query_id
stringlengths 1
41
| doc_id
stringlengths 1
109
| query
stringlengths 2
5.5k
| document
stringlengths 0
122k
|
|---|---|---|---|
15 | safr9z37 | how long can the coronavirus live outside the body | COVID-19 research has overall low methodological quality thus far: case in point for chloroquine/hydroxychloroquine What is new? KEY FINDINGS: Clinical decision-makers must be informed by the best, most trustworthy, highest-quality, robust evidence. This translates into how much confidence we can have in the research findings and thus be optimally informed for decision-making. The estimates of effect in clinical research depends on the underlying research methodology. COVID-19 disease is presenting global health systems, clinicians, and patients grave challenges. No treatment or prophylaxis currently exists for COVID-19. The overall body of COVID-19 research is very flawed methodologically. An examination of hydroxychloroquine-azithromycin research findings due to the recent media focus revealed very low-quality methodology underpins the research. Vast amounts of time and resources are being allocated to COVID-19 research, and being potentially squandered. WHAT THIS ADDS TO WHAT WAS KNOWN: Flawed methodology and sub-optimal reporting of research findings could lead to biased estimates of effect. This could lead to treatment decisions that are not optimal based on biased estimates which could harm the patient. This article provides specific suggestions for improving on the COVID-19 methods and reporting with a focus on the issues that researchers must consider in their methodology and reporting if we are to have confidence in the estimates of effect. Failure to consider harms in research could be detrimental to the patient. This article focuses on the potential harms when therapeutic agents such as hydroxychloroquine, are being considered. WHAT IS THE IMPLICATION AND WHAT SHOULD CHANGE NOW: Research thus far on finding an optimal therapeutic agent (s) for COVID-19 could be hampered by methodologically flawed research. COVID-19 researchers must immediately and acutely focus on improving their methodology and reporting. |
5 | 10ecm4wi | what drugs have been active against SARS-CoV or SARS-CoV-2 in animal studies? | Comparison of SARS-CoV-2 spike protein binding to ACE2 receptors from human, pets, farm animals, and putative intermediate hosts The emergence of a novel coronavirus, SARS-CoV-2, resulted in a pandemic. Here, we used X-ray structures of human ACE2 bound to the receptor-binding domain (RBD) of the spike protein (S) from SARS-CoV-2 to predict its binding to ACE2 proteins from different animals, including pets, farm animals, and putative intermediate hosts of SARS-CoV-2. Comparing the interaction sites of ACE2 proteins known to serve or not serve as receptor allows to define residues important for binding. From the 20 amino acids in ACE2 that contact S up to seven can be replaced and ACE2 can still function as the SARS-CoV-2 receptor. These variable amino acids are clustered at certain positions, mostly at the periphery of the binding site, while changes of the invariable residues prevent S-binding or infection of the respective animal. Some ACE2 proteins even tolerate the loss or the acquisition of N-glycosylation sites located near the S-interface. Of note, Pigs and dogs, which are not or not effectively infected and have only a few changes in the binding site, exhibit relatively low levels of ACE2 in the respiratory tract. Comparison of the RBD of S of SARS-CoV-2 with viruses from Bat-CoV-RaTG13 and Pangolin-CoV revealed that the latter contains only one substitution, whereas the Bat-CoV-RaTG13 exhibits five. However, ACE2 of pangolin exhibit seven changes relative to human ACE2, a similar number of substitutions is present in ACE2 of bats, raccoon, and civet suggesting that SARS-CoV-2 may not especially adapted to ACE2 of any of its putative intermediate hosts. These analyses provide new insight into the receptor usage and animal source/origin of SARS-CoV-2.IMPORTANCE SARS-CoV-2 is threatening people worldwide and there are no drugs or vaccines available to mitigate its spread. The origin of the virus is still unclear and whether pets and livestock can be infected and transmit SARS-CoV-2 are important and unknown scientific questions. Effective binding to the host receptor ACE2 is the first prerequisite for infection of cells and determines the host range. Our analysis provides a framework for the prediction of potential hosts of SARS-CoV-2. We found that ACE2 from species known to support SARS-CoV-2 infection tolerate many amino acid changes indicating that the species barrier might be low. An exception are dogs and especially pigs, which, however, revealed relatively low ACE2 expression levels in the respiratory tract. Monitoring of animals is necessary to prevent the generation of a new coronavirus reservoir. Finally, our analysis also showed that SARS-CoV-2 may not be specifically adapted to any of its putative intermediate hosts. |
5 | cgiok0ce | what drugs have been active against SARS-CoV or SARS-CoV-2 in animal studies? | An innovative approach to induce cross-protective immunity against porcine reproductive and respiratory syndrome virus in the lungs of pigs through adjuvanted nanotechnology-based vaccination Porcine reproductive and respiratory syndrome (PRRS) is an economically devastating respiratory disease of pigs. The disease is caused by the PRRS virus (PRRSV), an Arterivirus which is a highly mutating RNA virus. Widely used modified live PRRSV vaccines have failed to prevent PRRS outbreaks and reinfections; moreover, safety of the live virus vaccines is questionable. Though poorly immunogenic, inactivated PRRSV vaccine is safe. The PRRSV infects primarily the lung macrophages. Therefore, we attempted to strengthen the immunogenicity of inactivated/killed PRRSV vaccine antigens (KAg), especially in the pig respiratory system, through: 1) entrapping the KAg in biodegradable poly(lactic-co-glycolic acid) nanoparticles (NP-KAg); 2) coupling the NP-KAg with a potent mucosal adjuvant, whole cell lysate of Mycobacterium tuberculosis (M. tb WCL); and 3) delivering the vaccine formulation twice intranasally to growing pigs. We have previously shown that a single dose of NP-KAg partially cleared the challenged heterologous PRRSV. Recently, we reported that NP-KAg coupled with unentrapped M. tb WCL significantly cleared the viremia of challenged heterologous PRRSV. Since PRRSV is primarily a lung disease, our goal in this study was to investigate lung viral load and various immune correlates of protection at the lung mucosal surfaces and its parenchyma in vaccinated heterologous PRRSV-challenged pigs. Our results indicated that out of five different vaccine-adjuvant formulations, the combination of NP-KAg and unentrapped M. tb WCL significantly cleared detectable replicating infective PRRSV with a tenfold reduction in viral RNA load in the lungs, associated with substantially reduced gross and microscopic lung pathology. Immunologically, strong humoral (enhanced virus neutralization titers by high avidity antibodies) and cell-mediated immune responses (augmented population of interferon-γ secreting CD4(+) and CD8(+) lymphocytes and reduced secretion of immunosuppressive cytokines) in the lungs were observed. In conclusion, combination of NP-KAg and soluble M. tb WCL elicits broadly cross-protective anti-PRRSV immunity in the pig respiratory system. |
16 | ble8gn1l | how long does coronavirus remain stable on surfaces? | Physico-chemical properties of murine hepatitis virus, strain A59 The infectivity of murine hepatitis virus (MHV-A59) was optimally stable at pH 6.0 and was unaffected by ionic strength or at least 15 cycles of freezing and thawing. It was completely inactivated within 25 minutes at 56° C, but was protected by 1m magnesium chloride or magnesium sulphate. It was completely inactivated within 14 days at 37 and 22°C, but was relatively stable for as long as 72 days at 4°C and optimal pH. |
32 | bdt7snjp | Does SARS-CoV-2 have any subtypes, and if so what are they? | Etiology and genetic evolution of canine coronavirus circulating in five provinces of China, during 2018-2019 As the outbreaks of COVID-19 in worldwide, coronavirus has once again caught the attention of people. Canine coronavirus is widespread among dog population, and sometimes causes even fatal cases. Here, to characterize the prevalence and evolution of current circulating canine coronavirus (CCoV) strains in China, we collected 213 fecal samples from diarrheic pet dogs between 2018 and 2019. Of the 213 samples, we found 51 (23.94%) were positive for CCoV. Co-infection with canine parvovirus (CPV), canine astrovirus (CaAstV), canine kobuvirus (CaKV), Torque teno canis virus (TTCaV) were ubiquitous existed. Mixed infection of different CCoV subtypes exists extensively. Considering the limited sequences data in recent years, we sequenced 7 nearly complete genomes and 10 complete spike gene. Phylogenetic analysis of spike gene revealed a new subtype CCoV-II Variant and CCoV-IIa was the most prevalent subtype currently circulating. Moreover, we identified strain B906_ZJ_2019 shared 93.24% nucleotide identifies with previous strain A76, and both of them clustered with CCoV-II Variant, which were not well clustered with the known subtypes. Recombination analysis of B906_ZJ_2019 indicated that strain B906_ZJ_2019 may a recombinant variant between CCoV-I and CCoV-II, which is consistent with strain A76. Furthermore, amino acid variations widely existed among current CCoV-IIa strains circulating in China and the classic CCoV-IIa strains, in spite of the unknown functions. In a word, we report a useful information as to the etiology and evolution of canine coronavirus in China based on the available sequences, which is urgent for the devise of future effective disease prevention and control strategies. |
40 | chnj2ojk | What are the observed mutations in the SARS-CoV-2 genome and how often do the mutations occur? | Comparative Analysis of SARS-CoV2 with Special Emphasis on Genome Sequences Coronavirus disease 2019 (COVID-19), caused by severe acute respiratory syndrome coronavirus - 2 (SARS-CoV-2), was declared a global pandemic on 11th March, 2020 by World Health Organization As of now,27th May,2020, there are about 54,88,825 infected cases and 3,49,095 deaths globally Coronavirus samples collected from all the countries have been sequenced for advanced studies in a bid to understand the structure and functioning of the virus In our study we have tried working on every available sequence to setup both comparisons and co-relations There is no such available study as of now for reference and hence it can become a pioneer stone in this direction The mortality rate calculated turns out to be 9 19%,34 37% and 6 29% for SARS-2003, MERS-2012 and COVID-19 respectively The basic reproduction rate R0 was 2-5 for SARS-2003, 0 3-0 8 for MERS-2012 and 1 4-5 7 for COVID-19 We found out the relation between number of mutations and mortality as well as phylogenetic relations High number of mutations corresponded to higher mortality rate as in countries like Italy and Spain Alpha and Beta-coronaviruses show a common ancestor from which they descended Brazil and Iran have shown similar phylogenetic descent explaining their mortality rate India however showed a distant relation from the common ancestor of other genome sequences This study highlights the mutations of the SARS-CoV2 virus as well as sets up a comparison with the previous outbreaks Similar type of studies should be conducted when more genome samples are present These results can also contribute towards making an effective anti-viral therapy and vaccines |
27 | rcljauve | what is known about those infected with Covid-19 but are asymptomatic? | COVID-19 in the Cancer Patient The novel Coronavirus Disease 2019 (COVID-19) was first reported in China in December 2019. Since then, it has spread across the world to become one of the most serious life-threatening pandemics since the influenza pandemic of 1918. This review article will focus on the specific risks and nuanced considerations of COVID-19 in the cancer patient. Important perioperative management recommendations during this outbreak are emphasized, in addition to discussion of current treatment techniques and strategies available in the battle against COVID-19. |
26 | wcoch07b | what are the initial symptoms of Covid-19? | Severe Acute Respiratory Syndrome: Pertinent Clinical Characteristics and Therapy Severe acute respiratory syndrome (SARS) is a newly emerged infection that is caused by a previously unrecognized virus–a novel coronavirus designated as SARS-associated coronavirus (SARS-CoV). From November 2002 to July 2003 the cumulative number of worldwide cases was >8000, with a mortality rate of close to 10%. The mortality has been higher in older patients and those with co-morbidities. SARS has been defined using clinical and epidemiological criteria and cases are considered laboratory-confirmed if SARS coronavirus is isolated, if antibody to SARS coronavirus is detected, or a polymerase chain reaction test by appropriate criteria is positive. At the time of writing (24 May 2004), no specific therapy has been recommended. A variety of treatments have been attempted, but there are no controlled data. Most patients have been treated throughout the illness with broad-spectrum antimicrobials, supplemental oxygen, intravenous fluids, and other supportive measures. Transmission of SARS is facilitated by close contact with patients with symptomatic infection. The majority of cases have been reported among healthcare providers and family members of SARS patients. Since SARS-CoV is contagious, measures for prevention center on avoidance of exposure, and infection control strategies for suspected cases and contacts. This includes standard precautions (hand hygiene), contact precautions (gowns, goggles, gloves) and airborne precautions (negative pressure rooms and high efficiency masks). In light of reports of new cases identified during the winter of 2003–4 in China, it seems possible that SARS will be an important cause of pneumonia in the future, and the screening of outpatients at risk for SARS may become part of the pneumonia evaluation. |
9 | phepjf55 | how has COVID-19 affected Canada | On epidemic modeling in real time: An application to the 2009 Novel A (H1N1) influenza outbreak in Canada BACKGROUND: Management of emerging infectious diseases such as the 2009 influenza pandemic A (H1N1) poses great challenges for real-time mathematical modeling of disease transmission due to limited information on disease natural history and epidemiology, stochastic variation in the course of epidemics, and changing case definitions and surveillance practices. FINDINGS: The Richards model and its variants are used to fit the cumulative epidemic curve for laboratory-confirmed pandemic H1N1 (pH1N1) infections in Canada, made available by the Public Health Agency of Canada (PHAC). The model is used to obtain estimates for turning points in the initial outbreak, the basic reproductive number (R(0)), and for expected final outbreak size in the absence of interventions. Confirmed case data were used to construct a best-fit 2-phase model with three turning points. R(0 )was estimated to be 1.30 (95% CI 1.12-1.47) for the first phase (April 1 to May 4) and 1.35 (95% CI 1.16-1.54) for the second phase (May 4 to June 19). Hospitalization data were also used to fit a 1-phase model with R(0 )= 1.35 (1.20-1.49) and a single turning point of June 11. CONCLUSIONS: Application of the Richards model to Canadian pH1N1 data shows that detection of turning points is affected by the quality of data available at the time of data usage. Using a Richards model, robust estimates of R(0 )were obtained approximately one month after the initial outbreak in the case of 2009 A (H1N1) in Canada. |
3 | yq4dtf8n | will SARS-CoV2 infected people develop immunity? Is cross protection possible? | Severe acute respiratory syndrome and dentistry A retrospective view ABSTRACT Background Severe acute respiratory syndrome, or SARS, which has created panic in Asia and in some parts of North America, is the first epidemic of the new century. Although it has been well-contained, sporadic cases continue to emerge. Objectives The authors trace the emergence of the SARS outbreak from southern China and its spread worldwide, discuss the viral etiology of the infection and its clinical features, and review the infection control guidelines issued during the outbreak by the health authorities in Hong Kong, the Centers for Disease Control and Prevention, the World Health Organization and the American Dental Association. They also review the prospects for a new outbreak and preventive measures. Overview The disease, which is caused by a novel coronavirus termed the "SARS coronavirus," or SARS-CoV, essentially spreads through droplet infection and affects people of any age. It has a mortality rate ranging from 10 to 15 percent. A major hallmark of this disease has been the rate at which it has affected health care workers through nosocomial transmission; in some countries, up to one-fourth to one-third of those infected were in this category. However, no dental health care worker has been affected by SARS in a nosocomial or dental setting. Conclusions and Clinical Implications Researchers believe that a combination of factors, including the universal infection control measures that the dental community has implemented and/or the low degree of viral shedding in the prodromal phase of SARS, may have obviated the spread of the disease in dental settings. The dental community should reflect on this outbreak to reinforce the currently applied infection control measures. |
5 | unwxxt8s | what drugs have been active against SARS-CoV or SARS-CoV-2 in animal studies? | Anti-infective immunoadhesins from plants Immunoadhesins are recombinant proteins that combine the ligand-binding region of a receptor or adhesion molecule with immunoglobulin constant domains. All FDA-approved immunoadhesins are designed to modulate the interaction of a human receptor with its normal ligand, such as Etanercept (Enbrel(®)), which interferes with the binding of tumour necrosis factor (TNF) to the TNF-alpha receptor and is used to treat inflammatory diseases such as rheumatoid arthritis. Like antibodies, immunoadhesins have long circulating half-lives, are readily purified by affinity-based methods and have the avidity advantages conferred by bivalency. Immunoadhesins that incorporate normal cellular receptors for viruses or bacterial toxins hold great, but as yet unrealized, potential for treating infectious disease. As decoy receptors, immunoadhesins have potential advantages over pathogen-targeted monoclonal antibodies. Planet Biotechnology has specialized in developing anti-infective immunoadhesins using plant expression systems. An immunoadhesin incorporating the cellular receptor for anthrax toxin, CMG2, potently blocks toxin activity in vitro and protects animals against inhalational anthrax. An immunoadhesin based on the receptor for human rhinovirus, ICAM-1, potently blocks infection of human cells by one of the major causes of the common cold. An immunoadhesin targeting the MERS coronavirus is in an early stage of development. We describe here the unique challenges involved in designing and developing immunoadhesins targeting infectious diseases in the hope of inspiring further research into this promising class of drugs. |
