Corpus overview


Overview

MeSH Disease

Human Phenotype

Transmission

Seroprevalence
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    Serology assessment of antibody SERO response to SARS-CoV-2 in patients with COVID-19 by rapid IgM/IgG antibody test SERO

    Authors: Yang De Marinis; Torgny Sunnerhagen; Pradeep Bompada; Anna Blackberg; Runtao Yang; Joel Svensson; Ola Ekstrom; Karl-Fredrik Eriksson; Ola Hansson; Leif Groop; Isabel Goncalves; Magnus Rasmussen

    doi:10.1101/2020.08.05.20168815 Date: 2020-08-06 Source: medRxiv

    The coronavirus disease MESHD 2019 (COVID-19) pandemic has created a global health- and economic crisis. Lifting confinement restriction and resuming to normality depends greatly on COVID-19 immunity screening. Detection of antibodies SERO to severe acute respiratory syndrome MESHD coronavirus 2 (SARS-CoV-2) which causes COVID-19 by serological methods is important to diagnose a current or resolved infection MESHD. In this study, we applied a rapid COVID-19 IgM/IgG antibody test SERO and performed serology assessment of antibody SERO response to SARS-CoV-2. In PCR-confirmed COVID-19 patients (n=45), the total antibody SERO detection rate is 92% in hospitalized patients and 79% in non-hospitalized patients. We also studied antibody SERO response in relation to time after symptom onset TRANS and disease MESHD severity, and observed an increase in antibody SERO reactivity and distinct distribution patterns of IgM and IgG following disease progression MESHD. The total IgM and IgG detection is 63% in patients with < 2 weeks from disease MESHD onset; 85% in non-hospitalized patients with > 2 weeks disease MESHD duration; and 91% in hospitalized patients with > 2 weeks disease MESHD duration. We also compared different blood SERO sample types and suggest a potentially higher sensitivity SERO by serum SERO/ plasma SERO comparing with whole blood SERO measurement. To study the specificity of the test, we used 69 sera/ plasma SERO samples collected between 2016-2018 prior to the COVID-19 pandemic, and obtained a test specificity of 97%. In summary, our study provides a comprehensive validation of the rapid COVID-19 IgM/IgG serology test, and mapped antibody SERO detection patterns in association with disease MESHD progress and hospitalization. Our study supports that the rapid COVID-19 IgM/IgG test may be applied to assess the COVID-19 status both at the individual and at a population level.

    An improved methodology for estimating the prevalence SERO of SARS-CoV-2

    Authors: Virag Patel; Catherine McCarthy; Rachel A Taylor; Ruth Moir; Louise A Kelly; Emma L Snary

    doi:10.1101/2020.08.04.20168187 Date: 2020-08-06 Source: medRxiv

    Since the identification of Coronavirus disease MESHD 2019 (COVID-19) caused by severe acute respiratory syndrome MESHD coronavirus 2 (SARS-CoV-2) in China in December 2019, there have been more than 17 million cases of the disease MESHD in 216 countries worldwide. Comparisons of prevalence SERO estimates between different communities can inform policy decisions regarding safe travel TRANS between countries, help to assess when to implement (or remove) disease MESHD control measures and identify the risk of over-burdening healthcare providers. Estimating the true prevalence SERO can, however, be challenging because officially reported figures are likely to be significant underestimates of the true burden of COVID-19 within a community. Previous methods for estimating the prevalence SERO fail to incorporate differences between populations (such as younger populations having higher rates of asymptomatic TRANS cases) and so comparisons between, for example, countries, can be misleading. Here, we present an improved methodology for estimating COVID-19 prevalence SERO. We take the reported number of cases and deaths MESHD (together with population size) as raw prevalence SERO for the population. We then apply an age TRANS-adjustment to this which allows the age TRANS-distribution of that population to influence the case-fatality rate and the proportion of asymptomatic TRANS cases. Finally, we calculate the likely underreporting factor for the population and use this to adjust our prevalence SERO estimate further. We use our method to estimate the prevalence SERO for 166 countries (or the states of the United States of America, hereafter referred to as US state) where sufficient data were available. Our estimates show that as of the 30th July 2020, the top three countries with the highest estimated prevalence SERO are Brazil (1.26%, 95% CI: 0.96 - 1.37), Kyrgyzstan (1.10%, 95% CI: 0.82 - 1.19) and Suriname (0.58%, 95% CI: 0.44 - 0.63). Brazil is predicted to have the largest proportion of all the current global cases (30.41%, 95%CI: 27.52 - 30.84), followed by the USA (14.52%, 95%CI: 14.26 - 16.34) and India (11.23%, 95%CI: 11.11 - 11.24). Amongst the US states, the highest prevalence SERO is predicted to be in Louisiana (1.07%, 95% CI: 1.02 - 1.12), Florida (0.90%, 95% CI: 0.86 - 0.94) and Mississippi (0.77%, 95% CI: 0.74 - 0.81) whereas amongst European countries, the highest prevalence SERO is predicted to be in Montenegro (0.47%, 95% CI: 0.42 - 0.50), Kosovo (0.35%, 95% CI: 0.29 - 0.37) and Moldova (0.28%, 95% CI: 0.23 - 0.30). Our results suggest that Kyrgyzstan (0.04 tests per predicted case), Brazil (0.04 tests per predicted case) and Suriname (0.29 tests per predicted case) have the highest underreporting out of the countries in the top 25 prevalence SERO. In comparison, Israel (34.19 tests per predicted case), Bahrain (19.82 per predicted case) and Palestine (9.81 tests per predicted case) have the least underreporting. The results of this study may be used to understand the risk between different geographical areas and highlight regions where the prevalence SERO of COVID-19 is increasing most rapidly. The method described is quick and easy to implement. Prevalence SERO estimates should be updated on a regular basis to allow for rapid fluctuations in disease MESHD patterns.

