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5 | yvsyo4l9 | what drugs have been active against SARS-CoV or SARS-CoV-2 in animal studies? | SARS Abstract Severe acute respiratory syndrome (SARS) emerged in southern China in late 2002. It first spread within Guangdong Province and then to other parts of China. Via air travelers, it quickly reached various countries around the globe, causing several major hospital outbreaks. Within weeks, the causative agent, a previously unknown coronavirus (SARS-CoV), was identified, thanks to an unprecedented international effort led by the World Health Organization (WHO). Its origin was quickly traced to wild animals traded locally for culinary purposes. Masked palm civet and some other species seem to have acted as intermediate hosts. Since then, SARS-like coronaviruses were found in different bat species in China and elsewhere, and bats are now regarded as the wildlife reservoir for SARS-CoV. Fortunately, the SARS outbreak could be contained within months. Until July 2003, it had caused 8096 cases, with 774 deaths. Once adequate measures such as isolating patients and quarantining their contacts were strictly adhered to, further transmission between human beings could be interrupted. SARS is an example of how rapidly an infectious agent can spread in the modern world. At the same time, it should serve as a showcase of how international cooperation and modern science can help to combat the spread of infectious diseases. |
14 | ti4b03lh | what evidence is there related to COVID-19 super spreaders | SARS Coronavirus and Lung Fibrosis Severe acute respiratory syndrome (SARS) is an acute infectious disease with significant mortality. A novel coronavirus (SARS-CoV) has been shown to be the causative agent of SARS. The typical clinical feature associated with SARS is diffuse alveolar damage in lung, and lung fibrosis is evident in patients who died from this disease. The mechanisms by which SARS-CoV infection causes lung fibrosis are not fully understood, but transforming growth factor-β (TGF-β) and angiotensin-converting enzyme 2 (ACE2)-mediated lung fibrosis are among the most documented ones. The activation of the TGF-β/Smad pathway is critical to lung fibrosis. SARS-CoV infection not only enhances the expression of TGF-β, but also facilitates its signaling activity. The SARS-CoV receptor ACE2 is a negative regulator of lung fibrosis, and SARS-CoV infection decreases ACE2 expression. Therefore, SARS-CoV infection may lead to lung fibrosis through multiple signaling pathways and TGF-β activation is one of the major contributors. |
4 | gm1mb8w5 | what causes death from Covid-19? | Generic probabilistic modelling and non-homogeneity issues for the UK epidemic of COVID-19 Coronavirus COVID-19 spreads through the population mostly based on social contact. To gauge the potential for widespread contagion, to cope with associated uncertainty and to inform its mitigation, more accurate and robust modelling is centrally important for policy making. We provide a flexible modelling approach that increases the accuracy with which insights can be made. We use this to analyse different scenarios relevant to the COVID-19 situation in the UK. We present a stochastic model that captures the inherently probabilistic nature of contagion between population members. The computational nature of our model means that spatial constraints (e.g., communities and regions), the susceptibility of different age groups and other factors such as medical pre-histories can be incorporated with ease. We analyse different possible scenarios of the COVID-19 situation in the UK. Our model is robust to small changes in the parameters and is flexible in being able to deal with different scenarios. This approach goes beyond the convention of representing the spread of an epidemic through a fixed cycle of susceptibility, infection and recovery (SIR). It is important to emphasise that standard SIR-type models, unlike our model, are not flexible enough and are also not stochastic and hence should be used with extreme caution. Our model allows both heterogeneity and inherent uncertainty to be incorporated. Due to the scarcity of verified data, we draw insights by calibrating our model using parameters from other relevant sources, including agreement on average (mean field) with parameters in SIR-based models. We use the model to assess parameter sensitivity for a number of key variables that characterise the COVID-19 epidemic. We also test several control parameters with respect to their influence on the severity of the outbreak. Our analysis shows that due to inclusion of spatial heterogeneity in the population and the asynchronous timing of the epidemic across different areas, the severity of the epidemic might be lower than expected from other models. We find that one of the most crucial control parameters that may significantly reduce the severity of the epidemic is the degree of separation of vulnerable people and people aged 70 years and over, but note also that isolation of other groups has an effect on the severity of the epidemic. It is important to remember that models are there to advise and not to replace reality, and that any action should be coordinated and approved by public health experts with experience in dealing with epidemics. The computational approach makes it possible for further extensive scenario-based analysis to be undertaken. This and a comprehensive study of sensitivity of the model to different parameters defining COVID-19 and its development will be the subject of our forthcoming paper. In that paper, we shall also extend the model where we will consider different probabilistic scenarios for infected people with mild and severe cases. |
49 | nwu4tdgh | do individuals who recover from COVID-19 show sufficient immune response, including antibody levels and T-cell mediated immunity, to prevent re-infection? | Immunologic aspects of characteristics, diagnosis, and treatment of coronavirus disease 2019 (COVID-19) On March 11, 2020, the World Health Organization declared the worldwide spread of the infectious disease COVID-19, caused by a new strain of coronavirus, SARS-CoV-2, as a pandemic. Like in all other infectious diseases, the host immune system plays a key role in our defense against SARS-CoV-2 infection. However, viruses are able to evade the immune attack and proliferate and, in susceptible individuals, cause severe inflammatory response known as cytokine storm, particularly in the lungs. The advancement in our understanding of the mechanisms underlying the host immune responses promises to facilitate the development of approaches for prevention or treatment of diseases. Components of immune system, such as antibodies, can also be used to develop sensitive and specific diagnostic methods as well as novel therapeutic agents. In this review, we summarize our knowledge about how the host mounts immune responses to infection by SARS-CoV-2. We also describe the diagnostic methods being used for COVID-19 identification and summarize the current status of various therapeutic strategies, including vaccination, being considered for treatment of the disease. |
9 | muztaqox | how has COVID-19 affected Canada | Gastrointestinal and liver manifestations in patients with COVID-19 As the outbreak of coronavirus disease 2019 (COVID-19), caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), has rapidly spread over the world, the World Health Organization has declared the outbreak of COVID-19 an international public health emergency. Besides typical respiratory symptoms and signs of COVID-19, digestive symptoms and liver injury have been frequently reported during the course of the disease. In this review, we summarized the recent studies reporting of gastrointestinal and liver manifestations during the course of COVID-19. Digestive symptoms, including anorexia, nausea, vomiting, and diarrhea, are not uncommon in patients with COVID-19, and in some cases digestive symptoms may occur in the absence of any respiratory symptoms. Furthermore, SARS-CoV-2 could be detected in the stool of infected patients, implicating the possibility of fecal–oral transmission. Attention should also be paid to monitor liver function during the course of COVID-19, especially in patients with higher disease severity. |
3 | 99ttewb5 | will SARS-CoV2 infected people develop immunity? Is cross protection possible? | Livestock infectious diseases and zoonoses. Infectious diseases of livestock are a major threat to global animal health and welfare and their effective control is crucial for agronomic health, for safeguarding and securing national and international food supplies and for alleviating rural poverty in developing countries. Some devastating livestock diseases are endemic in many parts of the world and threats from old and new pathogens continue to emerge, with changes to global climate, agricultural practices and demography presenting conditions that are especially favourable for the spread of arthropod-borne diseases into new geographical areas. Zoonotic infections that are transmissible either directly or indirectly between animals and humans are on the increase and pose significant additional threats to human health and the current pandemic status of new influenza A (H1N1) is a topical example of the challenge presented by zoonotic viruses. In this article, we provide a brief overview of some of the issues relating to infectious diseases of livestock, which will be discussed in more detail in the papers that follow. |
40 | leiuve0f | What are the observed mutations in the SARS-CoV-2 genome and how often do the mutations occur? | Isolation of active peptides from plant hydrolysates that promote Vero cells growth in stirred cultures |
38 | bq5w3jk9 | What is the mechanism of inflammatory response and pathogenesis of COVID-19 cases? | Delayed Elimination of the LCM Virus from Acid Sphingomyelinase‐Deficient Mice due to Reduced Expansion of Virus‐Specific CD8(+) T Lymphocytes The phagolysosomally localized acid sphingomyelinase (ASMase) activated by proinflammatory cytokines such as TNF and IFN‐γ generates the signalling molecule ceramide which in turn results in the activation of proteases like cathepsin D. These characteristics of ASMase suggest a possible role of this molecule in the phagocytotic uptake and phagosomal degradation processes of antigens or in antigen presentation. We show here that ASMase(–/–) mice fail to eliminate the noncytopathic lymphocytic choriomeningitis (LCM) virus as rapidly as littermate wildtype mice. Investigation of the immune response revealed a reduced expansion of CD8(+) T cells. The secretion of IFN‐γ in response to contact with target cells as well as the cytolytic activity of virus‐specific CD8(+) T cells was severely impaired. Additionally, both phases of the LCM virus‐specific DTH response, mediated by CD8(+) and CD4(+) T cells consecutively, were diminished in ASMase(–/–) mice. However, the secondary memory response of virus‐specific CTL was not altered, and the virus was effectively controlled for at least 3 months by ASMase(–/–) mice. In conclusion, the results of this study suggest an involvement of the ASMase in the activation, expansion or maturation of virus‐specific CD8(+) T cells during the acute infection of mice with the LCM virus. |
36 | 6h1mm7y8 | What is the protein structure of the SARS-CoV-2 spike? | Virus against virus: a potential treatment for 2019-nCov (SARS-CoV-2) and other RNA viruses |
41 | 2kyeiima | What are the impacts of COVID-19 among African-Americans that differ from the rest of the U.S. population? | In the shadow of HIV & TB: A commentary on the COVID epidemic in South Africa While COVID-19 has become a global pandemic that has spread to all regions of the globe, local historic, health, and socio-environmental factors shape the epidemiological contours, response, and social challenges present within each affected nation. Thus, while countries like China, Italy, Iran, Brazil, and the United States have all been hard hit by the pandemic, there are critical differences across these nations in a number of variables (e.g. demographic features, health histories, healthcare systems, infection case rates, case fatality rates, national responses). In other words, within the global pandemic there are multiple importantly distinct national epidemics. Overcoming the grave threats to public health presented by COVID-19 requires both international cooperation and country-specific efforts that reflect local histories, needs, and resources. Already concerns are being expressed among health officials about how COVID-19 might be devastating in Africa. Currently, South Africa has the highest number of diagnosed COVID-19 cases on the continent and has been identified as being at high risk in the pandemic. This paper examines the public health response to the COVID-19 threat, how the prior and ongoing HIV and TB epidemics shape the COVID-19 epidemic and influence the response, and the potential ramifications of the response. |
26 | s7b3sw74 | what are the initial symptoms of Covid-19? | COVID-19: Specific and non-specific clinical manifestations and symptoms: The current state of knowledge Coronavirus disease 2019 (COVID-19), due to the severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2), has become an epidemiological threat and a worldwide concern. SARS-CoV-2 has spread to 210 countries worldwide and more than 6,500,000 confirmed cases and 384,643 deaths have been reported, while the number of both confirmed and fatal cases is continually increasing. COVID-19 is a viral disease that can affect every age group—from infants to the elderly—resulting in a wide spectrum of various clinical manifestations. COVID-19 might present different degrees of severity—from mild or even asymptomatic carriers, even to fatal cases. The most common complications include pneumonia and acute respiratory distress syndrome. Fever, dry cough, muscle weakness, and chest pain are the most prevalent and typical symptoms of COVID-19. However, patients might also present atypical symptoms that can occur alone, which might indicate the possible SARS-CoV-2 infection. The aim of this paper is to review and summarize all of the findings regarding clinical manifestations of COVID-19 patients, which include respiratory, neurological, olfactory and gustatory, gastrointestinal, ophthalmic, dermatological, cardiac, and rheumatologic manifestations, as well as specific symptoms in pediatric patients. |
13 | zkcaeeve | what are the transmission routes of coronavirus? | Vertical Transmission of Coronavirus Disease 19 (COVID-19) from Infected Pregnant Mothers to Neonates: A Review Background: Since early December 2019, the Coronavirus Disease 19 (COVID-19) infection has been prevalent in China and eventually spread to other countries. There are a few published cases of COVID-19 occurring during pregnancy and due the possibility of mother-fetal vertical transmission, there is a concern that the fetuses may be at risk of congenital COVID-19. Methods: We reviewed the risk of vertical transmission of COVID-19 to the fetus of infected mothers by using data of published articles or official websites up to March 4, 2020. Results: A total of 31 infected pregnant mothers with COVID-19 were reported. No COVID-19 infection was detected in their neonates or placentas. Two mothers died from COVID-19-related respiratory complications after delivery. Conclusions: Currently, based on limited data, there is no evidence for intrauterine transmission of COVID-19 from infected pregnant women to their fetuses. Mothers may be at increased risk for more severe respiratory complications. |
15 | 7q5s1vu1 | how long can the coronavirus live outside the body | Environmental chemistry is most relevant to study coronavirus pandemics |
14 | mhi6w4mr | what evidence is there related to COVID-19 super spreaders | Lopinavir/ritonavir for the treatment of COVID-19: A living systematic review protocol Objective To assess the efficacy and safety of lopinavir/ritonavir for the treatment of patients with COVID-19. Design This is the protocol of a living systematic review. Data sources We will conduct searches in PubMed/Medline, Embase, Cochrane Central Register of Controlled Trials (CENTRAL), grey literature and in a centralised repository in L-OVE (Living OVerview of Evidence). L-OVE is a platform that maps PICO questions to evidence from Epistemonikos database. In response to the COVID-19 emergency, L-OVE was adapted to expand the range of evidence it covers and customised to group all COVID-19 evidence in one place. The search will cover the period until the day before submission to a journal. Eligibility criteria for selecting studies and methods We adapted an already published common protocol for multiple parallel systematic reviews to the specificities of this question. We will include randomised trials evaluating the effect of lopinavir/ritonavir - as monotherapy or in combination with other drugs - versus placebo or no treatment in patients with COVID-19. Randomised trials evaluating lopinavir/ritonavir in infections caused by other coronaviruses, such as MERS-CoV and SARS-CoV, and non-randomised studies in COVID-19 will be searched in case no direct evidence from randomised trials is found, or if the direct evidence provides low- or very low-certainty for critical outcomes. Two reviewers will independently screen each study for eligibility, extract data, and assess the risk of bias. We will perform random-effects meta-analyses and use GRADE to assess the certainty of the evidence for each outcome. A living, web-based version of this review will be openly available during the COVID-19 pandemic. We will resubmit it if the conclusions change or there are substantial updates. Ethics and dissemination No ethics approval is considered necessary. The results of this review will be widely disseminated via peer-reviewed publications, social networks and traditional media. |
