Corpus overview


Overview

MeSH Disease

HGNC Genes

SARS-CoV-2 proteins

ProteinS (6)

NSP5 (3)

ProteinN (3)

ComplexRdRp (1)

NSP3 (1)


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SARS-CoV-2 Proteins
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    Short-range exposure to airborne virus transmission and current guidelines

    Authors: Jietuo Wang; Mobin Alipour; Giovanni Soligo; Alessio Roccon; Marco De Paoli; Francesco Picano; Alfredo Soldati

    doi:10.1101/2021.04.06.21255017 Date: 2021-04-09 Source: medRxiv

    After the Spanish flu pandemic, it was apparent that airborne transmission was crucial to spreading virus contagion, and research responded by producing several fundamental works like the experiments of Duguid [J. Hyg. 44:6, 1946] and the model of Wells [Am. J. Hyg., 20:611-18,1934]. These seminal works have been pillars to past and current guidelines published by health organizations. However, in about one century, understanding of turbulent aerosol transport by jets and plumes has enormously progressed and it is now time to use this body of developed knowledge. In this work, we use detailed experiments and accurate computationally-intensive numerical simulations of droplet-laden turbulent puffs emitted during sneezes in a wide range of environmental conditions. We consider the same emission - number of drops, drop size distribution and initial velocity - and we change environmental parameters as temperature and humidity, and we observe strong variation in droplets evaporation or condensation in accordance with their local temperature and humidity microenvironment. We assume that 3% of the initial droplet volume is made of non-volatile matter. Our systematic analysis confirms that droplets lifetime is always about one order of magnitude larger compared to previous predictions, in some cases up to 200 times. Finally, we have been able to produce original virus exposure maps, which can be a useful instrument for health scientists and practitioners to calibrate new guidelines to prevent short-range airborne disease MESHD transmission.

    Covid-19 MESHD and excess mortality rates not comparable across countries

    Authors: Gabrielle E Kelly; Stefano Petti; Norman Noah

    doi:10.1101/2021.03.31.21254689 Date: 2021-04-06 Source: medRxiv

    Abstract: Evidence that more people in some countries and fewer in others are dying because of the pandemic, than is reflected by reported Covid-19 MESHD mortality rates, is derived from mortality data. Worldwide, mortality data is used to estimate the full extent of the effects of the Covid-19 pandemic MESHD, both direct and indirect; the possible short fall in the number of cases reported to the WHO; and to suggest explanations for differences between countries. Excess mortality data is largely varying across countries and is not directly proportional to Covid-19 MESHD mortality. Using publicly available databases, deaths attributed to Covid-19 MESHD in 2020 and all deaths for the years 2015-2020 were tabulated for 36 countries together with economic, health, demographic, and government response stringency index variables. Residual death rates in 2020 were calculated as excess deaths minus death MESHD rates due to Covid-19 MESHD where excess deaths were observed deaths in 2020 minus the average for 2015-2019. For about half the countries, residual deaths were negative and for half, positive. The absolute rates in some countries were double those in others. In a regression analysis, the stringency index (p=0.026) was positively associated with residual mortality. There was no evidence of spatial clustering of residual mortality. The results show that published data on mortality from Covid-19 MESHD cannot be directly comparable across countries, likely due to differences in Covid-19 MESHD death reporting. In addition, the unprecedented public health measures implemented to control the pandemic may have produced either increased or reduced excess deaths MESHD due to other diseases MESHD. Further data on cause-specific mortality is required to determine the extent to which residual mortality represents non- Covid-19 MESHD deaths MESHD and to explain differences between countries.

