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11 | m40kwgcg | what are the guidelines for triaging patients infected with coronavirus? | Epidemiological and clinical characteristics of 99 cases of 2019 novel coronavirus pneumonia in Wuhan, China: a descriptive study Summary Background In December, 2019, a pneumonia associated with the 2019 novel coronavirus (2019-nCoV) emerged in Wuhan, China. We aimed to further clarify the epidemiological and clinical characteristics of 2019-nCoV pneumonia. Methods In this retrospective, single-centre study, we included all confirmed cases of 2019-nCoV in Wuhan Jinyintan Hospital from Jan 1 to Jan 20, 2020. Cases were confirmed by real-time RT-PCR and were analysed for epidemiological, demographic, clinical, and radiological features and laboratory data. Outcomes were followed up until Jan 25, 2020. Findings Of the 99 patients with 2019-nCoV pneumonia, 49 (49%) had a history of exposure to the Huanan seafood market. The average age of the patients was 55·5 years (SD 13·1), including 67 men and 32 women. 2019-nCoV was detected in all patients by real-time RT-PCR. 50 (51%) patients had chronic diseases. Patients had clinical manifestations of fever (82 [83%] patients), cough (81 [82%] patients), shortness of breath (31 [31%] patients), muscle ache (11 [11%] patients), confusion (nine [9%] patients), headache (eight [8%] patients), sore throat (five [5%] patients), rhinorrhoea (four [4%] patients), chest pain (two [2%] patients), diarrhoea (two [2%] patients), and nausea and vomiting (one [1%] patient). According to imaging examination, 74 (75%) patients showed bilateral pneumonia, 14 (14%) patients showed multiple mottling and ground-glass opacity, and one (1%) patient had pneumothorax. 17 (17%) patients developed acute respiratory distress syndrome and, among them, 11 (11%) patients worsened in a short period of time and died of multiple organ failure. Interpretation The 2019-nCoV infection was of clustering onset, is more likely to affect older males with comorbidities, and can result in severe and even fatal respiratory diseases such as acute respiratory distress syndrome. In general, characteristics of patients who died were in line with the MuLBSTA score, an early warning model for predicting mortality in viral pneumonia. Further investigation is needed to explore the applicability of the MuLBSTA score in predicting the risk of mortality in 2019-nCoV infection. Funding National Key R&D Program of China. |
5 | pth2d40p | what drugs have been active against SARS-CoV or SARS-CoV-2 in animal studies? | Asymptomatic carrier state, acute respiratory disease, and pneumonia due to severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2): Facts and myths Abstract Since the emergence of coronavirus disease 2019 (COVID-19) (formerly known as the 2019 novel coronavirus [2019-nCoV]) in Wuhan, China in December 2019, which is caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), more than 75,000 cases have been reported in 32 countries/regions, resulting in more than 2000 deaths worldwide. Despite the fact that most COVID-19 cases and mortalities were reported in China, the WHO has declared this outbreak as the sixth public health emergency of international concern. The COVID-19 can present as an asymptomatic carrier state, acute respiratory disease, and pneumonia. Adults represent the population with the highest infection rate; however, neonates, children, and elderly patients can also be infected by SARS-CoV-2. In addition, nosocomial infection of hospitalized patients and healthcare workers, and viral transmission from asymptomatic carriers are possible. The most common finding on chest imaging among patients with pneumonia was ground-glass opacity with bilateral involvement. Severe cases are more likely to be older patients with underlying comorbidities compared to mild cases. Indeed, age and disease severity may be correlated with the outcomes of COVID-19. To date, effective treatment is lacking; however, clinical trials investigating the efficacy of several agents, including remdesivir and chloroquine, are underway in China. Currently, effective infection control intervention is the only way to prevent the spread of SARS-CoV-2. |
6 | sonthitn | what types of rapid testing for Covid-19 have been developed? | Interpretable Artificial Intelligence for COVID-19 Diagnosis from Chest CT Reveals Specificity of Ground-Glass Opacities Background The use of CT imaging enhanced by artificial intelligence to effectively diagnose COVID-19, instead of or in addition to reverse transcription-polymerase chain reaction (RT-PCR), can improve widespread COVID-19 detection and resource allocation. Methods 904 axial lung window CT slices from 338 patients in 17 countries were collected and labeled. The data included 606 images from COVID-19 positive patients (confirmed via RT-PCR), 224 images of a variety of other pulmonary diseases including viral pneumonias, and 74 images of normal patients. We developed, trained, validated, and tested an object detection model which detects features in three categories: ground-glass opacities (GGOs) for COVID-19, GGOs for non-COVID-19 diseases, and features that are inconsistent with a COVID-19 diagnosis. These collected features are passed into an interpretable decision tree model to make a suggested diagnosis. Results On an independent test of 219 images from COVID-19 positive, a variety of pneumonia, and healthy patients, the model predicted COVID-19 diagnoses with an accuracy of 96.80 % (95% confidence interval [CI], 96.75 to 96.86) , AUC-ROC of 0.9664 (95% CI, 0.9659 to 0.9671) , sensitivity of 98.33% (95% CI, 98.29 to 98.40) , precision of 95.93% (95% CI, 95.83 to 95.99), and specificity of 94.95% (95% CI, 94.84 to 95.05). On an independent test of 34 images from asymptomatic COVID-19 positive patients, our model achieved an accuracy of 97.06% (95% CI, 96.81 to 97.06) and a sensitivity of 96.97% (95% CI, 96.71 to 96.97). Similarly high performance was also obtained for out-of-sample countries, and no significant performance difference was obtained between genders. Conclusion We present an interpretable artificial intelligence CT analysis tool to diagnose COVID-19 in both symptomatic and asymptomatic patients. Further, our model is able to differentiate COVID-19 GGOs from similar pathologies suggesting that GGOs can be disease-specific. |
15 | ioo17gc3 | how long can the coronavirus live outside the body | Transmission of SARS-CoV-2 via fecal-oral and aerosols–borne routes: Environmental dynamics and implications for wastewater management in underprivileged societies Abstract The advent of novel human coronavirus (SARS-CoV-2) and its potential transmission via fecal-oral and aerosols-borne routes are upcoming challenges to understand the fate of the virus in the environment. In this short communication, we specifically looked at the possibilities of these transmission routes based on the available literature directly related to the SARS-CoV-2 as well as on the closer phylogenetic relatives such as SARS-CoV-1. The available data suggest that, in addition to human-to-human contact, the virus may spread via fecal-oral and aerosols-borne routes. Existing knowledge states that coronaviruses have low stability in the environment due to the natural action of oxidants that disrupt the viral envelope. Previous recommended dosage of chlorination has been found to be not sufficient to inactivate SARS-CoV-2 in places where viral load is high such as hospitals and airports. Although there is no current evidence showing that coronaviruses can be transmitted through contaminated drinking water, there is a growing concern on the impact of the current pandemic wave on underprivileged societies because of their poor wastewater treatment infrastructures, overpopulation, and outbreak management strategies. More research is encouraged to trace the actual fate of SARS-CoV-2 in the environment and to develop/revise the disinfection strategies accordingly. |
14 | vwf2djd4 | what evidence is there related to COVID-19 super spreaders | Epidemiological and Clinical Aspects of COVID-19; a Narrative Review There are significant misconceptions and many obstacles in the way of illuminating the epidemiological and clinical aspects of COVID-19 as a new emerging epidemic. In addition, usefulness of some evidence published in the context of the recent epidemic for decision making in clinic as well as public health is questionable. However, misinterpreting or ignoring strong evidence in clinical practice and public health probably results in less effective and somehow more harmful decisions for individuals as well as subgroups in general populations of countries in the initial stages of this epidemic. Accordingly, our narrative review appraised epidemiological and clinical aspects of the disease including genetic diversity of coronavirus genus, mode of transmission, incubation period, infectivity, pathogenicity, virulence, immunogenicity, diagnosis, surveillance, clinical case management and also successful measures for preventing its spread in some communities. |
6 | 1ul6dszs | what types of rapid testing for Covid-19 have been developed? | Rapid Single Cell Evaluation of Human Disease and Disorder Targets Using REVEAL: SingleCell™ Single-cell (sc) sequencing performs unbiased profiling of individual cells and enables evaluation of less prevalent cellular populations, often missed using bulk sequencing. However, the scale and the complexity of the sc datasets poses a great challenge in its utility and this problem is further exacerbated when working with larger datasets typically generated by consortium efforts. As the scale of single cell datasets continues to increase exponentially, there is an unmet technological need to develop database platforms that can evaluate key biological hypothesis by querying extensive single-cell datasets. Large single-cell datasets like human cell atlas and COVID-19 cell atlas (collection of annotated sc datasets from various human organs) are excellent resources for profiling target genes involved in human diseases and disorders ranging from oncology, auto-immunity, as well as infectious diseases like COVID-19 caused by SARS-CoV-2 virus. SARS-CoV-2 infections have led to a worldwide pandemic with massive loss of lives, infections exceeding 7 million cases. The virus uses ACE2 and TMPRSS2 as key viral entry associated proteins expressed in human cells for infections. Evaluating the expression profile of key genes in large single-cell datasets can facilitate testing for diagnostics, therapeutics and vaccine targets; as the world struggles to cope with the on-going spread of COVID-19 infections. In this manuscript we describe, REVEAL: SingleCell which enables storage, retrieval and rapid query of single-cell datasets inclusive of millions of cells. The analytical database described here enables selecting and analyzing cells across multiple studies. Cells can be selected using individual metadata tags, more complex hierarchical ontology filtering, and gene expression threshold ranges, including co-expression of multiple genes. The tags on selected cells can be further evaluated for testing biological hypothesis. One such example includes identifying the most prevalent cell type annotation tag on returned cells. We used REVEAL: SingleCell to evaluate expression of key SARS-CoV-2 entry associated genes, and queried the current database (2.2 Million cells, 32 projects) to obtain the results in <60 seconds. We highlighted cells expressing COVID-19 associated genes are expressed on multiple tissue types, thus in part explains the multi-organ involvement in infected patients observed worldwide during the on-going COVID-19 pandemic. |
1 | yzcq3380 | what is the origin of COVID-19 | Meta-analysis of transcriptomes of SARS-Cov2 infected human lung epithelial cells identifies transmembrane serine proteases co-expressed with ACE2 and biological processes related to viral entry, immunity, inflammation and cellular stress The COVID-19 pandemic resulting from the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) which emerged in December 2019 in the Chinese city of Wuhan in the province Hubei has placed immense burden on national economies and global health. At present neither vaccination nor therapies are available although several antiviral agents such as remdesivir, originally an Ebola drug, nelfinavir, an HIV-1 protease inhibitor and other drugs such as lopinavir have been evaluated. Here, we performed a meta-analysis of RNA-sequencing data from three studies employing human lung epithelial cells. Of these one focused on lung epithelial cells infected with SARS-CoV-2. We aimed at identifying genes co-expressed with angiotensin I converting enzyme 2 (ACE2) the human cell entry receptor of SARS-CoV-2, and unveiled several genes correlated or inversely correlated with high significance, among the most significant of these was the transmembrane serine protease 4 (TMPRSS4). Serine proteases are known to be involved in the infection process by priming the virus spike protein. Pathway analysis revealed papilloma virus infection amongst the most significantly correlated pathways. Gene Ontologies revealed regulation of viral life cycle, immune responses, pro-inflammatory responses-several interleukins such as IL6, IL1, IL20 and IL33, IFI16 regulating the interferon response to a virus, chemo-attraction of macrophages, last and not least cellular stress resulting from activated Reactive Oxygen Species. We believe that this dataset will aid in a better understanding of the molecular mechanism(s) underlying COVID-19. |
16 | qk8g4c7e | how long does coronavirus remain stable on surfaces? | Two adjacent mutations on the dimer interface of SARS coronavirus 3C-like protease cause different conformational changes in crystal structure Abstract The 3C-like protease of SARS coronavirus (SARS-CoV 3CLpro) is vital for SARS-CoV replication and is a promising drug target. It has been extensively proved that only the dimeric enzyme is active. Here we discovered that two adjacent mutations (Ser139_Ala and Phe140_Ala) on the dimer interface resulted in completely different crystal structures of the enzyme, demonstrating the distinct roles of these two residues in maintaining the active conformation of SARS-CoV 3CLpro. S139A is a monomer that is structurally similar to the two reported monomers G11A and R298A. However, this mutant still retains a small fraction of dimer in solution, which might account for its remaining activity. F140A is a dimer with the most collapsed active pocket discovered so far, well-reflecting the stabilizing role of this residue. Moreover, a plausible dimerization mechanism was also deduced from structural analysis. Our work is expected to provide insight on the dimerization–function relationship of SARS-CoV 3CLpro. |
23 | im9v9ezp | what kinds of complications related to COVID-19 are associated with hypertension? | Risk factors for severity and mortality in adult COVID-19 inpatients in Wuhan BACKGROUND: In December 2019, the coronavirus disease 2019 (COVID-19) outbreak occurred in Wuhan. Data on the clinical characteristics and outcomes of patients with severe COVID-19 are limited. OBJECTIVE: We sought to evaluate the severity on admission, complications, treatment, and outcomes of patients with COVID-19. METHODS: Patients with COVID-19 admitted to Tongji Hospital from January 26, 2020, to February 5, 2020, were retrospectively enrolled and followed-up until March 3, 2020. Potential risk factors for severe COVID-19 were analyzed by a multivariable binary logistic model. Cox proportional hazard regression model was used for survival analysis in severe patients. RESULTS: We identified 269 (49.1%) of 548 patients as severe cases on admission. Older age, underlying hypertension, high cytokine levels (IL-2R, IL-6, IL-10, and TNF-α), and high lactate dehydrogenase level were significantly associated with severe COVID-19 on admission. The prevalence of asthma in patients with COVID-19 was 0.9%, markedly lower than that in the adult population of Wuhan. The estimated mortality was 1.1% in nonsevere patients and 32.5% in severe cases during the average 32 days of follow-up period. Survival analysis revealed that male sex, older age, leukocytosis, high lactate dehydrogenase level, cardiac injury, hyperglycemia, and high-dose corticosteroid use were associated with death in patients with severe COVID-19. CONCLUSIONS: Patients with older age, hypertension, and high lactate dehydrogenase level need careful observation and early intervention to prevent the potential development of severe COVID-19. Severe male patients with heart injury, hyperglycemia, and high-dose corticosteroid use may have a high risk of death. |
33 | 8p1agcm2 | What vaccine candidates are being tested for Covid-19? | Candidate targets for immune responses to 2019-Novel Coronavirus (nCoV): sequence homology- and bioinformatic-based predictions Effective countermeasures against the recent emergence and rapid expansion of the 2019-Novel Coronavirus (2019-nCoV) require the development of data and tools to understand and monitor viral spread and immune responses. However, little information about the targets of immune responses to 2019-nCoV is available. We used the Immune Epitope Database and Analysis Resource (IEDB) resource to catalog available data related to other coronaviruses, including SARS-CoV, which has high sequence similarity to 2019-nCoV, and is the best-characterized coronavirus in terms of epitope responses. We identified multiple specific regions in 2019-nCoV that have high homology to SARS virus. Parallel bionformatic predictions identified a priori potential B and T cell epitopes for 2019-nCoV. The independent identification of the same regions using two approaches reflects the high probability that these regions are targets for immune recognition of 2019-nCoV. ONE SENTENCE SUMMARY We identified potential targets for immune responses to 2019-nCoV and provide essential information for understanding human immune responses to this virus and evaluation of diagnostic and vaccine candidates. |
