), one of which was a serious adverse event. We are very uncertain whether convalescent plasma is effective for people admitted to hospital with COVID-19 as studies reported results inconsistently, making it difficult to compare results and to draw conclusions. We identified very low-certainty evidence on the effectiveness and safety of convalescent plasma therapy for people with COVID-19; all studies were at high risk of bias and reporting quality was low. No RCTs or controlled non-randomised studies evaluating benefits and harms of convalescent plasma have been completed. There are 47 ongoing studies evaluating convalescent plasma, of which 22 are RCTs, and one trial evaluating hyperimmune immunoglobulin. We will update this review as a living systematic review, based on monthly searches in the above mentioned databases and registries. These updates are likely to show different results to those reported here. |
11 | 0kss5r7u | what are the guidelines for triaging patients infected with coronavirus? | Suspected myocardial injury in patients with COVID-19: Evidence from front-line clinical observation in Wuhan, China Abstract Background A novel coronavirus disease (COVID-19) in Wuhan has caused an outbreak and become a major public health issue in China and great concern from international community. Myocarditis and myocardial injury were suspected and may even be considered as one of the leading causes for death of COVID-19 patients. Therefore, we focused on the condition of the heart, and sought to provide firsthand evidence for whether myocarditis and myocardial injury were caused by COVID-19. Methods We enrolled patients with confirmed diagnosis of COVID-19 retrospectively and collected heart-related clinical data, mainly including cardiac imaging findings, laboratory results and clinical outcomes. Serial tests of cardiac markers were traced for the analysis of potential myocardial injury/myocarditis. Results 112 COVID-19 patients were enrolled in our study. There was evidence of myocardial injury in COVID-19 patients and 14 (12.5%) patients had presented abnormalities similar to myocarditis. Most of patients had normal levels of troponin at admission, that in 42 (37.5%) patients increased during hospitalization, especially in those that died. Troponin levels were significantly increased in the week preceding the death. 15 (13.4%) patients have presented signs of pulmonary hypertension. Typical signs of myocarditis were absent on echocardiography and electrocardiogram. Conclusions The clinical evidence in our study suggested that myocardial injury is more likely related to systemic consequences rather than direct damage by the 2019 novel coronavirus. The elevation in cardiac markers was probably due to secondary and systemic consequences and can be considered as the warning sign for recent adverse clinical outcomes of the patients. |
43 | olo2ildg | How has the COVID-19 pandemic impacted violence in society, including violent crimes? | Considerations for pharmacoepidemiological analyses in the SARS-CoV-2 pandemic. The coronavirus disease 2019 (COVID-19) pandemic has triggered several hypotheses regarding use of specific medicines and risk of infection as well as prognosis. Under these unique circumstances, rapid answers require quick engagement in data collection and analyses, however, appropriate design and conduct of pharmacoepidemiologic studies is needed to generate valid and reliable evidence. In this paper, endorsed by the International Society for Pharmacoepidemiology, we provide methodological considerations for the conduct of pharmacoepidemiological studies in relation to the pandemic across eight domains: (1) timeliness of evidence, including the need to prioritize some questions over others in the acute phase of the pandemic; (2) the need to align observational and interventional research on efficacy; (3) the specific challenges related to 'real-time epidemiology' during an ongoing pandemic; (4) what design to use to answer a specific question; (5) considerations on the definition of exposures; (6) what covariates to collect; (7) considerations on the definition of outcomes; and (8) the need for transparent reporting. This article is protected by copyright. All rights reserved. |
19 | alo15byi | what type of hand sanitizer is needed to destroy Covid-19? | Recommendations for the prevention of transmission of SARS during GI endoscopy |
23 | 7kw9lws0 | what kinds of complications related to COVID-19 are associated with hypertension? | Comorbidities in COVID-19: Outcomes in hypertensive cohort and controversies with renin angiotensin system blockers Abstract Background and aims COVID-19 is already a pandemic. Emerging data suggest an increased association and a heightened mortality in patients of COVID-19 with comorbidities. We aimed to evaluate the outcome in hypertensive patients with COVID-19 and its relation to the use of renin-angiotensin system blockers (RASB). Methods We have systematically searched the medical database up to March 27, 2020 and retrieved all the published articles in English language related to our topic using MeSH key words. Results From the pooled data of all ten available Chinese studies (n = 2209) that have reported the characteristics of comorbidities in patients with COVID-19, hypertension was present in nearly 21%, followed by diabetes in nearly 11%, and established cardiovascular disease (CVD) in approximately 7% of patients. Although the emerging data hints to an increase in mortality