50 | isivkz8b | what is known about an mRNA vaccine for the SARS-CoV-2 virus? | Targets of T cell responses to SARS-CoV-2 coronavirus in humans with COVID-19 disease and unexposed individuals Summary Understanding adaptive immunity to SARS-CoV-2 is important for vaccine development, interpreting coronavirus disease 2019 (COVID-19) pathogenesis, and calibration of pandemic control measures. Using HLA class I and II predicted peptide 'megapools', circulating SARS-CoV-2−specific CD8+ and CD4+ T cells were identified in ∼70% and 100% of COVID-19 convalescent patients, respectively. CD4+ T cell responses to spike, the main target of most vaccine efforts, were robust and correlated with the magnitude of the anti-SARS-CoV-2 IgG and IgA titers. The M, spike and N proteins each accounted for 11-27% of the total CD4+ response, with additional responses commonly targeting nsp3, nsp4, ORF3a and ORF8, among others. For CD8+ T cells, spike and M were recognized, with at least eight SARS-CoV-2 ORFs targeted. Importantly, we detected SARS-CoV-2−reactive CD4+ T cells in ∼40-60% of unexposed individuals, suggesting cross-reactive T cell recognition between circulating 'common cold' coronaviruses and SARS-CoV-2. |
16 | pgr2uz16 | how long does coronavirus remain stable on surfaces? | A new infectious disease challenge: Urbani severe acute respiratory syndrome (SARS) associated coronavirus |
13 | rmia5w3x | what are the transmission routes of coronavirus? | Clinical and pathological characteristics of 2019 novel coronavirus disease (COVID-19): a systematic review Importance: In 2002-2003, a severe pulmonary infectious disease occurred in Guangdong, China. The disease was caused by SARS-CoV, 17 years apart, also happen in China, and SARS-CoV-2, this epidemic has posed a significant hazard to people health both China and the whole world. Objective: Summarized the latest epidemiological changes, clinical manifestations, auxiliary examination and pathological characteristics of COVID-19. Evidence Review: PubMed database were searched from 2019 to 2020 using the index terms novel coronavirus or COVID-19 or 2019-nCoV or SARS-CoV-2 and synonyms. Articles that reported clinical characteristics, laboratory results, imageological diagnosis and pathologic condition were included and were retrospectively reviewed for these cases. This paper adopts the method of descriptive statistics. Results: 34 COVID-19-related articles were eligible for this systematic review;Four of the articles were related to pathology. We found that Fever (86.0%), cough (63.9%) and Malaise/Fatigue (34.7%) were the most common symptoms in COVID-19. But in general, the clinical symptoms and signs of COVID-19 were not obvious. Compared with SARS, COVID-19 was transmitted in a more diverse way. The mortality rates of COVID-19 were 2.5%, and the overall infection rate of healthcare worker of COVID-19 was 3.9%. We also found that the pathological features of COVID-19 have greatly similar with SARS, which manifested as ARDS. But the latest pathological examination of COVID-19 revealed the obvious mucinous secretions in the lungs. Interpretation: The clinical and pathological characteristics of SARS and COVID-19 in China are very similar, but also difference. The latest finds of pathological examination on COVID-19 may upend existing treatment schemes, so the early recognition of disease by healthcare worker is very important. |
3 | f03ka7bd | will SARS-CoV2 infected people develop immunity? Is cross protection possible? | A highly conserved cryptic epitope in the receptor-binding domains of SARS-CoV-2 and SARS-CoV The outbreak of COVID-19, which is caused by SARS-CoV-2 virus, continues to spread globally, but there is currently very little understanding of the epitopes on the virus. In this study, we have determined the crystal structure of the receptor-binding domain (RBD) of the SARS-CoV-2 spike (S) protein in complex with CR3022, a neutralizing antibody previously isolated from a convalescent SARS patient. CR3022 targets a highly conserved epitope that enables cross-reactive binding between SARS-CoV-2 and SARS-CoV. Structural modeling further demonstrates that the binding site can only be accessed when at least two RBDs on the trimeric S protein are in the "up" conformation. Overall, this study provides structural and molecular insight into the antigenicity of SARS-CoV-2. ONE SENTENCE SUMMARY Structural study of a cross-reactive SARS antibody reveals a conserved epitope on the SARS-CoV-2 receptor-binding domain. |
34 | cb7k2zbe | What are the longer-term complications of those who recover from COVID-19? | The cognitive consequences of the COVID-19 epidemic: collateral damage? Recovery from coronavirus disease 2019 (COVID-19) will be principally defined in terms of remission from respiratory symptoms, however both clinical and animal studies have shown that coronaviruses may spread to the nervous system. A systematic search on previous viral epidemics revealed that while there has been relatively little research in this area, clinical studies have commonly reported neurological disorders and cognitive difficulties. Little is known with regard to their incidence, duration or underlying neural basis. The hippocampus appears to be particularly vulnerable to coronavirus infections, thus increasing the probability of post-infection memory impairment, and acceleration of neurodegenerative disorders such as Alzheimer's disease. Future knowledge of the impact of COVID-19, from epidemiological studies and clinical practice, will be needed to develop future screening and treatment programmes to minimize the long-term cognitive consequences of COVID-19. |
24 | pyaualqs | what kinds of complications related to COVID-19 are associated with diabetes | State cigarette excise taxes - United States, 2009. Increasing the price of cigarettes can reduce smoking substantially by discouraging initiation among youths and young adults, prompting quit attempts, and reducing average cigarette consumption among those who continue to smoke. Increasing cigarette excise taxes is one of the most effective tobacco control policies because it directly increases cigarette prices, thereby reducing cigarette use and smoking-related death and disease. All states and the District of Columbia (DC) impose an excise tax on cigarettes. Because many states increased their cigarette excise taxes in 2009, CDC conducted a survey of these tax increases. For this report, CDC reviewed data contained in a legislative database to identify cigarette excise tax legislation that was enacted during 2009 by the 50 states and DC. During that period, 15 states (including DC), increased their state excise tax on cigarettes, increasing the national mean from $1.18 per pack in 2008 to $1.34 per pack in 2009. However, none of the 15 states dedicated any of the new excise tax revenue by statute to tobacco control. Additionally, for the first time, two states (Connecticut and Rhode Island) had excise tax rates of at least $3.00 per pack. Additional increases in cigarette excise taxes, and dedication of all resulting revenues to tobacco control and prevention programs at levels recommended by CDC, could result in further reductions in smoking and associated morbidity and mortality. |
34 | p0byamym | What are the longer-term complications of those who recover from COVID-19? | Blood Donation and Collection |
11 | 5n4zooqp | what are the guidelines for triaging patients infected with coronavirus? | Covid-19 in China: ten critical issues for intensive care medicine |
49 | emtww5ga | do individuals who recover from COVID-19 show sufficient immune response, including antibody levels and T-cell mediated immunity, to prevent re-infection? | Malaria and the HIV virus: is there any interaction? |
44 | imv1ygf6 | How much impact do masks have on preventing the spread of the COVID-19? | COVID-19 and non-traditional mask use: How do various materials compare in reducing the infection risk for mask wearers? |
36 | alrbutoy | What is the protein structure of the SARS-CoV-2 spike? | Genetic variants in TMPRSS2 and Structure of SARS-CoV-2 spike glycoprotein and TMPRSS2 complex SARS-CoV-2, a highly transmittable pathogen has infected over 3.8 million people around the globe. The spike glycoprotein of SARS-CoV-2 engages host ACE2 for adhesion, TMPRSS2 for activation and entry. With the aid of whole-exome sequencing, we report a variant rs12329760 in TMPRSS2 gene and its mutant V160M, which might impede viral entry. Furthermore, we identified TMPRSS2 cleavage sites in S2 domain of spike glycoprotein and report the structure of TMPRSS2 in complex with spike glycoprotein. We also report the structures of protease inhibitors in complex with TMPRSS2, which could hamper the interaction with spike protein. These findings advance our understanding on the role of TMPRSS2 and in the development of potential therapeutics. |
40 | npcu4wq1 | What are the observed mutations in the SARS-CoV-2 genome and how often do the mutations occur? | Comprehensive evolution and molecular characteristics of a large number of SARS-CoV-2 genomes revealed its epidemic trend and possible origins Objectives To reveal epidemic trend and possible origins of SARS-CoV-2 by exploring its evolution and molecular characteristics based on a large number of genomes since it has infected millions of people and spread quickly all over the world. Methods Various evolution analysis methods were employed. Results The estimated Ka/Ks ratio of SARS-CoV-2 is 1.008 or 1.094 based on 622 or 3624 SARS-CoV-2 genomes, and the time to the most recent common ancestor (tMRCA) was inferred in late September 2019. Further 9 key specific sites of highly linkage and four major haplotypes H1, H2, H3 and H4 were found. The Ka/Ks, detected population size and development trends of each major haplotype showed H3 and H4 subgroups were going through a purify evolution and almost disappeared after detection, indicating H3 and H4 might have existed for a long time, while H1 and H2 subgroups were going through a near neutral or neutral evolution and globally increased with time. Notably the frequency of H1 was generally high in Europe and correlated to death rate (r>0.37). Conclusions In this study, the evolution and molecular characteristics of more than 16000 genomic sequences provided a new perspective for revealing epidemiology of SARS-CoV-2. |
50 | ksva9eah | what is known about an mRNA vaccine for the SARS-CoV-2 virus? | SARS-CoV-2 Isolation and Propagation from Turkish COVID-19 patients The novel coronavirus pneumonia, which was named later as Coronavirus Disease 2019 (COVID-19), is caused by the Severe Acute Respiratory Syndrome Coronavirus 2, namely SARS-CoV-2. It is a positive-strand RNA virus that is the seventh coronavirus known to infect humans. The COVID-19 outbreak presents enormous challenges for global health behind the pandemic outbreak. The first diagnosed patient in Turkey has been reported by the Republic of Turkey Ministry of Health on March 11, 2020. Today, over ninety thousand cases in Turkey, and two million cases around the world have been declared. Due to the urgent need for vaccine and anti-viral drug, isolation of the virus is crucial. Here, we report one of the first isolation and characterization studies of SARS-CoV-2 from nasopharyngeal and oropharyngeal specimens of diagnosed patients in Turkey. This study provides an isolation and replication methodology, and cell culture tropism of the virus that will be available to the research communities. Article Summary Scientists have isolated virus from Turkish COVID-19 patients. The isolation, propagation, and plaque and immune response assays of the virus described here will serve in following drug discovery and vaccine testing. |
5 | mkfwhv6v | what drugs have been active against SARS-CoV or SARS-CoV-2 in animal studies? | A new mouse-adapted strain of SARS-CoV as a lethal model for evaluating antiviral agents in vitro and in vivo Severe acute respiratory syndrome (SARS) is a highly lethal emerging disease caused by coronavirus SARS-CoV. New lethal animal models for SARS were needed to facilitate antiviral research. We adapted and characterized a new strain of SARS-CoV (strain v2163) that was highly lethal in 5–6 week old BALB/c mice. It had nine mutations affecting 10 amino acid residues. Strain v2163 increased IL-1α, IL-6, MIP-1α, MCP-1, and RANTES in mice, and high IL-6 expression correlated with mortality. The infection largely mimicked human disease, but lung pathology lacked hyaline membrane formation. In vitro efficacy against v2163 was shown with known inhihibitors of SARS-CoV replication. In v2163-infected mice, Ampligen™ was fully protective, stinging nettle lectin (UDA) was partially protective, ribavirin was disputable and possibly exacerbated disease, and EP128533 was inactive. Ribavirin, UDA and Ampligen™ decreased IL-6 expression. Strain v2163 provided a valuable model for anti-SARS research. |
29 | kc2r034w | which SARS-CoV-2 proteins-human proteins interactions indicate potential for drug targets. Are there approved drugs that can be repurposed based on this information? | Computational target-based drug repurposing of elbasvir, an antiviral drug predicted to bind multiple SARS-CoV-2 proteins. Coronavirus disease 19 (COVID-19) is a severe acute respiratory syndrome caused by SARS-CoV-2 (2019-nCoV). While no drugs have yet been approved to treat this disease, small molecules effective against other viral infections are under clinical evaluation for therapeutic abatement of SARS-CoV-2 infections. Ongoing clinical trials include Kaletra (a combination of two protease inhibitors approved for HIV treatment), remdesivir (an investigational drug targeting RNA-dependent RNA polymerase [RdRP] of SARS-CoV-2), and hydroxychloroquine (an approved anti-malarial and immuno-modulatory drug). Since SARS-CoV-2 replication depends on three virally encoded proteins (RdRP, papain-like proteinase, and helicase), we screened 54 FDA-approved antiviral drugs and ~3300 investigational drugs for binding to these proteins using targeted and unbiased docking simulations and computational modeling. Elbasvir, a drug approved for treating hepatitis C, is predicted to bind stably and preferentially to all three proteins. At the therapeutic dosage, elbasvir has low toxicity (liver enzymes transiently elevated in 1% of subjects) and well-characterized drug-drug interactions. We predict that treatment with elbasvir, alone or in combination with other drugs such as grazoprevir, could efficiently block SARS-CoV-2 replication. The concerted action of elbasvir on at least three targets essential for viral replication renders viral mutation to drug resistance extremely unlikely. |
3 | f936bioj | will SARS-CoV2 infected people develop immunity? Is cross protection possible? | A phased lift of control: a practical strategy to achieve herd immunity against Covid-19 at the country level Most countries are affected by the Covid-19 pandemic and experience rapidly increasing numbers of cases and deaths. Many have implemented nationwide stringent control to avoid overburdening the health care system. This paralyzes economic and social activities until the availability of a vaccine, which may take years. We propose an alternative exit strategy to develop herd immunity in a predictable and controllable way: a phased lift of control. This means that successive parts of the country (e.g. provinces) stop stringent control, and Covid-19-related IC admissions are distributed over the country as the whole. Importantly, vulnerable individuals need to be shielded until herd immunity has developed in their area. We explore the characteristics and duration of this strategy using a novel individual-based model for geographically stratified transmission of Covid-19 in a country. The model predicts that individuals will have to experience stringent control for about 14 months on average, but this duration may be significantly shortened by future developments (more IC beds, better drugs). Clearly, the strategy will have a profound impact on individuals and society, and should therefore be considered carefully by various other disciplines (e.g. health systems, ethics, economics) before actual implementation. |