19 | k7sltus2 | what type of hand sanitizer is needed to destroy Covid-19? | Effectiveness of Ultraviolet-C Light and a High-Level Disinfection Cabinet for Decontamination of N95 Respirators BACKGROUND: Shortages of personal protective equipment (PPE) including N95 respirators are an urgent concern in the setting of the global COVID-19 pandemic. Decontamination of PPE could be useful to maintain adequate supplies, but there is uncertainty regarding the efficacy of decontamination technologies. METHODS: A modification of the American Society for Testing and Materials standard quantitative carrier disk test method (ASTM E-2197-11) was used to examine the effectiveness of 3 methods, including ultraviolet-C (UV-C) light, a high-level disinfection cabinet that generates aerosolized peracetic acid and hydrogen peroxide, and dry heat at 70°C for 30 minutes. We assessed the decontamination of 3 commercial N95 respirators inoculated with methicillin-resistant Staphylococcus aureus (MRSA) and bacteriophages MS2 and Phi6; the latter is an enveloped RNA virus used as a surrogate for coronaviruses. Three and 6 log(10) reductions on respirators were considered effective for decontamination and disinfection, respectively. RESULTS: UV-C administered as a 1-minute cycle in a UV-C box or a 30-minute cycle by a room decontamination device reduced contamination but did not meet criteria for decontamination of the viruses from all sites on the N95s. The high-level disinfection cabinet was effective for decontamination of the N95s and achieved disinfection with an extended 31-minute cycle. Dry heat at 70°C for 30 minutes was not effective for decontamination of the bacteriophages. CONCLUSIONS: UV-C could be useful to reduce contamination on N95 respirators. However, the UV-C technologies studied did not meet pre-established criteria for decontamination under the test conditions used. The high-level disinfection cabinet was more effective and met criteria for disinfection with an extended cycle. |
14 | 99ri6x0y | what evidence is there related to COVID-19 super spreaders | SARS Severe acute respiratory syndrome (SARS) is an acute respiratory tract infectious disease induced by SARS-CoV and mainly transmitted through the short-distance air droplets and close contact. Its main clinical characteristics is abrupt onset of the disease and the initial symptom is fever accompanied with systematic symptoms of headache, soreness and fatigue, and respiratory tract symptoms such as cough, chest dullness, and dyspnea. A few cases may progress to acute respiratory distress syndrome (ARDS). Due to its self-limiting feature, the prognosis is predominantly good but may be poor in severe cases, with mortality about 9.3 %. Some patients may develop such complications such as lung fibrosis and necrosis of the head of femur. On April 8, 2003, SARS was defined as a legal infectious disease by the Ministry of Heath of China. |
34 | 1f8yhppi | What are the longer-term complications of those who recover from COVID-19? | The important role of polysaccharides from a traditional Chinese medicine-Lung Cleansing and Detoxifying Decoction against the COVID-19 pandemic Abstract The new coronavirus pneumonia, named COVID-19 by the World Health Organization, has become a pandemic. It is highly pathogenic and reproduces quickly. There are currently no specific drugs to prevent the reproduction and spread of COVID-19. Some traditional Chinese medicines, especially the Lung Cleansing and Detoxifying Decoction (Qing Fei Pai Du Tang), have shown therapeutic effects on mild and ordinary COVID-19 patients. Polysaccharides are important ingredients in this decoction. This review summarizes the potential pharmacological activities of polysaccharides isolated by hot water extraction from Lung Cleansing and Detoxifying Decoction, which is consistent with its production method, to provide the theoretical basis for ongoing research on its application. |
38 | n0d9b50t | What is the mechanism of inflammatory response and pathogenesis of COVID-19 cases? | SARS-CoV-2 COVID-19 susceptibility and lung inflammatory storm by smoking and vaping The current pandemic of COVID-19 has caused severe morbidity and mortality across the globe. People with a smoking history have severe disease outcomes by COVID-19 infection. Epidemiological studies show that old age and pre-existing disease conditions (hypertension and diabetes) result in severe disease outcome and mortality amongst COVID-19 patients. Evidences suggest that the S1 domain of the SARS-CoV-2 (causative agent of COVID-19) membrane spike has a high affinity towards the angiotensin-converting enzyme 2 (ACE2) receptor found on the host's lung epithelium. Likewise, TMPRSS2 protease has been shown to be crucial for viral activation thus facilitating the viral engulfment. The viral entry has been shown to cause 'cytokine storm' involving excessive production of pro-inflammatory cytokines/chemokines including IL-6, TNF-α, IFN-γ, IL-2, IL-7, IP-10, MCP-3 or GM-CSF, which is augmented by smoking. Future research could target these inflammatory-immunological responses to develop effective therapy for COVID-19. This mini-review provides a consolidated account on the role of inflammation and immune responses, proteases, and epithelial permeability by smoking and vaping during SARS-CoV2 infection with future directions of research, and provides a list of the potential targets for therapies particularly controlling cytokine storms in the lung. |
21 | ikx6cpfy | what are the mortality rates overall and in specific populations | Dynamic and Cell-Infiltratable Hydrogels as Injectable Carrier of Therapeutic Cells and Drugs for Treating Challenging Bone Defects [Image: see text] Biopolymeric hydrogels have been widely used as carriers of therapeutic cells and drugs for biomedical applications. However, most conventional hydrogels cannot be injected after gelation and do not support the infiltration of cells because of the static nature of their network structure. Here, we develop unique cell-infiltratable and injectable (Ci-I) gelatin hydrogels, which are physically cross-linked by weak and highly dynamic host–guest complexations and are further reinforced by limited chemical cross-linking for enhanced stability, and then demonstrate the outstanding properties of these Ci-I gelatin hydrogels. The highly dynamic network of Ci-I hydrogels allows injection of prefabricated hydrogels with encapsulated cells and drugs, thereby simplifying administration during surgery. Furthermore, the reversible nature of the weak host–guest cross-links enables infiltration and migration of external cells into Ci-I gelatin hydrogels, thereby promoting the participation of endogenous cells in the healing process. Our findings show that Ci-I hydrogels can mediate sustained delivery of small hydrophobic molecular drugs (e.g., icaritin) to boost differentiation of stem cells while avoiding the adverse effects (e.g., in treatment of bone necrosis) associated with high drug dosage. The injection of Ci-I hydrogels encapsulating mesenchymal stem cells (MSCs) and drug (icaritin) efficiently prevented the decrease in bone mineral density (BMD) and promoted in situ bone regeneration in an animal model of steroid-associated osteonecrosis (SAON) of the hip by creating the microenvironment favoring the osteogenic differentiation of MSCs, including the recruited endogenous cells. We believe that this is the first demonstration on applying injectable hydrogels as effective carriers of therapeutic cargo for treating dysfunctions in deep and enclosed anatomical sites via a minimally invasive procedure. |
16 | rjqanuk9 | how long does coronavirus remain stable on surfaces? | Consideration of the Aerosol Transmission for COVID‐19 and Public Health This article analyzes the available evidence to address airborne, aerosol transmission of the SARS‐CoV‐2. We review and present three lines of evidence: case reports of transmission for asymptomatic individuals in association with studies that show that normal breathing and talking produce predominantly small droplets of the size that are subject to aerosol transport; limited empirical data that have recorded aerosolized SARS‐CoV‐2 particles that remain suspended in the air for hours and are subject to transport over distances including outside of rooms and intrabuilding, and the broader literature that further supports the importance of aerosol transmission of infectious diseases. The weight of the available evidence warrants immediate attention to address the significance of aerosols and implications for public health protection. |
23 | skknfc6h | what kinds of complications related to COVID-19 are associated with hypertension? | Comorbid Diabetes Mellitus was Associated with Poorer Prognosis in Patients with COVID-19: A Retrospective Cohort Study Background The 2019 novel coronavirus disease (COVID-19) emerged in Wuhan, Hubei province, China, and was characterized as pandemic by the World Health Organization. Diabetes mellitus is an established risk factor for poor clinical outcomes, but the association of diabetes with the prognosis of COVID-19 have not been reported yet. Methods In this cohort study, we retrospectively reviewed 258 consecutive hospitalized COVID-19 patients with or without diabetes at the West Court of Union Hospital of Huazhong University of Science and Technology in Wuhan, China, recruited from January 29 to February 12, 2020. The cases were confirmed by real-time PCR and the demographic, clinical, laboratory, radiological, and treatment data were collected and analyzed. Prognosis was defined as hospitalization, discharged survivor and death, which was followed up until March 12, 2020. Results Of the 258 hospitalized patients (63 with diabetes) with COVID-19, the median age was 64 years (range 23-91), and 138 (53.5%) were male. No significant differences in age and sex were identified between patients with and without diabetes. Common symptoms included fever (82.2%), dry cough (67.1%), polypnea (48.1%), and fatigue (38%). Patients with diabetes had significantly higher leucocyte and neutrophil counts, and higher levels of fasting blood glucose, serum creatinine, urea nitrogen and creatine kinase isoenzyme MB at admission compared with those without diabetes. COVID-19 patients with diabetes were more likely to develop severe or critical disease condition with more complications at presentation, and had higher incidence rates of antibiotic therapy, non-invasive and invasive mechanical ventilation, and death (11.1% vs. 4.1%). Cox proportional hazard model showed that diabetes (adjusted hazard ratio [aHR]=3.64; 95% confidence interval [CI]: 1.09, 12.21) and fasting blood glucose (aHR=1.19; 95% CI: 1.08, 1.31) were associated with the fatality of COVID-19, adjusting for potential confounders. Conclusions Diabetes mellitus is associated with greater disease severity and a higher risk of mortality in patients with COVID-19. Primary and secondary prevention strategies are needed for COVID-19 patients with diabetes. |
43 | qj7e5o19 | How has the COVID-19 pandemic impacted violence in society, including violent crimes? | Connecting data, tools and people across Europe: ELIXIR's response to the COVID-19 pandemic ELIXIR, the European research infrastructure for life science data, provides open access to data, tools and workflows in the response to the COVID-19 pandemic. ELIXIR's 23 nodes have reacted swiftly to support researchers in their combined efforts against the pandemic setting out three joint priorities: 1. Connecting national COVID-19 data platforms to create federated European COVID-19 Data Spaces; 2. Fostering good data management to make COVID-19 data open, FAIR and reusable over the long term; 3. Providing open tools, workflows and computational resources to drive reproducible and collaborative science. ELIXIR's strategy is based on the support given by our national nodes - collectively spanning over 200 institutes - to research projects and on partnering with community initiatives to drive development and adoption of good data practice and community driven standards. ELIXIR Nodes provide support activities locally and internationally, from provisioning compute capabilities to helping collect viral sequence data from hospitals. Some Nodes have prioritised access to their national cloud and compute facilities for all COVID-19 research projects, while others have developed tools to search, access and share all data related to the pandemic in a national healthcare setting. |
11 | ajp2ls6g | what are the guidelines for triaging patients infected with coronavirus? | Managing ICU surge during the COVID-19 crisis: rapid guidelines Given the rapidly changing nature of COVID-19, clinicians and policy makers require urgent review and summary of the literature, and synthesis of evidence-based guidelines to inform practice. The WHO advocates for rapid reviews in these circumstances. The purpose of this rapid guideline is to provide recommendations on the organizational management of intensive care units caring for patients with COVID-19 including: planning a crisis surge response; crisis surge response strategies; triage, supporting families, and staff. ELECTRONIC SUPPLEMENTARY MATERIAL: The online version of this article (10.1007/s00134-020-06092-5) contains supplementary material, which is available to authorized users. |
18 | 8e4vo6zz | what are the best masks for preventing infection by Covid-19? | Precaution of 2019 novel coronavirus infection in department of oral and maxillofacial surgery Abstract The epidemic of the 2019 novel coronavirus (2019-nCoV) infection has presented as a critical period. Until February 23th 2020, more than 77 000 cases of 2019-nCoV infection have been confirmed in China, which has a great impact on economy and society. It has also interferred with ordinary medical practice of oral and maxillofacial surgery seriously. In order to protect oral and maxillofacial surgery medical staff from 2019-nCoV infection during the outbreak period, this paper suggests the necessary medical protective measures for oral and maxillofacial surgery outpatient and ward. |
46 | bmnmwobu | what evidence is there for dexamethasone as a treatment for COVID-19? | Outpatient treatment of COVID-19 with steroids in the phase of mild pneumonia without the need for admission as an opportunity to modify the course of the disease: A structured summary of a randomised controlled trial OBJECTIVES: The aim of this study is to explore the effectiveness and safety of oral corticosteroids (prednisone) in the treatment of early stage SARS-Cov-2 pneumonia in patients who do not yet meet hospital admission criteria. TRIAL DESIGN: Randomized clinical trial, controlled, open, parallel group, to evaluate the effectiveness of steroids in adult patients with confirmed COVID-19, with incipient pulmonary involvement, without hospital admission criteria. Patients will be stratified by the presence or not of radiological data on pneumonia. PARTICIPANTS: We will include patients with early stage SARS-Cov-2 pneumonia who do not meet hospital admission criteria from the reference hospital, the Hospital Universitario de Burgos, in the region of Castilla y León, Spain. Patients will be followed-up by specialist physicians and Primary Health Care professionals. INCLUSION CRITERIA: - Men and women. - Age between 18 and 75 years old. - Diagnosed SARS-CoV-2 infection, by PCR and/or IgM+ antibody test and/or antigen test. - Clinical diagnosis of lung involvement: (respiratory symptoms +/- pathological auscultation +/- O2 desaturation) - Chest X-ray with mild-moderate alterations or normal. - Patients who give their verbal informed consent in front of witnesses, which will be reflected in the patients' medical records. EXCLUSION CRITERIA: - Oxygen desaturation below 93% or P02 < 62. - Moderate-severe dyspnea or significant respiratory or general deterioration that makes admission advisable. - Chest X-ray with multifocal infiltrates. - Insulin-dependent diabetes with poor control or glycaemia in the emergency room test greater than 300 mg/ml (fasting or not). - Other significant comorbidities: Severe renal failure (creatinine clearance < 30 mL/min); cirrhosis or chronic liver disease, poorly controlled hypertension. - Heart rhythm disturbances (including prolonged QT). - Severe immunosuppression (HIV infection, long-term use of immunosuppressive agents); cancer. - Pregnant or breast-feeding women. - Patients under use of glucocorticoids for other diseases. - History of allergy or intolerance to any of the drugs in the study (prednisone, azithromycin or hydroxychloroquine). - Patients who took one or more of the study drugs in the 7 days prior to study inclusion. - Patients taking non-suppressible drugs with risk of QT prolongation or significant interactions. - Patients unwilling or unable to participate until study completion. - Participation in another study. INTERVENTION AND COMPARATOR: Eligible patients will be randomized to receive standard outpatient treatment only (group 1) or standard outpatient treatment plus prednisone (group 2). - Group 1: paracetamol 1 g/8 h (on demand) + hydroxychloroquine 400 mg/12h the first day, 200 mg/12 h for 4 days + azithromycin 500 mg/24h for 5 days. - Group 2: paracetamol 1 g/8 h (on demand) + hydroxychloroquine 400 mg/12h the first day, 200 mg/12 h for 4 days + azithromycin 500 mg/24h for 5 days + prednisone 60 mg / 24 h for 3 days, 30 mg / 24 h for 3 days and 15 mg / 24 h for 3 days. MAIN OUTCOMES: If the patient requires ambulatory observation, according to the protocol established in this respect in the Emergency Department, meets all the criteria for inclusion and none for exclusion, data will be taken by the person responsible on the data collection sheet. The main result is admission after 30 days. Secondary outcomes are 30-day ICU admission and hospital stay. The safety variable will be the occurrence of clinical symptoms or delirium related to the steroids. Also, the possible decompensations of diabetes will be measured. All tests will be on an intention-to-treat basis. RANDOMISATION: Treatment will be assigned according to stratified randomization by the presence or absence of radiological data of lung involvement (previously performed by random sequence 1:1 generated with Epidat and kept hidden by opaque, sealed envelopes, which will only be opened after inclusion and basal measurement). BLINDING (MASKING): Participants, caregivers and personnel responsible for outcomes measurement will not be blinded to group assignment, once the patient is included and the basal measurement performed, as per protocol design. NUMBERS TO BE RANDOMISED (SAMPLE SIZE): The percentage of patients with incipient lung involvement is unknown, but given that pulmonary involvement already exists it is estimated to be around 20%. We consider that the intervention could reduce this percentage to 5%, so the necessary sample size would be 200 subjects (100 per group), with a power of 80% and an estimated loss percentage of 10%. TRIAL STATUS: The protocol with code TAC-COVID-19, version 2.0 on date: April 16, 2020 is approved by the Spanish Drug Agency (AEMPS) and the local Ethics Committee. The trial is in the recruitment phase. Recruitment began 19 April, 2020 and is anticipated to be complete by April 2021. TRIAL REGISTRATION: The trial was registered under the title "OUTPATIENT TREATMENT OF EARLY PULMONARY COVID19 WITH CORTICOSTEROIDS AS AN OPPORTUNITY TO MODIFY THE COURSE OF THE DISEASE" with EudraCT number 2020-001622-64 , registered on 3 April 2020. FULL PROTOCOL: The full protocol is attached as an additional file, accessible from the Trials website (Additional file 1). In the interest in expediting dissemination of this material, the familiar formatting has been eliminated; this Letter serves as a summary of the key elements of the full protocol. |