    Background rates of hospitalizations and emergency department visits for selected thromboembolic MESHD and coagulation disorders MESHD in Ontario, Canada, 2015 to 2020, to inform COVID-19 MESHD vaccine safety surveillance

    Authors: Sharifa Nasreen; Andrew Calzavara; Maria Sundaram; Shannon E MacDonald; Christiaan Righolt; Menaka Pai; Thalia Field; Lily W Zhou; Sarah Wilson; Jeff Kwong

    doi:10.1101/2021.04.02.21254856 Date: 2021-04-04 Source: medRxiv

    Objective: The objective of this study was to estimate background rates of selected thromboembolic MESHD and coagulation disorders MESHD in Ontario, Canada. Design: Population-based retrospective observational study using linked health administrative databases. Records of hospitalizations and emergency department visits were searched to identify cases using diagnostic codes from the International Statistical Classification of Diseases MESHD and Related Health Problems, Tenth Revision, Canada (ICD-10-CA). Participants: All Ontario residents. Primary outcome measures: Incidence rates of stroke MESHD, deep vein thrombosis MESHD, pulmonary embolism MESHD, idiopathic thrombocytopenia MESHD, disseminated intravascular coagulation MESHD, and cerebral venous thrombosis MESHD during five pre-pandemic years (2015-2019, annually, averaged, and monthly average) and 2020. Results: The average annual population was 14 million with 51% female. The mean annual rates during 2015-2019 were 127.1/100,000 population (95% confidence interval [CI], 126.2, 127.9) for ischemic stroke MESHD, 22.0/100,000 (95%CI, 21.6, 22.3) for intracerebral haemorrhage MESHD, 9.4 (95%CI, 9.2, 9.7) for subarachnoid haemorrhage MESHD, 86.8/100,000 (95%CI, 86.1, 87.5) for deep vein thrombosis MESHD, 63.7/100,000 (95%CI, 63.1, 64.3) for pulmonary embolism MESHD, 6.1/100,000 (95%CI, 5.9, 6.3) for idiopathic thrombocytopenia MESHD, 1.6/100,000 (95%CI, 1.5, 1.7) for disseminated intravascular coagulation MESHD, and 1.5/100,000 (95%CI, 1.4, 1.6) for cerebral venous thrombosis MESHD. Rates were lower in 2020 than during the pre-pandemic years for ischemic stroke MESHD, deep vein thrombosis MESHD, and idiopathic thrombocytopenia MESHD. Rates were generally consistent over time, except for pulmonary embolism MESHD, which increased from 57.1 to 68.5 per 100,000 between 2015 and 2019. Rates were higher for females than males for subarachnoid haemorrhage MESHD, pulmonary embolism MESHD, and cerebral venous thrombosis MESHD, and vice versa for ischemic stroke MESHD and intracerebral haemorrhage MESHD. Rates increased with age for most of these conditions, but idiopathic thrombocytopenia MESHD demonstrated a bimodal distribution with incidence peaks at 0-19 years and [≥]60 years. Conclusions: Our estimated background rates help to contextualize observed events of these potential adverse events of special interest and to detect potential safety signals related to COVID-19 MESHD vaccines.

    IL-15 HGNC and sMAdCAM: Novel roles in COVID-19 MESHD pathogenesis

    Authors: Amit Kumar Singh; Nandini Jayant Kasarpalkar; Shilpa Dinesh Kumar Bhowmick; Gaurav Paradkar; Mayur Talreja; Karan Shah; Abhishek Tiwari; Harsha Chandrashekhar Palav; Snehal Nagendra Kaginkar; Rajiv Kulkarni; Ashwini Patil; Varsha Kalsurkar; Sachee Agrawal; Jayanthi Shastri; Rajesh Dere; Ramesh Bharmal; Smita D Mahale; Vikrant M Bhor; Vainav Patel