    Prediction of Single Point Mutations in Ganglioside-Binding Domain of SARS-CoV-2 S and Their Effects on Binding of 9-O-Acetylated Sialic Acid and Hidroxychloroquine

    Authors: Petar M. Mitrasinovic

    doi:10.26434/chemrxiv.12765953.v1 Date: 2020-08-06 Source: ChemRxiv

    The infectious disease MESHD CoViD-19 is caused by a new severe acute respiratory syndrome MESHD coronavirus 2 (SARS-CoV-2), also referred to as hCoV-19. A possible infection MESHD mechanism includes dual host receptor recognitions by the SARS-CoV-2 transmembrane spike (S) glycoproteins. SARS-CoV-2 S contains two different domains, the receptor-binding domain (RBD) and the N-terminal domain (NTD), which interact with the angiotensin-converting enzyme 2 (ACE2) and the ganglioside-rich domain of the plasma SERO membrane at the surface of respiratory cell, respectively. The NTD amino acid residues (111-162) form a functional ganglioside-binding domain (GBD) that is conserved in all clinical isolates. Herein, the single point mutations (SPMs) of the GBD residues to which the virus is prone during genetic adaptation are predicted using an in silico protein engineering approach. Consequently, their effects on the attachment of SARS-CoV-2 S to the ganglioside-linked 9-O-acetylated sialic acid (9-O-Ac-Sia) are explored using molecular docking simulations. Val120Tyr and Asn122Trp are found to be the most likely SPMs in the GBD of SARS-CoV-2 S being involved in very specific recognition with 9-O-Ac-Sia through electrostatic interactions. Val120Tyr and Asn122Trp are also found to be the most likely SPMs in the GBD of SARS-CoV-2 S that is involved in conspicuously hydrophobic recognition with hidroxychloroquine (Hcq), thereby indicating the ability of Hcq to competitively inhibit GBD interactions with lipid rafts. However, the considerably non-specific binding of Hcq and the micromolar range of the dissociation constants of the SARS-CoV-2 S/Hcq complexes do not support the proposal of treating Hcq as a drug candidate. Maintaining a clear resemblance of the structure of a potential drug candidate to a natural substrate, accompanied by essential functional group modifications, may be a usable guideline for the structure-based design of anti-CoViD-19 drugs.

    Structure of papain-like protease from SARS-CoV-2 and its complexes with non-covalent inhibitors

    Authors: Jerzy Osipiuk; Saara-Anne Azizi; Steve Dvorkin; Michael Endres; Robert Jedrzejczak; Krysten A. Jones; Rahul S. Kathayat; Vladislav G. Lisnyak; Samantha L. Maki; Soowon Kang; Youngchang Kim; Vlad Nicolaescu; Cooper A. Taylor; Christine Tesar; Yu-An Zhang; Zhiyao Zhou; Glenn Randall; Karolina Michalska; Scott A. Snyder; Bryan C. Dickinson; Andrzej Joachimiak