in COVID-19 patients with known hypertension, diabetes and CVD, it should be noted that it was not adjusted for multiple confounding factors. Harm or benefit in COVID-19 patients receiving RASB has not been typically assessed in these studies yet, although mechanistically and plausibly both, benefit and harm is possible with these agents, given that COVID-19 expresses to tissues through the receptor of angiotensin converting enzyme-2. Conclusion Special attention is definitely required in patients with COVID-19 with associated comorbidities including hypertension, diabetes and established CVD. Although the role of RASB has a mechanistic equipoise, patients with COVID-19 should not stop these drugs at this point of time, as recommended by various world organizations and without the advice of health care provider. |
1 | 5217c3jn | what is the origin of COVID-19 | Covid-19: UK budget gives £94 a week statutory sick pay to self-isolators and their carers |
4 | o35ff4zc | what causes death from Covid-19? | Flourishing Being part of, or witnessing, a terrible disaster is clearly very distressing. How do we minimize this kind of distress and continue to flourish in the future as we face extreme climate events such as wildfires and flooding? How do we identify and learn from past events lying hidden, unrecognized and unforeseen as failure incubated? What are the global 'grand challenges'—both natural and man-made? What are the UN Sustainable Development Goals? To achieve them do we need to reverse the fragmentation of the professions into 'silos'? What is 'joined-up' thinking in 'joined-up' organisations and nation states and how important is it? Despite all the advances in science, we know less actually than we think we know. Contingency planning that expects surprises must be the new norm. Learn anew how to learn together is the new wisdom. Use the golden rule 'do not do to others that you would not have them do to you', whatever you are told to believe, is our tenet. Behaviour is more important than belief—imperfect doing is better than uncertain knowing. But to do all of this collectively requires leadership that we can trust—perhaps the biggest challenge of all? |
26 | uqsjl4re | what are the initial symptoms of Covid-19? | Characteristics of registered clinical trials assessing treatments for COVID-19: a cross-sectional analysis OBJECTIVES: The coronavirus disease 2019 (COVID-19) pandemic has prompted many initiatives to identify safe and efficacious treatments, yet little is known regarding where early efforts have focused. We aimed to characterise registered clinical trials assessing drugs or plasma treatments for COVID-19. DESIGN, SETTING AND PARTICIPANTS: Cross-sectional analysis of clinical trials for the treatment of COVID-19 that were registered in the USA or in countries contributing to the WHO's International Clinical Trials Registry Platform. Relevant trial entries of drugs or plasma were downloaded on 26 March 2020, deduplicated, verified with reviews of major medical journals and WHO websites and independently analysed by two reviewers. MAIN OUTCOME(S): Trial intervention, sponsorship, critical design elements and specified outcomes RESULTS: Overall, 201 clinical trials were registered for testing the therapeutic benefits of 92 drugs or plasma, including 64 in monotherapy and 28 different combinations. Only eight (8.7%) products or combinations involved new molecular entities. The other test therapies had a wide range of prior medical uses, including as antivirals, antimalarials, immunosuppressants and oncology treatments. In 152 trials (75.7%), patients were randomised to treatment or comparator, including 55 trials with some form of blinding and 97 open-label studies. The 49 (24.4%) of trials without a randomised design included 29 single armed studies and 20 trials with some comparison group. Most trial designs featured multiple endpoints. Clinical endpoints were identified in 134 (66.7%) of trials and included COVID-19 symptoms, death, recovery, required intensive care and hospital discharge. Clinical scales were being used in 33 (16.4%) trials, most often measures of oxygenation and critical illness. Surrogate endpoints or biomarkers were studied in 88 (42.3%) of trials, primarily assays of viral load. Although the trials were initiated in more than 17 countries or regions, 100 (49.8%) were registered in China and 78 (37.8%) in the USA. Registered trials increased rapidly, with the number of registered trials doubling from 1 March to 26 March 2020. CONCLUSIONS: While accelerating morbidity and mortality from the COVID-19 pandemic has been paralleled by early and rapid clinical investigation, many trials lack features to optimise their scientific value. Global coordination and increased funding of high-quality research may help to maximise scientific progress in rapidly discovering safe and effective treatments. |