27 | atnz63pk | what is known about those infected with Covid-19 but are asymptomatic? | Estimating the Asymptomatic Proportion of 2019 Novel Coronavirus onboard the Princess Cruises Ship, 2020 The potential infectiousness of asymptomatic COVID-19 cases together with a substantial fraction of asymptomatic infections among all infections, have been highlighted in clinical studies. We conducted statistical modeling analysis to derive the delay-adjusted asymptomatic proportion of the positive COVID-19 infections onboard the Princess Cruises ship along with the timeline of infections. We estimated the asymptomatic proportion at 17.9% (95% CrI: 15.5%-20.2%), with most of the infections occurring before the start of the 2-week quarantine. |
12 | clf8f90t | what are best practices in hospitals and at home in maintaining quarantine? | Resumption of activity in gastroenterology departments. Recommendations by SEPD, AEEH, GETECCU and AEG Abstract The set of measures proposed by SEPD, AEEH, GETECCU and AEG are aimed to help departments in their resumption of usual activity. We have prepared a number of practical recommendations regarding patient management and the stepwise resumption of healthcare activity. These recommendations are based on the sparse, changing evidence available, and will be updated in the future according to daily needs and the availability of expendable materials to suit them; in each department they will be implemented depending upon the cumulative incidence of SARS-CoV-2 infection in each region, and the burden the pandemic has represented for each hospital. The general objectives of these recommendations include: • To protect our patients against the risks of infection with SARS-CoV-2 and to provide them with high-quality care. • To protect all healthcare professionals against the risks of infection with SARS-CoV-2. • To resume normal functioning of our departments in a setting of ongoing risk for infection with SARS-CoV-2. |
15 | b9unnsxk | how long can the coronavirus live outside the body | Infection respiratoire nosocomiale par le coronavirus dars une unité de réanimation néonatále: évaluation prospective |
40 | 46fmw0in | What are the observed mutations in the SARS-CoV-2 genome and how often do the mutations occur? | Abstracts of the EPSM-ABEC 2008 conference |
49 | 342thf3o | do individuals who recover from COVID-19 show sufficient immune response, including antibody levels and T-cell mediated immunity, to prevent re-infection? | SARS - CoV-2: Reasons of epidemiology of severe ill disease cases and therapeutic approach using trivalent vaccine (tetanus, diphtheria and Bordetella pertussis) The novel coronavirus Covid-19 follows transmission route and clinical presentation of all community-acquired coronaviruses. Instead, the rate of transmission is significative higher, with a faster spread of the virus responsible of the worldwide outbreak and a significative higher mortality rate due to the development of a severe lung injury. Most noteworthy is the distribution of death rate among age groups. Children and younger people are almost protected from severe clinical presentation. Possible explanation of this phenomenon could be the ability of past vaccinations (especially tetanic, diphtheria toxoids and inactivated bacteria as pertussis) to stimulate immune system and to generate a scattered immunity against non-self antigens in transit, as coronaviruses and other community-circulating viruses and make immune system readier to develop specific immunity against Covid-19. The first support to this hypothesis is the distribution of mortality rate during historical pandemics ("Spanish flu" 1918, "Asian flu" 1956 and "the Hong Kong flu" 1968) among age groups before and after the introduction of vaccines. The immunological support to the hypothesis derives from recent studies about immunotherapy for malignancies, which propose the use of oncolytic vaccines combined with toxoids in order to exploit CD4 + memory T cell recall in supporting the ongoing anti-tumour response. According to this hypothesis vaccine formulations (tetanus, diphtheria, Bordetella pertussis) could be re-administrate after the first contact with Covid-19, better before the development of respiratory severe illness and of course before full-blown ARDS (Acute Respiratory Distress Syndrome). The CD4 + memory exploiting could help immune system to recall immunity of already know antigens against coronaviruses, avoiding or limiting "lung crash" until virus specific immunity develops and making it faster and prolonged. Finally, this administration could be helpful not only in already infected patients, but also before infection. In fact, people could have an immune system more ready when the contact with the Covid-19 will occur. |
28 | m5u3cnvh | what evidence is there for the value of hydroxychloroquine in treating Covid-19? | Updating the diagnostic criteria of COVID-19 "suspected case" and "confirmed case" is necessary On 6 February 2020, our team had published a rapid advice guideline for diagnosis and treatment of 2019 novel coronavirus (2019-nCoV) infection, and this guideline provided our experience and make well reference for fighting against this pandemic worldwide. However, the coronavirus disease 2019 (COVID-19) is a new disease, our awareness and knowledge are gradually increasing based on the ongoing research findings and clinical practice experience; hence, the strategies of diagnosis and treatment are also continually updated. In this letter, we answered one comment on our guideline and provided the newest diagnostic criteria of "suspected case" and "confirmed case" according to the latest Diagnosis and Treatment Guidelines for COVID-19 (seventh version) that issued by the National Health Committee of the People's Republic of China. |
31 | m2cu5iof | How does the coronavirus differ from seasonal flu? | Molecular Mechanism of Evolution and Human Infection with SARS-CoV-2 The outbreak of a novel coronavirus, which was later formally named the severe acute respiratory coronavirus 2 (SARS-CoV-2), has caused a worldwide public health crisis. Previous studies showed that SARS-CoV-2 is highly homologous to SARS-CoV and infects humans through the binding of the spike protein to ACE2. Here, we have systematically studied the molecular mechanisms of human infection with SARS-CoV-2 and SARS-CoV by protein-protein docking and MD simulations. It was found that SARS-CoV-2 binds ACE2 with a higher affinity than SARS-CoV, which may partly explain that SARS-CoV-2 is much more infectious than SARS-CoV. In addition, the spike protein of SARS-CoV-2 has a significantly lower free energy than that of SARS-CoV, suggesting that SARS-CoV-2 is more stable and may survive a higher temperature than SARS-CoV. This provides insights into the evolution of SARS-CoV-2 because SARS-like coronaviruses have originated in bats. Our computation also suggested that the RBD-ACE2 binding for SARS-CoV-2 is much more temperature-sensitive than that for SARS-CoV. Thus, it is expected that SARS-CoV-2 would decrease its infection ability much faster than SARS-CoV when the temperature rises. These findings would be beneficial for the disease prevention and drug/vaccine development of SARS-CoV-2. |
12 | tc96t3tb | what are best practices in hospitals and at home in maintaining quarantine? | EFFECTS OF QUARANTINE ON MENTAL HEALTH OF POPULATIONS AFFECTED BY COVID-19 BACKGROUND: To prevent the spread of the The novel coronavirus (2019-nCOV), some classic public health measures are being taken, such as social distancing and quarantine METHOD: Studies were identified using large-circulation international journals found in two electronic databases: Scopus and Embase. RESULTS: The prolonged confinement is evidently related to psychological damage, considering that individuals would be subjected to stressors for a longer period of time . In some cases, these psychic losses lasted for many months after the end of this confinement CONCLUSIONS: It is necessary to develop and implement actions to minimize the population psychological distress in meeting the needs of the communities affected by COVID-19 Thus, as it occurred in China, it is necessary that the other affected nations promote the publication of regulations that guide the implementation of mental health services and the allocation of resources, in order to ensure that individuals are monitored by competent professionals, thus reducing the psychological damage that can be motivated by the social isolation period during the quarantine. |
10 | f49z2qhx | has social distancing had an impact on slowing the spread of COVID-19? | Infections: The Emergency of the New Millennium The New Millennium opened with alarming data on infections and antimicrobial resistance. Viral infections (SARS, MERS-CoV, Zika, Chikungunya, West Nile, Ebola virus infection, etc.) emerged or re-emerged with threatening outbreaks. However, viral emerging infections in some instances represented marginally a concern for developed countries that were just lapped by them. Currently, the new emergency is represented by antimicrobial resistance in bacterial infections, that is, a matter of extreme importance in developed and developing countries, where this issue has become a top priority for global policy makers and public health authorities. New mechanisms of resistance continue to emerge and spread globally, threatening our ability to treat common infections. The overuse and misuse of antimicrobials both in the human and animal field, and their dispersion in the environment pose a risk for selection of mechanisms of resistance of germs. Some settings, like the healthcare facilities, where the use of antimicrobials is obviously intense and infection prevention and control can be poor, represent the reservoir for multidrug-resistant organisms and, sometimes, the melting pot for pan-resistant strains. |
34 | dqour5jr | What are the longer-term complications of those who recover from COVID-19? | Characterization of spike glycoprotein of SARS-CoV-2 on virus entry and its immune cross-reactivity with SARS-CoV Since 2002, beta coronaviruses (CoV) have caused three zoonotic outbreaks, SARS-CoV in 2002–2003, MERS-CoV in 2012, and the newly emerged SARS-CoV-2 in late 2019. However, little is currently known about the biology of SARS-CoV-2. Here, using SARS-CoV-2 S protein pseudovirus system, we confirm that human angiotensin converting enzyme 2 (hACE2) is the receptor for SARS-CoV-2, find that SARS-CoV-2 enters 293/hACE2 cells mainly through endocytosis, that PIKfyve, TPC2, and cathepsin L are critical for entry, and that SARS-CoV-2 S protein is less stable than SARS-CoV S. Polyclonal anti-SARS S1 antibodies T62 inhibit entry of SARS-CoV S but not SARS-CoV-2 S pseudovirions. Further studies using recovered SARS and COVID-19 patients' sera show limited cross-neutralization, suggesting that recovery from one infection might not protect against the other. Our results present potential targets for development of drugs and vaccines for SARS-CoV-2. |
4 | kszep2kr | what causes death from Covid-19? | Localization to the nucleolus is a common feature of coronavirus nucleoproteins, and the protein may disrupt host cell division. The subcellular localization of transmissible gastroenteritis virus (TGEV) and mouse hepatitis virus (MHV) (group I and group II coronaviruses, respectively) nucleoproteins (N proteins) were examined by confocal microscopy. The proteins were shown to localize either to the cytoplasm alone or to the cytoplasm and a structure in the nucleus. This feature was confirmed to be the nucleolus by using specific antibodies to nucleolin, a major component of the nucleolus, and by confocal microscopy to image sections through a cell expressing N protein. These findings are consistent with our previous report for infectious bronchitis virus (group III coronavirus) (J. A. Hiscox et al., J. Virol. 75:506-512, 2001), indicating that nucleolar localization of the N protein is a common feature of the coronavirus family and is possibly of functional significance. Nucleolar localization signals were identified in the domain III region of the N protein from all three coronavirus groups, and this suggested that transport of N protein to the nucleus might be an active process. In addition, our results suggest that the N protein might function to disrupt cell division. Thus, we observed that approximately 30% of cells transfected with the N protein appeared to be undergoing cell division. The most likely explanation for this is that the N protein induced a cell cycle delay or arrest, most likely in the G(2)/M phase. In a fraction of transfected cells expressing coronavirus N proteins, we observed multinucleate cells and dividing cells with nucleoli (which are only present during interphase). These findings are consistent with the possible inhibition of cytokinesis in these cells. |
10 | 6ea06i4f | has social distancing had an impact on slowing the spread of COVID-19? | COVID-19 Pandemic: Power Law Spread and Flattening of the Curve In this paper, we analyze the real-time infection data of COVID-19 epidemic for nine nations. Our analysis is up to May 04, 2020. South Korea, China, Italy, France, Spain, and Germany have either flattened or close to flattening their epidemic curves. USA and Japan have transitioned to a linear regime, while India is still in a power-law phase. We argue that the transition from an exponential regime to a succession of power-law regimes is a good indicator for flattening of the epidemic curve. We also argue that lockdowns, long-term community transmission, and the transmission by asymptomatic carriers traveling long distances may be inducing the power-law growth of the epidemic. |
27 | z7lz9syq | what is known about those infected with Covid-19 but are asymptomatic? | Initial CT imaging characters of an imported family cluster of COVID-19 Abstract The objective of this report is to better understand the initial CT imaging spectrum and the relationship between clinical characteristics and initial CT imaging features of an imported family cluster cases involving 7 laboratory-confirmed COVID-19 patients. We find that initial CT findings of 4 patients were positive within one week after the onset of symptoms and 1 patient was negative before the onset of symptoms. Two asymptomatic patients had typical CT abnormalities. The initial CT imaging manifestations are mainly peripheral or subpleural ground-glass opacities and ground-glass with consolidation. Our report is of potential guiding value for the initial CT screening of imported familial cluster cases since the imported cases have an identified time of infection. |
38 | b1ca2own | What is the mechanism of inflammatory response and pathogenesis of COVID-19 cases? | Potential mechanisms of hemorrhagic stroke in elderly COVID-19 patients The novel severe acute respiratory syndrome coronavirus 2 is the causative agent of coronavirus disease 2019, a new human infectious disease. While fever, cough, and respiratory distress are typical first symptoms, a fraction of those affected present instead with neurological symptoms suggestive of central nervous system compromise. This review summarizes the potential contribution of coronavirus disease 2019 to hemorrhagic stroke in the elderly and proposes possible mechanisms. Reports show that the most affected patients have underlying chronic diseases such as hypertension and diabetes, which are two key risk factors for hemorrhagic stroke. Angiotensin-converting enzyme 2 is the main host cell surface receptor interacting with the severe acute respiratory syndrome coronavirus 2 spike glycoprotein to allow viral entry and infection. We speculate that ensuing downregulation of angiotensin-converting enzyme 2 expression may compound the risk conferred by pre-existing comorbidities and critically influence the pathogenesis of hemorrhagic stroke by elevating blood pressure and impairing cerebrovascular endothelial function. Additionally, both age- and/or disease-related immune dysfunction and enhanced catecholamine release secondary to anxiety and stress may also aggravate central nervous system symptoms of severe acute respiratory syndrome coronavirus 2 infection. Thus, assessment of systemic inflammatory biomarkers and tight control of hemodynamic parameters upon admission are crucial to minimize mortality and morbidity in coronavirus disease 2019 patients with central nervous system symptoms suggestive of incipient stroke. |
13 | py6qu4tl | what are the transmission routes of coronavirus? | Teicoplanin potently blocks the cell entry of 2019-nCoV Since December 2019, the outbreak of a new coronavirus, named 2019-nCoV, has greatly threatened the public health in China and raised great concerns worldwide. No specific treatment for this infection is currently available. We previously reported that teicoplanin, a glycopeptide antibiotic which has routinely been used in the clinic to treat bacterial infection with low toxicity, significantly inhibits the invasion of cells by Ebola virus, SARS-CoV and MERS-CoV, via specifically inhibiting the activity of cathepsin L. Here, we tested the efficacy of teicoplanin against 2019-nCoV virus infection and found that teicoplanin potently prevents the entrance of 2019-nCoV-Spike-pseudoviruses into the cytoplasm, with an IC50 of 1.66 μM. Although the inhibitory effect upon the replication of wildtype viruses ex vivo and in vivo remains to be determined, our preliminary result indicates that the potential antiviral activity of teicoplanin could be applied for the treatment of 2019-nCoV virus infection. |
38 | 8nye3nc8 | What is the mechanism of inflammatory response and pathogenesis of COVID-19 cases? | Mannan‐Binding Lectin, L‐Ficolin and H‐Ficolin Selectively Binds to Different Bacteria Mannan‐binding lectin (MBL), L‐ficolin and H‐ficolin are pattern recognition molecules of the innate immune system. We investigated the ability of these molecules to bind to different serotypes and noncapsulated variants of Streptococcus pneumonia and Staphylococcus aureus. We found that MBL binds to noncapsulated S. aureus strain (Wood) but not any of the examined S. pneumoniae serotypes. L‐ficolin binds to some capsulated S. pneumoniae serotypes (11A, 11D and 11F) as well as some capsulated S. aureus serotypes (Type‐1, ‐8, ‐9, ‐11 and ‐12). H‐ficolin does not bind to any of the examined S. pneumoniae and S. aureus serotypes included in this study but did bind to a strain of Aerococcus viridans. When bound to bacteria, MBL and H‐ficolin initiated activation of complement factor C4, whereas L‐ficolin did not. During this study, quantitative assays for the three proteins were developed and the concentration in 97 plasma samples were determined and the median values were estimated at 0.8 μg of MBL/ml, 3.3 μg of L‐ficolin/ml and 18.4 μg of H‐ficolin/ml, respectively. |