19 | jd2xab0m | what type of hand sanitizer is needed to destroy Covid-19? | Study of knowledge, attitude, anxiety & perceived mental healthcare need in Indian population during COVID-19 pandemic Novel Corona Virus Disease (COVID-19) originating from China has rapidly crossed borders, infecting people throughout the whole world. This phenomenon has led to a massive public reaction; the media has been reporting continuously across borders to keep all informed about the pandemic situation. All these things are creating a lot of concern for people leading to heightened levels of anxiety. Pandemics can lead to heightened levels of stress; Anxiety is a common response to any stressful situation. This study attempted to assess the knowledge, attitude, anxiety experience, and perceived mental healthcare need among adult Indian population during the COVID-19 pandemic. An online survey was conducted using a semi-structured questionnaire using a non-probability snowball sampling technique. A total of 662 responses were received. The responders had a moderate level of knowledge about the COVID-19 infection and adequate knowledge about its preventive aspects. The attitude towards COVID-19 showed peoples' willingness to follow government guidelines on quarantine and social distancing. The anxiety levels identified in the study were high. More than 80 % of the people were preoccupied with the thoughts of COVID-19 and 72 % reported the need to use gloves, and sanitizers. In this study, sleep difficulties, paranoia about acquiring COVID-19 infection and distress related social media were reported in 12.5 %, 37.8 %, and 36.4 % participants respectively. The perceived mental healthcare need was seen in more than 80 % of participants. There is a need to intensify the awareness and address the mental health issues of people during this COVID-19 pandemic. |
40 | 5tbb8df1 | What are the observed mutations in the SARS-CoV-2 genome and how often do the mutations occur? | The heterogeneous landscape and early evolution of pathogen-associated CpG dinucleotides in SARS-CoV-2 SARS-CoV-2 infection can lead to acute respiratory syndrome in patients, which can be due in part to dysregulated immune signalling. We analyze here the occurrences of CpG dinucleotides, which are putative pathogen-associated molecular patterns, along the viral sequence. Carrying out a comparative analysis with other ssRNA viruses and within the Coronaviridae family, we find the CpG content of SARS-CoV-2, while low compared to other betacoronaviruses, widely fluctuates along its primary sequence. While the CpG relative abundance and its associated CpG force parameter [1] are low for the spike protein (S) and comparable to circulating seasonal coronaviruses such as HKU1, they are much greater and comparable to SARS and MERS for the 3'-end of the viral genome. In particular, the nucleocapsid protein (N), whose transcripts are relatively abundant in the cytoplasm of infected cells and present in the 3'UTRs of all subgenomic RNA, has high CpG content. We speculate this dual nature of CpG content can confer to SARS-CoV-2 high ability to both enter the host and trigger pattern recognition receptors (PRRs) in different contexts. We then investigate the evolution of synonymous mutations since the outbreak of the COVID-19 pandemic. Using a new application of selective forces on dinucleotides to estimate context driven mutational processes, we find that synonymous mutations seem driven both by the viral codon bias and by the high value of the CpG force in the N protein, leading to a loss in CpG content. Sequence motifs preceding these CpG-loss-associated loci match recently identified binding patterns of the Zinc Finger anti-viral Protein (ZAP) protein. |
16 | g7qioapl | how long does coronavirus remain stable on surfaces? | Structural modeling of 2019-novel coronavirus (nCoV) spike protein reveals a proteolytically-sensitive activation loop as a distinguishing feature compared to SARS-CoV and related SARS-like coronaviruses The 2019 novel coronavirus (2019-nCoV) is currently causing a widespread outbreak centered on Hubei province, China and is a major public health concern. Taxonomically 2019-nCoV is closely related to SARS-CoV and SARS-related bat coronaviruses, and it appears to share a common receptor with SARS-CoV (ACE-2). Here, we perform structural modeling of the 2019-nCoV spike glycoprotein. Our data provide support for the similar receptor utilization between 2019-nCoV and SARS-CoV, despite a relatively low amino acid similarity in the receptor binding module. Compared to SARS-CoV, we identify an extended structural loop containing basic amino acids at the interface of the receptor binding (S1) and fusion (S2) domains, which we predict to be proteolytically-sensitive. We suggest this loop confers fusion activation and entry properties more in line with MERS-CoV and other coronaviruses, and that the presence of this structural loop in 2019-nCoV may affect virus stability and transmission. |
7 | 0retx7ty | are there serological tests that detect antibodies to coronavirus? | Human-animal interactions and bat coronavirus spillover potential among rural residents in Southern China Abstract Human interaction with animals has been implicated as a primary risk factor for several high impact zoonoses, including many bat-origin viral diseases. However the animal-to-human spillover events that lead to emerging diseases are rarely observed or clinically examined, and the link between specific interactions and spillover risk is poorly understood. To investigate this phenomenon, we conducted biological-behavioral surveillance among rural residents in Yunnan, Guangxi, and Guangdong districts of Southern China, where we have identified a number of SARS-related coronaviruses in bats. Serum samples were tested for four bat-borne coronaviruses using newly developed enzyme-linked immunosorbent assays (ELISA). Survey data were used to characterize associations between human-animal contact and bat coronavirus spillover risk. A total of 1,596 residents were enrolled in the study from 2015 to 2017. Nine participants (0.6%) tested positive for bat coronaviruses. 265 (17%) participants reported severe acute respiratory infections (SARI) and/or influenza-like illness (ILI) symptoms in the past year, which were associated with poultry, carnivore, rodent/shrew, or bat contact, with variability by family income and district of residence. This study provides serological evidence of bat coronavirus spillover in rural communities in Southern China. The low seroprevalence observed in this study suggests that bat coronavirus spillover is a rare event. Nonetheless, this study highlights associations between human-animal interaction and zoonotic spillover risk. These findings can be used to support targeted biological behavioral surveillance in high-risk geographic areas in order to reduce the risk of zoonotic disease emergence. |
28 | y74jbnb2 | what evidence is there for the value of hydroxychloroquine in treating Covid-19? | COVID-19 Clinical Trials: A Primer for the Cardiovascular and Cardio-Oncology Communities Abstract The COVID-19 pandemic has resulted in a proliferation of clinical trials that are designed to slow the spread of SARS-CoV-2, the virus that causes COVID-19. The overwhelming majority of cardiovascular and cancer patients are at increased risk for SARS-CoV-2 infection; accordingly, the cardiovascular and cardio-oncology communities are playing a major role in caring for COVID-19 patients. Many of the therapeutic agents that are being used to treat patients with COVID-19 are repurposed treatments for influenza, drugs that were not effective in Ebola patients, or treatments for malaria that were developed decades ago, and are unlikely to be familiar to the cardiovascular and cardio-oncology communities. Here we have provided a foundation for cardiovascular and cardio-oncology physicians who are on the frontline providing care to COVID-19 patients, so that they can better understand the emerging cardiovascular epidemiology of COVID-19, as well as the biological rationale for the clinical trials that are ongoing for the treatment of COVID-19 patients. |
32 | 9fngwsh3 | Does SARS-CoV-2 have any subtypes, and if so what are they? | Novel Coronavirus COVID-19 Strike on Arab Countries and Territories: A Situation Report I The novel Coronavirus (COVID-19) is an infectious disease caused by a new virus called COVID-19 or 2019-nCoV that first identified in Wuhan, China. The disease causes respiratory illness (such as the flu) with other symptoms such as a cough, fever, and in more severe cases, difficulty breathing. This new Coronavirus seems to be very infectious and has spread quickly and globally. In this work, information about COVID-19 is provided and the situation in Arab countries and territories regarding the COVID-19 strike is presented. The next few weeks main expectations is also given. |
50 | 19cdtkhg | what is known about an mRNA vaccine for the SARS-CoV-2 virus? | Direct High‐Throughput Screening Assay for mRNA Cap Guanine‐N7 Methyltransferase Activity In eukaryotes, mature mRNA is formed through modifications of precursor mRNA, one of which is 5′ cap biosynthesis, involving RNA cap guanine‐N7 methyltransferase (N7‐MTase). N7‐MTases are also encoded by some eukaryotic viruses and facilitate their replication. N7‐MTase inhibitors have therapeutic potential, but their discovery is difficult because long RNA substrates are usually required for activity. Herein, we report a universal N7‐MTase activity assay based on small‐molecule fluorescent probes. We synthesized 12 fluorescent substrate analogs (GpppA and GpppG derivatives) varying in the dye type, dye attachment site, and linker length. GpppA labeled with pyrene at the 3′‐O position of adenosine acted as an artificial substrate with properties of a turn‐off probe for all three tested N7‐MTases (human, parasite, and viral). Using this compound, a high‐throughput N7‐MTase inhibitor assay was developed and used for screening of synthetic substrate analogs and a commercial library. Several inhibitors with nanomolar activities were identified. |
44 | lmw1l7gz | How much impact do masks have on preventing the spread of the COVID-19? | Super-factors associated with transmission of occupational COVID-2019 infection among healthcare staff in Wuhan , China. BACKGROUND Globally, there have been many cases of COVID-2019 cases among medical staff, however, the main factors associated with the infection are not well understood. AIM To identify the super-factors causing COVID-19 infection in medical staff in China. METHODS A cross-sectional study was conducted between Jan. 1st, and Feb. 30th, 2020, where front line members of medical staff that took part in the care and treatment of patients with COVID-19 were enrolled. Epidemiological and demographic data between infected and uninfected groups were collected and compared. Social network analysis (SNA) was used to establish socio-metric social links between influencing factors. FINDINGS A total of 92 medical staff were enrolled. In all participant groups, the super-factor identified by the network was wearing a medical protective mask or surgical mask correctly (degree = 572; closeness =25; betweenness centrality = 3·23). Touching the cheek, nose, and mouth while working was the super-factor in the infected group. This was the biggest node in the network and had the strongest influence (degree = 370; closeness = 29; betweenness centrality = 0·37). Self-protection score was the super-factor in the uninfected group but was the isolated factor in the infected group (degree = 201; closeness = 28; betweenness centrality = 5·64). For family members, the exposure history to Huanan Seafood Wholesale Market and the contact history to wild animals were two isolated nodes. CONCLUSION High self-protection score was the main factor that prevented medical staff from contracting COVID-19 infection. The main factor that contributed to COVID-19 infections among medical staff was touching the cheek, nose and mouth while working. |
21 | fyna1euk | what are the mortality rates overall and in specific populations | Improved measurement of racial/ethnic disparities in COVID-19 mortality in the United States Different estimation methods produce diverging accounts of racial/ethnic disparities in COVID-19 mortality in the United States. The Center for Disease Control's decision to present the racial/ethnic distribution of COVID-19 deaths at the state level alongside the weighted racial/ethnic distribution of the counties within each state reporting those death -- in effect, a geographic adjustment -- makes it seem that Whites have the highest death rates. Age adjustment procedures used by others, including the New York City Department of Health and Mental Hygiene, lead to the opposite conclusion that Blacks and Hispanics are dying from COVID-19 at higher rates than Whites. In this paper, we use indirect standardization methods to adjust per capita death rates for both age and geography simultaneously, avoiding the one-sided adjustment procedures currently in use. Using CDC data, we find age-and-place-adjusted COVID-19 death rates are 80% higher for Blacks and over 50% higher for Hispanics, relative to Whites, on a national level. State-specific estimates show wide variation in mortality disparities. Comparison with nonepidemic mortality reveals potential roles for preexisting health disparities and differential rates of infection and care. |
32 | e92gylur | Does SARS-CoV-2 have any subtypes, and if so what are they? | Circulation of genetically distinct contemporary human coronavirus OC43 strains Abstract In this study, we report the complete genome sequence of two contemporary human coronavirus OC43 (HCoV-OC43) strains detected in 2003 and 2004, respectively. Comparative genetic analyses of the circulating strains and the prototype HCoV-OC43 strain (ATCC VR759) were performed. Remarkably, a lower than expected similarity is found between the complete genomes and more in particular between the spike genes of the BE03 and BE04 strains. This finding suggests the existence of two genetically distinct HCoV-OC43 strains, circulating in Belgium in 2003 and 2004. Spike gene sequencing of three additional 2003 and two additional 2004 HCoV-OC43 strains, and subsequent phylogenetic analysis confirm this assumption. Compared to the ATCC prototype HCoV-OC43 strain, an important amino acid substitution is present in the potential cleavage site sequence of the spike protein of all contemporary strains, restoring the N-RRXRR-C motif, associated with increased spike protein cleavability in bovine coronaviruses. We here describe specific characteristics associated with circulating HCoV-OC43 strains, and we provide substantial evidence for the genetic variability of HCoV-OC43. |
9 | ndk9atoa | how has COVID-19 affected Canada | Current Understanding of COVID-19 Clinical Course and Investigational Treatments Importance: Currently, there is no unified framework linking disease progression to established viral levels, clinical tests, inflammatory markers, and investigational treatment options. Objective: It may take many weeks or months to establish a standard treatment approach. Given the growing morbidity and mortality with respect to COVID-19, we present a treatment approach based on a thorough review of scholarly articles and clinical reports. Our focus is on staged progression, clinical algorithms, and individualized treatment. Evidence Review: We followed the protocol for a quality review article proposed by Heyn et. al.1 A literature search was conducted to find all relevant studies related to COVID-19. The search was conducted between April 1, 2020 and April 13, 2020 using the following electronic databases: PubMed (1809 to present), Google Scholar (1900 to present), MEDLINE (1946 to present), CINAHL (1937 to present), and Embase (1980 to present). Keywords used included COVID-19, 2019-nCov, SARS-CoV-2, SARS-CoV, and MERS-CoV, with terms such as efficacy, seroconversion, microbiology, pathophysiology, viral levels, inflammation, survivability, and treatment and pharmacology. No language restriction was placed on the search. Reference lists were manually scanned for additional studies. Findings: Of the articles found in the literature search, 70 were selected for inclusion in this study (67 cited in the body of the manuscript and 3 additional unique references in the Figures). The articles represent work from China, Japan, Taiwan, Vietnam, Rwanda, Israel, France, the United Kingdom, the Netherlands, Canada, and the United States. Most of the articles were cohort or case studies, but we also drew upon information found in guidelines from hospitals and clinics instructing their staff on procedures to follow. In addition, we based some decisions on data collected by agencies such as the CDC, FDA, IHME, ISDA, and Worldometer. None of the case studies or cohort studies used a large number of participants. The largest group of participants numbered less than 500 and some case studies had fewer than 30 patients. However, the review of the literature revealed the need for individualized treatment protocols due to the variability of patient clinical presentation and survivability. A number of factors appear to influence mortality: the stage at which the patient first presented for care, pre-existing health conditions, age, and the viral load the patient carried. Conclusion and Relevance: COVID-19 can be divided into three distinct Stages, beginning at the time of infection (Stage I), sometimes progressing to pulmonary involvement (Stage II, with or without hypoxemia) and less frequently to systemic inflammation (Stage III). In addition to modeling the stages of disease progression, we have also created a treatment algorithm which considers age, comorbidities, clinical presentation, and disease progression to suggest drug classes or treatment modalities. This paper presents the first evidence-based recommendations for individualized treatment for COVID-19. |