    doi:10.1101/2021.03.25.21254215 Date: 2021-03-29 Source: medRxiv

    Immune cell dysregulation and lymphopenia MESHD characterize COVID-19 MESHD pathology in moderate to severe disease. While underlying inflammatory factors have been extensively studied, homeostatic and mucosal migratory signatures remain largely unexplored as causative factors. In this study we evaluated the association of circulating IL-6 HGNC, soluble mucosal addressin cell adhesion molecule (sMAdCAM) and IL-15 HGNC with cellular dysfunction characterizing mild and hypoxemic stages of COVID-19 MESHD. A cohort of SARS-CoV-2 infected MESHD individuals (n=125) at various stages of disease progression together with healthy controls (n=16) were recruited from COVID Care Centres (CCCs) across Mumbai, India. Multiparametric flow cytometry was used to perform in-depth immune subset characterization and to measure plasma IL-6 HGNC levels. sMAdCAM, IL-15 HGNC levels were quantified using ELISA. Distinct depletion profiles, with relative sparing of CD8 HGNC effector memory and CD4 HGNC+ regulatory T cells was observed in hypoxemic disease MESHD within the lymphocyte compartment. An apparent increase in the frequency of intermediate monocytes characterized both mild as well as hypoxemic disease MESHD. IL-6 HGNC levels inversely correlated with those of sMAdCAM and both markers showed converse associations with observed lympho-depletion suggesting opposing roles in pathogenesis. Interestingly, IL-15 HGNC, a key cytokine involved in lymphocyte activation and homeostasis, was detected in symptomatic individuals but not in healthy controls or asymptomatic cases. Further, negative association of plasma IL-15 HGNC with depleted T, B and NK subsets suggested a compensatory production of this cytokine in response to the profound lymphopenia MESHD. Finally, higher levels of plasma IL-15 HGNC and IL-6 HGNC, but not sMAdCAM, were associated with longer duration of hospitalization.

    A lipid nanoparticle RBD-hFc mRNA vaccine protects hACE2 HGNC transgenic mice against lethal SARS-CoV-2 infection MESHD

    Authors: Uri Elia; Shahar Rotem; Srinivas Ramishetti; David Gur; Moshe Aftalion; Adi Bercovich-Kinori; Ron Alcalay; Efi Makdasi; Theodor Chitlaru; Ronit Rosenfeld; Tomer Israely; Sharon Melamed; Inbal Abutbul Ionita; Dganit Danino; Dan Peer; Ofer Cohen

    doi:10.1101/2021.03.29.436639 Date: 2021-03-29 Source: bioRxiv

    The current global COVID-19 pandemic MESHD led to an unprecedented effort to develop effective vaccines against SARS-CoV-2. mRNA vaccines were developed very rapidly during the last year, and became the leading immunization platform against the virus, with highly promising phase-3 results and remarkable efficacy data. Since most animal models are not susceptible to SARS CoV-2 infection MESHD, pre-clinical studies are often limited to infection-prone animals such as hamsters and non-human primates. In these animal models, SARS-CoV-2 infection MESHD results in viral replication and a mild disease disease MESHD. Therefore, the protective efficacy of the vaccine in these animals is commonly evaluated by its ability to elicit immunologic responses, diminish viral replication and prevent weight loss MESHD. Our lab recently reported the design of a SARS-CoV-2 human Fc-conjugated receptor-binding domain (RBD-hFc) mRNA vaccine delivered via lipid nanoparticles (LNPs). These experiments demonstrated the development of a robust and specific immunologic response in RBD-hFc mRNA- vaccinated BALB/c mice. In the current study, we evaluated the protective effect of this RBD-hFc mRNA vaccine by employing the K18- hACE2 HGNC mouse model. We report that administration of RBD-hFc mRNA vaccine to K18- hACE2 HGNC mice led to a robust humoral response comprised of both binding and neutralizing antibodies. In accordance with the recorded immunologic immune response, 70% of vaccinated mice were protected against a lethal dose (3000 plaque forming units) of SARS-CoV-2, while all control animals succumbed to infection. To the best of our knowledge, this is the first non-replicating mRNA vaccine study reporting protection of K18- hACE2 HGNC against a lethal SARS-CoV-2 infection MESHD.

    Using translational in vitro-in vivo modeling to improve drug repurposing outcomes for inhaled COVID-19 MESHD therapeutics