24 | ymheylhr | what kinds of complications related to COVID-19 are associated with diabetes | Advances in Gastrointestinal Surgery Carcinoma of the stomach is a global disease with the highest incidence in Asia, South America and Eastern Europe. The disease is least common in USA and Western Europe [1]. The disease is common among smokers. Other risk factors are H. pylori infection, atrophic gastritis, Menetrier's disease and previous gastrectomy. The disease can be genetic as in familial adenomatous polyposis, hereditary non-polyposis colorectal cancer, Peutz-Jegher's syndrome, etc. [2]. Screening for gastric carcinoma is done in high incidence areas such as Japan, Korea and China. |
27 | c93j35fl | what is known about those infected with Covid-19 but are asymptomatic? | COVID-19: asymptomatic carrier transmission is an underestimated problem At the present time, COVID-19 is spreading rapidly [1]. The global prevention and control of COVID-19 is focused on the estimation of the relevant incubation period, basic reproduction number (R(0)), effective reproduction number (R(t)) and death risk. Although the prevention and control of COVID-19 requires a reliable estimation of the relevant incubation period, R(0), R(t) and death risk. Another key epidemiological parameter-asymptomatic ratio that provides strength and range for social alienation strategies of COVID-19, which is widely defined as the proportion of asymptomatic infections among all disease infections. In fact, the ratio of asymptomatic infection is a useful indicator of the burden of disease and a better measurement of the transmissibility of the virus. So far, people have not paid enough attention to asymptomatic carriers. The asymptomatic carriers discussed in this study are recessive infections, that is, those who have never shown symptoms after onset of infection. We will discuss three aspects: detection, infectivity and proportion of healthy carriers. |
29 | mrgw2mnx | 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? | Human organs-on-chips as tools for repurposing approved drugs as potential influenza and COVID19 therapeutics in viral pandemics Rapidly spreading viral pandemics, such as those caused by influenza and SAR-CoV-2 (COVID19), require rapid action and the fastest way to combat this challenge is by repurposing existing drugs as anti-viral therapeutics. Here we first show that human organ-on-a-chip (Organ Chip) microfluidic culture devices lined by a highly differentiated, primary, human lung airway epithelium cultured under an air-liquid interface and fed by continuous medium flow can be used to model virus entry, replication, strain-dependent virulence, host cytokine production, and recruitment of circulating immune cells in response to infection by influenza, as well as effects of existing and novel therapeutics. These Airway Chips, which contain human lung epithelial cells that express high levels of ACE2 and TMPRSS2, were then used to assess the inhibitory activities of 7 clinically approved drugs (chloroquine, arbidol, toremifene, clomiphene, amodiaquine, verapamil, and amiodarone) that we found inhibit infection by viral pseudoparticles expressing SARS-CoV-2 spike protein in human Huh-7 cells, and others recently showed suppress infection by native SARS-CoV-2 in Vero cells. However, when these drugs were administered under flow at the maximal concentration in blood reported in clinical studies in human Airway Chips, only two of these drugs — amodiaquine and toremifene — significantly inhibited entry of the pseudotyped SARS-CoV-2 virus. This work suggests that human Organ Chip technology may be used in conjunction with existing rapid cell-based screening assays to study human disease pathogenesis and expedite drug repurposing in biothreat crises caused by pandemic viruses. |
47 | 2990fbda | what are the health outcomes for children who contract COVID-19? | [Pediatric impact of COVID-19] Children infected with SARS-CoV-2 are underrepresented during the current COVID-19 outbreak Unlike other respiratory viruses, SARS-CoV-2 rather infects adults who subsequently infect their children From recent Chinese and Italian data, children commonly present mild to moderate disease, a large proportion of them being asymptomatic In particular, children present significantly less fever, cough and pneumonia compared to adults However, more cases of pneumonia were reported from children infected with SARS-CoV-2 compared to those infected with H1N1 No vertical transmission of SARS-CoV-2 has been described so far |
45 | pl5hyzwp | How has the COVID-19 pandemic impacted mental health? | Flattening the mental ill-health curve: the importance of primary prevention in managing the mental health impacts of COVID19 The COVID19 pandemic is one the biggest challenges the global community has faced. The threat of the virus coupled with the impacts of the social and economic shut-down measures required to slow its spread, already appear to be impacting on people's mental health and wellbeing. Over the weeks, months and years ahead it is likely that many countries will experience a 'wave' of COVID19 related mental disorders as a result of an increase in risk factors linked to the pandemic such as social isolation; child-maltreatment; intimate partner violence; unemployment; housing and income stress; workplace trauma; and grief and loss. The 'two-pronged' approach used to deal with COVID19, provides an excellent blueprint for managing its mental health impacts as well. Nations must focus on preventing the occurrence of new cases of mental disorders as well as strengthening their mental healthcare response to support people who become mentally unwell. A focus on primary prevention is particularly important to 'flatten the curve' and avoid a surge in incidence of mental disorders stemming from the COVID19 pandemic. Many evidence-based interventions designed to prevent common disorders are already available and should be scaled-up. These interventions include parenting programs, social and emotional learning programs, self-care strategies, and workplace mental wellbeing programs, among others. |
32 | pmzdovna | Does SARS-CoV-2 have any subtypes, and if so what are they? | Politics, media and microbiologists Severe acute respiratory syndrome (SARS) took everybody by surprise. Its emergence was one of the most significant microbiological events of 2003. It challenged microbiologists to identify the aetiological agent and satisfy Koch's postulates — in so far as they ever can be met for a virus — in real time. Not only were the patients' respiratory secretions and the agents grown in cultured cells put under the microscope, but so were the actions of politicians. What lessons can we learn from SARS? |
31 | de8haxop | How does the coronavirus differ from seasonal flu? | Viral pathogens of acute lower respiratory tract infection in China. OBJECTIVES To document the viral etiology of acute lower respiratory tract infection (ALRIs) in Chinese children. SETTING Children Hospital, Zhejiang University, China. STUDY DESIGN Cross-sectional. PARTICIPANTS 34885 children with ALRI between January 2001 to December 2006. METHODS Nasopharyngeal aspirates were collected from all subjects. Respiratory syncytial virus (RSV), adenovirus (ADV), type 1 to 3 parainfluenza viruses (PIV), and type A and B influenza virus (Flu) were detected by direct immunofluorescence. RESULTS Viruses were identified in 32.3% cases, including RSV (23.6%), PIV 3 (4.3%), Flu A (2.0%), ADV (1.7%), PIV I (0.6%), Flu B (0.2%) and PIV 2 (0.1%). RSV and PIV 3 predominated in younger children while Flu A and Flu B predominated in older children (P<0.001, respectively). PIV 1 was more prevalent in children aged 1 to 3 years. The peak frequency of RSV, PIV 3 and Flu A were in early spring, June to August, and August and September, respectively. Flu B had a peak in the winter and spring. Adenovirus infections occurred in all seasons with a relatively constant frequency. CONCLUSIONS Viruses are an important cause of ALRIs in Chinese children constituting 1/3 of total cases. RSV is the most common pathogen. |
39 | kpff55on | What is the mechanism of cytokine storm syndrome on the COVID-19? | Adrenal Insufficiency and Glucocorticoid Use During the COVID-19 Pandemic The coronavirus disease 2019 (COVID-19) is an emerging pandemic challenge. Acute respiratory distress syndrome (ARDS) in COVID-19 is characterized by a severe cytokine storm. Patients undergoing glucocorticoid (GC) replacement therapy for adrenal insufficiency (AI) represent a highly vulnerable group that could develop severe complications due to the SARS-CoV-2 infection. In this review, we highlight the strategies to avoid an adrenal crisis in patients with AI and COVID-19. Adrenal crisis is a medical emergency and an important cause of death. Once patients with AI present symptoms of COVID-19, the dose of GC replacement therapy should be immediately doubled. In the presence of any emergency warning signs or inability to administer oral GC doses, we recommend that patients should immediately seek Emergency services to evaluate COVID-19 symptoms and receive 100 mg hydrocortisone by intravenous injection, followed by 50 mg hydrocortisone intravenously every 6 h or 200 mg/day by continuous intravenous infusion. |
24 | lah09pg8 | what kinds of complications related to COVID-19 are associated with diabetes | Fasting plasma glucose associated with mortality rate |
6 | 5n3btew9 | what types of rapid testing for Covid-19 have been developed? | Spectroscopy as a tool for detection and monitoring of Coronavirus (COVID-19) |
5 | 1v110xgs | what drugs have been active against SARS-CoV or SARS-CoV-2 in animal studies? | Generation of predictive pharmacophore model for SARS-coronavirus main proteinase Pharmacophore-based virtual screening is an effective, inexpensive and fast approach to discovering useful starting points for drug discovery. In this study, we developed a pharmacophore model for the main proteinase of severe acute respiratory syndrome coronavirus (SARS-CoV). Then we used this pharmacophore model to search NCI 3D database including 250, 251 compounds and identified 30 existing drugs containing the pharmacophore query. Among them are six compounds that already exhibited anti-SARS-CoV activity experimentally. This means that our pharmacophore model can lead to the discovery of potent anti-SARS-CoV inhibitors or promising lead compounds for further SARS-CoV main proteinase inhibitor development. |
22 | hpdl3z6k | are cardiac complications likely in patients with COVID-19? | SIOP ABSTRACTS |
27 | djpcwgc9 | what is known about those infected with Covid-19 but are asymptomatic? | People with Suspected COVID-19 Symptoms Were More Likely Depressed and Had Lower Health-Related Quality of Life: The Potential Benefit of Health Literacy The coronavirus disease 2019 (COVID-19) epidemic affects people's health and health-related quality of life (HRQoL), especially in those who have suspected COVID-19 symptoms (S-COVID-19-S). We examined the effect of modifications of health literacy (HL) on depression and HRQoL. A cross-sectional study was conducted from 14 February to 2 March 2020. 3947 participants were recruited from outpatient departments of nine hospitals and health centers across Vietnam. The interviews were conducted using printed questionnaires including participants' characteristics, clinical parameters, health behaviors, HL, depression, and HRQoL. People with S-COVID-19-S had a higher depression likelihood (OR, 2.88; p < 0.001), lower HRQoL-score (B, -7.92; p < 0.001). In comparison to people without S-COVID-19-S and low HL, those with S-COVID-19-S and low HL had 9.70 times higher depression likelihood (p < 0.001), 20.62 lower HRQoL-score (p < 0.001), for the people without S-COVID-19-S, 1 score increment of HL resulted in 5% lower depression likelihood (p < 0.001) and 0.45 higher HRQoL-score (p < 0.001), while for those people with S-COVID-19-S, 1 score increment of HL resulted in a 4% lower depression likelihood (p = 0.004) and 0.43 higher HRQoL-score (p < 0.001). People with S-COVID-19-S had a higher depression likelihood and lower HRQoL than those without. HL shows a protective effect on depression and HRQoL during the epidemic. |
24 | x0jfa1ib | what kinds of complications related to COVID-19 are associated with diabetes | Diabetic patients with COVID-19 infection are at higher risk of ICU admission and poor short-term outcome Abstract Background The prognostic significance of diabetes mellitus (DM) in patients with coronavirus 2019 disease (COVID-19) remains unknown. Objectives To assess the risk of ICU admission and morality risk in diabetic COVID-19 patients. Study desing A database search was conducted to identify studies comparing diabetic COVID-19 patients hospitalized in intensive care unit (ICU) and those reporting the overall mortality of these patients published up to March 25, 2020 within MEDLINE, Scopus and Web of Science. Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) guidelines were followed in abstracting data and assessing validity. Quality assessment was performed using the Newcastle-Ottawa quality assessment scale. The main outcome was the risk of ICU admission in diabetic patients with COVID-19 infection while the second was the mortality risk in overall diabetic COVID-19 patients. Data were pooled using the Mantel-Haenszel random effects models with odds ratio (OR) as the effect measure with the related 95 % confidence interval (CI). Statistical heterogeneity between groups was measured using the Higgins I2 statistic. Results Among 1382 patients (mean age 51.5 years, 798 males), DM resulted to be the second more frequent comorbidities. Diabetic patients resulted to have a significant increased risk of ICU admission (OR: 2.79, 95 % CI 1.85–4.22, p < 0.0001, I2 = 46 %). In 471 patients (mean age 56.6 years, 294 males) analysed for the secondary outcome diabetic subjects resulted to be at higher mortality risk (OR 3.21, 95 % CI 1.82–5.64, p < 0.0001, I2 = 16 %). Conclusions Diabetic patients with COVID-19 patients are at higher risk of ICU admission and show an higher mortality risk. |
21 | zrrxf617 | what are the mortality rates overall and in specific populations | Mortality rate and gender differences in COVID-19 patients dying in Italy: A comparison with other countries |
4 | uecdbanf | what causes death from Covid-19? | The Australian Institute of Sport Framework for Rebooting Sport in a COVID-19 Environment Abstract Sport makes an important contribution to the physical, psychological and emotional well-being of Australians. The economic contribution of sport is equivalent to 2–3% of Gross Domestic Product (GDP). The COVID-19 pandemic has had devastating effects on communities globally, leading to significant restrictions on all sectors of society, including sport. Resumption of sport can significantly contribute to the re-establishment of normality in Australian society. The Australian Institute of Sport (AIS), in consultation with sport partners (National Institute Network (NIN) Directors, NIN Chief Medical Officers (CMOs), National Sporting Organisation (NSO) Presidents, NSO Performance Directors and NSO CMOs), has developed a framework to inform the resumption of sport. National Principles for Resumption of Sport were used as a guide in the development of 'the AIS Framework for Rebooting Sport in a COVID-19 Environment' (the AIS Framework); and based on current best evidence, and guidelines from the Australian Federal Government, extrapolated into the sporting context by specialists in sport and exercise medicine, infectious diseases and public health. The principles outlined in this document apply to high performance/professional, community and individual passive (non-contact) sport. The AIS Framework is a timely tool of minimum baseline of standards, for 'how' reintroduction of sport activity will occur in a cautious and methodical manner, based on the best available evidence to optimise athlete and community safety. Decisions regarding the timing of resumption (the 'when' ) of sporting activity must be made in close consultation with Federal, State/Territory and Local Public Health Authorities. The priority at all times must be to preserve public health, minimising the risk of community transmission. |