19 | v8z5jyz2 | what type of hand sanitizer is needed to destroy Covid-19? | Coping with diabetes during the COVID – 19 lockdown in India: Results of an online pilot survey AIM: The management of diabetes has become a challenge due to the COVID 19 lockdown. An online-based pilot survey was conducted to study how people with diabetes were coping with their Diabetes during the COVID - 19 lockdown. METHOD: The questions were designed in an online survey, Survey Monkey, to conduct this cross-sectional study. The link was generated and sent to 100 registered patients of the MV Hospital for Diabetes Royapuram who had not contacted the hospital after the lockdown announcement. The survey was done between April 1 and April 15, 2020.Oral consent was obtained through telephone before the link was sent by Whatsapp to them.The questionnaire consisted of questions on home blood glucose monitoring, regularity in doing their physical activity and dietary compliance and anxiety about the viral infection. RESULTS: 92% of the participants had Type 2 diabetes. Only 28% of the participants were checking their blood glucose levels regularly. 80% of the participants mentioned that they were following regular exercise and diet control during the lockdown period. 40% of the participants were anxious about the Covid infection. CONCLUSION: SMBG needs to be practiced on regular basis, especially among the patients with diabetes on insulin therapy. Most of the people surveyed were coping well with their Diabetes. Patients have reported that they were able to maintain proper dietary compliance and be more physically active at home during this lockdown. These findings need to be ascertained in larger sample of patients. |
22 | zbogocki | are cardiac complications likely in patients with COVID-19? | Idiopathic acute myocarditis during treatment for controlled human malaria infection: a case report A 23-year-old healthy male volunteer took part in a clinical trial in which the volunteer took chloroquine chemoprophylaxis and received three intradermal doses at four-week intervals of aseptic, purified Plasmodium falciparum sporozoites to induce protective immunity against malaria. Fifty-nine days after the last administration of sporozoites and 32 days after the last dose of chloroquine the volunteer underwent controlled human malaria infection (CHMI) by the bites of five P. falciparum-infected mosquitoes. Eleven days post-CHMI a thick blood smear was positive (6 P. falciparum/μL blood) and treatment was initiated with atovaquone/proguanil (Malarone®). On the second day of treatment, day 12 post-CHMI, troponin T, a marker for cardiac tissue damage, began to rise above normal, and reached a maximum of 1,115 ng/L (upper range of normal = 14 ng/L) on day 16 post-CHMI. The volunteer had one ~20 minute episode of retrosternal chest pain and heavy feeling in his left arm on day 14 post-CHMI. ECG at the time revealed minor repolarization disturbances, and cardiac MRI demonstrated focal areas of subepicardial and midwall delayed enhancement of the left ventricle with some oedema and hypokinesia. A diagnosis of myocarditis was made. Troponin T levels were normal within 16 days and the volunteer recovered without clinical sequelae. Follow-up cardiac MRI at almost five months showed normal function of both ventricles and disappearance of oedema. Delayed enhancement of subepicardial and midwall regions decreased, but was still present. With the exception of a throat swab that was positive for rhinovirus on day 14 post-CHMI, no other tests for potential aetiologies of the myocarditis were positive. A number of possible aetiological factors may explain or have contributed to this case of myocarditis including, i) P. falciparum infection, ii) rhinovirus infection, iii) unidentified pathogens, iv) hyper-immunization (the volunteer received six travel vaccines between the last immunization and the CHMI), v) atovaquone/proguanil treatment, or vi) a combination of these factors. Definitive aetiology and pathophysiological mechanism for the myocarditis have not been established. |
10 | vw3h1m5y | has social distancing had an impact on slowing the spread of COVID-19? | Real-time monitoring the transmission potential of COVID-19 in Singapore, March 2020 BACKGROUND: As of March 31, 2020 the ongoing COVID-19 epidemic that started in China in December 2019 is now generating local transmission around the world. The geographic heterogeneity and associated intervention strategies highlight the need to monitor in real time the transmission potential of COVID-19. Singapore provides a unique case example for monitoring transmission, as there have been multiple disease clusters, yet transmission remains relatively continued. METHODS: Here we estimate the effective reproduction number, R(t), of COVID-19 in Singapore from the publicly available daily case series of imported and autochthonous cases by date of symptoms onset, after adjusting the local cases for reporting delays as of March 17, 2020. We also derive the reproduction number from the distribution of cluster sizes using a branching process analysis that accounts for truncation of case counts. RESULTS: The local incidence curve displays sub-exponential growth dynamics, with the reproduction number following a declining trend and reaching an estimate at 0.7 (95% CI: 0.3, 1.0) during the first transmission wave by February 14, 2020 while the overall R based on the cluster size distribution as of March 17, 2020 was estimated at 0.6 (95% CI: 0.4, 1.02). The overall mean reporting delay was estimated at 6.4 days (95% CI: 5.8, 6.9), but it was shorter among imported cases compared to local cases (mean 4.3 vs. 7.6 days, Wilcoxon test, p<0.001). CONCLUSION: The trajectory of the reproduction number in Singapore underscores the significant effects of successful containment efforts in Singapore, but it also suggests the need to sustain social distancing and active case finding efforts to stomp out all active chains of transmission. |
15 | t33cp9li | how long can the coronavirus live outside the body | Human coronaviruses and other respiratory infections in young adults on a university campus: Prevalence, symptoms, and shedding BACKGROUND: The prevalence, symptom course, and shedding in persons infected with the 4 most common human coronaviruses (HCoV)‐229E, HKU1, NL63, and OC43 are poorly described. OBJECTIVES: We estimate their prevalence and associated symptoms among college students identified via a social network study design. PATIENTS/METHODS: We collected 1‐3 samples (n = 250 specimens) from 176 participants between October 2012 and January 17, 2013: participants with acute respiratory infection (ARI; cough and body aches or chills or fever/feverishness) and their social contacts. Virus was detected using RT‐PCR. RESULTS: 30.4% (76/250) of specimens tested positive for any virus tested, and 4.8% (12/250) were positive for 2 or more viruses. Human coronaviruses (HCoVs [22.0%; 55/250]), rhinovirus (7.6%; 19/250), and influenza A (6.4%; 16/250) were most prevalent. Symptoms changed significantly over time among ARI participants with HCoV: the prevalence of cough and chills decreased over 6 days (P = .04, and P = .01, respectively), while runny nose increased over the same period (P = .02). HCoV‐NL63 was the most frequent virus detected 6 days following symptom onset (8.9%), followed by rhinovirus (6.7%). CONCLUSIONS: During a 3‐month period covering a single season, HCoVs were common, even among social contacts without respiratory symptoms; specific symptoms may change over the course of HCoV‐associated illness and were similar to symptoms from influenza and rhinovirus. |
42 | 0ifomuz4 | Does Vitamin D impact COVID-19 prevention and treatment? | Ocular abnormalities associated with hypovitaminosis A in Hanwoo calves: a report of two cases This study reports on two Hanwoo (a native Korean breed of cattle) calves, a 3- and 6-month-old presenting with diarrhea, anorexia and blindness. Ophthalmoscopic examination revealed bilateral papilledema in both calves. Reverse-transcription polymerase chain reaction tests for bovine viral diarrhea virus, rotavirus and coronavirus were all negative. The levels of serum vitamin A in the two affected calves were 0.317 µg/dl and 0.481 µg/dl, respectively. These values are much lower than the normal vitamin A levels; therefore, the calves were diagnosed with hypovitaminosis A. |
20 | kjdcg8nz | are patients taking Angiotensin-converting enzyme inhibitors (ACE) at increased risk for COVID-19? | Classical Renin-Angiotensin system in kidney physiology. The renin-angiotensin system has powerful effects in control of the blood pressure and sodium homeostasis. These actions are coordinated through integrated actions in the kidney, cardiovascular system and the central nervous system. Along with its impact on blood pressure, the renin-angiotensin system also influences a range of processes from inflammation and immune responses to longevity. Here, we review the actions of the "classical" renin-angiotensin system, whereby the substrate protein angiotensinogen is processed in a two-step reaction by renin and angiotensin converting enzyme, resulting in the sequential generation of angiotensin I and angiotensin II, the major biologically active renin-angiotensin system peptide, which exerts its actions via type 1 and type 2 angiotensin receptors. In recent years, several new enzymes, peptides, and receptors related to the renin-angiotensin system have been identified, manifesting a complexity that was previously unappreciated. While the functions of these alternative pathways will be reviewed elsewhere in this journal, our focus here is on the physiological role of components of the "classical" renin-angiotensin system, with an emphasis on new developments and modern concepts. |
20 | kkse855d | are patients taking Angiotensin-converting enzyme inhibitors (ACE) at increased risk for COVID-19? | COVID-19 Infection: Implications for Perioperative and Critical Care Physicians Healthcare systems worldwide are responding to Coronavirus Disease 2019 (COVID-19), an emerging infectious syndrome caused by the Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2) virus. Patients with COVID-19 can progress from asymptomatic or mild illness to hypoxemic respiratory failure or multisystem organ failure, necessitating intubation and intensive care management. Healthcare providers, and particularly anesthesiologists, are at the frontline of this epidemic, and they need to be aware of the best available evidence to guide therapeutic management of patients with COVID-19 and to keep themselves safe while doing so. Here, the authors review COVID-19 pathogenesis, presentation, diagnosis, and potential therapeutics, with a focus on management of COVID-19–associated respiratory failure. The authors draw on literature from other viral epidemics, treatment of acute respiratory distress syndrome, and recent publications on COVID-19, as well as guidelines from major health organizations. This review provides a comprehensive summary of the evidence currently available to guide management of critically ill patients with COVID-19. |
36 | 4mv6qwpc | What is the protein structure of the SARS-CoV-2 spike? | On the interactions of the receptor-binding domain of SARS-CoV-1 and SARS-CoV-2 spike proteins with monoclonal antibodies and the receptor ACE2 A new betacoronavirus named SARS-CoV-2 has emerged as a new threat to global health and economy. A promising target for both diagnosis and therapeutics treatments of the new disease named COVID-19 is the coronavirus (CoV) spike (S) glycoprotein. By constant-pH Monte Carlo simulations and the PROCEEDpKa method, we have mapped the electrostatic epitopes for four monoclonal antibodies and the angiotensin-converting enzyme 2 (ACE2) on both SARS-CoV-1 and the new SARS-CoV-2 S receptor binding domain (RBD) proteins. We also calculated free energy of interactions and shown that the S RBD proteins from both SARS viruses binds to ACE2 with similar affinities. However, the affinity between the S RBD protein from the new SARS-CoV-2 and ACE2 is higher than for any studied antibody previously found complexed with SARS-CoV-1. Based on physical chemical analysis and free energies estimates, we can shed some light on the involved molecular recognition processes, their clinical aspects, the implications for drug developments, and suggest structural modifications on the CR3022 antibody that would improve its binding affinities for SARS-CoV-2 and contribute to address the ongoing international health crisis. |
3 | 77gt3j5e | will SARS-CoV2 infected people develop immunity? Is cross protection possible? | SARS-CoV-2: virus dynamics and host response |
34 | xhsmfjt5 | What are the longer-term complications of those who recover from COVID-19? | The production of antibodies for SARS-CoV-2 and its clinical implication Background: Severe acute respiratory syndrome coronavirus 2(SARS-CoV-2), a novel betacoronavirus, has caused an outburst of pneumonia cases in Wuhan, China. We report the production of specific IgM and IgG antibodies after the infection of SARS-CoV-2 and its implication for the diagnosis, pathology and the course of the disease as well as the recurrence of positive nucleic acid tests after discharge. Methods: Test results for SARS-CoV-2 IgM and IgG antibodies of 221 confirmed COVID-19 patients were retrospectively examined, and their clinical data were collected and analyzed based on various subgroups. SARS-CoV-2 IgM and IgG antibodies were determined with the chemiluminescence method. Findings: The concentration (S/CO) of SARS-CoV-2 IgM and IgG antibodies peaked on day 19-21 after symptom onset, with a median of 17.38 (IQR 4.39-36.4) for IgM and 5.59 (IQR 0.73-13.65) for IgG. Detection rates reached highest on day 16-18 and day 19-21 for IgM and IgG, which were 73.6% and 98.6%, respectively, with significantly higher concentration of IgG in critically ill patients than in those with mild to moderate disease (P=0.027). The concentration of the antibodies on day 16-21 is not correlated with the course or outcome of the disease (Spearman r < 0.20, P > 0.05). Nasopharyngeal swabs revealed positive SARS-CoV-2 RNA in up to 52.7% of recovered patients after discharge, whose IgG proved to be significantly lower than that of those with negative RNA results (P = 0.009). IgG and IgM were tested twice within 14 days after discharge with a 7-day interval, and the second testing of these antibodies displayed a decrease in concentration of 21.2% (IQR, 11.2%34.48%) for IgG and 23.05% (IQR, -27.96%46.13%) for IgM, without statistical significance between the patients with re-detectable positive RNA results and those with negative RNA results after discharge. However, those with positive results experienced a count decrease in lymphocyte subsets. Interpretation: The concentration of SARS-CoV-2 IgM and IgG antibodies peaked on day 19-21 after symptom onset, and antibody testing on day 16-21 is associated with increased detection rates, but the antibody concentration does not affect the course and outcome of the infection. Recovering patients with re-detectable positive SARS-CoV-2 RNA displayed lower concentration of IgG, but the downward trend of IgG during recovery indicated its limited duration of protection, and the protective effect of IgG remains to be investigated. |