1 | tsb6gul8 | what is the origin of COVID-19 | Coronavirus infections of man associated with diseases other than the common cold About 14,000 paired sera, from patients with various types of acute infectious diseases with suspected viral origin, were screened by complement fixation against a wide set of viral antigens, including coronavirus OC43. A significant change in OC43 antibodies was recorded in 33 cases and a constant high titre, defined as a titre occurring in the respective age group in less than 1 % of all sera examined, was found in 45 cases. On the basis of careful retrospective analysis of hospital case records it was concluded that in 28 cases with an increase of OC43 antibody litres, and in two with titre decrease, a disease could be associated with an acute coronavirus infection. In 16 cases the disease was dominated by respiratory symptoms. Eight of these patients, four children and four adults, had pneumonia. Three of the eight pneumonia patients had, however, another concomitant infection, too. Four patients had neurological symptoms, one had severe perimyocarditis, and in five cases fever was the only symptom recorded. Among the patients with a statistically significant high titre of OC43 antibodies, there were 14 cases where a suggestive association with a disease could be envisaged on the basis of hospital records. Five of these patients had pneumonia. These results suggest that human coronaviruses, so far considered only as one group of causative agents of the common cold, may also be associated with other and more severe diseases in all age groups. |
35 | qb31rxnn | What new public datasets are available related to COVID-19? | Dataset of Ex-pat Teachers in Southeast Asia's Intention to Leave due to the COVID-19 pandemic The COVID-19 pandemic exerted an adverse influence on the global education system, especially since starting school lockdown. The growth of teacher unemployment figures climbed double-digit and spawned these unexpected sequels. For instance, while native teachers seemed indisposed to leave the profession with the aim of seeking another more profited and seasonal jobs, many ex-pat teachers presented themselves with moving or stayed dilemma in the way the government salvaged their situation. In preference with the ex-pat teacher's case, we elucidated further throughout an e-survey in the International Baccalaureate community on Facebook from 4 to 11 April 2020 for 18,000 ex-pat teachers, who are teaching at Southeast Asia. This dataset includes 307 responses of ex-pat teachers who are staying in Singapore, Thailand, Vietnam, the Philippines, and Indonesia during the pandemic. The dataset comprises (i) Survey partakers' Demographics; (ii) Ex-pat teachers' perceptions in the relation of national, regional and school plans were afoot to the pandemic; (iii) The degree of attachment of ex-pat teacher to their current society, the ex-pat community, friends, and families during the pandemic time; (iv) Ex-pat teachers' embryo intention to reconsider their current teaching location. |
1 | 629fwmgk | what is the origin of COVID-19 | Evolution of Viral Proteins Originated De Novo by Overprinting New protein-coding genes can originate either through modification of existing genes or de novo. Recently, the importance of de novo origination has been recognized in eukaryotes, although eukaryotic genes originated de novo are relatively rare and difficult to identify. In contrast, viruses contain many de novo genes, namely those in which an existing gene has been "overprinted" by a new open reading frame, a process that generates a new protein-coding gene overlapping the ancestral gene. We analyzed the evolution of 12 experimentally validated viral genes that originated de novo and estimated their relative ages. We found that young de novo genes have a different codon usage from the rest of the genome. They evolve rapidly and are under positive or weak purifying selection. Thus, young de novo genes might have strain-specific functions, or no function, and would be difficult to detect using current genome annotation methods that rely on the sequence signature of purifying selection. In contrast to young de novo genes, older de novo genes have a codon usage that is similar to the rest of the genome. They evolve slowly and are under stronger purifying selection. Some of the oldest de novo genes evolve under stronger selection pressure than the ancestral gene they overlap, suggesting an evolutionary tug of war between the ancestral and the de novo gene. |
14 | rz9cwhm3 | what evidence is there related to COVID-19 super spreaders | Contact tracing with a real-time location system: A case study of increasing relative effectiveness in an emergency department BACKGROUND: Contact tracing is the systematic method of identifying individuals potentially exposed to infectious diseases. Electronic medical record (EMR) use for contact tracing is time-consuming and may miss exposed individuals. Real-time location systems (RTLSs) may improve contact identification. Therefore, the relative effectiveness of these 2 contact tracing methodologies were evaluated. METHODS: During a pertussis outbreak in the United States, a retrospective case study was conducted between June 14 and August 31, 2016, to identify the contacts of confirmed pertussis cases, using EMR and RTLS data in the emergency department of a tertiary care medical center. Descriptive statistics and a paired t test (α = 0.05) were performed to compare contacts identified by EMR versus RTLS, as was correlation between pertussis patient length of stay and the number of potential contacts. RESULTS: Nine cases of pertussis presented to the emergency department during the identified time period. RTLS doubled the potential exposure list (P < .01). Length of stay had significant positive correlation with contacts identified by RTLS (ρ = 0.79; P = .01) but not with EMR (ρ = 0.43; P = .25). CONCLUSIONS: RTLS doubled the potential pertussis exposures beyond EMR-based contact identification. Thus, RTLS may be a valuable addition to the practice of contact tracing and infectious disease monitoring. |
18 | utigp2vi | what are the best masks for preventing infection by Covid-19? | RAN translation and frameshifting as translational challenges at simple repeats of human neurodegenerative disorders Repeat-associated disorders caused by expansions of short sequences have been classified as coding and noncoding and are thought to be caused by protein gain-of-function and RNA gain-of-function mechanisms, respectively. The boundary between such classifications has recently been blurred by the discovery of repeat-associated non-AUG (RAN) translation reported in spinocerebellar ataxia type 8, myotonic dystrophy type 1, fragile X tremor/ataxia syndrome and C9ORF72 amyotrophic lateral sclerosis and frontotemporal dementia. This noncanonical translation requires no AUG start codon and can initiate in multiple frames of CAG, CGG and GGGGCC repeats of the sense and antisense strands of disease-relevant transcripts. RNA structures formed by the repeats have been suggested as possible triggers; however, the precise mechanism of the translation initiation remains elusive. Templates containing expansions of microsatellites have also been shown to challenge translation elongation, as frameshifting has been recognized across CAG repeats in spinocerebellar ataxia type 3 and Huntington's disease. Determining the critical requirements for RAN translation and frameshifting is essential to decipher the mechanisms that govern these processes. The contribution of unusual translation products to pathogenesis needs to be better understood. In this review, we present current knowledge regarding RAN translation and frameshifting and discuss the proposed mechanisms of translational challenges imposed by simple repeat expansions. |
13 | ti7g7b42 | what are the transmission routes of coronavirus? | The cutting edge of thoracic anesthesia during the 2019 coronavirus disease (COVID-19) outbreak Coronavirus disease 2019 (COVID-19) has quickly spread globally, causing a real pandemic. In this critical scenario, lung cancer patients scheduled for surgical treatment need to continue to receive optimal care while protecting them from an eventual severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection. Adequate use of personal protective equipment (PPE) during aerosol-generating procedures (AGPs) and a COVID-19 specific intraoperative management are paramount in order to prevent cross infections. New suggestions or improvement of existing contagion control guidance are needed, even in case of non-symptomatic patients, possibly responsible for virus spread. |
41 | fxap5sw4 | What are the impacts of COVID-19 among African-Americans that differ from the rest of the U.S. population? | Time courses of COVID-19 infection and local variation in socioeconomic and health disparities in England Objective: To identify factors associated with local variation in the time course of COVID-19 case burden in England. Methods: We analyzed laboratory-confirmed COVID-19 case data for 150 upper tier local authorities, from the period from January 30 to May 6, 2020, as reported by Public Health England. Using methods suitable for time-series data, we identified clusters of local authorities with distinct trajectories of daily cases, after adjusting for population size. We then tested for differences in sociodemographic, economic, and health disparity factors between these clusters. Results: Two clusters of local authorities were identified: a higher case trajectory that rose faster over time to reach higher peak infection levels, and a lower case trajectory cluster that emerged more slowly, and had a lower peak. The higher case trajectory cluster (79 local authorities) had higher population density (p<0.001), higher proportion of Black and Asian residents (p=0.03; p=0.02), higher multiple deprivation scores (p<0.001), a lower proportions of older adults (p=0.005), and higher preventable mortality rates (p=0.03). Local authorities with higher proportions of Black residents were more likely to belong to the high case trajectory cluster, even after adjusting for population density, deprivation, proportion of older adults and preventable mortality (p=0.04). Conclusion: Areas belonging to the trajectory with significantly higher COVID-19 case burden were more deprived, and had higher proportions of ethnic minority residents. A higher proportion of Black residents in regions belonging to the high trajectory cluster was not fully explained by differences in population density, deprivation, and other overall health disparities between the clusters. |
30 | o29773cz | is remdesivir an effective treatment for COVID-19 | Pharmacologicaltreatment of COVID-19: lights and shadows At the end of December 2019, a novel coronavirus, the severe acute respiratory syndrome coronavirus 2, caused an outbreak of pneumonia spreading from Wuhan, Hubei province, to the whole country of China and then the entire world, forcing the World Health Organization to make the assessment that the coronavirus disease (COVID-19) can be characterized as a pandemic, the first ever caused by a coronavirus. To date, clinical evidence and guidelines based on reliable data and randomized clinical trials for the treatment of COVID-19 are lacking. In the absence of definitive management protocols, many treatments for COVID-19 are currently being evaluated and tested worldwide. Some of these options were soon abandoned due to ineffectiveness, while others showed promising results. The basic treatments are mainly represented by antiviral drugs, even if the evidence is not satisfactory. Among the antivirals, the most promising appears to be remdesivir. Corticosteroids and tocilizumab seem to guarantee positive results in selected patients so far, although the timing of starting therapy and the most appropriate therapeutic schemes remain to be clarified. Efficacy of the other drugs is still uncertain, and they are currently used as a cocktail of treatments in the absence of definitive guidelines. What will represent the real solution to the enormous problem taking place worldwide is the identification of a safe and effective vaccine, for which enormous efforts and investments are underway. |
25 | xykob69g | which biomarkers predict the severe clinical course of 2019-nCOV infection? | Coronavirus Pandemic as Black Swan Event Nowadays coronavirus is the hottest break news around the world. This paper aims to study why coronavirus became so meaningful for worldwide life. On one side many countries closed their boarders to prevent coronavirus spreading. On another side some people said that coronavirus is no scared than simple influence. Where is true? The health effects and mortality of coronavirus and influenza were compared. Situation Reports of World Health Organization have been analyzed and signs of Black Swan event considered. Total confirmed cases, total, deaths, and Rate of coronavirus distribution was calculated based on Situation Reports of the World Health Organization. To conclude this paper Coronavirus Pandemic recognized as Black Swan event according to considered figures and facts from recent references. |
22 | pth2d40p | are cardiac complications likely in patients with COVID-19? | Asymptomatic carrier state, acute respiratory disease, and pneumonia due to severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2): Facts and myths Abstract Since the emergence of coronavirus disease 2019 (COVID-19) (formerly known as the 2019 novel coronavirus [2019-nCoV]) in Wuhan, China in December 2019, which is caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), more than 75,000 cases have been reported in 32 countries/regions, resulting in more than 2000 deaths worldwide. Despite the fact that most COVID-19 cases and mortalities were reported in China, the WHO has declared this outbreak as the sixth public health emergency of international concern. The COVID-19 can present as an asymptomatic carrier state, acute respiratory disease, and pneumonia. Adults represent the population with the highest infection rate; however, neonates, children, and elderly patients can also be infected by SARS-CoV-2. In addition, nosocomial infection of hospitalized patients and healthcare workers, and viral transmission from asymptomatic carriers are possible. The most common finding on chest imaging among patients with pneumonia was ground-glass opacity with bilateral involvement. Severe cases are more likely to be older patients with underlying comorbidities compared to mild cases. Indeed, age and disease severity may be correlated with the outcomes of COVID-19. To date, effective treatment is lacking; however, clinical trials investigating the efficacy of several agents, including remdesivir and chloroquine, are underway in China. Currently, effective infection control intervention is the only way to prevent the spread of SARS-CoV-2. |
9 | 9d96e2t3 | how has COVID-19 affected Canada | Outbreak of SARS-CoV2: Pathogenesis of infection and cardiovascular involvement Since the new coronavirus SARS (SARS-CoV2) has emerged from china, the infection (COVID-19) has affected many countries and led to many deaths worldwide. Like SARS-CoV, ACE2 as a functional receptor for SARS-CoV2 is essential for virus to entry to the cell. ACE2 is a part of RAS which is expressed in several organs that opposes the AngII functions by converting Ang II to Ang (1-7), the one with vasodilation effects. The death rate of COVID-19 is estimated about 3.4%, however, some comorbid conditions like underlying cardiovascular disease, hypertension, and diabetes increase the risk of mortality. In addition, cardiovascular involvement by SARS-CoV2 could be direct through either ACE2 receptors which are expressed tremendously in heart, or by the surge of different cytokines or by ARDS-induced hypoxia. Traditional risk factors could aggravate the process of COVID-19 infection that urges the triage of these high risk patients for SARS-CoV2. Currently, there is no effective, proven treatment or vaccination for COVID-19, but many investigators are struggling to find a treatment strategy as soon as possible. Some potential medications like chloroquine by itself or in combination with azithromycin, and some protease inhibitors used for the treatment of COVID-19 have cardiovascular adverse effects that should be kept in mind in order to close monitor of the patients receiving these medications. |
25 | r7ihvt41 | which biomarkers predict the severe clinical course of 2019-nCOV infection? | Chinese herbal medicine for coronavirus disease 2019: a systematic review and meta-analysis Currently, coronavirus disease 2019 (COVID-19), which can lead to severe respiratory failure and death, is now a global pandemic with no specific anti-viral drugs or vaccines. However, It is worth noting that traditional Chinese medicine (TCM), especially Chinese herbal medicine (CHM), has been widely applied in mainland China since outbreak, bringing new hope for the prevention and control of COVID-19. A comprehensive literature searching was conducted in 7 electronic databases from their inception up to June 21, 2020 to evaluate the efficacy and safety of CHM for COVID-19. Eighteen randomized controlled trials (RCTs) involving 2275 patients were enrolled. Most of CHMs were originated from classical Chinese herbal formulas. Liquoric Root (Gancao, Radix Glycyrrhizae), Baical Skullcap Root (Huangqin, Radix Scutellariae Baicalensis), Pinellia Rhizome (Banxia, Rhizoma Pinelliae Tematae), Forsythia Fruit (Lianqiao, Fructus Forsythiae Suspensae), and Bitter Apricot Seed (Kuxingren, Semen Armeniacae Amarum) were most frequently used Chinese herbs. The most commonly used dosage formulation was decoction. Our meta-analyses found that comparing CHM group and conventional western medicine group, CHM group has improvements in several clinical parameters including lung CT, clinical cure rate, ranging from mild to critical cases, length of hospital stay, total score of clinical symptoms, fever reduction time, symptom score of fever, number of cough reduction cases, symptom score of cough, number of fatigue reduction cases, symptom score of fatigue, disappearing time of fatigue, TCM syndrome, viral nucleic acid testing, and inflammatory biomarkers (C-reactive protein). Besides, no severe adverse effects was identified by CHM. CHM, especially classical Chinese herbal formulas, could be used as potential candidates for COVID-19 in this battle. |