19 | 96jqjs64 | what type of hand sanitizer is needed to destroy Covid-19? | Chapter 15 Analysis of alkaloids (indole alkaloids, isoquinoline alkaloids, tropane alkaloids) Abstract Alkaloids are a large cluster of molecules found in Mother Nature all over the world. They are all secondary compounds and collection of miscellaneous elements and biomolecules, derived from amino acids or from transamination. This diverse chemical group is categorized, based on the amino acids that deliver their nitrogen atom and part of their skeleton. Alkaloids from a similar origin or having the same basic nucleus may have dissimilar biosynthetic pathways and different biological activity. They are derived from l-phenylalanine, l-tyrosine, anthranilic acid or acetate, l-histidine, l-ornithine, nicotinic acid, and l-lysine. Apart from other types of alkaloids, indole, tropane, and isoquinoline alkaloids are very important. People from all over the world are using them in their everyday life. Alkaloids can also have an animal origin, which may be endogenous or exogenous. This chapter highlights the phytochemistry of the main representatives among the diverse group of alkaloids. This chapter also focuses on their extraction, purification, fractionation, identification, and quantification procedures. A fundamental understanding of the biological activity of important alkaloids is also highlighted in this chapter. With the potential of revealing new compounds and diverse pharmacological properties, alkaloids still embrace a great potential for the future of drug discovery. |
26 | svoakvic | what are the initial symptoms of Covid-19? | A primer on viral‐associated olfactory loss in the era of COVID‐19 Early reports have suggested that smell loss may be an early symptom associated with the pandemic known as COVID‐19. The possibility that severe acute respiratory syndrome coronavirus 2 (SARS‐CoV‐2) might cause olfactory dysfunction is certainly plausible. Patients presenting to specialized smell clinics are commonly diagnosed with upper respiratory infection (URI)‐associated olfactory loss and most are presumed to be viral related. In acute phases of infection, it is common to experience some smell loss as a result of nasal inflammation, mucosal edema, and obstruction of airflow into the olfactory cleft. In most cases, these episodes of smell loss are self‐limiting and coincide with resolution of URI symptoms. However, in some cases the smell loss persists for months to years and this is presumed to occur through a more direct olfactory insult by the virus. It remains too early to know whether infection with SARS‐CoV‐2 causes persistent olfactory dysfunction. However, given the scale of this pandemic, if SARS‐CoV‐2 does cause chronic olfactory loss in even a small portion of those infected, then the overall population prevalence could be quite large. This review provides a brief, practical overview of viral‐associated olfactory loss, realizing that evidence related to COVID‐19 will likely not be clear for some time. Our goal is to highlight the existence and importance of this condition and provide information geared for both providers and patients. Practical suggestions regarding evaluation and treatment will be provided, realizing that there may be constraints on medical resources and the nature of this pandemic remains dynamic. This article is protected by copyright. All rights reserved |
36 | yqeifpoy | What is the protein structure of the SARS-CoV-2 spike? | Comparison of SARS-CoV-2 spike protein binding to human, pet, farm animals, and putative intermediate hosts ACE2 and ACE2 receptors The emergence of a novel coronavirus, SARS-CoV-2, resulted in a pandemic. Here, we used recently released X-ray structures of human ACE2 bound to the receptor-binding domain (RBD) of the spike protein (S) from SARS-CoV-2 to predict its binding to ACE2 proteins from different animals, including pets, farm animals, and putative intermediate hosts of SARS-CoV-2. Comparing the interaction sites of ACE2 proteins known to serve or not serve as receptor allows to define residues important for binding. From the 20 amino acids in ACE2 that contact S up to seven can be replaced and ACE2 can still function as the SARS-CoV-2 receptor. These variable amino acids are clustered at certain positions, mostly at the periphery of the binding site, while changes of the invariable residues prevent S-binding or infection of the respective animal. Some ACE2 proteins even tolerate the loss or the acquisition of N-glycosylation sites located near the S-interface. Of note, pigs and dogs which are not or not effectively infected, respectively, have only a few changes in the binding site have relatively low levels of ACE2 in the respiratory tract. Comparison of the RBD of S of SARS-CoV-2 with viruses from bat and pangolin revealed that the latter contains only one substitution, whereas the bat virus exhibits five. However, ACE2 of pangolin exhibit seven changes relative to human ACE2, a similar number of substitutions is present in ACE2 of bats, raccoon, and civet suggesting that SARS-CoV-2 may not especially adapted to ACE2 of any of its putative intermediate hosts. These analyses provide new insight into the receptor usage and animal source/origin of SARS-COV-2. IMPORTANCE SARS-CoV-2 is threatening people worldwide and there are no drugs or vaccines available to mitigate its spread. The origin of the virus is still unclear and whether pets and livestock can be infected and transmit SARS-CoV-2 are important and unknown scientific questions. Effective binding to the host receptor ACE2 is the first prerequisite for infection of cells and determines the host range. Our analysis provides a framework for the prediction of potential hosts of SARS-CoV-2. We found that ACE2 from species known to support SARS-CoV-2 infection tolerate many amino acid changes indicating that the species barrier might be low. However, the lower expression of ACE2 in the upper respiratory tract of some pets and livestock means more research and monitoring should be done to explore the animal source of infection and the risk of potential cross-species transmission. Finally, the analysis also showed that SARS-CoV-2 may not specifically adapted to any of its putative intermediate hosts. |
34 | n32iscmr | What are the longer-term complications of those who recover from COVID-19? | Nifedipine and Amlodipine Are Associated With Improved Mortality and Decreased Risk for Intubation and Mechanical Ventilation in Elderly Patients Hospitalized for COVID-19 Dihydropyridine calcium channel blockers (CCB) are typically used agents in the clinical management of hypertension. Yet, they have also been utilized in the treatment of various pulmonary disorders with vasoconstriction. Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) has been implicated in the development of vasoconstrictive, proinflammatory, and pro-oxidative effects. A retrospective review was conducted on CCB use in hospitalized patients in search of any difference in outcomes related to specific endpoints: survival to discharge and progression of disease leading to intubation and mechanical ventilation. The electronic medical records for all patients that tested positive for SARS-CoV-2 that were at or above the age of 65 and that expired or survived to discharge from a community hospital in Brooklyn, NY, between the start of the public health crisis due to the viral disease up until April 13, 2020, were included. Of the 77 patients that were identified, 18 survived until discharge and 59 expired. Seven patients from the expired group were excluded since they died within one day of presentation to the hospital. Five patients were excluded from the expired group since their age was above that of the eldest patient in the survival group (89 years old). With 65 patients left, 24 were found to have been administered either amlodipine or nifedipine (CCB group) and 41 were not (No-CCB group). Patients treated with a CCB were significantly more likely to survive than those not treated with a CCB: 12 (50%) survived and 12 expired in the CCB group vs. six (14.6%) that survived and 35 (85.4%) that expired in the No-CCB treatment group (P<.01; p=0.0036). CCB patients were also significantly less likely to undergo intubation and mechanical ventilation. Only one patient (4.2%) was intubated in the CCB group whereas 16 (39.0%) were intubated in the No-CCB treatment group (P<.01; p=0.0026). Nifedipine and amlodipine were found to be associated with significantly improved mortality and a decreased risk for intubation and mechanical ventilation in elderly patients hospitalized with COVID-19. Further clinical studies are warranted. Including either nifedipine or amlodipine in medication regimens for elderly patients with hypertension hospitalized for COVID-19 may be considered. |
3 | yl1qyh7j | will SARS-CoV2 infected people develop immunity? Is cross protection possible? | Severe Acute Respiratory Syndrome Coronavirus Nonstructural Proteins 3, 4, and 6 Induce Double-Membrane Vesicles Coronaviruses (CoV), like other positive-stranded RNA viruses, redirect and rearrange host cell membranes for use as part of the viral genome replication and transcription machinery. Specifically, coronaviruses induce the formation of double-membrane vesicles in infected cells. Although these double-membrane vesicles have been well characterized, the mechanism behind their formation remains unclear, including which viral proteins are responsible. Here, we use transfection of plasmid constructs encoding full-length versions of the three transmembrane-containing nonstructural proteins (nsps) of the severe acute respiratory syndrome (SARS) coronavirus to examine the ability of each to induce double-membrane vesicles in tissue culture. nsp3 has membrane disordering and proliferation ability, both in its full-length form and in a C-terminal-truncated form. nsp3 and nsp4 working together have the ability to pair membranes. nsp6 has membrane proliferation ability as well, inducing perinuclear vesicles localized around the microtubule organizing center. Together, nsp3, nsp4, and nsp6 have the ability to induce double-membrane vesicles that are similar to those observed in SARS coronavirus-infected cells. This activity appears to require the full-length form of nsp3 for action, as double-membrane vesicles were not seen in cells coexpressing the C-terminal truncation nsp3 with nsp4 and nsp6. |
21 | l0k1biap | what are the mortality rates overall and in specific populations | Coronavirus Disease (Covid-19): What Are We Learning in a Country With High Mortality Rate? |
2 | 4ry9b68l | how does the coronavirus respond to changes in the weather | On the global trends and spread of the COVID-19 outbreak: preliminary assessment of the potential relation between location-specific temperature and UV index The novel coronavirus, since its first outbreak in December, has, up till now, affected approximately 114,542 people across 115 countries. Many international agencies are devoting efforts to enhance the understanding of the evolving COVID-19 outbreak on an international level, its influences, and preparedness. At present, COVID-19 appears to affect individuals through person-to-person means, like other commonly found cold or influenza viruses. It is widely known and acknowledged that viruses causing influenza peak during cold temperatures and gradually subside in the warmer temperature, owing to their seasonality. Thus, COVID-19, due to its regular flu-like symptoms, is also expected to show similar seasonality and subside as the global temperatures rise in the northern hemisphere with the onset of spring. Despite these speculations, however, the systematic analysis in the global perspective of the relation between COVID-19 spread and meteorological parameters is unavailable. Here, by analyzing the region- and city-specific affected global data and corresponding meteorological parameters, we show that there is an optimum range of temperature and UV index strongly affecting the spread and survival of the virus, whereas precipitation, relative humidity, cloud cover, etc. have no effect on the virus. Unavailability of pharmaceutical interventions would require greater preparedness and alert for the effective control of COVID-19. Under these conditions, the information provided here could be very helpful for the global community struggling to fight this global crisis. It is, however, important to note that the information presented here clearly lacks any physiological evidences, which may merit further investigation. Thus, any attempt for management, implementation, and evaluation strategies responding to the crisis arising due to the COVID-19 outbreak must not consider the evaluation presented here as the foremost factor. |
29 | bcde0u7u | 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? | Moving-average based index to timely evaluate the current epidemic situation after COVID-19 outbreak A pneumonia outbreak caused by a novel coronavirus (COVID-19) occurred in Wuhan, China at the end of 2019 and then spread rapidly to the whole country. A total of 81,021 laboratory-confirmed cases, including 3,194 deaths (3.9%) had been reported in China by March 14, 2020, meanwhile, 61,518 laboratory-confirmed cases and 2,199 deaths were reported outside China. Common symptoms of COVID-19 pneumonia included fever, fatigue and dry cough. Faced with such a sudden outbreak of new infectious diseases, we have no history to learn from and no evidence to count on. Traditional models often predict inconsistent results. Aiming at estimate the epidemic trend timely after the outbreak, we mainly used 7-day moving average of log-transformed daily new cases (LMA) to establish a new index named "epidemic trend index", which will be used to predict the evolutionary trend of the epidemic situation and support epidemic control decision making processes. We used SARS epidemic data from Hong Kong in 2003 to verify the practicability of the new index, which shows that the index is acceptable. The epidemic trend index was then applied to the COVID-19 epidemic analysis in China. The results show that during the epidemic, the trend direction of different districts of China changed on different date. In the whole country and in Hubei Province alone, the epidemic reached the peak on February 9. While the peak appeared earlier, i.e. on February 5 in other provinces. It indicated that decisive outbreak control measures of the Chinese government are effective. While local governments should adjust management measures based on local risk level of epidemic. Although the epidemic has eased since late February, continued efforts in epidemic control are still needed to accelerate the end of the epidemic in China. However, the global COVID-19 epidemic outside China continues to expand as indicated by the epidemic trend index we proposed. In order to cope with the novel coronavirus pandemic, people all over the world should work together and governments of all countries should take efficient measures in the light of China's experience and according to national circumstances and local conditions. |
21 | awitk3se | what are the mortality rates overall and in specific populations | COVID-19 (Novel Coronavirus 2019) - recent trends. The World Health Organization (WHO) has issued a warning that, although the 2019 novel coronavirus (COVID-19) from Wuhan City (China), is not pandemic, it should be contained to prevent the global spread. The COVID-19 virus was known earlier as 2019-nCoV. As of 12 February 2020, WHO reported 45,171 cases and 1115 deaths related to COVID-19. COVID-19 is similar to Severe Acute Respiratory Syndrome coronavirus (SARS-CoV) virus in its pathogenicity, clinical spectrum, and epidemiology. Comparison of the genome sequences of COVID-19, SARS-CoV, and Middle East Respiratory Syndrome coronavirus (MERS-CoV) showed that COVID-19 has a better sequence identity with SARS-CoV compared to MERS CoV. However, the amino acid sequence of COVID-19 differs from other coronaviruses specifically in the regions of 1ab polyprotein and surface glycoprotein or S-protein. Although several animals have been speculated to be a reservoir for COVID-19, no animal reservoir has been already confirmed. COVID-19 causes COVID-19 disease that has similar symptoms as SARS-CoV. Studies suggest that the human receptor for COVID-19 may be angiotensin-converting enzyme 2 (ACE2) receptor similar to that of SARS-CoV. The nucleocapsid (N) protein of COVID-19 has nearly 90% amino acid sequence identity with SARS-CoV. The N protein antibodies of SARS-CoV may cross react with COVID-19 but may not provide cross-immunity. In a similar fashion to SARS-CoV, the N protein of COVID-19 may play an important role in suppressing the RNA interference (RNAi) to overcome the host defense. This mini-review aims at investigating the most recent trend of COVID-19. |
50 | ot7a2h9p | what is known about an mRNA vaccine for the SARS-CoV-2 virus? | Making the Mark: The Role of Adenosine Modifications in the Lifecycle of RNA Viruses Viral epitranscriptomics is a newly emerging field that has identified unique roles for RNA modifications in modulating lifecycles of RNA viruses. Despite the observation of a handful of modified viral RNAs five decades ago, very little was known about how these modifications regulate viral lifecycles, until recently. Here we review the pro- and anti-viral effects of methyl-6-adenosine in distinct viral life cycles, the role of 2′ O-methyl modifications in RNA stability and innate immune sensing, and functions of adenosine to inosine modifications in retroviral life cycles. With roles for over 100 modifications in RNA still unknown, this is a rapidly emerging field that is destined to suggest novel antiviral therapies. |
13 | db7zcdyh | what are the transmission routes of coronavirus? | Upper airway symptoms in coronavirus disease 2019 (COVID-19) |
7 | aeuy92bx | are there serological tests that detect antibodies to coronavirus? | Potent neutralization of 2019 novel coronavirus by recombinant ACE2-Ig 2019-nCoV, which is a novel coronavirus emerged in Wuhan, China, at the end of 2019, has caused at least infected 11,844 as of Feb 1, 2020. However, there is no specific antiviral treatment or vaccine currently. Very recently report had suggested that novel CoV would use the same cell entry receptor, ACE2, as the SARS-CoV. In this report, we generated a novel recombinant protein by connecting the extracellular domain of human ACE2 to the Fc region of the human immunoglobulin IgG1. An ACE2 mutant with low catalytic activity was also used in the study. The fusion proteins were then characterized. Both fusion proteins has high affinity binding to the receptor-binding domain (RBD) of SARS-CoV and 2019-nCoV and exerted desired pharmacological properties. Moreover, fusion proteins potently neutralized SARS-CoV and 2019-nCoV in vitro. As these fusion proteins exhibit cross-reactivity against coronaviruses, they could have potential applications for diagnosis, prophylaxis, and treatment of 2019-nCoV. |