27 | h2uaayo3 | what is known about those infected with Covid-19 but are asymptomatic? | Novel coronavirus disease with conjunctivitis and conjunctivitis as first symptom: Two cases report/ 中华实验眼科杂志 As the frontline health care workers at the center of the novel coronavirus disease (COVIN-19) outbreak, we have found many asymptomatic COVIN-19 patients or patients with mild symptoms since December 2019. A number of COVIN-19 cases with conjunctivitis or conjunctivitis as the first symptom have been observed in our clinical work. This paper reports the diagnosis and treatment of one COVIN-19 patient with conjunctivitis as the first symptom and one COVIN-19 patient with conjunctivitis. Case one occurred conjunctivitis at the third day after closely contacted with determined COVID-19 patient and visited to eye doctor, and the symptom of conjunctivitis following the topical administration of anti-virual eyedrops for 1 week, followed by COVID-19. Her 2019-nCoV RNA detection of nasopharynx swab was positive but that of conjunctival sac swab was a negative result. Case two had a positive epidemiological history and simultaneous onset of COVID-19 and conjunctivitis.She presented positive results of 2019-nCoV RNA detection in both nasopharynx and conjunctival sac swabs, and other lab results supported the diagnosis of COVID-19 but she had a normal CT findings of the chest. The ocular symptoms were disappeared after topical administration of anti-virual eyedrops for 1 week. |
1 | ljqrxjvv | what is the origin of COVID-19 | 04 – Apport des explorations microbiologiques au diagnostic des infections des voies respiratoires basses The diagnosis of community-acquired pneumonia is usually based on clinical and radiological criteria. The identification of a causative organism is not required for the diagnosis. Although numerous microbiological techniques are available, their sensitivity and specificity are not high enough to guide first-line antimicrobial therapy. Consequently, this treatment remains most often empiric. If the causative organism is identified, the antimicrobial treatment is adapted. Sputum analysis may be proposed as a diagnostic tool for patients with an acute exacerbation of chronic obstructive pulmonary disease, in specific cases (prior antibiotherapy, hospitalization, failure of the empiric antimicrobial treatment). |
13 | tikqy2qt | what are the transmission routes of coronavirus? | Duration of quarantine in hospitalized patients with severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection: a question needing an answer |
11 | sx2llame | what are the guidelines for triaging patients infected with coronavirus? | COVID-19 Lessons: The Alignment of Palliative Medicine and Trauma-Informed Care As the COVID-19 pandemic wears on, its psychological, emotional, and existential toll continues to grow and indeed may now rival the physical suffering caused by the illness. Patients, caregivers, and healthcare workers are particularly at risk for trauma responses and would be well served by trauma-informed care (TIC) practices to minimize both immediate and long-term psychological distress. Given the significant overlap between the core tenets of TIC and accepted guidelines for the provision of quality palliative care (PC), PC teams are particularly well poised to both incorporate such practices into routine care and to argue for their integration across health systems. We outline this intersection in order to highlight the uniquely powerful role PC teams can play to reduce the long-term psychological impact of the COVID-19 pandemic. |
11 | y50ou7gg | what are the guidelines for triaging patients infected with coronavirus? | Triage Considerations for Patients Referred for Structural Heart Disease Intervention During the Coronavirus Disease 2019 (COVID-19) Pandemic: An ACC /SCAI Consensus Statement. The COVID-19 pandemic has strained health care resources around the world causing many institutions to curtail or stop elective procedures. This has resulted in the inability to care for patients valvular and structural heart disease (SHD) in a timely fashion potentially placing these patients at increased risk for adverse cardiovascular complications including congestive heart failure and death. The effective triage of these patients has become challenging in the current environment as clinicians have had to weigh the risk of bringing susceptible patients into the hospital environment during the COVID-19 pandemic versus the risk of delaying a needed procedure. In this document, we suggest guidelines as to how to triage patients in need of SHD interventions and provide a framework of how to decide when it may be appropriate to proceed with intervention despite the ongoing pandemic. In particular, we address the triage of patients in need of trans-catheter aortic valve replacement and percutaneous mitral valve repair. We also address procedural issues and considerations for the function of structural heart disease teams during the COVID-19 pandemic. This article is protected by copyright. All rights reserved. |
24 | n52mmprb | what kinds of complications related to COVID-19 are associated with diabetes | The global diabetes epidemic: what does it mean for infectious diseases in tropical countries? Summary Tropical countries are experiencing a substantial rise in type 2 diabetes, which is often undiagnosed or poorly controlled. Since diabetes is a risk factor for many infectious diseases, this increase probably adds to the large infectious disease burden in tropical countries. We reviewed the literature to investigate the interface between diabetes and infections in tropical countries, including the WHO-defined neglected tropical diseases. Although solid data are sparse, patients with diabetes living in tropical countries most likely face increased risks of common and health-care-associated infections, as well as infected foot ulcers, which often lead to amputation. There is strong evidence that diabetes increases the severity of some endemic infections such as tuberculosis, melioidosis, and dengue virus infection. Some HIV and antiparasitic drugs might induce diabetes, whereas helminth infections appear to afford some protection against future diabetes. But there are no or very scarce data for most tropical infections and for possible biological mechanisms underlying associations with diabetes. The rise in diabetes and other non-communicable diseases puts a heavy toll on health systems in tropical countries. On the other hand, complications common to both diabetes and some tropical infections might provide an opportunity for shared services—for example, for eye health (trachoma and onchocerciasis), ulcer care (leprosy), or renal support (schistosomiasis). More research about the interaction of diabetes and infections in tropical countries is needed, and the infectious disease burden in these countries is another reason to step up global efforts to improve prevention and care for diabetes. |
27 | l5ogbl5p | what is known about those infected with Covid-19 but are asymptomatic? | Can we contain the COVID-19 outbreak with the same measures as for SARS? Summary The severe acute respiratory syndrome (SARS) outbreak in 2003 resulted in more than 8000 cases and 800 deaths. SARS was eventually contained by means of syndromic surveillance, prompt isolation of patients, strict enforcement of quarantine of all contacts, and in some areas top-down enforcement of community quarantine. By interrupting all human-to-human transmission, SARS was effectively eradicated. By contrast, by Feb 28, 2020, within a matter of 2 months since the beginning of the outbreak of coronavirus disease 2019 (COVID-19), more than 82 000 confirmed cases of COVID-19 have been reported with more than 2800 deaths. Although there are striking similarities between SARS and COVID-19, the differences in the virus characteristics will ultimately determine whether the same measures for SARS will also be successful for COVID-19. COVID-19 differs from SARS in terms of infectious period, transmissibility, clinical severity, and extent of community spread. Even if traditional public health measures are not able to fully contain the outbreak of COVID-19, they will still be effective in reducing peak incidence and global deaths. Exportations to other countries need not result in rapid large-scale outbreaks, if countries have the political will to rapidly implement countermeasures. |
17 | iys2ezkd | are there any clinical trials available for the coronavirus | Randomised controlled trial of rhinothermy for treatment of the common cold: a feasibility study OBJECTIVE: To determine the feasibility of a randomised controlled trial (RCT) of rhinothermy for the common cold. DESIGN: Open label, randomised, controlled feasibility study. SETTING: Single-centre research institute in New Zealand recruiting participants from the community. PARTICIPANTS: 30 adult participants with symptoms of a common cold, presenting within 48 hours of the onset of symptoms. INTERVENTIONS: Participants were randomly assigned 2:1 to receive either 35 L/min of 100% humidified air at 41°C via high flow nasal cannulae, 2 hours per day for up to 5 days (rhinothermy), or vitamin C 250 mg daily for 5 days (control). PRIMARY AND SECONDARY OUTCOME MEASURES: The primary outcome was the proportion of screened candidates who were randomised. Secondary outcomes included: proportion of randomised participants who completed the study; modified Jackson scores from randomisation to 10 days after initiation of randomised regimen; time until feeling 'a lot better' compared with study entry; time until resolution of symptoms or symptom score at 10 days postrandomisation; proportion of organisms identified by PCR analysis of nasal swabs taken at baseline; the patterns of use of the rhinothermy device; estimated adherence of the control group; and rhinothermy device tolerability. RESULTS: In all 30/79 (38%, 95% CI 27% to 50%) of potential participants screened for eligibility were randomised. Rhinothermy was well tolerated, and all randomised participants completed the study (100%, 95% CI 88% to 100%). The reduction from baseline in the modified Jackson score was greater with rhinothermy compared with control at days 2, 3, 4, 5 and 6, with the maximum difference at day 4 (−6.4, 95% CI −9.4 to −3.3). The substantial clinical benefit threshold for modified Jackson score was a 5-unit change. CONCLUSIONS: This study shows that an RCT of rhinothermy compared with low-dose vitamin C in the treatment of the common cold is feasible. TRIAL REGISTRATION NUMBER: ACTRN12616000470493; Results. |
37 | hf11qpsk | What is the result of phylogenetic analysis of SARS-CoV-2 genome sequence? | A Rare Deletion in SARS-CoV-2 ORF6 Dramatically Alters the Predicted Three-Dimensional Structure of the Resultant Protein The function of the SARS-CoV-2 accessory protein p6, encoded by ORF6, is not fully known. Based upon its similarity to p6 from SARS-CoV, it may play a similar role, namely as an antagonist of type I interferon (IFN) signaling. Here we report the sequencing of a SARS-CoV-2 strain passaged six times after original isolation from a clinical patient in Hong Kong. The genome sequence shows a 27 nt in-frame deletion (Δ27,264-27,290) within ORF6, predicted to result in a 9 aa deletion (ΔFKVSIWNLD) from the central portion of p6. This deletion is predicted to result in a dramatic alteration in the three-dimensional structure of the resultant protein (p6Δ22-30), possibly with significant functional implications. Analysis of the original clinical sample indicates that the deletion was not present, while sequencing of subsequent passages of the strain identifies the deletion as a majority variant. This suggests that the deletion originated ab initio during passaging and subsequently propagated into the majority, possibly due to the removal of selective pressure through the IFN-deficient Vero E6 cell line. The specific function of the SARS-CoV-2 p6 N-terminus, if any, has not yet been determined. However, this deletion is predicted to cause a shift from N-endo to N-ecto in the transmembrane localization of the SARS-CoV-2 p6Δ22-30 N-terminus, possibly leading to the ablation of its native function. |
35 | aj2kscs9 | What new public datasets are available related to COVID-19? | TweetsCOV19 -- A Knowledge Base of Semantically Annotated Tweets about the COVID-19 Pandemic Publicly available social media archives facilitate research in the social sciences and provide corpora for training and testing a wide range of machine learning, NLP and information retrieval methods. With respect to the recent outbreak of COVID-19, online discourse on Twitter reflects public opinion and perception related to the pandemic itself as well as mitigating measures and their societal impact. Understanding such discourse, its evolution and interdependencies with real-world events or (mis)information can foster valuable insights. On the other hand, such corpora are crucial facilitators for computational methods addressing tasks such as sentiment analysis, event detection or entity recognition. However, obtaining, archiving and semantically annotating large amounts of tweets is costly. In this paper, we describe TweetsCOV19, a publicly available knowledge base of currently more than 8 million tweets, spanning the period Oct'19-Apr'20. Metadata about the tweets as well as extracted entities, hashtags, user mentions, sentiments, and URLs are exposed using established RDF/S vocabularies, providing an unprecedented knowledge base for a range of knowledge discovery tasks. Next to a description of the dataset and its extraction and annotation process, we present an initial analysis, use cases and usage of the corpus. |
25 | rjqq1lxx | which biomarkers predict the severe clinical course of 2019-nCOV infection? | COVID-19 Tragic Pandemic: Concerns over Unintentional "Directed Accelerated Evolution" of Novel Coronavirus (SARS-CoV-2) and Introducing a Modified Treatment Method for ARDS Global health authorities are trying to work out the current status of the novel coronavirus (COVID-19) outbreak and explore methods to reduce the rate of its transmission to healthy individuals. In this viewpoint we provide insights concerning how health care professionals can unintentionally shift the novel coronavirus type to more drug-resistant forms. It is worth noting that viruses usually have different sensitivities to physical and chemical damaging agents such antiviral drugs, UV and heat ranging from extremely sensitive (ES) to extremely resistant (ER) based on a bell-shaped curve. Given this consideration, the widespread infection of people with such ER viruses would be a real disaster. Here, we introduce a modified treatment method for COVID-19-associated pneumonia. In this proposed method, COVID-19 patients will receive a single dose of 100, 180 or 250 mSv X-ray radiation that is less than the maximum annual radiation dose of the residents of high background radiation areas of Ramsar that is up to 260 mSv. In contrast with antiviral drugs, a single dose of either 100, 180 or 250 mSv of low LET X-rays cannot exert a significant selective pressure on the novel coronavirus (SARS-CoV-2) and hence does not lead to directed accelerated evolution of these viruses. Moreover, Low Dose Radiation (LDR) has the capacity of modulating excessive inflammatory responses, regulating lymphocyte counts, and controling bacterial co-infections in patients with COVID-19. |
13 | 4zk4sj2d | what are the transmission routes of coronavirus? | How will country-based mitigation measures influence the course of the COVID-19 epidemic? |
23 | ufcvecwo | what kinds of complications related to COVID-19 are associated with hypertension? | Outcome reporting from protocols of clinical trials of Coronavirus Disease 2019 (COVID-19): a review Objectives: To examine heterogeneity of outcomes in protocols of clinical trials of Coronavirus Disease 2019 (COVID-19) and to identify outcomes for prioritization in developing a core outcome set (COS) in this field. Design: This study is a review. Data sources: Databases of ICMJE-accepted clinical trial registry platform were searched on February 14, 2020. Eligibility Criteria: Randomized controlled trials (RCTs) and non-RCTs of COVID-19 were considered.Conditions of patients include common type, severe type or critical type. Interventions include traditional Chinese medicine (TCM) and Western medicine. We excluded trials that for discharged patients, psychological intervention and complications of COVID-19. Data extraction and synthesis: The general information and outcomes, outcome measurement instruments and measurement times were extracted. The results were analysed by descriptive analysis. Results: 19 registry platforms were searched. A total of 97 protocols were included from 160 protocols. For protocols of TCM clinical trials, 76 outcomes from 16 outcome domains were reported, and almost half (34/76, 44.74%) of outcomes were reported only once; the most frequently reported outcome was time of SARS-CoV-2 RNA turns to negative. 27 (27/76, 35.53%) outcomes were provided one or more outcome measurement instruments. 10 outcomes were provided one or more measurement time frame. For protocols of western medicine clinical trials, 126 outcomes from 17 outcome domains were reported; almost half (62/126, 49.21%) of outcomes were reported only once; the most frequently reported outcome was proportion of patients with negative SARS-CoV-2. 27 outcomes were provided one or more outcome measurement instruments. 40 (40/126, 31.75%) outcomes were provided one or more measurement time frame. Conclusion: Outcome reporting in protocols of clinical trials of COVID-19 is inconsistent. Thus, developing a core outcome set is necessary. Keywords: Outcomes; clinical trials, COVID-19; review. |