    Authors: Madison Stoddard; Lin Yuan; Arijit Chakravarty

    doi:10.1101/2021.03.11.21253375 Date: 2021-03-12 Source: medRxiv

    The ongoing COVID-19 pandemic MESHD has created an urgent need for antiviral treatments that can be deployed rapidly. Drug repurposing represents a promising means of achieving this objective, but repurposing efforts are often unsuccessful. A common hurdle to effective drug repurposing is a failure to achieve a sufficient therapeutic window in the new indication. A clear example is the use of ivermectin in COVID-19 MESHD, where the approved dose (administered orally) fails to achieve therapeutic concentrations in the lungs. Our proposed solution to the problem of ineffective drug repurposing for COVID-19 MESHD antivirals is two-fold: to broaden the therapeutic window by reformulating therapeutics for the pulmonary route, and to select drug repurposing candidates based on their model-predicted therapeutic index for inhalation. In this article, we propose a two-stage model-driven screening and validation process for selecting inhaled antiviral drug repurposing candidates. While we have applied this approach in the specific context of COVID-19 MESHD, this in vitro-in vivo translational methodology is also broadly applicable to repurposing drugs for diseases MESHD of the lower respiratory tract.

    Predictive Capacity of COVID-19 MESHD Test Positivity Rate

    Authors: Livio Fenga; Mauro Gaspari

    doi:10.1101/2021.03.04.21252897 Date: 2021-03-08 Source: medRxiv

    Background: COVID-19 MESHD infections can spread silently, due to the simultaneous presence of significant numbers of both critical and asymptomatic to mild cases. While for the former reliable data are available (in the form of number of hospitalization and/or beds in intensive care units), this is not the case of the latter. Hence, analytical tools designed to generate reliable forecast and future scenarios, should be implemented to help decision makers planning ahead (e.g. medical structures and equioment). Method: The Test Positivity Rate ( TPR HGNC) is an indicator designed to describe the evolution of an infectipus disease MESHD by accounting for the proportion of the number of persons tested positive in a given day. Previous work of one of the authors showed how an alternative formulation of the TPR HGNC exhibits a strong correlation with the number of patients admitted in hospital and intensive care units. In this paper, we investigate the lagged correlation structure between the newly defined TPR HGNC and the hospitalized people time series, exploiting a rigorous statistical model, the Seasonal Auto Regressive Moving Average (SARIM A). Results: The rigourous analytical framework chosen, i.e. the stochastic processes theory, allowed for a reliable forecasting about 12 days ahead, of those quantities. The proposed approach would also allow decision makers to forecast the number of beds in hospitals and intensive care units needed 12 days ahead. Conclusion: The obtained results show that a standardized TPR HGNC index is a valuable metric to monitor the growth of the COVID-19 MESHD epidemic. The index can be computed on daily basis and it is probably one of the best forecasting tools available today for predicting hospital and intensive care units overload, being an optimal compromise between simplicity of calculation and accuracy.

    SARS-COV-2 Spike Glycoprotein PROTEIN as Inhibitory Target for Insilico Screening of Natural Compounds

    Authors: Damilola Alex Omoboyowa; Balogun Toheeb A; Onyeka S. Chukwudozie; Victor N. Nweze; Oluwatosin A. Saibu; Alausa Abdulahi

    doi:10.21203/rs.3.rs-271483/v1 Date: 2021-02-23 Source: ResearchSquare

    Coronavirius disease MESHD 2019 ( Covid-19 MESHD) pandemic caused by SARS-Cov-2 has raised global health concern without approved drug for management of this lie threatening disease. The aim of this study was to predict the inhibitory potential of quercetin-3-o-rutinoside against SARS-Cov-2 spike glycoprotein PROTEIN. Targeting the SARS-Cov-2 spike protein PROTEIN from angiotensin converting enzyme 2 complex (pdb: 6lzg) is gaining importance. In this study, in silico computational relationship between plant-derived natural drug and spike glycoprotein PROTEIN was predicted. The results were evaluated based on glide (Schrodinger) dock score. Among the five (5) screened compounds, quercetin-3-o-rutinoside has the best docking score (-9.296) with the target. Molecular dynamic ( MD MESHD) simulation study was performed for 1000ps to confirm the stability behavior of the spike protein PROTEIN and quercetin-3-o-rutinoside complex. The MD simulation study validated the stability of quercetin-3-o-rutinoside in the spike protein PROTEIN binding pocket as potent inhibitor.