10 | jfiqj1mb | has social distancing had an impact on slowing the spread of COVID-19? | Using Partial Differential Equation with Google Mobility Data to Model COVID-19 in Arizona The outbreak of COVID-19 disrupts the life of many people in the world. The state of Arizona in the U.S. emerges as one of the country's newest COVID-19 hot spots. Accurate forecasting for COVID-19 cases will help governments to implement necessary measures and convince more people to take personal precautions to combat the virus. It is difficult to accurately predict the COVID-19 cases due to many human factors involved. This paper aims to provide a forecasting model for COVID-19 cases with the help of human activity data from the Google Community Mobility Reports. To achieve this goal, a specific partial differential equation (PDE) is developed and validated with the COVID-19 data from the New York Times at the county level in the state of Arizona in the U.S. The proposed model describes the combined effects of transboundary spread among county clusters in Arizona and human actives on the transmission of COVID-19. The results show that the prediction accuracy of this model is well acceptable (above 94\%). Furthermore, we study the effectiveness of human precautions such as wearing face masks and practicing social distancing on the decrease of COVID-19 cases at the local level. The localized analytical results can be used to help to slow down the spread of COVID-19 in Arizona. To the best of our knowledge, this work is the first attempt to apply PDE models on COVID-19 prediction with the Google Community Mobility Reports. |
5 | totc93f4 | what drugs have been active against SARS-CoV or SARS-CoV-2 in animal studies? | Diacerein: A potential multi-target therapeutic drug for COVID-19 Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), which causes coronavirus disease 19 (COVID-19), was declared pandemic by the World Health Organization in March 2020. SARS-CoV-2 binds its host cell receptor, angiotensin-converting enzyme 2 (ACE2), through the viral spike (S) protein. The mortality related to severe acute respiratory distress syndrome (ARDS) and multi-organ failure in COVID-19 patients has been suggested to be connected with cytokine storm syndrome (CSS), an excessive immune response that severely damages healthy lung tissue. In addition, cardiac symptoms, including fulminant myocarditis, are frequent in patients in a severe state of illness. Diacerein (DAR) is an anthraquinone derivative drug whose active metabolite is rhein. Different studies have shown that this compound inhibits the IL-1, IL-2, IL-6, IL-8, IL-12, IL-18, TNF-α, NF-κB and NALP3 inflammasome pathways. The antiviral activity of rhein has also been documented. This metabolite prevents hepatitis B virus (HBV) replication and influenza A virus (IAV) adsorption and replication through mechanisms involving regulation of oxidative stress and alterations of the TLR4, Akt, MAPK, and NF-κB signalling pathways. Importantly, rhein inhibits the interaction between the SARS-CoV S protein and ACE2 in a dose-dependent manner, suggesting rhein as a potential therapeutic agent for the treatment of SARS-CoV infection. Based on these findings, we hypothesize that DAR is a multi-target drug useful for COVID-19 treatment. This anthraquinone may control hyperinflammatory conditions by multi-faceted cytokine inhibition and by reducing viral infection. |
31 | u81fflce | How does the coronavirus differ from seasonal flu? | COVID-19 Pandemia and Public and Global Mental Health from the Perspective of Global Health Securit The Coronavirus disease 2019 (COVID-19) pandemic emerged in Wuhan, China and has spread all over the world and has caused huge threats to health and lives. It has affected different frontiers of lives and induced many psychiatric individual and collective problems such as panic, anxiety, depression, post-traumatic stress disorders, suspiciousness, infodemia, cacophony, xenophobia, racisms, etc. The COVID-19 outbreak has induced public and global mental health crisis as well as a huge psycho-social experiment. Psychiatry and other mental health sciences can play very useful role in supporting the well-being of COVID-19 patients and their families, healthcare personnel and the society. For successful fighting with present and future pandemics we have to learn more about psychiatric and psychological aspects of COVID-19 from the perspectives of public and global mental health. |
49 | u5nxm9tu | do individuals who recover from COVID-19 show sufficient immune response, including antibody levels and T-cell mediated immunity, to prevent re-infection? | Human coronavirus reinfection dynamics: lessons for SARS-CoV-2 In the current SARS-CoV-2 pandemic a key unsolved question is the quality and duration of acquired immunity in recovered individuals. This is crucial to solve, however SARS-CoV-2 has circulated for under five months, precluding a direct study. We therefore monitored 10 subjects over a time span of 35 years (1985-2020), providing a total of 2473 follow up person-months, and determined a) their antibody levels following infection by any of the four seasonal human coronaviruses, and b) the time period after which reinfections by the same virus can occur. An alarmingly short duration of protective immunity to coronaviruses was found by both analyses. We saw frequent reinfections at 12 months post-infection and a substantial reduction in antibody levels as soon as 6 months post-infection. |
25 | qzev2reb | which biomarkers predict the severe clinical course of 2019-nCOV infection? | Diabetes and metabolic syndrome as risk factors for COVID-19 BACKGROUND AND AIMS: Clinical evidence exists that patients with diabetes are at higher risk for Coronavirus disease 2019 (COVID-19). We investigated the physiological origins of this clinical observation linking diabetes with severity and adverse outcome of COVID-19. METHODS: Publication mining was applied to reveal common physiological contexts in which diabetes and COVID-19 have been investigated simultaneously. Overall, we have acquired 1,121,078 publications from PubMed in the time span between 01 and 01-2000 and 17-04-2020, and extracted knowledge graphs interconnecting the topics related to diabetes and COVID-19. RESULTS: The Data Mining revealed three pathophysiological pathways linking diabetes and COVID-19. The first pathway indicates a higher risk for COVID-19 because of an upregulation of Angiotensin-converting enzyme 2. The other two important physiological links between diabetes and COVID-19 are liver dysfunction and chronic systemic inflammation. A deep network analysis has suggested clinical biomarkers predicting the higher risk: Hypertension, elevated serum Alanine aminotransferase, high Interleukin-6, and low Lymphocytes count. CONCLUSIONS: The revealed biomarkers can be applied directly in clinical practice. For newly infected patients, the medical history needs to be checked for evidence of a long-term, chronic dysregulation of these biomarkers. In particular, patients with diabetes, but also those with prediabetic state, deserve special attention. |
3 | 9nri1ln6 | will SARS-CoV2 infected people develop immunity? Is cross protection possible? | Clinical performance of different SARS‐CoV‐2 IgG antibody tests SARS‐CoV‐2 serological assays are urgently needed for rapid diagnosis, contact tracing and for epidemiological studies. So far, there is limited data on how commercially available tests perform with real patient samples and if positive tested samples show neutralizing abilities. Focusing on IgG antibodies, we demonstrate the performance of two ELISA assays (Euroimmun SARS‐CoV‐2 IgG and Vircell COVID‐19 ELISA IgG) in comparison to one lateral flow assay ((LFA) FaStep COVID‐19 IgG/IgM Rapid Test Device) and two in‐house developed assays (immunofluorescence assay (IFA) and plaque reduction neutralization test (PRNT)). We tested follow up serum/plasma samples of individuals PCR‐diagnosed with COVID‐19. Most of the SARS‐CoV‐2 samples were from individuals with moderate to severe clinical course, who required an in‐patient hospital stay. For all examined assays, the sensitivity ranged from 58.8 to 76.5% for the early phase of infection (days 5‐9) and from 93.8 to 100% for the later period (days 10‐18). With exception of one sample, all positive tested COVID‐19 follow up‐samples, using the commercially available assays examined (including the in‐house developed IFA), demonstrated neutralizing properties in the PRNT. Regarding specificity, some samples of endemic coronavirus (HCoV‐OC43, HCoV‐229E) and Epstein Barr virus (EBV) infected individuals cross‐reacted in the ELISA assays and IFA, in one case generating a false positive result. This article is protected by copyright. All rights reserved. |
32 | jn3aqdck | Does SARS-CoV-2 have any subtypes, and if so what are they? | Hierarchical Clustering Using the Arithmetic-Harmonic Cut: Complexity and Experiments Clustering, particularly hierarchical clustering, is an important method for understanding and analysing data across a wide variety of knowledge domains with notable utility in systems where the data can be classified in an evolutionary context. This paper introduces a new hierarchical clustering problem defined by a novel objective function we call the arithmetic-harmonic cut. We show that the problem of finding such a cut is [Image: see text]-hard and [Image: see text]-hard but is fixed-parameter tractable, which indicates that although the problem is unlikely to have a polynomial time algorithm (even for approximation), exact parameterized and local search based techniques may produce workable algorithms. To this end, we implement a memetic algorithm for the problem and demonstrate the effectiveness of the arithmetic-harmonic cut on a number of datasets including a cancer type dataset and a corona virus dataset. We show favorable performance compared to currently used hierarchical clustering techniques such as [Image: see text]-Means, Graclus and Normalized-Cut. The arithmetic-harmonic cut metric overcoming difficulties other hierarchal methods have in representing both intercluster differences and intracluster similarities. |
38 | i6q5ltn4 | What is the mechanism of inflammatory response and pathogenesis of COVID-19 cases? | Interleukin-22: A Bridge Between Epithelial Innate Host Defense and Immune Cells Interleukin-22 (IL-22), an IL-10 family cytokine, is produced by various leukocytes. The receptor of IL-22, however, is preferentially detected on peripheral tissue epithelial cells. IL-22 functions as a unique messenger from immune system to tissue epithelial cells and to regulate homeostasis of epithelia. IL-22 is able to directly enhance antimicrobial defense mechanisms in epithelial cells and to facilitate epithelial barrier repair and wound healing process. It, therefore, possesses an irreplaceable role in host defense against certain pathogens that specifically invade epithelial cells. In addition, IL-22 can help to preserve the integrity and homeostasis of various epithelial organs during infection or inflammation. The importance of its tissue-protective function is manifested in many inflammatory situations such as inflammatory bowel diseases (IBD) and hepatitis. On the other hand, as a cytokine, IL-22 is capable of induction of proinflammatory responses, especially in synergy with other cytokines. Consequently, IL-22 contributes to pathogenesis of certain inflammatory diseases for example psoriasis. |
24 | lhwkthzx | what kinds of complications related to COVID-19 are associated with diabetes | Evidence for Use or Disuse of Renin-Angiotensin System Modulators in Patients Having COVID-19 With an Underlying Cardiorenal Disorder Coronavirus disease 19 (COVID-19) originated in Wuhan, China, in December 2019 has been declared pandemic by World Health Organization due to an exponential rise in the number of infected and deceased persons across the globe. Emerging reports suggest that susceptibility and mortality rates are higher in patients with certain comorbidities when compared to the average population. Cardiovascular diseases and diabetes are important risk factors for a lethal outcome of COVID-19. Extensive research ensuing the outbreak of coronavirus-related severe acute respiratory syndrome in the year 2003, and COVID-19 recently revealed a role of renin-angiotensin system (RAS) components in the entry of coronavirus wherein angiotensin-converting enzyme 2 (ACE2) had garnered the significant attention. This raises the question whether the use of RAS inhibitors, the backbone of treatment of cardiovascular, neurovascular, and kidney diseases could increase the susceptibility for coronavirus infection or unfortunate outcomes of COVID-19. Thus, currently, there is a lack of consensus regarding the effects of RAS inhibitors in such patients. Moreover, expert bodies like American Heart Association, American College of Cardiology, and so on have now released official statements that RAS inhibitors must be continued, unless suggested otherwise by a physician. In this brief review, we will elaborate on the role of RAS and ACE2 in pathogenesis of COVID-19. Moreover, we will discuss the potential effect of the use and disuse of RAS inhibitors in patients having COVID-19 with cardiometabolic comorbidities. |
29 | 6u3a9nez | 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? | Foundations for the Study of Structure and Function of Proteins Proteins are the most abundant biological macromolecules, occurring in all cells and all parts of cells. Moreover, proteins exhibit enormous diversity of biological function and are the most final products of the information pathways. Protein is a major component of protoplasm, which is the basis of life. It is translated from RNA and composed of amino acid connected by peptide bonds. It participates in a series of complicated chemical reactions and finally leads to the phenomena of life. So we can say it is the workhorse molecule and a major player of life activity. Biologists focus on the diction of structure and function of proteins by the study of the primary, secondary, tertiary, and quaternary dimensional structures of proteins, posttranscriptional modifications, protein-protein interactions, the DNA-proteins interactions, and so on. |
4 | onyryfty | what causes death from Covid-19? | Gross and histopathological pulmonary findings in a COVID-19 associated death during self-isolation Forensic investigations generally contain extensive morphological examinations to accurately diagnose the cause of death. Thus, the appearance of a new disease often creates emerging challenges in morphological examinations due to the lack of available data from autopsy- or biopsy-based research. Since late December 2019, an outbreak of a novel seventh coronavirus disease has been reported in China caused by "severe acute respiratory syndrome coronavirus 2" (SARS-CoV-2). On March 11, 2020, the new clinical condition COVID-19 (Corona-Virus-Disease-19) was declared a pandemic by the World Health Organization (WHO). Patients with COVID-19 mainly have a mild disease course, but severe disease onset might result in death due to proceeded lung injury with massive alveolar damage and progressive respiratory failure. However, the detailed mechanisms that cause organ injury still remain unclear. We investigated the morphological findings of a COVID-19 patient who died during self-isolation. Pathologic examination revealed massive bilateral alveolar damage, indicating early-phase "acute respiratory distress syndrome" (ARDS). This case emphasizes the possibility of a rapid severe disease onset in previously mild clinical condition and highlights the necessity of a complete autopsy to gain a better understanding of the pathophysiological changes in SARS-CoV-2 infections. |
10 | gi6bzymv | has social distancing had an impact on slowing the spread of COVID-19? | A Vision-based Social Distancing and Critical Density Detection System for COVID-19 Social distancing has been proven as an effective measure against the spread of the infectious COronaVIrus Disease 2019 (COVID-19). However, individuals are not used to tracking the required 6-feet (2-meters) distance between themselves and their surroundings. An active surveillance system capable of detecting distances between individuals and warning them can slow down the spread of the deadly disease. Furthermore, measuring social density in a region of interest (ROI) and modulating inflow can decrease social distancing violation occurrence chance. On the other hand, recording data and labeling individuals who do not follow the measures will breach individuals' rights in free-societies. Here we propose an Artificial Intelligence (AI) based real-time social distancing detection and warning system considering four important ethical factors: (1) the system should never record/cache data, (2) the warnings should not target the individuals, (3) no human supervisor should be in the detection/warning loop, and (4) the code should be open-source and accessible to the public. Against this backdrop, we propose using a monocular camera and deep learning-based real-time object detectors to measure social distancing. If a violation is detected, a non-intrusive audio-visual warning signal is emitted without targeting the individual who breached the social distancing measure. Also, if the social density is over a critical value, the system sends a control signal to modulate inflow into the ROI. We tested the proposed method across real-world datasets to measure its generality and performance. The proposed method is ready for deployment, and our code is open-sourced. |