38 | 5rfxis6f | What is the mechanism of inflammatory response and pathogenesis of COVID-19 cases? | Vitamin D Receptor stimulation to reduce Acute Respiratory Distress Syndrome (ARDS) in patients with Coronavirus SARS-CoV-2 infections: Revised Ms SBMB 2020_166 Coronavirus infection is a serious health problem awaiting an effective vaccine and/or antiviral treatment. The major complication of coronavirus disease 2019 (COVID-19), the Acute Respiratory Distress syndrome (ARDS), is due to a variety of mechanisms including cytokine storm, dysregulation of the renin-angiotensin system, neutrophil activation and increased (micro)coagulation. Based on many preclinical studies and observational data in humans, ARDS may be aggravated by vitamin D deficiency and tapered down by activation of the vitamin D receptor. Several randomized clinical trials using either oral vitamin D or oral Calcifediol (25OHD) are ongoing. Based on a pilot study, oral calcifediol may be the most promising approach. These studies are expected to provide guidelines within a few months. |
31 | fl6cn72h | How does the coronavirus differ from seasonal flu? | Chapter 3 Applications of Molecular Tools to Infectious Disease Epidemiology Publisher Summary Molecular tools enhance outbreak investigation and surveillance, facilitate description of the transmission system, and increase understanding of the epidemiology. Molecular tools enhance case definitions, increasing specificity and reducing misclassification, and are now a standard tool in outbreak investigations. Although it is assumed during an outbreak that a single microbe is causing the clinical symptoms, it is possible that a microbe of the same genus and species but different strain is causing disease during the same time period. Molecular typing can distinguish between outbreak and nonoutbreak strains. Molecular tools also facilitate estimating parameters key to understanding the transmission system, including the incidence, prevalence, transmission probability, duration of carriage, effective dose, and probability of effective contact. Molecular tools enable one to trace the dissemination of a particular subtype across time and space and thus develop theories of transmission and dissemination, determine the origin of an epidemic and test theories about reservoirs and evolution of a particular pathogen, follow the emergence of new infections as they cross species, testing the hypotheses about the apparent transmissibility and rate of evolution, and follow mobile genetic elements conferring antimicrobial resistance or virulence between strains within a species or between species, and so develop theories about evolution and transmission within the populations of pathogens. |
12 | baheh8i5 | what are best practices in hospitals and at home in maintaining quarantine? | Tracking COVID-19 by Tracking Infectious Trajectories Nowadays, the coronavirus pandemic has and is still causing large numbers of deaths and infected people. Although governments all over the world have taken severe measurements to slow down the virus spreading (e.g., travel restrictions, suspending all sportive, social, and economic activities, quarantines, social distancing, etc.), a lot of persons have died and a lot more are still in danger. Indeed, a recently conducted study~\cite{ref2} has reported that 79\% of the confirmed infections in China were caused by undocumented patients who had no symptoms. In the same context, in numerous other countries, since coronavirus takes several days before the emergence of symptoms, it has also been reported that the known number of infections is not representative of the real number of infected people (the actual number is expected to be much higher). That is to say, asymptomatic patients are the main factor behind the large quick spreading of coronavirus and are also the major reason that caused governments to lose control over this critical situation. To contribute to remedying this global pandemic, in this paper, we propose an IoT (Internet of Things) investigation system that was specifically designed to spot both undocumented patients and infectious places. The goal is to help the authorities to disinfect high-contamination sites and confine persons even if they have no apparent symptoms. The proposed system also allows determining all persons who had close contact with infected or suspected patients. Consequently, rapid isolation of suspicious cases and more efficient control over any pandemic propagation can be achieved. |
38 | mm3ab7cr | What is the mechanism of inflammatory response and pathogenesis of COVID-19 cases? | Inflammatory pattern recognition receptors and their ligands: factors contributing to the pathogenesis of preeclampsia PROBLEM: Preeclampsia, a pregnancy-specific hypertensive syndrome, is one of the leading causes of premature births as well as fetal and maternal death. Preeclampsia lacks effective therapies because of the poor understanding of disease pathogenesis. The aim of this paper is to review molecular signaling pathways that could be responsible for the pathogenesis of preeclampsia. METHOD OF STUDY: This article reviews the English-language literature for pathogenesis and pathophysiological mechanisms of preeclampsia based on genome-wide gene expression profiling and proteomic studies. RESULTS: We show that the expression of the genes and proteins involved in response to stress, host-pathogen interactions, immune system, inflammation, lipid metabolism, carbohydrate metabolism, growth and tissue remodeling was increased in preeclampsia. Several significant common pathways observed in preeclampsia overlap the datasets identified in TLR (Toll-like receptor)- and RAGE (receptor for advanced glycation end products)-dependent signaling pathways. Placental oxidative stress and subsequent chronic inflammation are considered to be major contributors to the development of preeclampsia. CONCLUSION: This review summarizes recent advances in TLR- and RAGE-mediated signaling and the target molecules, and provides new insights into the pathogenesis of preeclampsia. |
8 | 0v5wo0ty | how has lack of testing availability led to underreporting of true incidence of Covid-19? | Lessons from a rapid systematic review of early SARS-CoV-2 serosurveys Background. As the world grapples with the COVID-19 pandemic, there is increasing global interest in the role of serological testing for population monitoring and to inform public policy. However, limitations in serological study designs and test standards raise concerns about the validity of seroprevalence estimates and their utility in decision-making. There is now a critical window of opportunity to learn from early SARS-CoV-2 serology studies. We aimed to synthesize the results of SARS-CoV-2 serosurveillance projects from around the world and provide recommendations to improve the coordination, strategy, and methodology of future serosurveillance efforts. Methods. This was a rapid systematic review of cross-sectional and cohort studies reporting seroprevalence outcomes for SARS-CoV 2. We included completed, ongoing, and proposed serosurveys. The search included electronic databases (PubMed, MedRXIV, BioRXIV, and WHO ICTPR); five medical journals (NEJM, BMJ, JAMA, The Lancet, Annals of Internal Medicine); reports by governments, NGOs, and health systems; and media reports (Google News) from December 1, 2019 to May 1, 2020. We extracted data on study characteristics and critically appraised prevalence estimates using Joanna Briggs Institute criteria. Results. Seventy records met inclusion criteria, describing 73 studies. Of these, 23 reported prevalence estimates: eight preprints, 14 news articles, and one government report. These studies had a total sample size of 35,784 and reported 42 prevalence estimates. Seroprevalence estimates ranged from 0.4% to 59.3%. No estimates were found to have a low risk of bias (43% high risk, 21% moderate risk, 36% unclear). Fifty records reported characteristics of ongoing or proposed serosurveys. Overall, twenty countries have completed, ongoing, or proposed serosurveys. Discussion. Study design, quality, and prevalence estimates of early SARS-CoV2 serosurveys are heterogeneous, suggesting that the urgency to examine seroprevalence may have compromised methodological rigour. Based on the limitations of included studies, future serosurvey investigators and stakeholders should ensure that: i) serological tests used undergo high-quality independent evaluations that include cross-reactivity; ii) all reports of serosurvey results, including media, describe the test used, sample size, and sampling method; and iii) initiatives are coordinated to prevent test fatigue, minimize redundant efforts, and encourage better study methodology. Other. PROSPERO: CRD42020183634. No third-party funding. |
49 | 98m2qy49 | do individuals who recover from COVID-19 show sufficient immune response, including antibody levels and T-cell mediated immunity, to prevent re-infection? | Immune Responses to Middle East Respiratory Syndrome Coronavirus During the Acute and Convalescent Phases of Human Infection BACKGROUND: An understanding of immune responses against the Middle East respiratory syndrome (MERS) is important for the development of treatments and preventive measures. Here, we investigated the spectrum of immune responses occurring in patients with MERS during the early period of infection. METHODS: We obtained peripheral blood samples from 27 hospitalized patients recruited during the epidemic that occurred in 2015 in South Korea. Plasma cytokines/chemokines and antibodies were quantified. Virus-specific T cells were examined by intracellular cytokine staining after stimulation of peripheral blood mononuclear cells with overlapping peptides spanning whole virus structural proteins. RESULTS: At the acute phase of infection, elevated levels of plasma proinflammatory cytokines/chemokines were detected in proportion to the severity of the disease. Distinctively high frequencies of MERS coronavirus–reactive CD8(+) T cells were also observed in patients with severe/moderate illness, whereas antibody and CD4(+) T-cell responses were minimally detected at this stage. At the convalescent phase, disease severity–dependent antibody responses emerged and antigen-reactive cells were identified in both T-cell subsets. These T cells belonged to the T-helper 1 or type 1 cytotoxic T cell subtypes. While CD8(+) T cells responded preferentially to the viral S protein compared with E/M/N proteins, especially at the acute stage, slightly more CD4(+) T cells recognized E/M/N proteins compared with S protein at the convalescent phase. CONCLUSIONS: Our findings show an association between the early CD8(+) T-cell response and the severity of the infection, and also provide basic information that may help to prepare effective control strategies for MERS in humans. |
27 | f3w2gu8c | what is known about those infected with Covid-19 but are asymptomatic? | Anaesthesia and COVID-19: infection control Summary The world is currently facing an unprecedented healthcare crisis caused by a pandemic novel beta coronavirus, severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). The pathogen is spread by human-to-human transmission via droplets exposure and contact transfer, causing mild symptoms in the majority of cases, but critical illness, bilateral viral pneumonia, and acute respiratory distress syndrome (ARDS) in a minority. Currently, controlling infection to prevent the spread of SARS-CoV-2 is the primary public healthcare intervention used. The pace of transmission and global scale of SARS-CoV-2 infections has implications for strategic oversight, resource management, and responsiveness in infection control. This article presents a summary of learning points in epidemiological infection control from the SARS epidemic, alongside a review of evidence connecting current understanding of the virologic and environmental contamination properties of SARS-CoV-2. We present suggestions for how personal protective equipment policies relate to the viral pandemic context and how the risk of transmission by and to anaesthetists, intensivists, and other healthcare workers can be minimised. |
20 | 5svfhlzh | are patients taking Angiotensin-converting enzyme inhibitors (ACE) at increased risk for COVID-19? | COVID-19 and heart failure: from infection to inflammation and angiotensin II stimulation. Searching for evidence from a new disease Patients with cardiovascular disease and, namely, heart failure are more susceptible to coronavirus disease 2019 (COVID-19) and have a more severe clinical course once infected. Heart failure and myocardial damage, shown by increased troponin plasma levels, occur in at least 10% of patients hospitalized for COVID-19 with higher percentages, 25% to 35% or more, when patients critically ill or with concomitant cardiac disease are considered. Myocardial injury may be elicited by multiple mechanisms, including those occurring with all severe infections, such as fever, tachycardia, adrenergic stimulation, as well as those caused by an exaggerated inflammatory response, endotheliitis and, in some cases, myocarditis that have been shown in patients with COVID-19. A key role may be that of the renin-angiotensin-aldosterone system. Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infects human cells binding to angiotensin-converting enzyme 2 (ACE2), an enzyme responsible for the cleavage of angiotensin II into angiotensin 1-7, which has vasodilating and anti-inflammatory effects. Virus-mediated down-regulation of ACE2 may increase angiotensin II stimulation and contribute to the deleterious hyper-inflammatory reaction of COVID-19. On the other hand, ACE2 may be up-regulated in patients with cardiac disease and treated with ACE inhibitors or angiotensin receptor blockers. ACE2 up-regulation may increase the susceptibility to COVID-19 but may be also protective vs. angiotensin II-mediated vasoconstriction and inflammatory activation. Recent data show the lack of untoward effects of ACE inhibitors or angiotensin receptor blockers for COVID-19 infection and severity. Prospective trials are needed to ascertain whether these drugs may have protective effects. |
35 | g1guxror | What new public datasets are available related to COVID-19? | Sexual and reproductive health (SRH): a key issue in the emergency response to the coronavirus disease (COVID- 19) outbreak The novel coronavirus disease (COVID-19) outbreak was first declared in China in December 2019, and WHO declared the pandemic on 11 March 2020. A fast-rising number of confirmed cases has been observed in all continents, with Europe at the epicentre of the outbreak at this moment. Sexual and reproductive health (SRH) and rights is a significant public health issue during the epidemics. The novel coronavirus (SARS-CoV-2) is new to humans, and only limited scientific evidence is available to identify the impact of the disease COVID-19 on SRH, including clinical presentation and outcomes of the infection during pregnancy, or for persons with STI/HIV-related immunosuppression. Beyond the clinical scope of SRH, we should not neglect the impacts at the health system level and disruptions or interruptions in regular provision of SRH services, such as pre- and postnatal checks, safe abortion, contraception, HIV/AIDS and sexually transmitted infections. Furthermore, other aspects merit attention such as the potential increase of gender-based violence and domestic abuse, and effects of stigma and discrimination associated with COVID-19 and their effects on SRH clients and health care providers. Therefore, there is an urgent need for the scientific community to generate sound clinical, epidemiological, and psycho-social behavioral links between COVID-19 and SRH and rights outcomes. |