    doi:10.1101/2020.08.06.240192 Date: 2020-08-06 Source: bioRxiv

    The number of new cases world-wide for the COVID-19 disease MESHD is increasing dramatically, while efforts to contain Severe Acute Respiratory Syndrome MESHD Coronavirus 2 is producing varied results in different countries. There are three key SARS-CoV-2 enzymes potentially targetable with antivirals: papain-like protease (PLpro), main protease (Mpro), and RNA-dependent RNA polymerase. Of these, PLpro is an especially attractive target because it plays an essential role in several viral replication processes, including cleavage and maturation of viral polyproteins, assembly of the replicasetranscriptase complex (RTC), and disruption of host viral response machinery to facilitate viral proliferation and replication. Moreover, this enzyme is conserved across different coronaviruses and promising inhibitors have already been discovered for its SARS-CoV variant. Here we report a substantive body of structural, biochemical, and virus replication studies that identify several inhibitors of the enzyme from SARS-CoV-2 in both wild-type and mutant forms. These efforts include the first structures of wild-type PLpro, the active site C111S mutant, and their complexes with inhibitors, determined at 1.60-2.70 Angstroms. This collection of structures provides fundamental molecular and mechanistic insight to PLpro, and critically, illustrates details for inhibitors recognition and interactions. All presented compounds inhibit the peptidase activity of PLpro in vitro, and some molecules block SARS-CoV-2 replication in cell culture assays. These collated findings will accelerate further structure-based drug design efforts targeting PLpro, with the ultimate goal of identifying high-affinity inhibitors of clinical value for SARS-CoV-2.

    Analysis of the potential impact of genomic variants in SARS-CoV-2 genomes from India on molecular diagnostic assays

    Authors: Abhinav Jain; Mercy Rophina; Saurabh Mahajan; Bhavya Balaji Krishnan; Manasa Sharma; Sreya Mandal; Teresa Fernandez; Sumayra Sultanji; Samatha Mathew; Sridhar Sivasubbu; Vinod Scaria

    doi:10.1101/2020.08.05.238618 Date: 2020-08-05 Source: bioRxiv

    An isolated epidemic of Severe Acute Respiratory Syndrome MESHD Coronavirus 2 (SARS-CoV-2) causing Coronavirus Diseases MESHD (C0VID-19) originating in Wuhan, China has now rapidly emerged into a global pandemic affecting millions of people worldwide. Molecular detection of SARS-CoV-2 using reverse transcription polymerase chain reaction (RT-PCR) forms the mainstay in screening, diagnosis and epidemiology of disease MESHD. The virus has been evolving through base substitutions. The recent availability of genomes of SARS-CoV-2 isolates from different countries including India motivated us to assess the presence and potential impact of variations in target sites for the oligonucleotide primers and probes used in molecular diagnosis. We catalogued a total of 132 primers or probes sequences from the literature and the public domain. Our analysis revealed a total of 125 unique genetic variants in 80 either primers or probes binding sites. A total of 13 unique variants had allele frequency of [≥] 1% in Indian SARS-CoV-2 genomes mapped to the primers or probes binding sites. A total of 15 primers or probes binding sites had cumulative variant frequency of [≥] 1% in the SARS-CoV-2 genomes. These included primers or probes sites which are widely used in India and across the world for molecular diagnosis as well as approved by national and international agencies. This highlights the need for sequencing genomes of emerging pathogens to make evidence based policies for development and approval of diagnostics. To the best of our knowledge, ours is the most comprehensive analysis of genomic variants in genomes of SARS-CoV-2 isolates from India and their potential impact on efficacy of molecular diagnostics. Keywords: COVID-19, genomes, SARS-CoV-2, variations, reverse transcription polymerase chain reaction, Gibbs free energy

    A distinct innate immune signature marks progression from mild to severe COVID-19

    Authors: Stéphane Chevrier; Yves Zurbuchen; Carlo Cervia; Sarah Adamo; Miro E Raeber; Natalie de Souza; Sujana Sivapatham; Andrea Jacobs; Esther Bächli; Alain Rudiger; Melina Stüssi-Helbling; Lars C Huber; Dominik J Schaer; Jakob Nilsson; Onur Boyman; Bernd Bodenmiller