11 | ubqexcof | what are the guidelines for triaging patients infected with coronavirus? | Risk factors of critical & mortal COVID-19 cases: A systematic literature review and meta-analysis Abstract Background An epidemic of Coronavirus Disease 2019 (COVID-19) began in December 2019 and triggered a Public Health Emergency of International Concern (PHEIC). We aimed to find risk factors for the progression of COVID-19 to help reducing the risk of critical illness and death for clinical help. Methods The data of COVID-19 patients until March 20, 2020 were retrieved from four databases. We statistically analyzed the risk factors of critical/mortal and non-critical COVID-19 patients with meta-analysis. Results Thirteen studies were included in Meta-analysis, including a total number of 3027 patients with SARS-CoV-2 infection. Male, older than 65, and smoking were risk factors for disease progression in patients with COVID-19 (male: OR = 1.76, 95% CI (1.41, 2.18), P < 0.00001; age over 65 years old: OR =6.06, 95% CI(3.98, 9.22), P < 0.00001; current smoking: OR =2.51, 95% CI(1.39, 3.32), P = 0.0006). The proportion of underlying diseases such as hypertension, diabetes, cardiovascular disease, and respiratory disease were statistically significant higher in critical/mortal patients compared to the non-critical patients (diabetes: OR=3.68, 95% CI (2.68, 5.03), P < 0.00001; hypertension: OR = 2.72, 95% CI (1.60,4.64), P = 0.0002; cardiovascular disease: OR = 5.19, 95% CI(3.25, 8.29), P < 0.00001; respiratory disease: OR = 5.15, 95% CI(2.51, 10.57), P < 0.00001). Clinical manifestations such as fever, shortness of breath or dyspnea were associated with the progression of disease [fever: 0R = 0.56, 95% CI (0.38, 0.82), P = 0.003;shortness of breath or dyspnea: 0R=4.16, 95% CI (3.13, 5.53), P < 0.00001]. Laboratory examination such as aspartate amino transferase(AST) > 40U/L, creatinine(Cr) ≥ 133mol/L, hypersensitive cardiac troponin I(hs-cTnI) > 28pg/mL, procalcitonin(PCT) > 0.5ng/mL, lactatede hydrogenase(LDH) > 245U/L, and D-dimer > 0.5mg/L predicted the deterioration of disease while white blood cells(WBC)<4 × 109/L meant a better clinical status[AST > 40U/L:OR=4.00, 95% CI (2.46, 6.52), P < 0.00001; Cr ≥ 133μmol/L: OR = 5.30, 95% CI (2.19, 12.83), P = 0.0002; hs-cTnI > 28 pg/mL: OR = 43.24, 95% CI (9.92, 188.49), P < 0.00001; PCT > 0.5 ng/mL: OR = 43.24, 95% CI (9.92, 188.49), P < 0.00001;LDH > 245U/L: OR = 43.24, 95% CI (9.92, 188.49), P < 0.00001; D-dimer > 0.5mg/L: OR = 43.24, 95% CI (9.92, 188.49), P < 0.00001; WBC < 4 × 109/L: OR = 0.30, 95% CI (0.17, 0.51), P < 0.00001]. Conclusion Male, aged over 65, smoking patients might face a greater risk of developing into the critical or mortal condition and the comorbidities such as hypertension, diabetes, cardiovascular disease, and respiratory diseases could also greatly affect the prognosis of the COVID-19. Clinical manifestation such as fever, shortness of breath or dyspnea and laboratory examination such as WBC, AST, Cr, PCT, LDH, hs-cTnI and D-dimer could imply the progression of COVID-19. |
32 | cbc98t7x | Does SARS-CoV-2 have any subtypes, and if so what are they? | A Genomic Survey of SARS-CoV-2 Reveals Multiple Introductions into Northern California without a Predominant Lineage The COVID-19 pandemic caused by the novel coronavirus SARS-CoV-2 has spread globally, resulting in >300,000 reported cases worldwide as of March 21st, 2020. Here we investigate the genetic diversity and genomic epidemiology of SARS-CoV-2 in Northern California using samples from returning travelers, cruise ship passengers, and cases of community transmission with unclear infection sources. Virus genomes were sampled from 29 patients diagnosed with COVID-19 infection from Feb 3rd through Mar 15th. Phylogenetic analyses revealed at least 8 different SARS-CoV-2 lineages, suggesting multiple independent introductions of the virus into the state. Virus genomes from passengers on two consecutive excursions of the Grand Princess cruise ship clustered with those from an established epidemic in Washington State, including the WA1 genome representing the first reported case in the United States on January 19th. We also detected evidence for presumptive transmission of SARS-CoV-2 lineages from one community to another. These findings suggest that cryptic transmission of SARS-CoV-2 in Northern California to date is characterized by multiple transmission chains that originate via distinct introductions from international and interstate travel, rather than widespread community transmission of a single predominant lineage. Rapid testing and contact tracing, social distancing, and travel restrictions are measures that will help to slow SARS-CoV-2 spread in California and other regions of the USA. |
6 | tnnhx51r | what types of rapid testing for Covid-19 have been developed? | Clinical evaluation of self-collected saliva by RT-qPCR, direct RT-qPCR, RT-LAMP, and a rapid antigen test to diagnose COVID-19 Background The clinical performance of six molecular diagnostic tests and a rapid antigen test for severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) were clinically evaluated for the diagnosis of coronavirus disease 2019 (COVID-19) in self-collected saliva. Methods Saliva samples from 103 patients with laboratory-confirmed COVID-19 (15 asymptomatic and 88 symptomatic) were collected on the day of hospital admission. SARS-CoV-2 RNA in saliva was detected using a quantitative reverse-transcription polymerase chain reaction (RT-qPCR) laboratory-developed test (LDT), a cobas SARS-CoV-2 high-throughput system, three direct RT-qPCR kits, and reverse-transcription loop mediated isothermal amplification (RT-LAMP). Viral antigen was detected by a rapid antigen immunochromatographic assay. Results Of the 103 samples, viral RNA was detected in 50.5-81.6% of the specimens by molecular diagnostic tests and an antigen was detected in 11.7% of the specimens by the rapid antigen test. Viral RNA was detected at a significantly higher percentage (65.6-93.4%) in specimens collected within 9 d of symptom onset compared to that of specimens collected after at least 10 d of symptom onset (22.2-66.7%) and that of asymptomatic patients (40.0-66.7%). Viral RNA was more frequently detected in saliva from males than females. Conclusions Self-collected saliva is an alternative specimen diagnosing COVID-19. LDT RT-qPCR, cobas SARS-CoV-2 high-throughput system, direct RT-qPCR except for one commercial kit, and RT-LAMP showed sufficient sensitivity in clinical use to be selectively used according to clinical settings and facilities. The rapid antigen test alone is not recommended for initial COVID-19 diagnosis because of its low sensitivity. |
41 | vs4qb91t | What are the impacts of COVID-19 among African-Americans that differ from the rest of the U.S. population? | Understanding COVID-19 Risks and Vulnerabilities among Black Communities in America: The Lethal Force of Syndemics Black communities in the United States are bearing the brunt of the COVID-19 pandemic and the underlying conditions that exacerbate its negative consequences. Syndemic theory provides a useful framework for understanding how such interacting epidemics to develop under conditions of health and social disparity. Multiple historical and present-day factors have created the syndemic conditions within which Black Americans experience the lethal force of COVID-19. These factors include racism and its manifestations (e.g., chattel slavery, mortgage redlining, political gerrymandering, lack of Medicaid expansion, employment discrimination, and healthcare provider bias). Improving racial disparities in COVID-19 will require that we implement policies that address structural racism at the root of these disparities. |
6 | bah2ege0 | what types of rapid testing for Covid-19 have been developed? | Clinical performance of SARS-CoV-2 IgG antibody tests and potential protective immunity As the current SARS-CoV-2 pandemic continues, serological assays are urgently needed for rapid diagnosis, contact tracing and for epidemiological studies. So far, there is little data on how commercially available tests perform with real patient samples and if detected IgG antibodies provide protective immunity. Focusing on IgG antibodies, we demonstrate the performance of two ELISA assays (Euroimmun SARS-CoV-2 IgG & Vircell COVID-19 ELISA IgG) in comparison to one lateral flow assay ((LFA) FaStep COVID-19 IgG/IgM Rapid Test Device) and two in-house developed assays (immunofluorescence assay (IFA) and plaque reduction neutralization test (PRNT)). We tested follow up serum/plasma samples of individuals PCR-diagnosed with COVID-19. Most of the SARS-CoV-2 samples were from individuals with moderate to severe clinical course, who required an in-patient hospital stay. For all examined assays, the sensitivity ranged from 58.8 to 76.5% for the early phase of infection (days 5-9) and from 93.8 to 100% for the later period (days 10-18) after PCR-diagnosed with COVID-19. With exception of one sample, all positive tested samples in the analysed cohort, using the commercially available assays examined (including the in-house developed IFA), demonstrated neutralizing (protective) properties in the PRNT, indicating a potential protective immunity to SARS-CoV-2. Regarding specificity, there was evidence that samples of endemic coronavirus (HCoV-OC43, HCoV-229E) and Epstein Barr virus (EBV) infected individuals cross-reacted in the ELISA assays and IFA, in one case generating a false positive result (may giving a false sense of security). This need to be further investigated. |
5 | 3gv060cu | what drugs have been active against SARS-CoV or SARS-CoV-2 in animal studies? | The looming pandemic of COVID-19: What therapeutic options do we have now? |
14 | we62087x | what evidence is there related to COVID-19 super spreaders | Sentinel Event Surveillance to Estimate Total SARS-CoV-2 Infections, United States Human infections with a novel coronavirus (SARS-CoV-2) were first identified via syndromic surveillance in December of 2019 in Wuhan China. Since identification, infections (coronavirus disease-2019; COVID-19) caused by this novel pathogen have spread globally, with more than 180,000 confirmed cases as of March 16, 2020. Effective public health interventions, including social distancing, contact tracing, and isolation/quarantine rely on the rapid and accurate identification of confirmed cases. However, testing capacity (having sufficient tests and laboratory throughput) to support these non-pharmaceutical interventions remains a challenge for containment and mitigation of COVID-19 infections. We undertook a sentinel event strategy (where single health events signal emerging trends) to estimate the incidence of COVID-19 in the US. Data from a recent national conference, the Conservative Political Action Conference, (CPAC) near Washington, DC and from the outbreak in Wuhan, China were used to fit a simple exponential growth model to estimate the total number of incident SARS- CoV-2 infections in the United States on March 1, 2020, and to forecast subsequent infections potentially undetected by current testing strategies. Our analysis and forecasting estimates a total of 54,100 SARS-CoV-2 infections (80 % CI 5,600 to 125,300) have occurred in the United States to March 12, 2020. Our forecast predicts that a very substantial number of infections are undetected, and without extensive and far-reaching non-pharmaceutical interventions, the number of infections should be expected to grow at an exponential rate. |
21 | mipdahk4 | what are the mortality rates overall and in specific populations | Comparison of different exit scenarios from the lock-down for COVID-19 epidemic in the UK and assessing uncertainty of the predictions We model further development of the COVID-19 epidemic in the UK given the current data and assuming different scenarios of handling the epidemic. In this research, we further extend the stochastic model suggested in [1] and incorporate in it all available to us knowledge about parameters characterising the behaviour of the virus and the illness induced by it. The models we use are flexible, comprehensive, fast to run and allow us to incorporate the following: - time-dependent strategies of handling the epidemic; - spatial heterogeneity of the population and heterogeneity of development of epidemic in different areas; - special characteristics of particular groups of people, especially people with specific medical pre-histories and elderly. Standard epidemiological models such as SIR and many of its modifications are not flexible enough and hence are not precise enough in the studies that requires the use of the features above. Decision-makers get serious benefits from using better and more flexible models as they can avoid of nuanced lock-downs, better plan the exit strategy based on local population data, different stages of the epidemic in different areas, making specific recommendations to specific groups of people; all this resulting in a lesser impact on economy, improved forecasts of regional demand upon NHS allowing for intelligent resource allocation. |
22 | 8m0vyxq8 | are cardiac complications likely in patients with COVID-19? | An outbreak of leptospirosis with predominant cardiac involvement: a case series BACKGROUND: Severe leptospirosis is known to cause multi organ dysfunction including cardiac involvement. In the clinical setting with limited resources, high degree of suspicion is needed to diagnose cardiac involvement including myocarditis. Although myocarditis is not reported as a common complication due to lack of diagnostic facilities, there are evidence to support myocarditis is more prevalent in post mortem studies of patients died due to leptospirosis. We present a case series of severe leptospirosis with cardiac involvement observed during a period of one month at Colombo-North Teaching Hospital, Sri Lanka. CASE PRESENTATION: We report here five patients with severe leptospirosis complicated with cardiac involvement, admitted to a single medical ward, Colombo-North Teaching Hospital, Sri Lanka during a one-month period. Out of six suspected leptospirosis patients admitted during that period, five in a raw developed severe leptospirosis with cardiac involvement. In this case series, four patients were confirmed serologically or quantitative PCR and one patient had possible leptospirosis. All patients developed shock during their course of illness. Two patients developed rapid atrial fibrillation. One patient had dynamic T wave changes in ECG and the other two had sinus tachycardia. Two patients had evidence of myocarditis in 2D echocardiogram, whereas other two patients had nonspecific findings and one patient had normal 2D echocardiogram. All five patients had elevated cardiac troponin I titre and it was normalized with the recovery. All five patients developed acute kidney injury. Four patients needed inotropic/vasopressor support to maintain mean arterial pressure and one patient recovered from shock with fluid resuscitation. All patients were recovered from their illness and repeat 2D echocardiograms after recovery did not show residual complications. One patient had serologically proven dengue co-infection with leptospirosis. CONCLUSIONS: Myocarditis and cardiac involvement in leptospirosis may be overlooked due to non-specific clinical findings and co-existing multi-organ dysfunction. Atypical presentation of this case series may be due to micro-geographic variation and unusual outbreak of leptospirosis. Co-infection of dengue with leptospirosis should be considered in managing patients especially in endemic areas. |
28 | hq846hko | what evidence is there for the value of hydroxychloroquine in treating Covid-19? | Intracellular ABCB1 as a Possible Mechanism to Explain the Synergistic Effect of Hydroxychloroquine-Azithromycin Combination in COVID-19 Therapy The co-administration of hydroxychloroquine with azithromycin is proposed in COVID-19 therapy. We hypothesize a new mechanism supporting the synergistic interaction between these drugs. Azithromycin is a substrate of ABCB1 (P-glycoprotein) which is localized in endosomes and lysosomes with a polarized substrate transport from the cell cytosol into the vesicle interior. SARS-CoV-2 and drugs meet in these acidic organelles and both basic drugs, which are potent lysosomotropic compounds, will become protonated and trapped within these vesicles. Consequently, their intra-vesicular concentrations can attain low micromolar effective cytotoxic concentrations on SARS-CoV-2 while concomitantly increase the intra-vesicular pH up to around neutrality. This last effect inhibits lysosomal enzyme activities responsible in virus entry and replication cycle. Based on these considerations, we hypothesize that ABCB1 could be a possible enhancer by confining azithromycin more extensively than expected when the trapping is solely dependent on the passive diffusion. This additional mechanism may therefore explain the synergistic effect when azithromycin is added to hydroxychloroquine, leading to apparently more rapid virus clearance and better clinical benefit, when compared to monotherapy with hydroxychloroquine alone. |
14 | 571v43ml | what evidence is there related to COVID-19 super spreaders | Griffithsin protects mice from genital herpes by preventing cell-to-cell spread. Griffithsin, which binds N-linked glycans on gp120 to prevent HIV entry, has the most potent HIV-1 inhibitory activity described for any antiviral lectin and is being developed for topical preexposure prophylaxis. The current studies were designed to further assess its potential by exploring its activity against herpes simplex virus 2 (HSV-2), a cofactor for HIV acquisition, in vitro and in a murine model. Safety was evaluated by examining its impact on epithelial barrier integrity in polarized cultures and testing whether repeated intravaginal dosing potentiates the susceptibility of mice to genital herpes. Griffithsin displayed modest inhibitory activity against HSV-2 if present during viral entry but completely blocked plaque formation if present postentry, reduced plaque size, and prevented cell-to-cell spread. These in vitro findings translated to significant protection against genital herpes in mice treated with 0.1% griffithsin gel. Griffithsin, but not placebo gel, prevented viral spread (visualized with a luciferase-expressing virus), significantly reduced disease scores, and resulted in greater survival (P < 0.05, log rank test). Protection persisted when HSV-2 was introduced in seminal plasma. Although griffithsin triggered a small decline in transepithelial electrical resistance in polarized cultures, this did not translate to any significant increase in the ability of HIV to migrate from the apical to the basolateral chamber nor to an increase in susceptibility to HSV-2 in mice treated with griffithsin gel for 7 days. These findings demonstrate that griffithsin inhibits HSV-2 by a unique mechanism of blocking cell-to-cell spread and support its further development for HIV and HSV-2 prevention. |