6 | ekal5251 | what types of rapid testing for Covid-19 have been developed? | Relationship between Average Daily Temperature and Average Cumulative Daily Rate of Confirmed Cases of COVID-19 The rapid outbreak of the new Coronavirus (COVID-19) pandemic and the spread of the virus worldwide, especially in the Northern Hemisphere, have prompted various investigations about the impact of environmental factors on the rate of development of this epidemic. Different studies have called the attention to various parameters that may have influenced the spread of the virus, and in particular, the impact of climatic parameters has been emphasized. The main purpose of this study is to investigate the correlation between the average daily temperature and the rate of coronavirus epidemic growth in the infected regions. The main hypothesis object of our research is that between regions exhibiting a significant difference in the mean daily temperature, a significant difference is also observed in the average cumulative daily rate of confirmed cases, and that this does not happen if there is no significant difference in mean daily temperature. To test this research hypothesis, we carried on the case study of three regions in each of five countries and analyzed the correlation through F-test, and Independent-Samples T-Test. In all five selected countries, we found that when there is a significant difference in the daily mean temperature between two regions of a country, a significant difference exists also in the average cumulative daily rate of confirmed cases. Conversely, if there are no significant differences in the mean daily temperature of two regions in the same country, no significant difference is observed in the average cumulative daily rate of confirmed cases for these regions. |
16 | 6e3gpb93 | how long does coronavirus remain stable on surfaces? | Guidelines for dental care provision during the COVID-19 pandemic Abstract Since the coronavirus disease 2019 (COVID-19) outbreak was declared a pandemic on 11 March 2020. Several dental care facilities in affected countries have been completely closed or have been only providing minimal treatment for emergency cases. However, several facilities in some affected countries are still providing regular dental treatment. This can in part be a result of the lack of universal protocol or guidelines regulating the dental care provision during such a pandemic. This lack of guidelines can on one hand increase the nosocomial COVID-19 spread through dental health care facilities, and on the other hand deprive patients' in need of the required urgent dental care. Moreover, ceasing dental care provision during such a period will incense the burden on hospitals emergency departments already struggle with the pandemic. This work aimed to develop guidelines for dental patients' management during and after the COVID-19 pandemic. Guidelines for dental care provision during the COVID-19 pandemic were developed after considering the nature of COVID-19 pandemic, and were based on grouping the patients according to condition and need, and considering the procedures according to risk and benefit. It is hoped that the guidelines proposed in this work will help in the management of dental care around the world during and after this COVID-19 pandemic. |
1 | sis4fjh5 | what is the origin of COVID-19 | Mathematical Models of Infectious Diseases in Livestock: Concepts and Application to the Spread of Highly Pathogenic Avian Influenza Virus Strain Type H5N1 Animal health governance faces new challenges as the ecology of infectious livestock diseases is changing (Tomley and Shirley 2009). Environmental and climate changes, intensification of livestock production, modification in land-use and agricultural practices, globalization of human travel, the development of the trade of livestock and livestock products have created conditions for an increase in the emergence and re-emergence of infectious agents in the last decades (Weiss and McMichael 2004; Randolph and Rogers 2010; Jones et al. 2008; Gibbs 2005). The frequency of emergence of new highly pathogenic avian influenza viruses (HPAIV) has increased over the past 20 years, as well as the economic impact of associated outbreaks (Alexander and Brown 2009). Bluetongue virus serotypes have continuously increased their spatial distribution, specifically in a northern direction. Treatment-resistant strains, such as methicillin-resistant Staphylococcus aureus (MRSA), have appeared. Numerous infectious diseases such as foot-and-mouth disease (FMD) are endemic in many parts of the world, and may have a high impact on animal health and farmer livelihood. Moreover, they constrain the ability of affected countries to trade livestock and livestock-derived products. Production systems in developed countries are also vulnerable. For example, outbreaks of FMD in United Kingdom in 2001, classical swine fever in Holland in 1997/1998, and highly pathogenic avian influenza H7N7 in Holland in 2003 resulted in the loss of millions of animals, mainly as a result of culling of affected and exposed animals. Finally, infectious livestock diseases are a threat for public health: about 75% of human infectious agents that emerged in the last 25 years had an animal origin (King et al. 2006). |
50 | 9yenf9w3 | what is known about an mRNA vaccine for the SARS-CoV-2 virus? | Emergence of deadly severe acute respiratory syndrome coronavirus-2 during 2019-2020 Wuhan, the city in Hubei province in China is in the focus of global community due to the outbreak of coronavirus disease 2019 (COVID-19) caused by severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2), formerly known as 2019-nCoV. The virus emerged in humans from Wuhan seafood market probably via zoonotic transmission. Within a few days the virus spread its tentacles rapidly to neighboring cities in China and to different geographical regions through travelers and to some extent by human to human transmission leading to significant disease burden globally. More than 2,00,000 people (including more than 8000 deaths) have been infected with this respiratory illness across 167 countries and territories worldwide leading to a pandemic. The present review provides an outline about emergence and spread of SARS-CoV-2 from Wuhan, China in 2019-2020. We have also provided information about the classification, genome, proteins, clinical presentation of COVID-19, type of clinical specimens to be collected and diagnostic methods adopted to identify the respiratory illness. In addition we have also provided information about transmission dynamics, prevention measures and treatment options that are available at the present. Subsequently, we have given a comprehensive overview of the spread of this infection from China to the other parts of the globe. Management of the ongoing outbreak of SARS-CoV-2 encompassing surveillance, clinical, immunological, genetic and evolutionary investigations are likely to provide the desired results. Joint efforts of global scientific community are needed at this hour in terms of enhancement of research on development of accurate diagnostics, antiviral therapeutics and finally into formation of an effective vaccine against the emerging novel coronavirus. |
7 | 7atoko6c | are there serological tests that detect antibodies to coronavirus? | Evaluation of recombinant nucleocapsid and spike proteins for serological diagnosis of novel coronavirus disease 2019 (COVID-19) Background: The colloidal gold immunochromatography assay (GICA) is a rapid diagnostic tool for novel coronavirus disease 2019 (COVID-19) infections. However, with significant numbers of false negatives, improvements to GICA are needed. Methods: Six recombinant HCoV-19 nucleocapsid and spike proteins were prepared and evaluated. The optimal proteins were employed to develop a sandwich-format GICA strip to detect total antibodies (IgM and IgG) against HCoV-19. GICA performance was assessed with comparison of viral RNA detection. Results: Recombinant HCoV-19 proteins were obtained, including three prokaryotically expressed rN, rN1, rN2 nucleocapsid proteins, and three eukaryotically expressed rS1, rS-RBD, rS-RBD-mFc spike proteins. The recombinant proteins with the highest ELISA titers (rS1 and rS-RBD-mFc) against coronavirus-specific IgM and IgG were chosen for GICA development. The GICA has a sensitivity and specificity of 86.89% (106/122) and 99.39% (656/660), respectively. Furthermore, 65.63% (21/32) of the clinically confirmed but RT-PCR negative samples were GICA positive. Conclusions: The eukaryotically-expressed spike proteins (rS1and rS-RBD-mFc) are more suitable than the prokaryotically expressed nucleocapsid proteins for HCoV-19 serological diagnosis. The GICA sandwich used to detect total antibodies is a powerful complement to the current standard RNA-based tests. |
46 | pec5ezyy | what evidence is there for dexamethasone as a treatment for COVID-19? | Routine antiemetic prophylaxis with dexamethasone during COVID-19: Should oncologists reconsider? The ongoing pandemic caused by severe acute respiratory syndrome (SARS) coronavirus type 2 (SARS-CoV-2, also known as COVID-19) has caused unprecedented strain on the global healthcare system, causing thousands of deaths worldwide. Patients with underlying conditions such as cancer are at substantial risk of acquiring and dying from this novel coronavirus. Numerous reports have shown that infection with SARS-CoV-2 causes depletion of B- and T-lymphocytes, including CD4 and CD8 T-cells, and is associated with severe illness and death and that patients with higher lymphocyte levels may have better outcomes. Dexamethasone, a widely prescribed antiemetic for acute and delayed nausea and vomiting from a variety of cancer drugs, causes B and T cell depletion, which may augment immunosuppression. Since it seems that lymphocytes are vital in the immune response to novel coronavirus, oncologists should reconsider the routine use of prophylactic dexamethasone in uninfected patients, to avoid inducing lymphopenia, which may increase risk of infection or lead to inferior outcomes if a cancer patient subsequently becomes infected. Since many cancer drugs and malignant diseases inherently cause lymphopenia, further reduction of lymphocytes with dexamethasone should be avoided if possible and if safe and effective alternative antiemetics are available during the COVID-19 crisis. |
19 | ifxbrx4p | what type of hand sanitizer is needed to destroy Covid-19? | The state of the science |
6 | 6kpgt70s | what types of rapid testing for Covid-19 have been developed? | Rapid Detection of Novel Coronavirus (COVID-19) by Reverse Transcription-Loop-Mediated Isothermal Amplification Novel Corona virus (COVID-19 or 2019-nCoV) is an emerging global health concern that requires a rapid diagnostic test. Quantitative reverse transcription PCR (qRT-PCR) is currently the standard for COVID-19 detection; however, Reverse Transcription Loop-Mediated Isothermal Amplification (RT-LAMP) may allow for faster and cheaper field based testing at point-of-risk. The objective of this study was to develop a rapid screening diagnostic test that could be completed in under 30 minutes. Simulated patient samples were generated by spiking serum, urine, saliva, oropharyngeal swabs, and nasopharyngeal swabs with a portion of the COVID-19 nucleic sequence. The samples were tested using RT-LAMP as well as by conventional qRT-PCR. Specificity of the RT-LAMP was evaluated by also testing against other related coronaviruses. RT-LAMP specifically detected COVID-19 in simulated patient samples. This test was performed in under 30 minutes. This approach could be used for monitoring of exposed individuals or potentially aid with screening efforts in the field and potential ports of entry. |
29 | f59c4idd | 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? | Human enterovirus 71 protein interaction network prompts antiviral drug repositioning As a predominant cause of human hand, foot, and mouth disease, enterovirus 71 (EV71) infection may lead to serious diseases and result in severe consequences that threaten public health and cause widespread panic. Although the systematic identification of physical interactions between viral proteins and host proteins provides initial information for the recognition of the cellular mechanism involved in viral infection and the development of new therapies, EV71-host protein interactions have not been explored. Here, we identified interactions between EV71 proteins and host cellular proteins and confirmed the functional relationships of EV71-interacting proteins (EIPs) with virus proliferation and infection by integrating a human protein interaction network and by functional annotation. We found that most EIPs had known interactions with other viruses. We also predicted ATP6V0C as a broad-spectrum essential host factor and validated its essentiality for EV71 infection in vitro. EIPs and their interacting proteins were more likely to be targets of anti-inflammatory and neurological drugs, indicating their potential to serve as host-oriented antiviral targets. Thus, we used a connectivity map to find drugs that inhibited EIP expression. We predicted tanespimycin as a candidate and demonstrated its antiviral efficiency in vitro. These findings provide the first systematic identification of EV71-host protein interactions, an analysis of EIP protein characteristics and a demonstration of their value in developing host-oriented antiviral therapies. |
29 | 7hwscr6i | 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? | Middle East respiratory syndrome coronavirus (MERS-CoV) entry inhibitors targeting spike protein Abstract The recent outbreak of Middle East respiratory syndrome (MERS) coronavirus (MERS-CoV) infection has led to more than 800 laboratory-confirmed MERS cases with a high case fatality rate (∼35%), posing a serious threat to global public health and calling for the development of effective and safe therapeutic and prophylactic strategies to treat and prevent MERS-CoV infection. Here we discuss the most recent studies on the structure of the MERS-CoV spike protein and its role in virus binding and entry, and the development of MERS-CoV entry/fusion inhibitors targeting the S1 subunit, particularly the receptor-binding domain (RBD), and the S2 subunit, especially the HR1 region, of the MERS-CoV spike protein. We then look ahead to future applications of these viral entry/fusion inhibitors, either alone or in combination with specific and nonspecific MERS-CoV replication inhibitors, for the treatment and prevention of MERS-CoV infection. |
11 | f7ylxcog | what are the guidelines for triaging patients infected with coronavirus? | Extracorporeal Membrane Oxygenation for Pediatric Patients With Coronavirus Disease 2019-Related Illness. OBJECTIVE To describe current hospital guidelines and the opinions of extracorporeal membrane oxygenation leaders at U.S. children's hospitals concerning the use of extracorporeal membrane oxygenation for coronavirus disease 2019-positive pediatric patients. DESIGN Confidential, self-administered questionnaire. SETTING One hundred twenty-seven U.S. pediatric extracorporeal membrane oxygenation centers. SUBJECTS Extracorporeal membrane oxygenation center program directors and coordinators. INTERVENTIONS None. MEASUREMENTS AND MAIN RESULTS In March 2020, a survey was sent to 127 pediatric extracorporeal membrane oxygenation centers asking them to report their current hospital extracorporeal membrane oxygenation guidelines for coronavirus disease 2019-positive patients. Respondents were also asked their opinion on three ethical dilemmas including: prioritization of children over adults for extracorporeal membrane oxygenation use, institution of do-not-resuscitate orders, and the use of extracorporeal cardiopulmonary resuscitation for coronavirus disease 2019-positive patients. Forty-seven extracorporeal membrane oxygenation centers had enacted guidelines including 46 (100%) that offer venovenous-extracorporeal membrane oxygenation and 42 (89%) that offer venoarterial-extracorporeal membrane oxygenation for coronavirus disease 2019-positive pediatric patients. Forty-four centers (94%) stated that the indications for extracorporeal membrane oxygenation candidacy in coronavirus disease 2019 disease were similar to those used in other viral illnesses, such as respiratory syncytial virus or influenza. Most program directors (98%) did not endorse that children hospitalized with coronavirus disease 2019 should be made do-not-resuscitate and had variable opinions on whether children should be given higher priority over adults when rationing extracorporeal membrane oxygenation. Over half of program directors (60%) did not support the use of extracorporeal cardiopulmonary resuscitation for coronavirus disease 2019. CONCLUSIONS The majority of pediatric extracorporeal membrane oxygenation centers have proactively established guidelines for the use of extracorporeal membrane oxygenation for coronavirus disease 2019-related illnesses. Further work is needed to help guide the fair allocation of extracorporeal membrane oxygenation resources and to determine the appropriateness of extracorporeal cardiopulmonary resuscitation. |
40 | 53atdvlv | What are the observed mutations in the SARS-CoV-2 genome and how often do the mutations occur? | Why do RNA viruses recombine? Recombination occurs in many RNA viruses and can be of major evolutionary significance. However, rates of recombination vary dramatically among RNA viruses, which can range from clonal to highly recombinogenic. Here, we review the factors that might explain this variation in recombination frequency and show that there is little evidence that recombination is favoured by natural selection to create advantageous genotypes or purge deleterious mutations, as predicted if recombination functions as a form of sexual reproduction. Rather, recombination rates seemingly reflect larger-scale patterns of viral genome organization, such that recombination may be a mechanistic by-product of the evolutionary pressures acting on other aspects of virus biology. |