39 | w6b1h1of | What is the mechanism of cytokine storm syndrome on the COVID-19? | The possible pathophysiology mechanism of cytokine storm in elderly adults with COVID-19 infection: the contribution of "inflame-aging" PURPOSE: Novel Coronavirus disease 2019 (COVID-19), is an acute respiratory distress syndrome (ARDS), which is emerged in Wuhan, and recently become worldwide pandemic. Strangely, ample evidences have been shown that the severity of COVID-19 infections varies widely from children (asymptomatic), adults (mild infection), as well as elderly adults (deadly critical). It has proven that COVID-19 infection in some elderly critical adults leads to a cytokine storm, which is characterized by severe systemic elevation of several pro-inflammatory cytokines. Then, a cytokine storm can induce edematous, ARDS, pneumonia, as well as multiple organ failure in aged patients. It is far from clear till now why cytokine storm induces in only COVID-19 elderly patients, and not in young patients. However, it seems that aging is associated with mild elevated levels of local and systemic pro-inflammatory cytokines, which is characterized by "inflamm-aging". It is highly likely that "inflamm-aging" is correlated to increased risk of a cytokine storm in some critical elderly patients with COVID-19 infection. METHODS: A systematic search in the literature was performed in PubMed, Scopus, Embase, Cochrane Library, Web of Science, as well as Google Scholar pre-print database using all available MeSH terms for COVID-19, Coronavirus, SARS-CoV-2, senescent cell, cytokine storm, inflame-aging, ACE2 receptor, autophagy, and Vitamin D. Electronic database searches combined and duplicates were removed. RESULTS: The aim of the present review was to summarize experimental data and clinical observations that linked the pathophysiology mechanisms of "inflamm-aging", mild-grade inflammation, and cytokine storm in some elderly adults with severe COVID-19 infection. |
43 | 6qs6m7h7 | How has the COVID-19 pandemic impacted violence in society, including violent crimes? | What does COVID‐19 distract us from? A migration studies perspective on the inequities of attention |
26 | 94xxzksq | what are the initial symptoms of Covid-19? | Epidemiological and initial clinical characteristics of patients with family aggregation of COVID-19 Abstract Background Since December 2019, a new outbreak of the coronavirus disease 2019 (COVID-19) in Wuhan (Hubei, China) and rapidly spread throughout China, however, confirmed cases are still increasing worldwide. Objectives To investigate the epidemiological history and initial clinical characteristics of 10 patients with family aggregation of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection in Western Chongqing, China. Study design Ten patients positive for SARS-CoV-2 nucleic acid detection by real time Reverse Transcription-Polymerase Chain Reaction (RT-PCR), were collected from The People's Hospital of Dazu District, Chongqing. Epidemiological data and laboratory and imaging results were collected on the first day of admission, and analyzed based on the Diagnosis and Treatment Guideline for COVID-19 (5th edition, China). Results Of the 10 cases, case A had a history of a temporary stay in Wuhan and transmitted the virus to the others through family gathering, living together, and sharing vehicles. The average age was 56.5 years (± 11.16), six patients were males, and the incubation period was 2–14 days. Dry cough was the main symptom, followed by fever and fatigue. Most patients were clinically classified as ordinary-type, with three cases being severe-type. Chest computed tomography results were nonspecific, mainly with ground-glass attenuation and/or shadow images. Extensive lesion distribution was seen in severe cases. CD4+ lymphocyte counts were 61, 180, and 348 cells/uL in severe-type patients, respectively. Notably, viral nucleic acid values in nasopharyngeal swabs were lower (19, 25, and 26) than those of ordinary-type patients, suggesting a higher viral load. Neutrophil-lymphocyte ratio (NLR) was also higher in severe-type patients Conclusions Initial examination results of lower CD4+ lymphocyte counts and RT-PCR-CT values coupled with higher NLR may indicate the severity of COVID-19 infection for these family clusters. |
34 | d8iy1u9c | What are the longer-term complications of those who recover from COVID-19? | Mitigating the wider health effects of covid-19 pandemic response |
31 | mlshkaid | How does the coronavirus differ from seasonal flu? | COVID-19: Lessons for an Urban(izing) World The COVID-19 crisis has changed the face of many of our cities and questioned how we should manage urban life in the wake of a pandemic. This Commentary points to the need to learn urban governance lessons and to the potential value of urban experimentation in crisis. |
27 | 8ruux4sw | what is known about those infected with Covid-19 but are asymptomatic? | Discovering drugs to treat coronavirus disease 2019 (COVID-19). The SARS-CoV-2 virus emerged in December 2019 and then spread rapidly worldwide, particularly to China, Japan, and South Korea. Scientists are endeavoring to find antivirals specific to the virus. Several drugs such as chloroquine, arbidol, remdesivir, and favipiravir are currently undergoing clinical studies to test their efficacy and safety in the treatment of coronavirus disease 2019 (COVID-19) in China; some promising results have been achieved thus far. This article summarizes agents with potential efficacy against SARS-CoV-2. |
21 | ilnrvbpa | what are the mortality rates overall and in specific populations | Factors associated with increased all-cause mortality during the COVID-19 pandemic in Italy Abstract Background The number of excess deaths in February-March 2020 in Italy, in comparison to the previous years, was considerably higher than recorded COVID19-related deaths. The present study is aimed at exploring the associations of excess mortality with some indices related to the epidemic and its management. Methods Data on all-cause mortality from February 20th to March 31st, in years from 2015 to 2020, and demographic, socioeconomic and healthcare organization data of each Italian region were obtained from Italian Institute of Statistics. Non-COVID19-Imputed Excess Mortality (NCIEM) was calculated as the difference between excess 2020 mortality and reported COVID19 mortality. The association of NCIEM with the rate of COVID-19 cases, COVID-19 mortality, and other potential moderators was assessed using linear regression models. Results The nationwide number of excess deaths, COVID-19 deaths was 26,701 and 13,710, respectively, with a difference of 12,991. NCIEM in different Regions showed a direct correlation with COVID-19 mortality (r2 = 0.61, p < 0.001) and total cases (r2 = 0.30, p = 0.012), and an inverse correlation with cases/total tests ratio (r2 = 0.49, p = 0.001). Direct correlations were also found with the proportion of institutionalized elderly, whereas inverse correlations were observed with prevalence of diabetes, cardiovascular mortality, and density of general practitioners. Conclusions The impact of the COVID19 epidemic on all-cause mortality is considerably greater than that indicated by official counts of victims. Limited testing capacity and causes of death other than COVID19 could contribute to the increase in overall mortality rates. |
39 | zvvdqk4b | What is the mechanism of cytokine storm syndrome on the COVID-19? | Highlight of Immune Pathogenic Response and Hematopathologic Effect in SARS-CoV, MERS-CoV, and SARS-Cov-2 Infection A sudden outbreak of COVID-19 caused by a novel coronavirus, SARS-CoV-2, in Wuhan, China in December 2019 quickly grew into a global pandemic, putting at risk not only the global healthcare system, but also the world economy. As the disease continues to spread rapidly, the development of prophylactic and therapeutic approaches is urgently required. Although some progress has been made in understanding the viral structure and invasion mechanism of coronaviruses that may cause severe cases of the syndrome, due to the limited understanding of the immune effects caused by SARS-CoV-2, it is difficult for us to prevent patients from developing acute respiratory distress syndrome (ARDS) and pulmonary fibrosis (PF), the major complications of coronavirus infection. Therefore, any potential treatments should focus not only on direct killing of coronaviruses and prevention strategies by vaccine development, but also on keeping in check the acute immune/inflammatory responses, resulting in ARDS and PF. In addition, potential treatments currently under clinical trials focusing on killing coronaviruses or on developing vaccines preventing coronavirus infection largely ignore the host immune response. However, taking care of SARS-CoV-2 infected patients with ARDS and PF is considered to be the major difficulty. Therefore, further understanding of the host immune response to SARS-CoV-2 is extremely important for clinical resolution and saving medication cost. In addition to a breif overview of the structure, infection mechanism, and possible therapeutic approaches, we summarized and compared the hematopathologic effect and immune responses to SARS-CoV, MERS-CoV, and SARS-CoV-2. We also discussed the indirect immune response caused by SARS and direct infection, replication, and destroying of immune cells by MERS-CoV. The molecular mechanisms of SARS-CoV and MERS-CoV infection-induced lymphopenia or cytokine storm may provide some hint toward fight against SARS-CoV-2, the novel coronavirus. This may provide guidance over using immune therapy as a combined treatment to prevent patients developing severe respiratory syndrome and largely reduce complications. |
22 | mjdg84ny | are cardiac complications likely in patients with COVID-19? | Determinants of cardiac adverse events of chloroquine and hydroxychloroquine in 20 years of drug safety surveillance reports Chloroquine (CQ) and hydroxychloroquine (HCQ) are on the World Health Organization's List of Essential Medications for treating non-resistant malaria, rheumatoid arthritis (RA) and systemic lupus erythematosus (SLE). In addition, both drugs are currently used off-label in hospitals worldwide and in numerous clinical trials for the treatment of SARS-CoV-2 infection. However, CQ and HCQ use has been associated with cardiac side effects, which is of concern due to the higher risk of COVID-19 complications in patients with heart related disorders, and increased mortality associated with COVID-19 cardiac complications. In this study we analyzed over thirteen million adverse event reports form the United States Food and Drug Administration Adverse Event Reporting System to confirm and quantify the association of cardiac side effects of CQ and HCQ. Additionally, we identified several confounding factors, including male sex, NSAID coadministration, advanced age, and prior diagnoses contributing to the risk of drug related cardiotoxicity. These findings may help guide therapeutic decision making and ethical trial design for COVID-19 treatment. |
45 | fclvx75h | How has the COVID-19 pandemic impacted mental health? | COVID-19 pandemic: every day feels like a weekday to most The COVID-19 outbreak has clear clinical and economic impacts, but also affects behaviors e.g. through social distancing, and may increase stress and anxiety. However, while case numbers are tracked daily, we know little about the psychological effects of the outbreak on individuals in the moment. Here we examine the psychological and behavioral shifts over the initial stages of the outbreak in the United States in an observational longitudinal study. Through GPS phone data we find that homestay is increasing, while being at work dropped precipitously. Using regular real-time experiential surveys we observe an overall increase in stress and mood levels which is similar in size to the weekend vs. weekday differences. As there is a significant difference between weekday and weekend mood and stress levels, this is an important decrease in wellbeing. For some, especially those affected by job loss, the mental health impact is severe. |
25 | 7nzws8jt | which biomarkers predict the severe clinical course of 2019-nCOV infection? | Proposal for detection of 2019-nCoV nucleic acid in clinical laboratories/ 中华检验医学杂志 In December, the outbreak of a novel coronavirus (2019-nCoV) in Wuhan, China, has attracted extensive global attention. On January 20, 2020,the Chinese health authorities upgraded the coronavirus to a Class B infectious disease in the Law of the People's Republic of China on the Prevention and Treatment of Infectious Diseases, and considered it as Class A infectious diseases in disease control and prevention. On January 22, 2020, the 2019-nCoV nucleic acid detection test was listed as the diagnostic criteria in the "guidelines for diagnosis and treatment of pneumonia due to 2019-nCoV (Trial Version 2)" . Therefore, standardizing the operation process of the 2019-nCoV nucleic acid detection in clinical laboratories has become a top priority. It is of paramount importance to establish standard protocols for detection of the 2019-nCoV nucleic acids in clinical laboratories to improve the reliability of the results and ensure the biosafety of laboratory personnel. |
30 | pgxew3yk | is remdesivir an effective treatment for COVID-19 | A search for medications to treat COVID-19 via in silico molecular docking models of the SARS-CoV-2 spike glycoprotein and 3CL protease Abstract Background The COVID-19 has now been declared a global pandemic by the World Health Organization. There is an emergent need to search for possible medications. Method Utilization of the available sequence information, homology modeling, and in slico docking a number of available medications might prove to be effective in inhibiting the SARS-CoV-2 two main drug targets, the spike glycoprotein, and the 3CL protease. Results Several compounds were determined from the in silico docking models that might prove to be effective inhibitors for SARS-CoV-2. Several antiviral medications: Zanamivir, Indinavir, Saquinavir, and Remdesivir show potential as and 3CLPRO main proteinase inhibitors and as a treatment for COVID-19. Conclusion Zanamivir, Indinavir, Saquinavir, and Remdesivir are among the exciting hits on the 3CLPRO main proteinase. It is also exciting to uncover that Flavin Adenine Dinucleotide (FAD) Adeflavin, B2 deficiency medicine, and Coenzyme A, a coenzyme, may also be potentially used for the treatment of SARS-CoV-2 infections. The use of these off-label medications may be beneficial in the treatment of the COVID-19. |
25 | rsf8uvd1 | which biomarkers predict the severe clinical course of 2019-nCOV infection? | The discovery and identification of a candidate proteomic biomarker of active tuberculosis BACKGROUND: Noninvasive and convenient biomarkers for early diagnosis of tuberculosis (TB) remain an urgent need. The aim of this study was to discover and identify potential biomarkers specific for TB. METHODS: The surface-enhanced laser desorption ionization time of flight mass spectrometry (SELDI-TOF MS) combined with weak cation exchange (WCX) magnetic beads was used to screen serum samples from 180 cases of TB and 211 control subjects. A classification model was established by Biomarker Pattern Software (BPS). Candidate protein biomarkers were purified by reverse phase-high performance liquid chromatography (RP-HPLC), identified by MALDI-TOF MS, LC-MS/MS and validated using enzyme-linked immunosorbent assay (ELISA). RESULTS: A total of 35 discriminating m/z peaks were detected that were related to TB (P < 0.01). The model of biomarkers based on the four biomarkers (2554.6, 4824.4, 5325.7, and 8606.8 Da) was established which could distinguish TB from controls with the sensitivity of 83.3% and the specificity of 84.2%. The candidate biomarker with m/z of 2554.6 Da was found to be up-regulated in TB patients, and was identified as a fragment of fibrinogen, alpha polypeptide isoform alpha-E preproprotein. Analysis in 22 patients with TB showed increased fibrinogen degradation product (FDP) (5,005 ± 1,297 vs. 4,010 ± 1,181 ng/mL, P < 0.05) and in 142 patients showed elevated plasma fibrinogen levels. CONCLUSIONS: A diagnostic model for TB with high sensitivity and specificity was developed using mass spectrometry combined with magnetic beads. Fibrinogen was identified as a potential biomarker for TB and showed diagnostic values in clinical application. |