9 | nux8g0cm | how has COVID-19 affected Canada | Novel Coronavirus and Related Public Health Interventions Are Negatively Impacting Mental Health Services |
41 | z49nb5ej | What are the impacts of COVID-19 among African-Americans that differ from the rest of the U.S. population? | The association between age, COVID-19 symptoms, and social distancing behavior in the United States BACKGROUND: Public health authorities recommend that people practice social distancing, especially if they have symptoms of coronavirus disease (COVID-19), or are older and more at risk of serious illness if they become infected. We test the hypothesis that these groups are following these recommendations and are more likely to undertake social distancing. METHODS: We conducted an open online survey of 4,676 U.S. adults aged 18 and older between April 4 and April 7, 2020. We model the effects of age and common COVID-19 symptoms in the last two weeks on going out of the home for non-healthcare reasons the day before taking the survey, using a logistic model and the number of close contacts (within 6 feet) that respondents had with non-household members, using a Poisson count model. Our models control for several covariates, including other flu-like symptoms, sex, education, income, whether the respondent worked in February, household size, population density in the respondent's ZIP code, state fixed effects, and the day of completion of the survey. We also weight our analyses to make the sample representative of the U.S. adult population. FINDINGS: About 52 percent of the adult United States population went out of their home the previous day. On average, adults had close contact with 1.9 non-household members. We find that having at least one COVID-19 symptom (fever, dry cough, or shortness of breath) increased the likelihood of going out the previous day and having additional close contacts with non-household members; however, the estimates were not statistically significant. When disaggregating our analysis by COVID-19 symptoms, we find no strong evidence of greater social distancing by people with a fever or cough in the last two weeks, but we do find that those who experienced shortness of breath have fewer close contacts, with an incidence rate ratio (IRR) of 0.49 (95% CI: 0.30–0.78). Having other flu-like symptoms reduces the odds of going out by 0.32 (95% CI: 0.18–0.60) and the incidence rate of having close contacts by 42 percent (IRR = 0.58; 95% CI: 0.38–0.88). We find that older people are just as likely to leave their homes as younger people, but people over the age of 50 had less than half the predicted number of close contacts than those who were younger than 30. Our approach has the limitation that the survey sample is self-selected. Our findings may therefore be subject to selection bias that is not adequately controlled for by weighting. In addition, the possibility exists of confounding of the results due to omitted variable bias. CONCLUSIONS: We provide evidence that older people are having significantly fewer close contacts than younger people, which is in line with the public health authorities' recommendations. We also find that people experiencing shortness of breath are practicing more intense social distancing. However, we find that those with two other common COVID-19 symptoms, fever and dry cough, are not engaging in greater social distancing, suggesting that increased targeting on relevant symptoms, and messaging, may be required. |
49 | bb2lq2fo | do individuals who recover from COVID-19 show sufficient immune response, including antibody levels and T-cell mediated immunity, to prevent re-infection? | The presence of alpha interferon at the time of infection alters the innate and adaptive immune responses to porcine reproductive and respiratory syndrome virus. Porcine reproductive and respiratory syndrome (PRRS) is one of the most devastating and costly diseases to the swine industry worldwide. Overall, the adaptive immune response to PRRS virus (PRRSV) is weak, which results in delayed elimination of virus from the host and inferior vaccine protection. PRRSV has been shown to induce a meager alpha interferon (IFN-α) response, and we hypothesized that elevated IFN-α levels early in infection would shorten the induction time and increase elements of the adaptive immune response. To test this, we measured both antibody and cell-mediated immunity in pigs after the administration of a nonreplicating human adenovirus type 5 vector expressing porcine IFN-α (Ad5-pIFN-α) at the time of PRRSV infection and compared the results to those for pigs infected with PRRSV alone. Viremia was delayed, and there was a decrease in viral load in the sera of pigs administered the Ad5-pIFN-α. Although seroconversion was slightly delayed in pigs receiving Ad5-pIFN-α, probably due to the early reduction in viral replication, little difference in the overall or neutralizing antibody response was seen. However, there was an increase in the number of virus-specific IFN-γ-secreting cells detected in the pigs receiving Ad5-pIFN-α, as well as an altered cytokine profile in the lung at 14 days postinfection, indicating that the presence of IFN-α at the time of infection can alter innate and adaptive immune responses to PRRSV. |
37 | umoowoa2 | What is the result of phylogenetic analysis of SARS-CoV-2 genome sequence? | SARS-CoV-2 spread across the Colombian-Venezuelan border Venezuela and Colombia both adopted measures of containment early in response to the COVID-19 pandemic. However, Venezuelan ongoing humanitarian crisis has decimated its health care system, and forced millions of Venezuelans to flee through its porous border with Colombia. The extensive shared border, and illegal cross-border transit through improvised trails between the two countries are major challenges for public health authorities. We report the first SARS-CoV-2 genomes from Venezuela, and present a snapshot of the SARS-CoV-2 epidemiologic landscape in the Colombian-Venezuelan border region. We sequenced and assembled viral genomes from total RNA extracted from nasopharyngeal (NP) clinical specimens using a custom reference-based analysis pipeline. Three assemblies obtained were subjected to typing using the Phylogenetic Assignment of Named Global Outbreak LINeages Pangolin tool. A total of 376 publicly available SARS-CoV-2 genomes from South America were obtained from the GISAID database to perform comparative genomic analyses. Additionally, the Wuhan-1 strain was used as reference. We found that two of the SARS-CoV-2 genomes from Venezuela belonged to the B1 lineage, and the third to the B.1.13 lineage. We observed a point mutation in the Spike protein gene (D614G substitution), previously reported to be associated with increased infectivity, in all three Venezuelan genomes. An additional three mutations (R203K/G204R substitution) were present in the nucleocapsid (N) gene of one Venezuelan genome. Conclusions: Genomic sequencing demonstrates similarity between SARS-CoV-2 lineages from Venezuela and viruses collected from patients in bordering areas in Colombia and from Brazil, consistent with cross-border transit despite administrative measures including lockdowns. The presence of mutations associated with increased infectivity in the 3 Venezuelan genomes we report and Colombian SARS-CoV-2 genomes from neighboring borders areas may pose additional challenges for control of SARS-CoV-2 spread in the complex epidemiological landscape in Latin American countries. Public health authorities should carefully follow the progress of the pandemic and its impact on displaced populations within the region. |
35 | 3wuh6k6g | What new public datasets are available related to COVID-19? | Understand Research Hotspots Surrounding COVID-19 and Other Coronavirus Infections Using Topic Modeling Background: Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) is a virus that causes severe respiratory illness in humans, which eventually results in the current outbreak of novel coronavirus disease (COVID-19) around the world. The research community is interested to know what are the hotspots in coronavirus (CoV) research and how much is known about COVID-19. This study aimed to evaluate the characteristics of publications involving coronaviruses as well as COVID-19 by using a topic modeling analysis. Methods: We extracted all abstracts and retained the most informative words from the COVID-19 Open Research Dataset, which contains all the 35,092 pieces of coronavirus related literature published up to March 20, 2020. Using Latent Dirichlet Allocation modeling, we trained an eight-topic model from the corpus. We then analyzed the semantic relationships between topics and compared the topic distribution between COVID-19 and other CoV infections. Results: Eight topics emerged overall: clinical characterization, pathogenesis research, therapeutics research, epidemiological study, virus transmission, vaccines research, virus diagnostics, and viral genomics. It was observed that COVID-19 research puts more emphasis on clinical characterization, epidemiological study, and virus transmission at present. In contrast, topics about diagnostics, therapeutics, vaccines, genomics and pathogenesis only accounted for less than 10% or even 4% of all the COVID-19 publications, much lower than those of other CoV infections. Conclusions: These results identified knowledge gaps in the area of COVID-19 and offered directions for future research. Keywords: COVID-19, coronavirus, topic modeling, hotspots, text mining |
29 | q1yz9y8k | 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? | Reducing mortality and morbidity in patients with severe COVID-19 disease by advancing ongoing trials of Mesenchymal Stromal (stem) Cell (MSC) therapy - achieving global consensus and visibility for cellular host-directed therapies Abstract As of May 11th 2020, the coronavirus disease 2019 (COVID-19) pandemic, caused by the novel, the severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2) has caused 274,361 deaths out of 3,917,366 (7% case fatality rate). As with the two other novel coronavirus zoonotic diseases of humans, SARS and MERS, no specific treatments for reducing mortality or morbidity are yet available. Deaths from COVID-19 will continue to rise globally until effective and appropriate treatments and vaccines are found. With no specific treatments being available for treating COVID-19 patients, the global medical, scientific, pharma and funding communities have rapidly initiated over 500 COVID-19 clinical on a range of antiviral drug regimens, biologics, repurposed drugs in various combinations. We focus this editorial specifically on the background to, and the rationale for, the use and evaluation of mesenchymal stromal (Stem) cells (MSCs) in treatment trials of patients with severe COVID-19 disease. This is an area which has been eclipsed by the current emphasis the huge number of trials evaluating new anti-viral drugs, repurposed drugs and combinations thereof. MSCs should also be trialed for treatment of severe cases of MERS where mortality rates are upto 34% and MERS-CoV remains a WHO priority Blueprint pathogen. It's about time funding agencies now invest more into development MSCs per se and other host-directed therapies in combination with other therapeutic interventions. MSC therapy could turn out to be an important contribution to bringing an end to the high COVID-19 and MERS death rates. |
6 | lzk4qpqe | what types of rapid testing for Covid-19 have been developed? | Rapid response research to emerging infectious diseases: lessons from SARS New and emerging infectious diseases continue to plague the world, and there is significant concern that recombinant infectious agents can be used as bioterrorism threats. Microbiologists are increasingly being asked to apply their scientific knowledge to respond to these threats. The recent pandemic caused by the severe acute respiratory syndrome (SARS) coronavirus illustrated not only how a newly evolved pathogen can rapidly spread throughout the world but also how the global community can unite to identify the causative agent and control its spread. Rapid response research mechanisms, such as those used by the SARS Accelerated Vaccine Initiative (SAVI), have shown that the application of emergency management techniques, together with rapid response research, can be highly effective when applied appropriately to new infectious diseases. |
31 | zuxm7ayk | How does the coronavirus differ from seasonal flu? | Emerging viral diseases and infectious disease risks Summary. New pathogens and antimicrobial‐resistant forms of older pathogens continue to emerge, some with the potential for rapid, global spread and high morbidity and mortality. Pathogens can emerge either through introduction into a new population or when the interaction with the vector changes; emergence is also influenced by microbiological adaptation and change, global travel patterns, domestic and wild animal contact and other variants in human ecology and behaviour. Quick, decisive action to detect and control novel pathogens, and thereby contain outbreaks and prevent further transmission, is frequently hampered by incomplete or inadequate data about a new or re‐emerging pathogen. Three examples of pathogens that are current causes for human health concern are avian influenza, West Nile virus (WNV) and the severe acute respiratory syndrome (SARS) coronavirus. Pathogens directly or indirectly transmitted by aerosolized droplets, such as avian influenza and SARS, pose considerable containment challenges. Rapid screening tests for other newly described pathogens such as WNV require time for development and may be <100% reliable. The importance of vigilance in the detection and control of newly recognized infectious threats cannot be overstressed. The presence of infectious agents in the blood supply could again have a significant impact on the safe use of both blood and blood‐derived products in the care of patients with haemophilia, as did the human immunodeficiency virus in the 1980s. Emerging pathogens will continue to be a reality requiring the collaborative efforts of public health and individual healthcare providers worldwide to contain outbreaks and prevent transmission. |
24 | 29z5fvyi | what kinds of complications related to COVID-19 are associated with diabetes | Caring for patients with diabetes during COVID-19 pandemic: Important considerations for pharmacists The current pandemic of the COVID-19 infection, coupled with the increased global burden of diabetes, has imposed significant challenges to the healthcare providers in providing effective and sustained care to patients with diabetes care during the ongoing pandemic. It is, therefore, important for healthcare providers to understand and follow the recommended changes in the delivery of care, lifestyle modifications, and pharmacotherapy to ensure optimal care to the patients during and post-pandemic era. This commentary aims to discuss the impact of COVID-19 on diabetes care and the important considerations for pharmacists during this pandemic. |
14 | oz8zjd6p | what evidence is there related to COVID-19 super spreaders | The effect of human mobility and control measures on the COVID-19 epidemic in China The ongoing coronavirus disease 2019 (COVID-19) outbreak expanded rapidly throughout China. Major behavioral, clinical, and state interventions were undertaken to mitigate the epidemic and prevent the persistence of the virus in human populations in China and worldwide. It remains unclear how these unprecedented interventions, including travel restrictions, affected COVID-19 spread in China. We used real-time mobility data from Wuhan and detailed case data including travel history to elucidate the role of case importation in transmission in cities across China and to ascertain the impact of control measures. Early on, the spatial distribution of COVID-19 cases in China was explained well by human mobility data. After the implementation of control measures, this correlation dropped and growth rates became negative in most locations, although shifts in the demographics of reported cases were still indicative of local chains of transmission outside of Wuhan. This study shows that the drastic control measures implemented in China substantially mitigated the spread of COVID-19. |
22 | rzns8mn5 | are cardiac complications likely in patients with COVID-19? | Heart failure management during COVID‐19 outbreak in Italy. Telemedicine experience from a heart failure university tertiary referral centre |