38 | za3qypgg | What is the mechanism of inflammatory response and pathogenesis of COVID-19 cases? | Associations between immune-suppressive and stimulating drugs and novel COVID-19—a systematic review of current evidence BACKGROUND: Cancer and transplant patients with COVID-19 have a higher risk of developing severe and even fatal respiratory diseases, especially as they may be treated with immune-suppressive or immune-stimulating drugs. This review focuses on the effects of these drugs on host immunity against COVID-19. METHODS: Using Ovid MEDLINE, we reviewed current evidence for immune-suppressing or -stimulating drugs: cytotoxic chemotherapy, low-dose steroids, tumour necrosis factorα (TNFα) blockers, interlukin-6 (IL-6) blockade, Janus kinase (JAK) inhibitors, IL-1 blockade, mycophenolate, tacrolimus, anti-CD20 and CTLA4-Ig. RESULTS: 89 studies were included. Cytotoxic chemotherapy has been shown to be a specific inhibitor for severe acute respiratory syndrome coronavirus in in vitro studies, but no specific studies exist as of yet for COVID-19. No conclusive evidence for or against the use of non-steroidal anti-inflammatory drugs (NSAIDs) in the treatment of COVID-19 patients is available, nor is there evidence indicating that TNFα blockade is harmful to patients in the context of COVID-19. COVID-19 has been observed to induce a pro-inflammatory cytokine generation and secretion of cytokines, such as IL-6, but there is no evidence of the beneficial impact of IL-6 inhibitors on the modulation of COVID-19. Although there are potential targets in the JAK-STAT pathway that can be manipulated in treatment for coronaviruses and it is evident that IL-1 is elevated in patients with a coronavirus, there is currently no evidence for a role of these drugs in treatment of COVID-19. CONCLUSION: The COVID-19 pandemic has led to challenging decision-making about treatment of critically unwell patients. Low-dose prednisolone and tacrolimus may have beneficial impacts on COVID-19. The mycophenolate mofetil picture is less clear, with conflicting data from pre-clinical studies. There is no definitive evidence that specific cytotoxic drugs, low-dose methotrexate for auto-immune disease, NSAIDs, JAK kinase inhibitors or anti-TNFα agents are contraindicated. There is clear evidence that IL-6 peak levels are associated with severity of pulmonary complications. |
5 | ql8ubuok | what drugs have been active against SARS-CoV or SARS-CoV-2 in animal studies? | Tropism, replication competence, and innate immune responses of the coronavirus SARS-CoV-2 in human respiratory tract and conjunctiva: an analysis in ex-vivo and in-vitro cultures BACKGROUND: Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) emerged in December 2019, causing a respiratory disease (coronavirus disease 2019, COVID-19) of varying severity in Wuhan, China, and subsequently leading to a pandemic. The transmissibility and pathogenesis of SARS-CoV-2 remain poorly understood. We evaluate its tissue and cellular tropism in human respiratory tract, conjunctiva, and innate immune responses in comparison with other coronavirus and influenza virus to provide insights into COVID-19 pathogenesis. METHODS: We isolated SARS-CoV-2 from a patient with confirmed COVID-19, and compared virus tropism and replication competence with SARS-CoV, Middle East respiratory syndrome-associated coronavirus (MERS-CoV), and 2009 pandemic influenza H1N1 (H1N1pdm) in ex-vivo cultures of human bronchus (n=5) and lung (n=4). We assessed extrapulmonary infection using ex-vivo cultures of human conjunctiva (n=3) and in-vitro cultures of human colorectal adenocarcinoma cell lines. Innate immune responses and angiotensin-converting enzyme 2 expression were investigated in human alveolar epithelial cells and macrophages. In-vitro studies included the highly pathogenic avian influenza H5N1 virus (H5N1) and mock-infected cells as controls. FINDINGS: SARS-CoV-2 infected ciliated, mucus-secreting, and club cells of bronchial epithelium, type 1 pneumocytes in the lung, and the conjunctival mucosa. In the bronchus, SARS-CoV-2 replication competence was similar to MERS-CoV, and higher than SARS-CoV, but lower than H1N1pdm. In the lung, SARS-CoV-2 replication was similar to SARS-CoV and H1N1pdm, but was lower than MERS-CoV. In conjunctiva, SARS-CoV-2 replication was greater than SARS-CoV. SARS-CoV-2 was a less potent inducer of proinflammatory cytokines than H5N1, H1N1pdm, or MERS-CoV. INTERPRETATION: The conjunctival epithelium and conducting airways appear to be potential portals of infection for SARS-CoV-2. Both SARS-CoV and SARS-CoV-2 replicated similarly in the alveolar epithelium; SARS-CoV-2 replicated more extensively in the bronchus than SARS-CoV. These findings provide important insights into the transmissibility and pathogenesis of SARS-CoV-2 infection and differences with other respiratory pathogens. FUNDING: US National Institute of Allergy and Infectious Diseases, University Grants Committee of Hong Kong Special Administrative Region, China; Health and Medical Research Fund, Food and Health Bureau, Government of Hong Kong Special Administrative Region, China. |
49 | 3ngrtmb0 | do individuals who recover from COVID-19 show sufficient immune response, including antibody levels and T-cell mediated immunity, to prevent re-infection? | No indications for overt innate immune suppression in critically ill COVID-19 patients At the end of March 2020, there were in excess of 800.000 confirmed cases of coronavirus disease 2019 (COVID-19) worldwide. Several reports suggest that, in severe cases, COVID-19 may cause a hyperinflammatory 'cytokine storm'. However, unlike SARS-CoV infection, high levels of anti-inflammatory mediators have also been reported in COVID-19 patients. One study reported that 16% of COVID-19 patients who died developed secondary infection, which might indicate an immune-suppressed state. We explored kinetics of mHLA-DR expression, the most widely used marker of innate immune suppression in critically ill patients, in COVID-19 patients admitted to the ICU. Twenty-four confirmed COVID-19 patients were included, of which 75% was male and 79% had comorbidities. All patients were mechanically ventilated and exhibited large high levels of inflammatory parameters such as CRP and PCT. mHLA-DR expression levels were mostly within the normal range of 15000 - 45000 mAb/cell and showed no change over time. COVID-19 patients displayed notably higher mHLA-DR expression levels compared with bacterial septic shock patients. None of the COVID-19 patients developed a secondary infection. In conclusion, despite a pronounced inflammatory response, mHLA-DR expression kinetics indicate no overt innate immune suppression in COVID-19 patients. These data signify that innate immune suppression as a negative feedback mechanism following PAMP-induced inflammation appears not to be present in COVID-19. |
3 | p5h752r6 | will SARS-CoV2 infected people develop immunity? Is cross protection possible? | Guidelines for the management of surgical departments in non-uniform hospitals during the COVID-19 pandemic In the last several weeks we have been witnessing the exponentially progressing pandemic SARS-CoV-2 coronavirus. As the number of people infected with SARS-CoV2 escalates, the problem of surgical management of patients requiring urgent surgery is increasing. Patients infected with SARS-CoV2 virus but with negative test results will appear in general hospitals and may pose a risk to other patients and hospital staff. Health care workers constitutes nearly 17% of infected population in Poland, therefore early identification of infected people becomes a priority to protect human resources and to ensure continuity of the access to a surgical care. Both surgical operations, and endoscopic procedures are considered as interventions with an increased risk of infection. Therefore, determining the algorithm becomes crucial for qualifying patients for surgical treatment, but also to stratify the risk of personnel being infected during surgery and to adequately protect staff. Each hospital should be logistically prepared for the need to perform urgent surgery on a patient with suspected or confirmed infection, including personal protective equipment. Limited availability of the equipment, working under pressure and staff shortages in addition to a highly contagious pathogen necessitate a pragmatic management of human resources in health care. Instant synchronized action is needed, and clear uniform guidelines are essential for the healthcare system to provide citizens with the necessary surgical care while protecting both patients, and staff. This document presents current recommendations regarding surgery during the COVID-19 pandemic in Poland. |
26 | lav794w0 | what are the initial symptoms of Covid-19? | Consensus for prevention and management of coronavirus disease 2019 (COVID-19) for neurologists Coronavirus disease 2019 (COVID‐19) has become a pandemic disease globally. Although COVID-19 directly invades lungs, it also involves the nervous system. Therefore, patients with nervous system involvement as the presenting symptoms in the early stage of infection may easily be misdiagnosed and their treatment delayed. They become silent contagious sources or 'virus spreaders'. In order to help neurologists to better understand the occurrence, development and prognosis, we have developed this consensus of prevention and management of COVID‐19. It can also assist other healthcare providers to be familiar with and recognise COVID-19 in their evaluation of patients in the clinic and hospital environment. |
16 | 4gj9d181 | how long does coronavirus remain stable on surfaces? | Prolonged Persistence of SARS-CoV-2 RNA in Body Fluids. We prospectively assessed 49 coronavirus disease cases in Guangdong, China, to estimate the frequency and duration of detectable severe acute respiratory syndrome coronavirus 2 RNA in human body fluids. The prolonged persistence of virus RNA in various body fluids may guide the clinical diagnosis and prevention of onward virus transmission. |
23 | s2x3mhic | what kinds of complications related to COVID-19 are associated with hypertension? | Prevalence and Impact of Myocardial Injury in Patients Hospitalized with COVID-19 Infection ABSTRACT Importance: It is postulated that myocardial injury may be common in Coronavirus Disease (COVID-19) reflected by troponin elevation. The nature, degree and mechanism of myocardial injury in affected patients in the United States are unknown. Objective: To describe the severity and trends of myocardial injury in a large cohort of hospitalized patients with confirmed COVID-19. Design: Retrospective cohort study of data captured between February 27th and April 12th, 2020. Setting: Patients were admitted to one of five hospitals in the Mount Sinai Health System (MSHS) in New York City. Data was collected from the electronic health record (EHR) databases within the hospital system. Participants: We included all patients with confirmed COVID-19 admitted to the aforementioned hospitals during the study period who had at least one troponin-I measured within 24 hours of admission. Exposure(s) (for observational studies): SARS-CoV-2 infection as confirmed by real-time reverse transcriptase polymerase chain reaction (RT-PCR) assay of nasal and pharyngeal swabs. Main Outcome(s) and Measure(s): During the study period, 2736 patients met the inclusion criteria. Demographics, medical history, admission labs, and all troponin-I measurements during hospitalization were recorded for each patient. Admission troponin levels were characterized as mildly elevated (between one and three times the upper limit of normal) and elevated (above three times the upper limit of normal). Results: The median age was 66.4 years, with 59.6% men and 40.7% over age 70. In those patients with elevated troponins, cardiovascular disease (CVD) including coronary artery disease, atrial fibrillation, and heart failure, were more prevalent as were conditions of chronic kidney disease, hypertension and diabetes. Inflammatory markers were higher among patients with more substantial troponin elevations as well. Patients who had lower hemoglobin, hypo- or hypertension, or tachycardia generally presented with higher troponins. Conclusions and Relevance: Myocardial injury, manifesting as troponin elevation appears to be common among patients hospitalized with COVID-19 but present at generally low levels. Patients with a history of CVD are more likely to have myocardial injury than patients without CVD or risk factors for CVD. Troponin elevation among patients hospitalized with COVID-19 likely represents non-ischemic or secondary myocardial injury. |
44 | 971d0sir | How much impact do masks have on preventing the spread of the COVID-19? | The SARS-CoV-2 outbreak from a one health perspective Abstract The SARS-CoV-2 is a new human coronavirus candidate recently detected in China that is now reported in people on inhabited continents. The virus shares a high level of identity with some bat coronaviruses and is recognised as a potentially zoonotic virus. We are utilizing the One Health concept to understand the emergence of the virus, as well as to point to some possible control strategies that might reduce the spread of the virus across the globe; thus, containment of such virus would be possible. |
31 | y7f04w89 | How does the coronavirus differ from seasonal flu? | A comparative analysis of host responses to avian influenza infection in ducks and chickens highlights a role for the interferon-induced transmembrane proteins in viral resistance BACKGROUND: Chickens are susceptible to infection with a limited number of Influenza A viruses and are a potential source of a human influenza pandemic. In particular, H5 and H7 haemagglutinin subtypes can evolve from low to highly pathogenic strains in gallinaceous poultry. Ducks on the other hand are a natural reservoir for these viruses and are able to withstand most avian influenza strains. RESULTS: Transcriptomic sequencing of lung and ileum tissue samples from birds infected with high (H5N1) and low (H5N2) pathogenic influenza viruses has allowed us to compare the early host response to these infections in both these species. Chickens (but not ducks) lack the intracellular receptor for viral ssRNA, RIG-I and the gene for an important RIG-I binding protein, RNF135. These differences in gene content partly explain the differences in host responses to low pathogenic and highly pathogenic avian influenza virus in chicken and ducks. We reveal very different patterns of expression of members of the interferon-induced transmembrane protein (IFITM) gene family in ducks and chickens. In ducks, IFITM1, 2 and 3 are strongly up regulated in response to highly pathogenic avian influenza, where little response is seen in chickens. Clustering of gene expression profiles suggests IFITM1 and 2 have an anti-viral response and IFITM3 may restrict avian influenza virus through cell membrane fusion. We also show, through molecular phylogenetic analyses, that avian IFITM1 and IFITM3 genes have been subject to both episodic and pervasive positive selection at specific codons. In particular, avian IFITM1 showed evidence of positive selection in the duck lineage at sites known to restrict influenza virus infection. CONCLUSIONS: Taken together these results support a model where the IFITM123 protein family and RIG-I all play a crucial role in the tolerance of ducks to highly pathogenic and low pathogenic strains of avian influenza viruses when compared to the chicken. ELECTRONIC SUPPLEMENTARY MATERIAL: The online version of this article (doi:10.1186/s12864-015-1778-8) contains supplementary material, which is available to authorized users. |
6 | dfz7e1pp | what types of rapid testing for Covid-19 have been developed? | Massive Multiplexing Can Deliver a $1 Test for COVID-19 The severe acute respiratory syndrome virus, SARS-CoV-2 (hereafter COVID-19), rapidly achieved global pandemic status, provoking large-scale screening programs in many nations. Their activation makes it imperative to identify methods that can deliver a diagnostic result at low cost. This paper describes an approach which employs sequence variation in the gene coding for its envelope protein as the basis for a scalable, inexpensive test for COVID-19. It achieves this by coupling a simple RNA extraction protocol with low-volume RT-PCR, followed by E-Gel screening and sequencing on high-throughput platforms to analyze 10,000 samples in a run. Slight modifications to the protocol could support screening programs for other known viruses and for viral discovery. Just as the $1,000 genome is transforming medicine, a $1 diagnostic test for viral and bacterial pathogens would represent a major advance for public health. |
20 | e103fkda | are patients taking Angiotensin-converting enzyme inhibitors (ACE) at increased risk for COVID-19? | Ectopeptidases in pathophysiology Ectopeptidases are transmembrane proteins present in a wide variety of tissues and cell types. Dysregulated expression of certain ectopeptidases in human malignancies suggests their value as clinical markers. Ectopeptidase interaction with agonistic antibodies or their inhibitors has revealed that these ectoenzymes are able to modulate bioactive peptide responses and to influence growth, apoptosis and differentiation, as well as adhesion and motility, all functions involved in normal and tumoral processes. There is evidence that ectopeptidase‐mediated signal transduction frequently involves tyrosine phosphorylation. Combined analyses of gene organization and regulation of ectopeptidases by various physiological factors have provided insights into their structure–function relationships. Understanding the roles of ectopeptidases in pathophysiology may have implications in considering them as therapeutic targets. BioEssays 23:251–260, 2001. © 2001 John Wiley & Sons, Inc. |
22 | jnqqgd2g | are cardiac complications likely in patients with COVID-19? | Clinical features of deaths in the novel coronavirus epidemic in China In response to the recent novel coronavirus outbreak originating in Wuhan, Hubei province, China, observations concerning novel coronavirus mortality are of urgent public health importance. The present work presents the first review of the fatal novel coronavirus cases in China. Clinical data of fatal cases published by the Chinese Government were studied. As of 2 February 2020, the clinical data of 46 fatal cases were identified. The case fatality rate was significantly higher in Hubei province than the rest of China. While 67% of all deceased patients were male, gender was unlikely to be associated with mortality. Diabetes was likely to be associated with mortality. There is, however, not yet sufficient evidence to support the association between hypertension and mortality as similar prevalence of hypertension was also observed in the Hubei population. |
3 | 68inp2ps | will SARS-CoV2 infected people develop immunity? Is cross protection possible? | The Role of T Cell Epitopes in Coronavirus Infection Multiple MHV-specific CD4 and CD8 T cell epitopes have been identified in C57Bl/6 and BALB/c mice. In particular, at least two CD8 T cell epitopes are recognized in C57Bl/6 mice. In one model of MHV persistence, mutations are detected in the immunodominant CD8 T cell epitope recognized in this strain. These mutations contribute to virus persistence and to the development of more severe clinical disease. |