    doi:10.1101/2020.08.04.236315 Date: 2020-08-04 Source: bioRxiv

    Coronavirus disease MESHD 2019 (COVID-19) manifests with a range of severities, but immune signatures of mild and severe disease MESHD are still not fully understood. Excessive inflammation MESHD has been postulated to be a major factor in the pathogenesis of severe COVID-19 and innate immune mechanisms are likely to be central in the inflammatory response. We used 40-plex mass cytometry and targeted serum SERO proteomics to profile innate immune cell populations from peripheral blood SERO of patients with mild or severe COVID-19 and healthy controls. Sampling at different stages of COVID-19 allowed us to reconstruct a pseudo-temporal trajectory of the innate immune response. Despite the expected patient heterogeneity, we identified consistent changes during the course of the infection MESHD. A rapid and early surge of CD169+ monocytes associated with an IFN{gamma}+MCP-2+ signature quickly followed symptom onset TRANS; at symptom onset TRANS, patients with mild and severe COVID-19 had a similar signature, but over the course of the disease MESHD, the differences between patients with mild and severe disease MESHD increased. Later in the disease MESHD course, we observed a more pronounced re-appearance of intermediate/non-classical monocytes and mounting systemic CCL3 and CCL4 levels in patients with severe disease MESHD. Our data provide new insights into the dynamic nature of the early inflammatory response to severe acute respiratory syndrome MESHD coronavirus 2 (SARS-CoV-2) infection MESHD and identifies sustained pathological innate immune responses as a likely key mechanism in severe COVID-19, further supporting investigation of targeted anti-inflammatory interventions in severe COVID-19.

    The Lebanese Cohort for COVID-19; A Challenge for the ABO Blood SERO Group System

    Authors: Athar Khalil; Mahmoud Hassoun; Rita Feghali

    doi:10.1101/2020.08.02.20166785 Date: 2020-08-04 Source: medRxiv

    A sudden outbreak of pneumonia MESHD pneumonia HP caused by the Severe Acute Respiratory Syndrome MESHD Coronavirus 2 (SARS-CoV-2) has rapidly spread all over the world facilitating the declaration of the resultant disease MESHD as a pandemic in March,2020. In Lebanon, the fast action of announcing a state of emergency MESHD with strict measures was among the factors that helped in achieving a successful containment of the disease MESHD in the country. Predisposing factors for acquiring COVID-19 and for developing a severe form of this disease MESHD were postulated to be related to epidemiological and clinical characteristics as well as the genomics signature of a given population or its environment. Biological markers such as the ABO blood SERO group system was amongst those factors that were proposed to be linked to the variability in the disease MESHD course and/or the prevalence SERO of this infection MESHD among different groups. We therefore conducted the first retrospective case-control study in the Middle-East and North Africa that tackles the association between the blood SERO group types and the susceptibility as well as the severity of SARS-CoV2 infection MESHD. Opposing to the current acknowledged hypothesis, our results have challenged the association significance of this system with COVID-19. Herein, we highlighted the importance of studying larger cohorts using more rigorous approaches to diminish the potential confounding effect of some underlying comorbidities and genetic variants that are known to be associated with the ABO blood SERO group system.

    Epidemiological characteristics of SARS-COV-2 in Myanmar

    Authors: Aung Min Thway; Htun Tayza; Tun Tun Win; Ye Minn Tun; Moe Myint Aung; Yan Naung Win; Kyaw M Tun

    doi:10.1101/2020.08.02.20166504 Date: 2020-08-04 Source: medRxiv

    Coronavirus disease MESHD (COVID-19) is an infectious disease MESHD caused by a newly discovered severe acute respiratory syndrome MESHD coronavirus 2 (SARS-CoV-2). In Myanmar, first COVID-19 reported cases were identified on 23rd March 2020. There were 336 reported confirmed cases TRANS, 261 recovered and 6 deaths MESHD through 13th July 2020. The study was a retrospective case series and all COVID-19 confirmed cases TRANS from 23rd March to 13th July 2020 were included. The data series of COVID-19 cases were extracted from the daily official reports of the Ministry of Health and Sports (MOHS), Myanmar and Centers for Disease MESHD Control and Prevention (CDC), Myanmar. Among 336 confirmed cases TRANS, there were 169 cases with reported transmission TRANS events. The median serial interval TRANS was 4 days (IQR 3, 2-5) with the range of 0 - 26 days. The mean of the reproduction number TRANS was 1.44 with (95% CI = 1.30-1.60) by exponential growth method and 1.32 with (95% CI = 0.98-1.73) confident interval by maximum likelihood method. This study outlined the epidemiological characteristics and epidemic parameters of COVID-19 in Myanmar. The estimation parameters in this study can be comparable with other studies and variability of these parameters can be considered when implementing disease MESHD control strategy in Myanmar.