3 | l6bnxi40 | will SARS-CoV2 infected people develop immunity? Is cross protection possible? | Long period dynamics of viral load and antibodies for SARS-CoV-2 infection: an observational cohort study ABSTRACT OBJECTIVE To investigate the dynamics of viral RNA, IgM, and IgG and their relationships in patients with SARS-CoV-2 pneumonia over an 8-week period. DESIGN Retrospective, observational case series. SETTING Wenzhou Sixth Peoples Hospital PARTICIPANTS Thirty-three patients with laboratory confirmed SARS-CoV-2 pneumonia admitted to hospital. Data were collected from January 27 to April 10, 2020. MAIN OUTCOME MEASURES Throat swabs, sputum, stool, and blood samples were collected, and viral load was measured by reverse transcription PCR (RT-PCR). Specific IgM and IgG against spike protein (S), spike protein receptor binding domain (RBD), and nucleocapsid (N) were analyzed. RESULTS At the early stages of symptom onset, SARS-CoV-2 viral load is higher in throat swabs and sputum, but lower in stool. The median (IQR) time of undetectable viral RNA in throat swab, sputum, and stool was 18.5 (13.25-22) days, 22 (18.5-27.5) days, and 17 (11.5-32) days, respectively. In sputum, 17 patients (51.5%) had undetectable viral RNA within 22 days (short persistence), and 16 (48.5%) had persistent viral RNA more than 22 days (long persistence). Three patients (9.1%) had a detectable relapse of viral RNA in sputum within two weeks of their discharge from the hospital. One patient had persistent viral RNA for 59 days or longer. The median (IQR) seroconversion time of anti-S IgM, anti-RBD IgM, and anti-N IgM was 10.5 (7.75-15.5) days, 14 (9-24) days, and 10 (7-14) days, respectively. The median (IQR) seroconversion time of anti-S IgG, anti-RBD IgG, and anti-N IgG was 10 (7.25-16.5) days, 13 (9-17) days, and 10 (7-14) days, respectively. By week 8 after symptom onset, IgM were negative in many of the previously positive patients, and IgG levels remained less than 50% of the peak levels in more than 20% of the patients. In about 40% of the patients, anti-RBD IgG levels were 4-times higher in convalescence than in acute phase. SARS-CoV-2 RNA coexisted with antibodies for more than 50 days. Anti-RBD IgM and IgG levels, including anti-RBD IgM levels at presentation and peak time, were significantly higher in viral RNA short persistence patients than in long persistence patients. CONCLUSION This study adds important new information about the features of viral load and antibody dynamics of SARS-CoV-2. It is clear from these results that the viral RNA persists in sputum and stool specimens for a relatively long time in many patients. Anti-RBD may also serve as a potential protective antibody against SARS-CoV-2 infection, as viral persistence appears to be related to anti-RBD levels. Earlier treatment intervention also appears to be a factor in viral persistence. |
7 | rw3p6wle | are there serological tests that detect antibodies to coronavirus? | Understanding Antibody Testing for COVID-19 The orthopedic community has seen the COVID-19 pandemic decimate elective surgical volumes in most geographies. Patients and essential workers, such as health care providers, remain rightfully concerned about how to appropriately begin to return to work and community activity in a safe and responsible manner. Many believe that testing for the presence of antibodies on a widespread scale could help drive evidence-based decision-making, both on an individual and societal scale. Much information, and an equal amount of misinformation, has been produced on antibody testing. Education about the role and science of such testing is critically important for programs to be effectively understood and managed. |
24 | e27dd9d4 | what kinds of complications related to COVID-19 are associated with diabetes | À propos de chirurgie et COVID-19 : quelques précautions complémentaires. Réponse à : « Stratégie pour la pratique de la chirurgie digestive et oncologique en situation d'épidémie de COVID-19 »() |
20 | 7byl5jre | are patients taking Angiotensin-converting enzyme inhibitors (ACE) at increased risk for COVID-19? | Continuing versus suspending angiotensin-converting enzyme inhibitors and angiotensin receptor blockers: Impact on adverse outcomes in hospitalized patients with severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2)--The BRACE CORONA Trial Angiotensin-converting enzyme-2 (ACE2) expression may increase due to upregulation in patients using angiotensin-converting enzyme inhibitors (ACEI) and angiotensin receptor blockers (ARBs). Because renin-angiotensin system blockers increase levels of ACE2, a protein that facilitates coronavirus entry into cells, there is concern that these drugs could increase the risk of developing a severe and fatal form of COVID-19. The impact of discontinuing ACEI and ARBs in patients with COVID-19 remains uncertain. DESIGN: BRACE CORONA is a pragmatic, multicenter, randomized, phase IV, clinical trial that aims to enroll around 500 participants at 34 sites in Brazil. Participants will be identified from an ongoing national registry of suspected and confirmed cases of COVID-19. Eligible patients using renin-angiotensin system blockers (ACEI/ARBs) with a confirmed diagnosis of COVID-19 will be randomized to a strategy of continued ACEI/ARB treatment versus temporary discontinuation for 30 days. The primary outcome is the median days alive and out of the hospital at 30 days. Secondary outcomes include progression of COVID-19 disease, all-cause mortality, death from cardiovascular causes, myocardial infarction, stroke, transient ischemic attack, new or worsening heart failure, myocarditis, pericarditis, arrhythmias, thromboembolic events, hypertensive crisis, respiratory failure, hemodynamic decompensation, sepsis, renal failure, and troponin, B-type natriuretic peptide (BNP), N-terminal-proBNP, and D-dimer levels. SUMMARY: BRACE CORONA will evaluate whether the strategy of continued ACEI/ARB therapy compared with temporary discontinuation of these drugs impacts clinical outcomes among patients with COVID-19. |
32 | 6a4ds69d | Does SARS-CoV-2 have any subtypes, and if so what are they? | Ontology-based systematic classification and analysis of coronaviruses, hosts, and host-coronavirus interactions towards deep understanding of COVID-19 Given the existing COVID-19 pandemic worldwide, it is critical to systematically study the interactions between hosts and coronaviruses including SARS-Cov, MERS-Cov, and SARS-CoV-2 (cause of COVID-19). We first created four host-pathogen interaction (HPI)-Outcome postulates, and generated a HPI-Outcome model as the basis for understanding host-coronavirus interactions (HCI) and their relations with the disease outcomes. We hypothesized that ontology can be used as an integrative platform to classify and analyze HCI and disease outcomes. Accordingly, we annotated and categorized different coronaviruses, hosts, and phenotypes using ontologies and identified their relations. Various COVID-19 phenotypes are hypothesized to be caused by the backend HCI mechanisms. To further identify the causal HCI-outcome relations, we collected 35 experimentally-verified HCI protein-protein interactions (PPIs), and applied literature mining to identify additional host PPIs in response to coronavirus infections. The results were formulated in a logical ontology representation for integrative HCI-outcome understanding. Using known PPIs as baits, we also developed and applied a domain-inferred prediction method to predict new PPIs and identified their pathological targets on multiple organs. Overall, our proposed ontology-based integrative framework combined with computational predictions can be used to support fundamental understanding of the intricate interactions between human patients and coronaviruses (including SARS-CoV-2) and their association with various disease outcomes. |
26 | fpj5urao | what are the initial symptoms of Covid-19? | Moderate mutation rate in the SARS coronavirus genome and its implications BACKGROUND: The outbreak of severe acute respiratory syndrome (SARS) caused a severe global epidemic in 2003 which led to hundreds of deaths and many thousands of hospitalizations. The virus causing SARS was identified as a novel coronavirus (SARS-CoV) and multiple genomic sequences have been revealed since mid-April, 2003. After a quiet summer and fall in 2003, the newly emerged SARS cases in Asia, particularly the latest cases in China, are reinforcing a wide-spread belief that the SARS epidemic would strike back. With the understanding that SARS-CoV might be with humans for years to come, knowledge of the evolutionary mechanism of the SARS-CoV, including its mutation rate and emergence time, is fundamental to battle this deadly pathogen. To date, the speed at which the deadly virus evolved in nature and the elapsed time before it was transmitted to humans remains poorly understood. RESULTS: Sixteen complete genomic sequences with available clinical histories during the SARS outbreak were analyzed. After careful examination of multiple-sequence alignment, 114 single nucleotide variations were identified. To minimize the effects of sequencing errors and additional mutations during the cell culture, three strategies were applied to estimate the mutation rate by 1) using the closely related sequences as background controls; 2) adjusting the divergence time for cell culture; or 3) using the common variants only. The mutation rate in the SARS-CoV genome was estimated to be 0.80 – 2.38 × 10(-3 )nucleotide substitution per site per year which is in the same order of magnitude as other RNA viruses. The non-synonymous and synonymous substitution rates were estimated to be 1.16 – 3.30 × 10(-3 )and 1.67 – 4.67 × 10(-3 )per site per year, respectively. The most recent common ancestor of the 16 sequences was inferred to be present as early as the spring of 2002. CONCLUSIONS: The estimated mutation rates in the SARS-CoV using multiple strategies were not unusual among coronaviruses and moderate compared to those in other RNA viruses. All estimates of mutation rates led to the inference that the SARS-CoV could have been with humans in the spring of 2002 without causing a severe epidemic. |
41 | 6ub9yh27 | What are the impacts of COVID-19 among African-Americans that differ from the rest of the U.S. population? | Monitoring trends and differences in COVID-19 case fatality rates using decomposition methods: Contributions of age structure and age-specific fatality The population-level case fatality rate (CFR) associated with COVID-19 varies substantially, both across countries and within countries over time. We analyze the contribution of two key determinants of the variation in the observed CFR: the age-structure of diagnosed infection cases and age-specific case-fatality rates. We use data on diagnosed COVID-19 cases and death counts attributable to COVID-19 by age for China, France, Germany, Italy, South Korea, Spain, and the United States. We calculate the CFR for each country at the latest data point and for Italy also over time. We use demographic decomposition to break the difference between CFRs into unique contributions arising from the age-structure of confirmed cases and the age-specific case-fatality. CFRs vary from 0.7% in Germany and 1.6% in South Korea to 8.6% in Spain and 10.6% in Italy. The age-structure of detected cases can explain a substantial proportion of cross-country variation in the CFR. For example, 57% of Spain's difference with respect to South Korea is explained by the observed cases being older. In Italy, the CFR increased from 4.2% to 10.6% between March 9 and March 29, 2020, and more than 95% of the change was due to increasing age-specific case fatality rates. The importance of the age-structure of infected cases likely reflects several factors, including different testing regimes and differences in transmission trajectories; while increasing age-specific case fatality rates indicate the worsening health outcomes of those infected with COVID-19. Our findings lend support to recommendations for data to be disaggregated by age, and potentially other variables, to facilitate a better understanding of population-level differences in CFRs. They also show the need for well designed seroprevalence studies to ascertain the extent to which differences in testing regimes drive differences in the age-structure of detected cases. |
34 | 8ojxsgup | What are the longer-term complications of those who recover from COVID-19? | 2019-novel Coronavirus (2019-nCoV): estimating the case fatality rate - a word of caution. |
8 | kd0h5sy7 | how has lack of testing availability led to underreporting of true incidence of Covid-19? | Modelling the evolution of COVID-19 in high-incidence European countries and regions: estimated number of infections and impact of past and future intervention measures A previously developed mechanistic model of COVID-19 transmission has been adapted and applied here to study the evolution of the disease and the effect of intervention measures in some European countries and territories where the disease had major impact. A clear impact of the major intervention measures on the reproduction number (Rt) has been found in all studied countries and territories, as already suggested by the drop in the number of deaths over time. Interestingly, the impact of such major intervention measures seems to be the same in most of these countries. The model has also provided realistic estimates of the total number of infections, active cases and future outcome. While the predictive capabilities of the model are much more uncertain before the peak of the outbreak, we could still reliably predict the evolution of the disease after a major intervention by assuming the afterwards reproduction number from current study. More challenging is to foresee the long-term impact of softer intervention measures, but this model can estimate the outcome of different scenarios and help planning changes in the implementation of control measures in a given country or region. |
34 | zi98dq1v | What are the longer-term complications of those who recover from COVID-19? | COVID-19, SARS and MERS: are they closely related? Abstract Background The 2019 novel coronavirus (SARS-CoV-2) is a new human coronavirus which is spreading with epidemic features in China and other Asian countries; cases have also been reported worldwide. This novel coronavirus disease (COVID-19) is associated with a respiratory illness that may lead to severe pneumonia and acute respiratory distress syndrome (ARDS). Although related to the severe acute respiratory syndrome (SARS) and the Middle East respiratory syndrome (MERS), COVID-19 shows some peculiar pathogenetic, epidemiological and clinical features which to date are not completely understood. Aims To provide a review of the differences in pathogenesis, epidemiology and clinical features of COVID-19, SARS and MERS. Sources The most recent literature in the English language regarding COVID-19 has been reviewed, and extracted data have been compared with the current scientific evidence about SARS and MERS epidemics. Content COVID-19 seems not to be very different from SARS regarding its clinical features. However, it has a fatality rate of 2.3%, lower than that of SARS (9.5%) and much lower than that of MERS (34.4%). The possibility cannot be excluded that because of the less severe clinical picture of COVID-19 it can spread in the community more easily than MERS and SARS. The actual basic reproductive number (R0) of COVID-19 (2.0–2.5) is still controversial. It is probably slightly higher than the R0 of SARS (1.7–1.9) and higher than that of MERS (<1). A gastrointestinal route of transmission for SARS-CoV-2, which has been assumed for SARS-CoV and MERS-CoV, cannot be ruled out and needs further investigation. Implications There is still much more to know about COVID-19, especially as concerns mortality and its capacity to spread on a pandemic level. Nonetheless, all of the lessons we learned in the past from the SARS and MERS epidemics are the best cultural weapons with which to face this new global threat. |
27 | h2kllvta | what is known about those infected with Covid-19 but are asymptomatic? | Severe Acute Respiratory Syndrome Coronavirus 2 Infection among Returnees to Japan from Wuhan, China, 2020 In early 2020, Japan repatriated 566 nationals from China. Universal laboratory testing and 14-day monitoring of returnees detected 12 cases of severe acute respiratory syndrome coronavirus 2 infection; initial screening results were negative for 5. Common outcomes were remaining asymptomatic (n = 4) and pneumonia (n = 6). Overall, screening performed poorly. |
8 | e74x31ev | how has lack of testing availability led to underreporting of true incidence of Covid-19? | SARS-CoV-2 and gastrointestinal tract: the dark side of the pandemic |
15 | 80ev0j5a | how long can the coronavirus live outside the body | Isothermal evaporation rate of deposited liquid aerosols and the SARS-CoV-2 coronavirus survival It is shown that the evaporation rate of a liquid sample containing the culture of coronavirus affects its survival on a substrate. Possible mechanisms of such influence can be due to the appearance of large, about 140 bar, non comprehensive capillary pressures and the associated dynamic forces during the movement of the evaporation front in a sample with the virus. A simulation of isothermal evaporation of a thin liquid sample based on the Stefan problem was performed. The comparison of simulation data and recent experiments on the coronavirus survival on various surfaces showed that the rate of isothermal evaporation of aqueous samples, which is higher for heat-conducting materials, correlates well with the lifetime of the coronavirus on these surfaces. |
11 | ae493hem | what are the guidelines for triaging patients infected with coronavirus? | Evolution of COVID-19 Guidelines for University of Washington Oral and Maxillofacial Surgery Patient Care Abstract The emergence of coronavirus disease 2019 (COVID-19), caused by the SARS-CoV-2 (SC2) virus, in late December 2019 has placed an overwhelming strain on healthcare institutions nationwide. The modern healthcare system has never dealt with a pandemic of this magnitude, the ramifications of which will undoubtedly lead to lasting changes in policy and protocol development for viral testing guidelines, personal protective equipment (PPE), surgical scheduling, and residency education and training. The State of Washington (WA) had the first reported case and death related to COVID 19 in the United States (US). Oral and maxillofacial surgeons are at a unique risk of exposure to SC2 and developing COVID-19 due to our proximity of working in and around the oro- and nasopharynx. This article summarizes the evolution of COVID-19 guidelines in four key areas: 1. preoperative SARS-CoV-2 (SC2) testing, 2. personal protective equipment (PPE) stewardship, 3. surgical scheduling guidelines, and 4. resident education and training for oral and maxillofacial surgery (OMS) at the University of Washington, Seattle, WA. |