47 | sbfk60wy | what are the health outcomes for children who contract COVID-19? | Coronavirus disease 2019 (COVID-19) in children: a systematic review of imaging findings BACKGROUND: COVID-19 is a novel coronavirus infection that can cause a severe respiratory illness and has been declared a pandemic by the World Health Organization (WHO). Because children appear to be less severely affected than adults, their imaging appearances have not been extensively reported. OBJECTIVE: To systematically review available literature regarding imaging findings in paediatric cases of COVID-19. MATERIALS AND METHODS: We searched four databases (Medline, Embase, Cochrane, Google Scholar) for articles describing imaging findings in children with COVID-19. We included all modalities, age <18 years, and foreign language articles, using descriptive statistics to identify patterns and locations of imaging findings, and their association with outcomes. RESULTS: Twenty-two articles were included, reporting chest imaging findings in 431 children, of whom 421 (97.7%) underwent CT. Criteria for imaging were lacking. At diagnosis, 143/421 (34.0%) had a normal CT. Abnormalities were more common in the lower lobes and were predominantly unilateral. The most common imaging pattern was ground-glass opacification (159/255, 62.4%). None of the studies described lymphadenopathy, while pleural effusions were rare (three cases). Improvement at follow-up CT imaging (3-15 days later) was seen in 29/100 (29%), remained normal in 25/100 (25%) and progressed in 9/100 (9%). CONCLUSION: CT chest findings in children with COVID-19 are frequently normal or mild. Lower lobes are predominantly affected by patchy ground-glass opacification. Appearances at follow-up remain normal or improve in the majority of children. Chest CT imaging adds little to the further management of the patient and should be reserved for severe cases or for identifying alternative diagnoses. |
48 | 6n29eryp | what are the benefits and risks of re-opening schools in the midst of the COVID-19 pandemic? | Psychiatric symptoms, risk, and protective factors among university students in quarantine during the COVID-19 pandemic in China This study investigated psychiatric symptoms (depression, anxiety, and traumatic stress) during state-enforced quarantine among university students in China. We conducted a cross-sectional survey with 1,912 university students during March and April 2020. Psychiatric symptoms in the mild or higher range based on clinical cut-offs were alarmingly prevalent: 67.05% reported traumatic stress symptoms, 46.55% had depressive symptoms, and 34.73% reported anxiety symptoms. Further, 19.56% endorsed some degree of suicidal ideation. We explored factors that may contribute to poor psychological health as well as those that may function as protective factors. Risk and protective factors examined included demographic variables, two known protective factors for mental health (mindfulness, perceived social support), four COVID-specific factors (COVID-19 related efficacy, perceived COVID-19 threat, perceived COVID-19 societal stigma, COVID-19 prosocial behavior) and screen media usage. Across psychiatric symptom domains, mindfulness was associated with lower symptom severity, while COVID-19 related financial stress, perceived COVID-19 societal stigma, and perceived COVID-19 threat were associated with higher symptom severity. COVID-19 threat and COVID-19 stigma showed main and interactive effects in predicting all mental health outcomes, with their combination associated with highest symptom severity. Average screen media device usage was 6 hours and usage was positively associated with depression. Female gender and COVID-19 prosocial behavior were associated with higher anxiety, while COVID-19 self-efficacy associated with lower anxiety symptoms. Study limitations and implications for treatment and prevention of affective disorders during crisis are discussed. |
5 | mghgvr76 | what drugs have been active against SARS-CoV or SARS-CoV-2 in animal studies? | Adenoviral expression of a truncated S1 subunit of SARS-CoV spike protein results in specific humoral immune responses against SARS-CoV in rats Abstract The causative agent of severe acute respiratory syndrome (SARS) has been identified as SARS-associated coronavirus (SARS-CoV), but the prophylactic treatment of SARS-CoV is still under investigation. We constructed a recombinant adenovirus containing a truncated N-terminal fragment of the SARS-CoV Spike (S) gene (from −45 to 1469, designated Ad-SN), which encoded a truncated S protein (490 amino-acid residues, a part of 672 amino-acid S1 subunit), and investigated whether this construct could induce effective immunity against SARS-CoV in Wistar rats. Rats were immunized either subcutaneously or intranasally with Ad-SN once a week for three consecutive weeks. Our results showed that all of the immunized animals generated humoral immunity against the SARS-CoV spike protein, and the sera of immunized rats showed strong capable of protecting from SARS-CoV infection in vitro. Histopathological examination did not find evident side effects in the immunized animals. These results indicate that an adenoviral-based vaccine carrying an N-terminal fragment of the Spike gene is able to elicit strong SARS-CoV-specific humoral immune responses in rats, and may be useful for the development of a protective vaccine against SARS-CoV infection. |