34 | jcqhxzih | What are the longer-term complications of those who recover from COVID-19? | Risk of drug-induced Long QT Syndrome associated with the use of repurposed COVID-19 drugs: a systematic review Background: The World Health Organization first declared SARS-CoV-2 (COVID-19) a pandemic on March 11, 2020. There are currently no vaccines or therapeutic agents proven efficacious to treat COVID-19. So, whether existing approved drugs could be repurposed and used off-label for the treatment of novel COVID-19 disease is being explored. Methods: A thorough literature search was performed to gather information on the pharmacological properties and toxicity of 6 drugs (azithromycin, chloroquine, favipiravir, hydroxychloroquine, lopinavir/ritonavir, remdesivir) proposed to be repurposed to treat COVID-19. Researchers emphasized affinity of these drugs to block the rapid component of the delayed rectifier cardiac potassium current (IKr) encoded by the human ether-a-go-go gene (hERG), their propensity to prolong cardiac repolarization (QT interval) and cause torsade de pointes (TdP). Risk of drug-induced Long QT Syndrome (LQTS) for these drugs was quantified by comparing six indices used to assess such risk and by querying the U.S. Food and Drug Administration (FDA) Adverse Event Reporting System database with specific key words. Data are also provided to compare the level of risk for drug-induced LQTS by these drugs to 23 other, well-recognized, torsadogenic compounds. Results: Estimators of LQTS risk levels indicated a very-high or high risk for all COVID-19 repurposed drugs except for azithromycin, although cases of TdP have been reported following the administration of this drug. There was an excellent agreement among the various indices used to assess risk of drug-induced LQTS for the six repurposed drugs and the 23 torsadogenic compounds. Conclusion: The risk-benefit assessment for the use of repurposed drugs to treat COVID-19 is complicated since benefits are currently anticipated, not proven. Mandatory monitoring of the QT interval shall be performed as such monitoring is possible for hospitalized patients or by the use of biodevices for outpatients initiated on these drugs. |
26 | lwipktcs | what are the initial symptoms of Covid-19? | First documentation of persistent SARS-CoV-2 infection presenting with late acute severe myocarditis A 64 year-old man presented with severe myocarditis 6 weeks after an initial almost asymptomatic SARS-CoV2 infection. He was found to have a persistent positive swab. Mechanisms explaining myocardial injury in patients with COVID-19 remains unclear, but this case suggests that severe acute myocarditis can develop in the late phase of COVID-19 infection, even after a symptom-free interval. |
15 | c5gnm728 | how long can the coronavirus live outside the body | A safe and convenient pseudovirus-based inhibition assay to detect neutralizing antibodies and screen for viral entry inhibitors against the novel human coronavirus MERS-CoV BACKGROUND: Evidence points to the emergence of a novel human coronavirus, Middle East respiratory syndrome coronavirus (MERS-CoV), which causes a severe acute respiratory syndrome (SARS)-like disease. In response, the development of effective vaccines and therapeutics remains a clinical priority. To accomplish this, it is necessary to evaluate neutralizing antibodies and screen for MERS-CoV entry inhibitors. METHODS: In this study, we produced a pseudovirus bearing the full-length spike (S) protein of MERS-CoV in the Env-defective, luciferase-expressing HIV-1 backbone. We then established a pseudovirus-based inhibition assay to detect neutralizing antibodies and anti-MERS-CoV entry inhibitors. RESULTS: Our results demonstrated that the generated MERS-CoV pseudovirus allows for single-cycle infection of a variety of cells expressing dipeptidyl peptidase-4 (DPP4), the confirmed receptor for MERS-CoV. Consistent with the results from a live MERS-CoV-based inhibition assay, the antisera of mice vaccinated with a recombinant protein containing receptor-binding domain (RBD, residues 377–662) of MERS-CoV S fused with Fc of human IgG exhibited neutralizing antibody response against infection of MERS-CoV pseudovirus. Furthermore, one small molecule HIV entry inhibitor targeting gp41 (ADS-J1) and the 3-hydroxyphthalic anhydride-modified human serum albumin (HP-HSA) could significantly inhibit MERS-CoV pseudovirus infection. CONCLUSION: Taken together, the established MERS-CoV inhibition assay is a safe and convenient pseudovirus-based alternative to BSL-3 live-virus restrictions and can be used to rapidly screen MERS-CoV entry inhibitors, as well as evaluate vaccine-induced neutralizing antibodies against the highly pathogenic MERS-CoV. |
35 | nao75cs1 | What new public datasets are available related to COVID-19? | Spatial transmission of COVID-19 via public and private transportation in China |
18 | gpr86lxe | what are the best masks for preventing infection by Covid-19? | SARS-CoV-2 and SARS-CoV differ in their cell tropism and drug sensitivity profiles SARS-CoV-2 is a novel coronavirus currently causing a pandemic. We show that the majority of amino acid positions, which differ between SARS-CoV-2 and the closely related SARS-CoV, are differentially conserved suggesting differences in biological behaviour. In agreement, novel cell culture models revealed differences between the tropism of SARS-CoV-2 and SARS-CoV. Moreover, cellular ACE2 (SARS-CoV-2 receptor) and TMPRSS2 (enables virus entry via S protein cleavage) levels did not reliably indicate cell susceptibility to SARS-CoV-2. SARS-CoV-2 and SARS-CoV further differed in their drug sensitivity profiles. Thus, only drug testing using SARS-CoV-2 reliably identifies therapy candidates. Therapeutic concentrations of the approved protease inhibitor aprotinin displayed anti-SARS-CoV-2 activity. The efficacy of aprotinin and of remdesivir (currently under clinical investigation against SARS-CoV-2) were further enhanced by therapeutic concentrations of the proton pump inhibitor omeprazole (aprotinin 2.7-fold, remdesivir 10-fold). Hence, our study has also identified anti-SARS-CoV-2 therapy candidates that can be readily tested in patients. |
43 | ps2nssey | How has the COVID-19 pandemic impacted violence in society, including violent crimes? | Top Concerns of Tweeters During the COVID-19 Pandemic: Infoveillance Study BACKGROUND: The recent coronavirus disease (COVID-19) pandemic is taking a toll on the world's health care infrastructure as well as the social, economic, and psychological well-being of humanity. Individuals, organizations, and governments are using social media to communicate with each other on a number of issues relating to the COVID-19 pandemic. Not much is known about the topics being shared on social media platforms relating to COVID-19. Analyzing such information can help policy makers and health care organizations assess the needs of their stakeholders and address them appropriately. OBJECTIVE: This study aims to identify the main topics posted by Twitter users related to the COVID-19 pandemic. METHODS: Leveraging a set of tools (Twitter's search application programming interface (API), Tweepy Python library, and PostgreSQL database) and using a set of predefined search terms ("corona," "2019-nCov," and "COVID-19"), we extracted the text and metadata (number of likes and retweets, and user profile information including the number of followers) of public English language tweets from February 2, 2020, to March 15, 2020. We analyzed the collected tweets using word frequencies of single (unigrams) and double words (bigrams). We leveraged latent Dirichlet allocation for topic modeling to identify topics discussed in the tweets. We also performed sentiment analysis and extracted the mean number of retweets, likes, and followers for each topic and calculated the interaction rate per topic. RESULTS: Out of approximately 2.8 million tweets included, 167,073 unique tweets from 160,829 unique users met the inclusion criteria. Our analysis identified 12 topics, which were grouped into four main themes: origin of the virus; its sources; its impact on people, countries, and the economy; and ways of mitigating the risk of infection. The mean sentiment was positive for 10 topics and negative for 2 topics (deaths caused by COVID-19 and increased racism). The mean for tweet topics of account followers ranged from 2722 (increased racism) to 13,413 (economic losses). The highest mean of likes for the tweets was 15.4 (economic loss), while the lowest was 3.94 (travel bans and warnings). CONCLUSIONS: Public health crisis response activities on the ground and online are becoming increasingly simultaneous and intertwined. Social media provides an opportunity to directly communicate health information to the public. Health systems should work on building national and international disease detection and surveillance systems through monitoring social media. There is also a need for a more proactive and agile public health presence on social media to combat the spread of fake news. |
16 | j3wrtsxj | how long does coronavirus remain stable on surfaces? | Similar environmental survival patterns of Streptococcus pyogenes strains of different epidemiologic backgrounds and clinical severity |
30 | ptnmtvzj | is remdesivir an effective treatment for COVID-19 | Effectiveness and safety of antiviral or antibody treatments for coronavirus: A rapid review Background: To identify safe and effective medical countermeasures (e.g., antivirals/antibodies) to address the current outbreak of a novel coronavirus (COVID-19) Methods: Comprehensive literature searches were developed by an experienced librarian for MEDLINE, EMBASE, the Cochrane Library, and biorxiv.org/medrxiv.org; additional searches for ongoing trials and unpublished studies were conducted in clinicaltrials.gov and the Global Infectious Diseases and Epidemiology Network (GIDEON). Title/abstract and full-text screening, data abstraction, and risk of bias appraisal were carried out by single reviewers. Results: 54 studies were included in the review: three controlled trials, 10 cohort studies, seven retrospective medical record/database studies, and 34 case reports or series. These studies included patients with severe acute respiratory syndrome (SARs, n=33), middle east respiratory syndrome (MERS, n=16), COVID-19 (n=3), and unspecified coronavirus (n=2). The most common treatment was ribavirin (n=41), followed by oseltamivir (n=10) and the combination of lopinavir/ritonavir (n=7). Additional therapies included broad spectrum antibiotics (n=30), steroids (n=39) or various interferons (n=12). No eligible studies examining monoclonal antibodies for COVID-19 were identified. One trial found that ribavirin prophylactic treatment statistically significantly reduced risk of MERS infection in people who had been exposed to the virus. Of the 21 studies reporting rates of ICU admission in hospitalized SARS or MERS patients, none reported statistically significant results in favour of or against antiviral therapies. Of the 40 studies reporting mortality rates in hospitalized SARS or MERS patients, one cohort study (MERS) and one retrospective study (SARS) found a statistically significant increase in the mortality rate for patients treated with ribavirin. Eighteen studies reported potential drug-related adverse effects including gastrointestinal symptoms, anemia, and altered liver function in patients receiving ribavirin. Conclusion: The current evidence for the effectiveness and safety of antiviral therapies for coronavirus is inconclusive and suffers from a lack of well-designed prospective trials or observational studies, preventing any treatment recommendations from being made. However, it is clear that the existing body of evidence is weighted heavily towards ribavirin (41/54 studies), which has not shown conclusive evidence of effectiveness and may cause harmful adverse events so future investigations may consider focusing on other candidates for antiviral therapy. |
35 | mn3b6nrs | What new public datasets are available related to COVID-19? | Association of inflammatory markers with the severity of COVID-19 Background: The ongoing worldwide epidemic of Coronavirus Disease 2019 (COVID-19), caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), has posed a huge threat to global public health. However, with regard to the effects of inflammatory markers on the severity of COVID-19, studies have reported associations that vary in strength and direction. Aims: In the meta-analysis, we aimed to provide an overview of the association of inflammatory markers with severity of COVID-19. Methods: The following databases were searched: PubMed, Embase, Cochrane Library, Wanfang database and CNKI (China National Knowledge Infrastructure) database until March 20, 2020. Weighted mean difference (WMD) and 95% confidence intervals (CIs) were pooled using random or fixed-effects models. Results: A total of 16 studies were included in our analysis comprising of 3962 patients with COVID-19. Random-effects results demonstrated that patients with COVID-19 in non-severe group had lower levels for CRP (WMD = -41.78 mg/l, 95% CI = [-52.43, -31.13], P < 0.001), PCT (WMD = -0.13 ng/ml, 95% CI = [-0.20, -0.05], P < 0.001), IL-6 (WMD = -21.32 ng/l, 95% CI = [-28.34, -14.31], P < 0.001), ESR (WMD = -8.40 mm/h, 95% CI = [-14.32, -2.48], P = 0.005), SAA (WMD = -43.35 μg/ml, 95% CI = [-80.85, -5.85], P = 0.020) and serum ferritin (WMD = -398.80 mg/l, 95% CI = [-625.89, -171.71], P < 0.001), compared with those in severe group. Moreover, survivors had lower level for IL-6 than non-survivors with COVID-19 (WMD = -4.80 ng/ml, 95% CI = [-5.87, -3.73], P < 0.001). These results were consistent through sensitivity analysis and publication bias assessment. Conclusions: The meta-analysis highlights the association of inflammatory markers with the severity of COVID-19. Measurement of inflammatory markers might help clinicians to monitor and evaluate the severity and prognosis of COVID-19. |
32 | 7tpdgxx8 | Does SARS-CoV-2 have any subtypes, and if so what are they? | [Simultaneous detection of respiratory viruses and influenza A virus subtypes using multiplex PCR]. This study was conducted to investigate the respiratory viruses and subtyping of influenza A virus when positive by multiplex PCR in patients with flu-like symptoms, after the pandemic caused by influenza A (H1N1)pdm09. Nasopharyngeal swab samples collected from 700 patients (313 female, 387 male; age range: 24 days-94 yrs, median age: 1 yr) between December 2010 - January 2013 with flu-like symptoms including fever, headache, sore throat, rhinitis, cough, myalgia as defined by the World Health Organization were included in the study. Nucleic acid extractions (Viral DNA/RNA Extraction Kit, iNtRON, South Korea) and cDNA synthesis (RevertAid First Strand cDNA Synthesis Kits, Fermentas, USA) were performed according to the manufacturer's protocol. Multiplex amplification of nucleic acids was performed using DPO (dual priming oligonucleotide) primers and RV5 ACE Screening Kit (Seegene, South Korea) in terms of the presence of influenza A (INF-A) virus, influenza B (INF-B) virus, respiratory syncytial virus (RSV), and the other respiratory viruses. PCR products were detected by automated polyacrylamide gel electrophoresis using Screen Tape multiple detection system. Specimens which were positive for viral nucleic acids have been further studied by using specific DPO primers, FluA ACE Subtyping and RV15 Screening (Seegene, South Korea) kits. Four INF-A virus subtypes [human H1 (hH1), human H3 (hH3), swine H1 (sH1), avian H5 (aH5)] and 11 other respiratory viruses [Adenovirus, parainfluenza virus (PIV) types 1-4, human bocavirus (HBoV), human metapneumovirus (HMPV), rhinovirus types A and B, human coronaviruses (HCoV) OC43, 229E/NL63] were investigated with those tests. In the study, 53.6% (375/700) of the patients were found to be infected with at least one virus and multiple respiratory virus infections were detected in 15.7% (59/375) of the positive cases, which were mostly (49/59, 83%) in pediatric patients. RSV and rhinovirus coinfections were the most prevalent (18/29, 62.7%) dual infections. The distribution of 436 respiratory viruses identified from 375 patients were as follows; 189 (43.3%) RSV, 93 (21.4%) rhinovirus, 86 (19.8%) INF-A, seven (1.6%) INF-B, 22 (5%) PIV types 1-3, 14 (3.2%) HMPV, 11 (2.5%) HCoV, nine (2%) HBoV, and five (1.2%) adenovirus. Fifty-five (64%) out of 86 INF-A viruses were subtyped as hH3, 24 (27.9%) were sH1 and seven (8.1%) were hH1. Avian H5 was not detected in any samples. The overall prevalence rates of INF-A, INF-B, RSV and other respiratory viruses were 12%, 1%, 27%, and 14.6%, respectively. RSV was the most prevalent respiratory agent in pediatric (161/313, 51%) cases, while INF-A virus in adult (24/62, 38.7%) patients. Influenza viruses were detected as responsible pathogens in 13.3% (93/700) of the patients with flu-like symptoms. Among the cases, a 1-month-old baby was infected with three virus strains (INF-A hH1+INF-A sH1+HCoV OC43) and a 82-year-old patient was infected with two INF-A virus subtypes (hH3 + sH1). INF-A viruses were mostly detected (79/86) in winter period, from December to March. INF-A virus sH1, was the most prevalent subtype in flu cases till February 2011 (22/86), after replaced by INF-A virus hH3. Beginning from February 2012, a significant increase observed in the cases infected with INF-A virus subtype hH3 (39/86). In conclusion, the identification and surveillance of influenza virus types and subtypes circulating in populations have importance both for epidemiological data and selection of vaccine strains. |
11 | 29wzpwvr | what are the guidelines for triaging patients infected with coronavirus? | Coronavirus Name of Virus: Coronavirus |
40 | 1bvsn9e8 | What are the observed mutations in the SARS-CoV-2 genome and how often do the mutations occur? | Coronaviruses: a paradigm of new emerging zoonotic diseases A novel type of coronavirus (2019-nCoV) infecting humans appeared in Wuhan, China, at the end of December 2019. Since the identification of the outbreak the infection quickly spread involving in one month more than 31,000 confirmed cases with 638 death. Molecular analysis suggest that 2019-nCoV could be originated from bats after passaging in intermediate hosts, highlighting the high zoonotic potential of coronaviruses. |