21 | 8eevfmj2 | what are the mortality rates overall and in specific populations | Scaling COVID-19 against inequalities: should the policy response consistently match the mortality challenge? Background The mortality impact of COVID-19 has thus far been described in terms of crude death counts. We aimed to calibrate the scale of the modelled mortality impact of COVID-19 using age-standardised mortality rates and life expectancy contribution against other, socially-determined, causes of death in order to inform governments and the public. Methods We compared mortality attributable to suicide, drug poisoning and socioeconomic inequality with estimates of mortality from an infectious disease model of COVID-19. We calculated age-standardised mortality rates and life expectancy contributions for the UK and its constituent nations. Results Mortality from a fully unmitigated COVID-19 pandemic is estimated to be responsible for a negative life expectancy contribution of -5.96 years for the UK. This is reduced to -0.33 years in the fully mitigated scenario. The equivalent annual life expectancy contributions of suicide, drug poisoning and socioeconomic inequality-related deaths are -0.25, -0.20 and -3.51 years respectively. The negative impact of fully unmitigated COVID-19 on life expectancy is therefore equivalent to 24 years of suicide deaths, 30 years of drug poisoning deaths, and 1.7 years of inequality-related deaths for the UK. Conclusion Fully mitigating COVID-19 is estimated to prevent a loss of 5.63 years of life expectancy for the UK. Over 10 years there is a greater negative life expectancy contribution from inequality than around six unmitigated COVID-19 pandemics. To achieve long-term population health improvements it is therefore important to take this opportunity to introduce post-pandemic economic policies to build back better. |
27 | 7h7v6abe | what is known about those infected with Covid-19 but are asymptomatic? | Patients asymptomatiques du SARS-CoV-2 et transmission du virus : Où en sont nos connaissances?/ Asymptomatic carriage and transmission of SARS-CoV-2: What do we know? PURPOSE: Risk to healthcare workers treating asymptomatic patients infected with severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) in the operating room depends on multiple factors. This review examines the evidence for asymptomatic or pre-symptomatic carriage of SARS-CoV-2, the risk of transmission from asymptomatic patients, and the specific risks associated with aerosol-generating procedures. Protective measures, such as minimization of aerosols and use of personal protective equipment in the setting of treating asymptomatic patients, are also reviewed. SOURCE: We examined the published literature as well as Societal guidelines. PRINCIPAL FINDINGS: There is evidence that a proportion of those infected with SARS-CoV-2 have detectable viral loads prior to exhibiting symptoms, or without ever developing symptoms. The degree of risk of transmission from asymptomatic patients to healthcare providers will depend on the prevalence of disease in the population, which is difficult to assess without widespread population screening. Aerosol-generating procedures increase the odds of viral transmission from infected symptomatic patients to healthcare providers, but transmission from asymptomatic patients has not been reported. Techniques to minimize aerosolization and appropriate personal protective equipment may help reduce the risk to healthcare workers in the operating room. Some societal guidelines recommend the use of airborne precautions during aerosol-generating procedures on asymptomatic patients during the coronavirus disease pandemic, although evidence supporting this practice is limited. CONCLUSION: Viral transmission from patients exhibiting no symptoms in the operating room is plausible and efforts to reduce risk to healthcare providers include reducing aerosolization and wearing appropriate personal protective equipment, the feasibility of which will vary based on geographic risk and equipment availability. |
16 | d4t6ccvd | how long does coronavirus remain stable on surfaces? | Development of a Laboratory-safe and Low-cost Detection Protocol for SARS-CoV-2 of the Coronavirus Disease 2019 (COVID-19) The severe acute respiratory coronavirus 2 (SARS-CoV-2), which emerged in December 2019 in Wuhan, China, has spread rapidly to over a dozen countries. Especially, the spike of case numbers in South Korea sparks pandemic worries. This virus is reported to spread mainly through personto- person contact via respiratory droplets generated by coughing and sneezing, or possibly through surface contaminated by people coughing or sneezing on them. More critically, there have been reports about the possibility of this virus to transmit even before a virus-carrying person to show symptoms. Therefore, a low-cost, easy-access protocol for early detection of this virus is desperately needed. Here, we have established a real-time reverse-transcription PCR (rtPCR)-based assay protocol composed of easy specimen self-collection from a subject via pharyngeal swab, Trizolbased RNA purification, and SYBR Green-based rtPCR. This protocol shows an accuracy and sensitivity limit of 1-10 virus particles as we tested with a known lentivirus. The cost for each sample is estimated to be less than 15 US dollars. Overall time it takes for an entire protocol is estimated to be less than 4 hours. We propose a cost-effective, quick-and-easy method for early detection of SARS-CoV-2 at any conventional Biosafety Level II laboratories that are equipped with a rtPCR machine. Our newly developed protocol should be helpful for a first-hand screening of the asymptomatic virus-carriers for further prevention of transmission and early intervention and treatment for the rapidly propagating virus. |
22 | hxj4z228 | are cardiac complications likely in patients with COVID-19? | FOCIS abstract supplement |
9 | vn9ba1ku | how has COVID-19 affected Canada | Optimizing Access to Heart Failure Care in Canada during the COVID-19 Pandemic The traditional model of heart failure (HF) care in Canada, which relies upon a multi-disciplinary team and clinic based care processes, has been undermined as a result of the COVID-19 pandemic. As the pandemic continues, we will be challenged to improve or maintain the health status of those with HF by optimizing guideline-directed care despite physical distancing constraints and a reduction in the healthcare workforce. This will require development of new strategies specifically targeted at decreasing the risk of decompensation and resultant HF hospitalization. As such, we must quickly pivot to the adoption and application of novel technologies and revise usual care models, processes, and workflow. The unprecedented COVID-19 crisis has delivered the Canadian HF community a burning platform for the design and implementation of innovative approaches to support the vulnerable population we serve; born out of necessity, we now have the opportunity to explore innovative approaches that may inform the future of HF care delivery in Canada. Herein, we provide perspectives from leadership within the Canadian Heart Failure Society (CHFS) on how to optimize HF care during the COVID-19 pandemic. |
22 | kwvvg9xk | are cardiac complications likely in patients with COVID-19? | Challenges with the management of older patients with cancer during the COVID-19 pandemic |
12 | qnnt7e6s | what are best practices in hospitals and at home in maintaining quarantine? | First Pediatric Case of Coronavirus Disease 2019 in Korea The large outbreak of coronavirus disease 2019 (COVID-19) that started in Wuhan, China has now spread to many countries worldwide. Current epidemiologic knowledge suggests that relatively few cases are seen among children, which limits opportunities to address pediatric specific issues on infection control and the children's contribution to viral spread in the community. Here, we report the first pediatric case of COVID-19 in Korea. The 10-year-old girl was a close contact of her uncle and her mother who were confirmed to have COVID-19. In this report, we present mild clinical course of her pneumonia that did not require antiviral treatment and serial viral test results from multiple specimens. Lastly, we raise concerns on the optimal strategy of self-quarantine and patient care in a negative isolation room for children. |
13 | qs7dsxn5 | what are the transmission routes of coronavirus? | The spatiotemporal estimation of the dynamic risk and the international transmission of 2019 Novel Coronavirus (COVID-19) outbreak: A global perspective An ongoing novel coronavirus SARS-CoV-2 pneumonia infection outbreak called COVID-19 started in Wuhan, Hubei Province, China, in December 2019. It both spread rapidly to all provinces in China and started spreading around the world quickly through international human movement from January 2020. Currently, the spatiotemporal epidemic transmission patterns, prediction models, and possible risk analysis for the future are insufficient for COVID-19 but we urgently need relevant information, particularly from the global perspective. We have developed a novel two-stage simulation model to simulate the spatiotemporal changes in the number of COVID-19 cases and estimate the future worldwide risk. Based on the connectivity of countries to China and the country's medical and epidemic prevention capabilities, different scenarios are generated to analyze the possible transmission throughout the world and use this information to evaluate each country's vulnerability to and the dynamic risk of COVID-19. Countries' vulnerability to the COVID-19 outbreak from China is calculated for 63 countries around the world. Taiwan, South Korea, Hong Kong, and Japan are the most vulnerable areas. The relationship between each country's vulnerability and days before the first imported case occurred shows a very high exponential decrease. The cumulative number of cases in each country also has a linear relationship with vulnerability, which can compare and quantify the initial epidemic prevention capabilities to various countries' management strategies. In total, 1,000 simulation results of future cases around the world are generated for the spatiotemporal risk assessment. According to the simulation results of this study, if there is no specific medicine for it, it will likely form a global pandemic. This method can be used as a preliminary risk assessment of the spatiotemporal spread for a new global epidemic. * Note: This study was completed on February 15, 2020. |
32 | 87yq2317 | Does SARS-CoV-2 have any subtypes, and if so what are they? | Influenza Virus (H5N1) in Live Bird Markets and Food Markets, Thailand A surveillance program for influenza A viruses (H5N1) was conducted in live bird and food markets in central Thailand during July 2006–August 2007. Twelve subtype H5N1 viruses were isolated. The subtype H5N1 viruses circulating in the markets were genetically related to those that circulated in Thailand during 2004–2005. |
21 | m5pz84q5 | what are the mortality rates overall and in specific populations | Critical Care during the Coronavirus Crisis – challenges and considerations for the cardiothoracic and vascular anesthesia community |
12 | sttytp25 | what are best practices in hospitals and at home in maintaining quarantine? | Trust in and Ethical Design of Carebots: The Case for Ethics of Care The paper has two main objectives: to examine the challenges arising from the use of carebots as well as to discuss how the design of carebots can deal with these challenges. First, it notes that the use of carebots to take care of the physical and mental health of the elderly, children and the disabled as well as to serve as assistive tools and social companions encounter a few main challenges. They relate to the extent of the care robots' ability to care for humans, potential deception by robot morphology and communications, (over)reliance on or attachment to robots, and the risks of carebot use without informed consent and potential infringements of privacy. Secondly, these challenges impinge upon issues of ethics and trust which are somewhat overlapping in terms of concept and practice. The existing ethical guidelines, standards and regulations are general in nature and lack a central ethical framework and concrete principles applicable to the care contexts. Hence, to deal with these important challenges, it is proposed in the third part of the paper that carebots be designed by taking account of Ethics of Care as the central ethical framework. It argues that the Ethics of Care offer the following advantages: (a) it provides sufficiently concrete principles and embodies values that are sensitive and applicable to the design of carebots and the contexts of caring practices; (b) it coheres with the tenets of Principlism and select ethical theories (utilitarianism, deontology and virtue ethics); and (c) it is closely associated with the preservation and maintenance of trust. |
12 | e57bamrt | what are best practices in hospitals and at home in maintaining quarantine? | Construction of Integrated Emergency Management Model for Novel Coronavirus Pneumonia Epidemic Prevention and Control in Hospital Pharmacy Department/ 中国药房 OBJECTIVE: To provide reference for improving emergency capacity of the hospital pharmacy department in response to the novel coronavirus pneumonia (COVID-19) epidemic. METHODS :According to the related regulations and requirements of Law of the People 's Republic of China on the Prevention and Control of Infectious Diseases ,combined with the situation of COVID- 19 epidemic prevention and control ,and management experience of relevant hospitals ,on the basis of in-depth analysis of drug supply and quality assurance ,drug dispensing management ,provision of clinical pharmaceutical services and other related material support of hospital pharmacy department,integrated emergency management model was constructed for COVID- 19 epidemic prevention and control ,and the precautions and response measures of each link were sorted out. RESULTS :Integruted emergency management mode for COVID-19 epidemic prevention and control in hospital pharmacy department included but was not limited to human resource management,drug and disinfection products supply management (mainly including key treatment drugs and disinfection product list formulation,control,inventory increase ,etc.);drug dispensing management (mainly including prescription ,pharmacy window , planning quantitative reserve , drug return , etc.);clinical pharmaceutical care management (mainly including providing pharmaceutical information support ,online pharmaceutical service ,monitoring drug safety ,etc.);personnel protection and disinfection (mainly including personnel protection ,environment and window ,equipment and container ,paper prescription disinfection,etc.);special management of donated drugs ;prevention and control knowledge training ;pharmaceutical education and scientific research management ,etc. CONCLUSIONS :The integrated emergency management model for epidemic prevention and control is helpful for hospital pharmacy to manage public health emergencies. During the outbreak of COVID- 19,hospital pharmacy department should start integrated emergency management mode for epidemic prevention and control ,strengthen the risk control of each link ,and play a good role in the key functional departments in the special period. |
18 | 8g27pktv | what are the best masks for preventing infection by Covid-19? | 2019 Novel coronavirus: where we are and what we know There is a current worldwide outbreak of a new type of coronavirus (2019-nCoV), which originated from Wuhan in China and has now spread to 17 other countries. Governments are under increased pressure to stop the outbreak spiraling into a global health emergency. At this stage, preparedness, transparency, and sharing of information are crucial to risk assessments and beginning outbreak control activities. This information should include reports from outbreak sites and from laboratories supporting the investigation. This paper aggregates and consolidates the virology, epidemiology, clinical management strategies from both English and Chinese literature, official news channels, and other official government documents. In addition, by fitting the number of infections with a single-term exponential model, we report that the infection is spreading at an exponential rate, with a doubling period of 1.8 days. |
45 | tmk2c9eh | How has the COVID-19 pandemic impacted mental health? | Neurosurgery Residents Perspective on the COVID-19: Knowledge, Readiness, and Impact of this Pandemic. Abstract Background The novel Coronavirus disease (COVID-19) is a life-threatening illness, which represents a challenge to all the health-care workers. Neurosurgeons around the world are being affected in different ways. Objectives This is the first study regarding the readiness of neurosurgery residents towards the COVID-19 pandemic and its impact. The aim is to identify the level of knowledge, readiness, and the impact of this virus among neurosurgery residents in different programs. Methods A cross-sectional analysis in which 52 neurosurgery residents from different centers were selected to complete a questionnaire-based survey. The questionnaire comprised of three sections and 27 questions that ranged from knowledge to impact of the current pandemic on various features. Results The median knowledge score was 4 out of 5. The proportion of participants with satisfactory knowledge level was 60%. There was a statistically significant difference between the knowledge score and location of the program. Around 48% of the neurosurgery residents dealt directly with COVID-19 patients. Receiving a session about personal protective equipment (PPE) was reported by 57.7%. The neurosurgery training at the hospital was affected. About 90% believed that this pandemic influenced their mental health. Conclusion Neurosurgery residents have a relatively good knowledge about COVID-19. The location of the program was associated with knowledge level. Most of the participants did not receive a sufficient training about PPE. Almost all responders agree that their training at the hospital was affected. Further studies are needed to study the impact of this pandemic on neurosurgery residents. |
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