    SARS-CoV-2 infection MESHD, disease MESHD and transmission TRANS in domestic cats

    Authors: Natasha N Gaudreault; Jessie D Trujillo; Mariano Carossino; David A Meekins; Igor Morozov; Daniel W Madden; Sabarish V Indran; Dashzeveg Bold; Velmurugan Balaraman; Taeyong Kwon; Bianca Libanori Artiaga; Konner Cool; Adolfo Garcia-Sastre; Wenjun Ma; William C Wilson; Jamie Henningson; Udeni BR Balasuriya; Juergen A Richt

    doi:10.1101/2020.08.04.235002 Date: 2020-08-04 Source: bioRxiv

    Severe Acute Respiratory Syndrome MESHD Coronavirus 2 (SARS-CoV-2) is the cause of Coronavirus Disease MESHD 2019 (COVID-19) and responsible for the current pandemic. Recent SARS-CoV-2 susceptibility and transmission TRANS studies in cats show that the virus can replicate in these companion animals and transmit to other cats. Here, we present an in-depth study of SARS-CoV-2 infection MESHD, associated disease MESHD and transmission TRANS dynamics in domestic cats. Six 4- to 5-month-old cats were challenged with SARS-CoV-2 via intranasal and oral routes simultaneously. One day post challenge (DPC), two sentinel contact cats were co-mingled with the principal infected animals. Animals were monitored for clinical signs, clinicopathological abnormalities and viral shedding throughout the 21 DPC observation period. Postmortem examinations were performed at 4, 7 and 21 DPC to investigate disease progression MESHD. Viral RNA was not detected in blood SERO but transiently in nasal, oropharyngeal and rectal swabs and bronchoalveolar lavage fluid as well as various tissues. Tracheobronchoadenitis of submucosal glands with the presence of viral RNA and antigen was observed in airways of the infected cats on 4 and 7 DPC. Serology showed that both, principal and sentinel cats, developed SARS-CoV-2-specific and neutralizing antibodies to SARS-CoV-2 SERO detectable at 7 DPC or 10 DPC, respectively. All animals were clinically asymptomatic TRANS during the course of the study and capable of transmitting SARS-CoV-2 to sentinels within 2 days of comingling. The results of this study are critical for our understanding of the clinical course of SARS-CoV-2 in a naturally susceptible host species, and for risk assessment of the maintenance of SARS-CoV-2 in felines and transmission TRANS to other animals and humans.

    COVID-19 Vaccine Candidates by Identification of B and T Cell Multi-Epitopes Against SARS-COV-2

    Authors: Suresh Kumar; Sarmilah Mathavan; Wee Jia Jin; Nur Azznira Bt Azman; Devindren Subramanaiam; Nur Afiqah Binti Zainalabidin; Dhivashini Lingadaran; Zainah Binti Abdul Sattar; Danniya Lakshmi Manickam; Priscilla Sheba Anbananthan; Johan Ahmad Taqiyuddin; Yuvapriya Thevarajan

    id:10.20944/preprints202008.0092.v1 Date: 2020-08-04 Source: Preprints.org

    Coronavirus disease MESHD (COVID-19) is a new discovered strain where WHO officially declares the disease MESHD as COVID-19 while the virus responsible for it called Severe Acute Respiratory Syndrome MESHD Coronavirus 2 or SARS-CoV-2. The incubation period TRANS of this disease MESHD is between 14 days. Ordinary clinical symptoms that reported around the world include fever MESHD fever HP, cough MESHD cough HP, fatigue MESHD fatigue HP, diarrhoea and vomiting MESHD vomiting HP as well as asymptomatic TRANS for certain people. Infection MESHD is spread mainly through broad droplets. In early March 2020, WHO again has announced that COVID-19 is a pandemic with currently no specific treatment. The potential use of SARS-COV-2 proteome as a vaccine candidate by analysing through B-cell and T-cell antigenicity by using a immunoinformatics approach as a vaccine development early stage. In this study, we used consensus sequence for SARS-COV-2 proteome that was retrieved from NCBI database. VaxiJen 2.0 was mainly used to identify the antigenic property of SARS-COV-2 proteins. IEDB then used to analyse the B-cell epitope, the presence of T cell immunogenic epitope in SARS-COV-2 proteins was obtained by using compromise method of MHC class I and II tools that accessible respectively using ProPred-1 server and MHC II Binding Prediction in IEDB database. The best epitopes of B and T-cell epitopes were predicted with high antigencity and the information is disseminated through web-based database resource (https://covid-19.omicstutorials.com/epitopes/). This study will be useful to find a new epitope-based candidate for SARS-COV-2. However, further study needs to be done for the next stages of vaccine development.

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MeSH Disease
Human Phenotype
Transmission
Seroprevalence


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