6 | ino9srb6 | what types of rapid testing for Covid-19 have been developed? | An overview on COVID-19: reality and expectation Recently, severe acute respiratory syndrome coronavirus 2 (SARS-COV-2), commonly known as coronavirus disease-2019 (COVID-19) has rapidly spread across China and around the world. By the declaration of WHO, COVID-19 outbreak considered as a public health problem of international concern. The aim of this study is to provide a comprehensive view on COVID-19 and the future expectations to control virus progression. Patients with liver disease, diabetes, high blood pressure, and obesity are more susceptible to the incidence of COVID-19 infection. So, there is a rapid need for disease diagnosis, vaccine development, and drug discovery to detect, prevent, and treat this sudden and lethal virus. Real-time polymerase chain reaction (RT-PCR) is considered as a rapid, accurate, and specific tool for disease diagnosis. Under this emergency situation that the world facing against COVID-19, there are about 15 potential vaccine candidates tested globally based on messenger RNA, DNA-based, nanoparticle, synthetic, and modified virus-like particle. Certain drugs that are clinically approved for other diseases were tested against COVID-19 as chloroquine, hydroxychloroquine, ivermectin, favipiravir, ribavirin, and remdesivir. Convalescent plasma transfusion and traditional herbal medicine were also taken into consideration. Due to the absence of effective treatment or vaccines against COVID-19 so far, the precautionary measures according to WHO's strategic objectives are the only way to confront this crisis. Governments should adopt national medical care programs to reduce the risk of exposure to any future viral outbreaks especially to patients with pre-existing medical conditions. |
18 | yq9xbka0 | what are the best masks for preventing infection by Covid-19? | Preparedness among Ophthalmologists: During and Beyond the COVID-19 Pandemic |
12 | qrcv4iuq | what are best practices in hospitals and at home in maintaining quarantine? | Practice recommendations for lung cancer radiotherapy during the COVID-19 pandemic: An ESTRO-ASTRO consensus statement BACKGROUND: The COVID-19 pandemic has caused radiotherapy resource pressures and led to increased risks for lung cancer patients and healthcare staff. An international group of experts in lung cancer radiotherapy established this practice recommendation pertaining to whether and how to adapt radiotherapy for lung cancer in the COVID-19 pandemic. METHODS: For this ESTRO & ASTRO endorsed project, 32 experts in lung cancer radiotherapy contributed to a modified Delphi consensus process. We assessed potential adaptations of radiotherapy in two pandemic scenarios. The first, an early pandemic scenario of risk mitigation, is characterized by an altered risk–benefit ratio of radiotherapy for lung cancer patients due to their increased susceptibility for severe COVID-19 infection, and minimization of patient travelling and exposure of radiotherapy staff. The second, a later pandemic scenario, is characterized by reduced radiotherapy resources requiring patient triage. Six common lung cancer cases were assessed for both scenarios: peripherally located stage I NSCLC, locally advanced NSCLC, postoperative radiotherapy after resection of pN2 NSCLC, thoracic radiotherapy and prophylactic cranial irradiation for limited stage SCLC and palliative thoracic radiotherapy for stage IV NSCLC. RESULTS: In a risk-mitigation pandemic scenario, efforts should be made not to compromise the prognosis of lung cancer patients by departing from guideline-recommended radiotherapy practice. In that same scenario, postponement or interruption of radiotherapy treatment of COVID-19 positive patients is generally recommended to avoid exposure of cancer patients and staff to an increased risk of COVID-19 infection. In a severe pandemic scenario characterized by reduced resources, if patients must be triaged, important factors for triage include potential for cure, relative benefit of radiation, life expectancy, and performance status. Case-specific consensus recommendations regarding multimodality treatment strategies and fractionation of radiotherapy are provided. CONCLUSION: This joint ESTRO-ASTRO practice recommendation established pragmatic and balanced consensus recommendations in common clinical scenarios of radiotherapy for lung cancer in order to address the challenges of the COVID-19 pandemic. |
36 | cpu38ryy | What is the protein structure of the SARS-CoV-2 spike? | Malignant mesothelioma Malignant mesothelioma is a fatal asbestos-associated malignancy originating from the lining cells (mesothelium) of the pleural and peritoneal cavities, as well as the pericardium and the tunica vaginalis. The exact prevalence is unknown but it is estimated that mesotheliomas represent less than 1% of all cancers. Its incidence is increasing, with an expected peak in the next 10–20 years. Pleural malignant mesothelioma is the most common form of mesothelioma. Typical presenting features are those of chest pain and dyspnoea. Breathlessness due to a pleural effusion without chest pain is reported in about 30% of patients. A chest wall mass, weight loss, sweating, abdominal pain and ascites (due to peritoneal involvement) are less common presentations. Mesothelioma is directly attributable to occupational asbestos exposure with a history of exposure in over 90% of cases. There is also evidence that mesothelioma may result from both para-occupational exposure and non-occupational "environmental" exposure. Idiopathic or spontaneous mesothelioma can also occur in the absence of any exposure to asbestos, with a spontaneous rate in humans of around one per million. A combination of accurate exposure history, along with examination radiology and pathology are essential to make the diagnosis. Distinguishing malignant from benign pleural disease can be challenging. The most helpful CT findings suggesting malignant pleural disease are 1) a circumferential pleural rind, 2) nodular pleural thickening, 3) pleural thickening of > 1 cm and 4) mediastinal pleural involvement. Involvement of a multidisciplinary team is recommended to ensure prompt and appropriate management, using a framework of radiotherapy, chemotherapy, surgery and symptom palliation with end of life care. Compensation issues must also be considered. Life expectancy in malignant mesothelioma is poor, with a median survival of about one year following diagnosis. |
39 | pobmam24 | What is the mechanism of cytokine storm syndrome on the COVID-19? | Single-cell analysis of severe COVID-19 patients reveals a monocyte-driven inflammatory storm attenuated by Tocilizumab Despite the current devastation of the COVID-19 pandemic, several recent studies have suggested that the immunosuppressive drug Tocilizumab can powerfully treating inflammatory responses that occur in this disease. Here, by employing single-cell analysis of the immune cell composition of severe-stage COVID-19 patients and these same patients in post Tocilizumab-treatment remission, we have identified a monocyte subpopulation specific to severe disease that contributes to inflammatory storms in COVID-19 patients. Although Tocilizumab treatment attenuated the strong inflammatory immune response, we found that immune cells including plasma B cells and CD8+ T cells still exhibited an intense humoral and cell-mediated anti-virus immune response in COVID-19 patients after Tocilizumab treatment. Thus, in addition to providing a rich, very high-resolution data resource about the immune cell distribution at multiple stages of the COVID-19 disease, our work both helps explain Tocilizumab's powerful therapeutic effects and defines a large number of potential new drug targets related to inflammatory storms. |
19 | 7v4jyzl3 | what type of hand sanitizer is needed to destroy Covid-19? | Growth of a murine coronavirus in a microcarrier cell culture system Abstract The growth of the murine coronavirus MHV-A59 on murine DBT cells adapted to dextran-made Cytodex 1 microcarriers was studied in comparison with cells grown on plastic dishes. With a microcarrier concentration of 5 g/l in spinner flasks, a density of 3 × 106 cells/ml was reached in 7 days. Under these conditions, cells supported virus growth to the same extent as when they were grown on the plastic substratum. This was shown by a similar development of virus-induced syncytia, the release of an equivalent number of infectious progeny virions per cell, similar recoveries observed after concentration and purification and an identical appearance of the purified virus under the electron microscope. On the other hand, the technical convenience of microcarriers and the ease of scale-up emphasize their potential for the growth of coronaviruses. |
3 | 1qniriu0 | will SARS-CoV2 infected people develop immunity? Is cross protection possible? | Machine intelligence design of 2019-nCoV drugs Wuhan coronavirus, called 2019-nCoV, is a newly emerged virus that infected more than 9692 people and leads to more than 213 fatalities by January 30, 2020. Currently, there is no effective treatment for this epidemic. However, the viral protease of a coronavirus is well-known to be essential for its replication and thus is an effective drug target. Fortunately, the sequence identity of the 2019-nCoV protease and that of severe-acute respiratory syndrome virus (SARS-CoV) is as high as 96.1%. We show that the protease inhibitor binding sites of 2019-nCoV and SARS-CoV are almost identical, which means all potential anti-SARS-CoV chemotherapies are also potential 2019-nCoV drugs. Here, we report a family of potential 2019-nCoV drugs generated by a machine intelligence-based generative network complex (GNC). The potential effectiveness of treating 2019-nCoV by using some existing HIV drugs is also analyzed. |
1 | b5329o75 | what is the origin of COVID-19 | Perspectives on monoclonal antibody therapy as potential therapeutic intervention for Coronavirus disease-19 (COVID-19). Last decade witnessed the outbreak of many life-threatening human pathogens including Nipah, Ebola, Chikungunya, Zika, Middle East respiratory syndrome coronavirus (MERS-CoV), Severe Acute respiratory syndrome coronavirus (SARS-CoV) and more recently novel coronavirus (2019-nCoV or SARS-CoV-2). The disease condition associated with novel coronavirus, referred to as Coronavirus disease (COVID-19). The emergence of novel coronavirus in 2019 in Wuhan, China marked the third highly pathogenic coronavirus infecting humans in the 21st century. The continuing emergence of coronaviruses at regular intervals poses a significant threat to human health and economy. Ironically, even after a decade of research on coronavirus, still there are no licensed vaccines or therapeutic agents to treat coronavirus infection which highlights an urgent need to develop effective vaccines or post-exposure prophylaxis to prevent future epidemics. Several clinical, genetic and epidemiological features of COVID-19 resemble SARS-CoV infection. Hence, the research advancements on SARS-CoV treatment might help scientific community in quick understanding of this virus pathogenesis and develop effective therapeutic/prophylactic agents to treat and prevent this infection. Monoclonal antibodies represent the major class of biotherapeutics for passive immunotherapy to fight against viral infection. The therapeutic potential of monoclonal antibodies has been well recognized in the treatment of many diseases. Here, we summarize the potential monoclonal antibody based therapeutic intervention for COVID-19 by considering the existing knowledge on the neutralizing monoclonal antibodies against similar coronaviruses SARS-CoV and MERS-CoV. Further research on COVID-19 pathogenesis could identify appropriate therapeutic targets to develop specific anti-virals against this newly emerging pathogen. |
23 | ff04vt1d | what kinds of complications related to COVID-19 are associated with hypertension? | COVID-19 and diabetes: What does the clinician need to know? COVID-19 and diabetes are currently two global pandemics. Epidemiological studies indicate that diabetes is the second most common comorbidity in COVID-19. This review aims to summarize currently available data about prevalence, possible pathophysiological mechanisms and management of patients with diabetes and COVID-19. |
38 | u4co0lhh | What is the mechanism of inflammatory response and pathogenesis of COVID-19 cases? | COVID-19 cytokine storm: the interplay between inflammation and coagulation |
38 | cn3bpmwj | What is the mechanism of inflammatory response and pathogenesis of COVID-19 cases? | Mechanism of inflammatory response in associated comorbidities in COVID-19 BACKGROUND AND AIMS: The outbreak of the new coronavirus, SARS-CoV-2, causes a respiratory disease and individuals with pre-existing cardiometabolic disorders display worse prognosis through the infection course. The aim of this minireview is to present epidemiological data related to metabolic comorbidities in association with the SARS-CoV-2. METHODS: This is a narrative mini-review with Pubmed search until April 23, 2020 using the keywords COVID-19, SARS-CoV-2, treatment of coronavirus and following terms: diabetes mellitus, obesity, arterial hypertension, ACE-inhibitors, cytokine storm, immune response and vitamin D. RESULTS: Studies indicate that obese individuals are more likely to develop infections, and that adipose tissue serves as a pathogen reservoir. In diabetic individuals higher rate of inflammatory processes is seen due to constant glucose recognition by C type lectin receptors. Hypertensive individuals, usually grouped with other conditions, are treated with drugs to reduce blood pressure mostly through ACEi and ARB, that leads to increased ACE2 expression, used by SARS-CoV-2 for human's cell entry. Until now, the studies have shown that individuals with those conditions and affected by COVID-19 present an uncontrolled release of pro-inflammatory cytokines and an unbalanced immune response, leading to the cytokine storm phenomenon. Vitamin D is highlighted as a potential therapeutic target, because in addition to acting on the immune system, it plays an important role in the control of cardiometabolic diseases. CONCLUSION: Currently, since there is no proven and effective antiviral therapy for SARS-CoV-2, the efforts should focus on controlling inflammatory response and reduce the risks of associated complications. |
38 | 0tdt0wej | What is the mechanism of inflammatory response and pathogenesis of COVID-19 cases? | COVID-19 and diabetes: Knowledge in progress AIMS: We aimed to briefly review the general characteristics of the novel coronavirus (SARS-CoV-2) and provide a better understanding of the coronavirus disease (COVID-19) in people with diabetes, and its management. METHODS: We searched for articles in PubMed and Google Scholar databases till 02 April 2020, with the following keywords: "SARS-CoV-2", "COVID-19", "infection", "pathogenesis", "incubation period", "transmission", "clinical features", "diagnosis", "treatment", "diabetes", with interposition of the Boolean operator "AND". RESULTS: The clinical spectrum of COVID-19 is heterogeneous, ranging from mild flu-like symptoms to acute respiratory distress syndrome, multiple organ failure and death. Older age, diabetes and other comorbidities are reported as significant predictors of morbidity and mortality. Chronic inflammation, increased coagulation activity, immune response impairment, and potential direct pancreatic damage by SARS-CoV-2 might be among the underlying mechanisms of the association between diabetes and COVID-19. No conclusive evidence exists to support the discontinuation of angiotensin-converting enzyme inhibitors (ACEI), angiotensin receptor blockers or thiazolidinediones because of COVID-19 in people with diabetes. Caution should be taken to potential hypoglycemic events with the use of chloroquine in these subjects. Patient tailored therapeutic strategies, rigorous glucose monitoring and careful consideration of drug interactions might reduce adverse outcomes. CONCLUSIONS: Suggestions are made on the possible pathophysiological mechanisms of the relationship between diabetes and COVID-19, and its management. No definite conclusions can be made based on current limited evidence. Further research regarding this relationship and its clinical management is warranted. |
8 | 92tvskxw | how has lack of testing availability led to underreporting of true incidence of Covid-19? | Estimation of Excess Deaths Associated With the COVID-19 Pandemic in the United States, March to May 2020. Importance Efforts to track the severity and public health impact of coronavirus disease 2019 (COVID-19) in the United States have been hampered by state-level differences in diagnostic test availability, differing strategies for prioritization of individuals for testing, and delays between testing and reporting. Evaluating unexplained increases in deaths due to all causes or attributed to nonspecific outcomes, such as pneumonia and influenza, can provide a more complete picture of the burden of COVID-19. Objective To estimate the burden of all deaths related to COVID-19 in the United States from March to May 2020. Design, Setting, and Population This observational study evaluated the numbers of US deaths from any cause and deaths from pneumonia, influenza, and/or COVID-19 from March 1 through May 30, 2020, using public data of the entire US population from the National Center for Health Statistics (NCHS). These numbers were compared with those from the same period of previous years. All data analyzed were accessed on June 12, 2020. Main Outcomes and Measures Increases in weekly deaths due to any cause or deaths due to pneumonia/influenza/COVID-19 above a baseline, which was adjusted for time of year, influenza activity, and reporting delays. These estimates were compared with reported deaths attributed to COVID-19 and with testing data. Results There were approximately 781 000 total deaths in the United States from March 1 to May 30, 2020, representing 122 300 (95% prediction interval, 116 800-127 000) more deaths than would typically be expected at that time of year. There were 95 235 reported deaths officially attributed to COVID-19 from March 1 to May 30, 2020. The number of excess all-cause deaths was 28% higher than the official tally of COVID-19-reported deaths during that period. In several states, these deaths occurred before increases in the availability of COVID-19 diagnostic tests and were not counted in official COVID-19 death records. There was substantial variability between states in the difference between official COVID-19 deaths and the estimated burden of excess deaths. Conclusions and Relevance Excess deaths provide an estimate of the full COVID-19 burden and indicate that official tallies likely undercount deaths due to the virus. The mortality burden and the completeness of the tallies vary markedly between states. |
Subsets and Splits
No community queries yet
The top public SQL queries from the community will appear here once available.