    Heparin Induced Thrombocytopenia MESHD in Patients with COVID-19 MESHD

    Authors: Surbhi Warrior; Elizabeth Behrens; Sefer Gezer; Parameswaran Venugopal; Shivi Jain

    doi:10.21203/rs.3.rs-194846/v1 Date: 2021-01-31 Source: ResearchSquare

    Background Acute respiratory and renal failure MESHD as well as systemic coagulopathy MESHD are critical aspects of the morbidity and mortality in patients with COVID-19 MESHD. Heparin Induced Thrombocytopenia MESHD ( HIT MESHD) occurs when IgG antibodies form against platelet factor 4-Heparin complex, resulting in platelet activation and removal, leading to a prothrombotic state. Studies have shown that only 6% who are investigated serologically for HIT MESHD actually have the diagnosis.Methods A retrospective analysis was performed on all COVID-19 MESHD positive patients hospitalized between March and June 2020. Patients with suspicion for HIT MESHD were tested for HIT MESHD antibodies with IgG-specific platelet factor 4( PF4 HGNC)-dependent enzyme immunoassay (EIA). Confirmatory testing with serotonin release assay ( SRA HGNC) and heparin-induced platelet aggregation MESHD were used in cases with intermediate or low optical density (OD) with EIA positivity (EIA+). Due to rarity of disease MESHD, a through literature review on HIT MESHD in COVID-19 MESHD patients was also analyzed.Results Incidence of EIA + in COVID-19 MESHD patients was 0.6%, significantly higher than in the general population 0.2% (p < 0.0001). The incidence of thromboembolic MESHD events in EIA + patients was 87.5%, significantly higher than the rate of 10.90% in all COVID-19 MESHD patients (p < 0.0001). The mortality rate in EIA + patients was 50%, significantly greater than the mortality rate of 12% in all hospitalized COVID-19 MESHD patients (p = 0.0011). Serological confirmation of HIT MESHD diagnosis was 37.5% which is significantly higher than confirmation of HIT MESHD in non COVID-19 MESHD patients 6% (p < 0.0001). Of 39 HIT MESHD antibody positive patients in the literature, 23.07% had positive confirmatory testing (6 SRA HGNC, 3 HIPAA) which is significantly higher than 5.6% in the general population (p = 0.00001). The incidence of thrombosis MESHD in EIA +  COVID-19 MESHD patients in the literature was 56.4% which is significantly higher than reported rates of thrombotic MESHD events in in all COVID-19 MESHD patients in the literature at 4.8%1 (p = 0.00001).Conclusion Our study indicates incidence of HIT MESHD is higher in the COVID-19 MESHD population. This can be attributed to the cytokine storm and severe sepsis MESHD seen in critically ill COVID-19 MESHD patients. Our study also suggests that development of HIT MESHD can contribute to increased risk for thromboembolic MESHD events as well as mortality of COVID-19 MESHD patients, however, our study is limited due to small sample size.

    Seroprevalence of SARS-CoV-2 antibodies in South Korea

    Authors: Kwangmin Lee; Seongil Jo; Jaeyong Lee

    id:2101.11991v1 Date: 2021-01-28 Source: arXiv

    In $2020$, Korea Disease MESHD Control and Prevention Agency reported three rounds of surveys on seroprevalence of severe acute respiratory syndrome coronavirus 2 MESHD (SARS-CoV-2) antibodies in South Korea. We analyze the seroprevalence surveys using a Bayesian method with an informative prior distribution on the seroprevalence parameter, and the sensitivity and specificity of the diagnostic test. We construct the informative prior using the posterior distribution obtained from the clinical evaluation data based on the plaque reduction neutralization test. The constraint of the seroprevalence parameter induced from the known confirmed coronavirus 2019 cases can be imposed naturally in the proposed Bayesian model. We also prove that the confidence interval of the seroprevalence parameter based on the Rao's test can be the empty set, while the Bayesian method renders a reasonable interval estimator. As of the $30$th of October $2020$, the $95\%$ credible interval of the estimated SARS-CoV-2 positive population does not exceed $307,448$, approximately $0.6\%$ of the Korean population.

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MeSH Disease
HGNC Genes
SARS-CoV-2 Proteins


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