27 | m3nqa321 | what is known about those infected with Covid-19 but are asymptomatic? | Incidence of novel coronavirus (2019-nCoV) infection among people under home quarantine in Shenzhen, China Since the outbreak of 2019-nCoV in December, Chinese government has implemented various measures including travel bans, centralized treatments, and home quarantines to slowing the transmission across the country. In this study, we aimed to estimate the incidence of 2019-nCoV infection among people under home quarantine in Shenzhen, China. Methods: We used a stratified multistage random sampling method to recruit participants and collected demographic information and laboratory results of people under home quarantine. We conducted descriptive analysis to estimate the basic characteristics and to calculate the incidence in out study population. Results: A total of 2004 people under home quarantine participated in this study, of which 1637 participants finished the questionnaire with a response rate of 81.7%. Mean age of the participants was 33.7 years, ranging from 0.3 to 80.2 years. Of people who provided clear travel history, 129 people have traveled to Wuhan city and 1,046 people have traveled to other cities in Hubei province within 14 days before the home quarantine. Few (less than 1%) participants reported contact history with confirmed or suspected cases during their trip and most of these arrived at Shenzhen between Jan 24, 2020 to Jan 27, 2020. The incidence of COVID-19 in the sample was 1.5‰ (95% CI: 0.31‰–4.37‰). Conclusion: Home quarantine has been effective in preventing the early transmission of COVID-19, but that more needs to be done to improve early detection of COVID-19 infection. |
38 | 6b6kn9l8 | What is the mechanism of inflammatory response and pathogenesis of COVID-19 cases? | Anti-TNF-α Agents in Inflammatory Bowel Disease and Course of COVID-19 |
39 | 0khg28ex | What is the mechanism of cytokine storm syndrome on the COVID-19? | Power of Artificial Intelligence to Diagnose and Prevent Further COVID-19 Outbreak: A Short Communication Novel coronavirus-19 (2019-nCoV or COVID-19) is by far the most dangerous coronavirus ever identified for the third time in the three decades capable of infecting not only the animals but also the humans across the globe. Nearly 6000 deaths have been recorded due mainly to COVID-19 outbreak worldwide and more than 50% of these deaths appeared to have evolved from China where the virus was thought to originate. The endemicity of COVID-19 dramatically surpassed severe acute respiratory syndrome coronavirus (SARS-CoV) and Middle East respiratory syndrome coronavirus (MERS-CoV) that were so far discovered in 2003 and 2012 respectively. Thus, the World Health Organization (WHO) has declared the 2019-nCoV outbreak not only a public health emergency but also pandemic in nature. Currently, over 120 countries including Nigeria were reported to have more than 157,844 confirmed cases and 5,846 deaths due mainly to COVID-19 outbreak as of March 15, 2020, 10:55 GMT. Artificial Intelligence (AI) is widely used to aid in the prediction, detection, response, recovery of disease and making clinical diagnosis. In this study, we highlighted the power of AI in the containment and mitigation of the spread of COVID-19 outbreak in African countries such as Nigeria where human to human contact is apparently inevitable. |
46 | da61tfr9 | what evidence is there for dexamethasone as a treatment for COVID-19? | New insights on the antiviral effects of chloroquine against coronavirus: what to expect for COVID-19? ABSTRACT Recently, a novel coronavirus (2019-nCoV), officially known as severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), emerged in China. Despite drastic containment measures, the spread of this virus is ongoing. SARS-CoV-2 is the aetiological agent of coronavirus disease 2019 (COVID-19) characterised by pulmonary infection in humans. The efforts of international health authorities have since focused on rapid diagnosis and isolation of patients as well as the search for therapies able to counter the most severe effects of the disease. In the absence of a known efficient therapy and because of the situation of a public-health emergency, it made sense to investigate the possible effect of chloroquine/hydroxychloroquine against SARS-CoV-2 since this molecule was previously described as a potent inhibitor of most coronaviruses, including SARS-CoV-1. Preliminary trials of chloroquine repurposing in the treatment of COVID-19 in China have been encouraging, leading to several new trials. Here we discuss the possible mechanisms of chloroquine interference with the SARS-CoV-2 replication cycle. |
22 | 9jnixy2b | are cardiac complications likely in patients with COVID-19? | Urgent Guidance for Navigating and Circumventing the QTc-Prolonging and Torsadogenic Potential of Possible Pharmacotherapies for Coronavirus Disease 19 (COVID-19) Abstract As the coronavirus disease 19 (COVID-19) global pandemic rages across the globe, the race to prevent and treat this deadly disease has led to the "off-label" repurposing of drugs such as hydroxychloroquine and lopinavir/ritonavir, which has the potential for unwanted QT-interval prolongation and a risk of drug-induced sudden cardiac death. With the possibility that a considerable proportion of the world's population soon could receive COVID-19 pharmacotherapies with torsadogenic potential for therapy or postexposure prophylaxis, this document serves to help health care professionals mitigate the risk of drug-induced ventricular arrhythmias while minimizing risk of COVID-19 exposure to personnel and conserving the limited supply of personal protective equipment. |
37 | eyi5609q | What is the result of phylogenetic analysis of SARS-CoV-2 genome sequence? | Phylogenetic Analysis of the Novel Coronavirus Reveals Important Variants in Indian Strains Recently classified as a pandemic by WHO, novel Corononavirus 2019 has affected almost every corner of the globe causing human deaths in a range of hundred thousands. The virus having its roots in Wuhan (China) has been spread over the world by its own property to change itself accordingly. These changes correspond to its transmission and pathogenicity due to which the concept of social distancing appeared into the picture. In this paper, a few findings from the whole genome sequence analysis of viral genome sequences submitted from India are presented. The data used for analysis comprises 440 collective genome sequences of virus submitted in GenBank, GISAID, and SRA projects, from around the world as well as 28 viral sequences from India. Multiple sequence alignment of all genome sequences was performed and analysed. A novel non-synonymous mutation 4809C>T (S1515F) in NSP3 gene of SARS-CoV2 Indian strains is reported along with other frequent and important changes from around the world: 3037C>T, 14408C>T, and 23403A>G. The novel change was observed in samples collected in the month of March, whereas was found to be absent in samples collected in January with the respective persons' travel history to China. Phylogenetic analysis clustered the sequences with this change as one separate clade. Mutation was predicted as stabilising change by insilco tool DynaMut. A second patient in the world to our knowledge with multiple (Wuhan and USA) strain contraction was observed in this study. The infected person is among the two early infected patients with travel history to China. Strains sequenced in Iran stood out to have different variants, as most of the reported frequent variants were not observed. The objective of this paper is to highlight the similarities and changes observed in the submitted Indian viral strains. This helps to keep track on the activity, that how virus is changing into a new subtype. Major strains observed were European with the novel change in India and other being emergent clade of Iran. Its important to observe the changes in NSP3 gene, as this gene has been reported with extensive positive selection as well as potential drug target. Extensive Positive Selection Drives the Evolution of Nonstructural Proteins. With the limited number of sequences this was the only frequent novel non-synonymous change observed from Indian strains, thereby making this change vulnerable for investigation in future. This paper has a special focus on tracking of Indian viral sequences submitted in public domain. |
23 | as6tbfrh | what kinds of complications related to COVID-19 are associated with hypertension? | Clinical characteristics associated with COVID-19 severity in California Given the rapidly progressing COVID-19 pandemic, this report on a US cohort of 54 COVID-19 patients from Stanford Hospital and data regarding risk factors for severe disease obtained at initial clinical presentation is of high importance and is immediately clinically relevant. We identified low presenting oxygen saturation as predictive of severe disease outcomes, such as diagnosis of pneumonia, acute respiratory distress syndrome (ARDS), and admission to the ICU, and also replicated data from China suggesting a link between hypertension and disease severity. Clinicians will benefit by tools to rapidly risk stratify patients at presentation by likelihood of progression to severe disease. |
32 | hj830rxs | Does SARS-CoV-2 have any subtypes, and if so what are they? | Genotyping SARS-CoV-2 through an interactive web application |
9 | 3qqzthx8 | how has COVID-19 affected Canada | Caring for persons in detention suffering with mental illness during the Covid-19 outbreak |
18 | r1oqwdkz | what are the best masks for preventing infection by Covid-19? | Medical mask or N95 respirator: When and how to use? COVID-19 pandemic is now a global threat to human health reaching up to 2 million infected people all around the world. Since its first recognition in Wuhan, many topics were discussed intensively about COVID-19, both in the public and scientific community. Personal protective equipment, especially masks, has been among the hottest topics during this pandemic. Regardless of which mask is used, performing hand hygiene frequently with an alcohol-based hand rub or with soap and water if hands are dirty is the most effective preventive measure for COVID-19. The type of mask used when caring for COVID-19 patients will vary according to the setting, type of personnel/person, and activity. Although the main transmission route for COVID-19 is droplets, during aerosol generating procedures airborne transmission may occur. Keeping the distancing and medical masks and eye protection during close contact efficiently protects against respiratory diseases transmitted via droplets. Airborne precautions include goggles and respiratory protection with the use of an N95 or an equivalent mask respirator to prevent airborne transmission. |
29 | totc93f4 | which SARS-CoV-2 proteins-human proteins interactions indicate potential for drug targets. Are there approved drugs that can be repurposed based on this information? | Diacerein: A potential multi-target therapeutic drug for COVID-19 Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), which causes coronavirus disease 19 (COVID-19), was declared pandemic by the World Health Organization in March 2020. SARS-CoV-2 binds its host cell receptor, angiotensin-converting enzyme 2 (ACE2), through the viral spike (S) protein. The mortality related to severe acute respiratory distress syndrome (ARDS) and multi-organ failure in COVID-19 patients has been suggested to be connected with cytokine storm syndrome (CSS), an excessive immune response that severely damages healthy lung tissue. In addition, cardiac symptoms, including fulminant myocarditis, are frequent in patients in a severe state of illness. Diacerein (DAR) is an anthraquinone derivative drug whose active metabolite is rhein. Different studies have shown that this compound inhibits the IL-1, IL-2, IL-6, IL-8, IL-12, IL-18, TNF-α, NF-κB and NALP3 inflammasome pathways. The antiviral activity of rhein has also been documented. This metabolite prevents hepatitis B virus (HBV) replication and influenza A virus (IAV) adsorption and replication through mechanisms involving regulation of oxidative stress and alterations of the TLR4, Akt, MAPK, and NF-κB signalling pathways. Importantly, rhein inhibits the interaction between the SARS-CoV S protein and ACE2 in a dose-dependent manner, suggesting rhein as a potential therapeutic agent for the treatment of SARS-CoV infection. Based on these findings, we hypothesize that DAR is a multi-target drug useful for COVID-19 treatment. This anthraquinone may control hyperinflammatory conditions by multi-faceted cytokine inhibition and by reducing viral infection. |
4 | 6wbrv9o1 | what causes death from Covid-19? | Clinical and virological data of the first cases of COVID-19 in Europe: a case series BACKGROUND: On Dec 31, 2019, China reported a cluster of cases of pneumonia in people at Wuhan, Hubei Province. The responsible pathogen is a novel coronavirus, named severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). We report the relevant features of the first cases in Europe of confirmed infection, named coronavirus disease 2019 (COVID-19), with the first patient diagnosed with the disease on Jan 24, 2020. METHODS: In this case series, we followed five patients admitted to Bichat-Claude Bernard University Hospital (Paris, France) and Pellegrin University Hospital (Bordeaux, France) and diagnosed with COVID-19 by semi-quantitative RT-PCR on nasopharyngeal swabs. We assessed patterns of clinical disease and viral load from different samples (nasopharyngeal and blood, urine, and stool samples), which were obtained once daily for 3 days from hospital admission, and once every 2 or 3 days until patient discharge. All samples were refrigerated and shipped to laboratories in the National Reference Center for Respiratory Viruses (The Institut Pasteur, Paris, and Hospices Civils de Lyon, Lyon, France), where RNA extraction, real-time RT-PCR, and virus isolation and titration procedures were done. FINDINGS: The patients were three men (aged 31 years, 48 years, and 80 years) and two women (aged 30 years and 46 years), all of Chinese origin, who had travelled to France from China around mid-January, 2020. Three different clinical evolutions are described: (1) two paucisymptomatic women diagnosed within a day of exhibiting symptoms, with high nasopharyngeal titres of SARS-CoV-2 within the first 24 h of the illness onset (5·2 and 7·4 log(10) copies per 1000 cells, respectively) and viral RNA detection in stools; (2) a two-step disease progression in two young men, with a secondary worsening around 10 days after disease onset despite a decreasing viral load in nasopharyngeal samples; and (3) an 80-year-old man with a rapid evolution towards multiple organ failure and a persistent high viral load in lower and upper respiratory tract with systemic virus dissemination and virus detection in plasma. The 80-year-old patient died on day 14 of illness (Feb 14, 2020); all other patients had recovered and been discharged by Feb 19, 2020. INTERPRETATION: We illustrated three different clinical and biological types of evolution in five patients infected with SARS-CoV-2 with detailed and comprehensive viral sampling strategy. We believe that these findings will contribute to a better understanding of the natural history of the disease and will contribute to advances in the implementation of more efficient infection control strategies. FUNDING: REACTing (Research & Action Emerging Infectious Diseases). |
15 | 8pkrg0mx | how long can the coronavirus live outside the body | The Coronavirus Nucleocapsid Is a Multifunctional Protein The coronavirus nucleocapsid (N) is a structural protein that forms complexes with genomic RNA, interacts with the viral membrane protein during virion assembly and plays a critical role in enhancing the efficiency of virus transcription and assembly. Recent studies have confirmed that N is a multifunctional protein. The aim of this review is to highlight the properties and functions of the N protein, with specific reference to (i) the topology; (ii) the intracellular localization and (iii) the functions of the protein. |
15 | eec649x4 | how long can the coronavirus live outside the body | Data analytics for novel coronavirus disease This paper describes different aspects of novel coronavirus disease (COVID-19), presents visualization of the spread of the infection, and discusses the potential applications of data analytics on this viral infection. Firstly, a literature survey is done on COVID-19 highlighting a number of factors including its origin, its similarity with previous coronaviruses, its transmission capacity, its symptoms, etc. Secondly, data analytics is applied on a dataset of Johns Hopkins University to find out the spread of the viral infection. It is shown here that although the disease started in China in December 2019, the highest number of confirmed cases up to June 04, 2020 is in the USA. Thirdly, the worldwide increase in the number of confirmed cases over time is modelled here using a polynomial regression algorithm with degree 2. Fourthly, classification algorithms are applied on a dataset of 5644 samples provided by Hospital Israelita Albert Einstein of Brazil in order to diagnose COVID-19. It is shown here that multilayer perceptron (MLP), XGBoost and logistic regression can classify COVID-19 patients at an accuracy above 91%. Finally, a discussion is presented on the potential applications of data analytics in several important factors of COVID-19. |
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