9 | 4ihv80au | how has COVID-19 affected Canada | Strong evolutionary convergence of receptor-binding protein spike between COVID-19 and SARS-related coronaviruses Coronavirus Disease 2019 (COVID-19) and severe acute respiratory syndrome (SARS)-related coronaviruses (e.g., 2019-nCoV and SARS-CoV) are phylogenetically distantly related, but both are capable of infecting human hosts via the same receptor, angiotensin-converting enzyme 2, and cause similar clinical and pathological features, suggesting their phenotypic convergence. Yet, the molecular basis that underlies their phenotypic convergence remains unknown. Here, we used a recently developed molecular phyloecological approach to examine the molecular basis leading to their phenotypic convergence. Our genome-level analyses show that the spike protein, which is responsible for receptor binding, has undergone significant Darwinian selection along the branches related to 2019-nCoV and SARS-CoV. Further examination shows an unusually high proportion of evolutionary convergent amino acid sites in the receptor binding domain (RBD) of the spike protein between COVID-19 and SARS-related CoV clades, leading to the phylogenetic uniting of their RBD protein sequences. In addition to the spike protein, we also find the evolutionary convergence of its partner protein, ORF3a, suggesting their possible co-evolutionary convergence. Our results demonstrate a strong adaptive evolutionary convergence between COVID-19 and SARS-related CoV, possibly facilitating their adaptation to similar or identical receptors. Finally, it should be noted that many observed bat SARS-like CoVs that have an evolutionary convergent RBD sequence with 2019-nCoV and SARS-CoV may be pre-adapted to human host receptor ACE2, and hence would be potential new coronavirus sources to infect humans in the future. |
43 | a25elc4a | How has the COVID-19 pandemic impacted violence in society, including violent crimes? | Beijing's Hard and Soft Repression in Hong Kong Hong Kong's new Police Commissioner Chris Tang announced in Beijing on December 7, 2019, that he would use "both hard and soft approaches" to end the anti-government protests. This article argues that such "approaches" amount to physical and non-physical repression—hard power, but employed by Hong Kong, rather than mainland, forces, combined with sharp power exercised by both Beijing and the local authorities. These measures are responses to the limits on what Beijing can do under the "one country, two systems" model. As Beijing cannot send the People's Liberation Army (PLA), it has subverted Hong Kong's once-respected civilian police force to act like the mainland's public security. And as Hong Kong's judiciary is relatively autonomous and many of the arrested would not be convicted or sentenced, the police have resorted to a decapacitation campaign to inflict direct violence on protesters. Moreover, as the city's freedom has allowed the public to support protesters in various ways, Beijing has launched a program of dismissal of pro-democracy individuals in both public and private sectors. To zoom in on Beijing's hard and soft repression, this article examines in closer detail the other "frontliners" at protest sites who provide professional services vital to the sustainability of protests: medics, firefighters, lawyers, journalists, and educators. |
41 | dhkvh45t | What are the impacts of COVID-19 among African-Americans that differ from the rest of the U.S. population? | Increased serum aminotransferase activity and clinical outcomes in Coronavirus disease 2019 OBJECTIVE: Elevation of hepatic aminotransferases (aspartate aminotransferase [AST]/alanine aminotransferase [ALT]) is commonly noted among COVID-19 patients. It is unclear if they can predict the clinical outcomes among hospitalized COVID-19 patients. We aim to assess if elevations in AST/ALT were associated with poor outcomes in hospitalized COVID-19 patients. METHODS: We retrospectively evaluated hospitalized COVID-19 patients with clinically significant elevated aminotransferases (defined as >2 times upper limit of normal) and compared them with COVID-19 patients without an elevation in aminotransferases. RESULTS: The prevalence of elevation in AST/ALT was found to be 13.7% (20/145). The two groups were similar in baseline demographics, comorbidities, and the majority of laboratory tests. There was no difference in the mortality (50% vs. 36.8%, P=0.32) and median hospital stay (7 days vs. 7 days, P=0.78). However, there was a statistically significant increase in the rates of mechanical ventilation among elevated aminotransferases group compared to individuals without elevation (50% vs. 24%, P= 0.028). However, this difference was not observed after adjusting for inflammatory markers such as ferritin, lactate dehydrogenase (LDH), and lactic acid levels. CONCLUSION: Elevated aminotransferases among hospitalized COVID-19 patients is associated with higher rates of mechanical ventilation, but did not achieve statistical significance after controlling for inflammatory markers. Also, patients with elevated aminotransferases did not have higher rates of mortality or prolonged length of stay. |
5 | ei3kkp30 | what drugs have been active against SARS-CoV or SARS-CoV-2 in animal studies? | Arbidol: A potential antiviral drug for the treatment of SARS-CoV-2 by blocking the trimerization of viral spike glycoprotein ? Abstract The SARS-CoV-2 pandemic is an urgent global public health emergency and warrants investigating studies on bonafide antivirals for combat. Here we report the drug target and mechanism of action of potential antiviral drug Arbidol for SARS-CoV-2 infections. Our structural and molecular dynamics studies show how Arbidol targets the SARS-CoV-2 spike glycoprotein and impede the trimerization of spike glycoprotein, which is a key for host cell adhesion and hijacking, thus placing Arbidol as a potential drug for repurposing. This study also abets in the development of other new therapeutics for COIVD-19 disease based on Arbidol binding mode and using structure-guided drug designing. |
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