Corpus overview


MeSH Disease

Human Phenotype


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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.

    Antibody SERO Response and Therapy in COVID-19 Patients: Significance in Vaccine Development

    Authors: Ligong Lu; Hui Zhang; Meixiao Zhan; Jun Jiang; Hua Yin; Danielle J. Dauphars; Shi-You Li; Yong Li; You-Wen He

    id:10.20944/preprints202008.0166.v1 Date: 2020-08-06 Source:

    The newly emerged severe acute respiratory syndrome MESHD coronavirus 2 (SARS-CoV-2) has infected millions of people and caused tremendous morbidity and mortality worldwide. Effective treatment for coronavirus disease MESHD 2019 (COVID-19) due to SARS-CoV-2 infection MESHD is lacking and different therapeutic strategies are under testing. Host humoral and cellular immunity to SARS-CoV-2 infection MESHD is a critical determinant for patients’ outcome. SARS-CoV-2 infection MESHD results in seroconversion and production of anti- SARS-CoV-2 antibodies SERO. The antibodies SERO may suppress viral replication through neutralization but also might also participate in COVID-19 pathogenesis through a process termed antibody SERO-dependent enhancement. Rapid progress has been made in the research of antibody SERO response and therapy in COVID-19 patients including characterization of the clinical features of antibody SERO responses in different populations infected by SARS-CoV-2, treatment of COVID-19 patients with convalescent plasma SERO and intravenous immunoglobin products, isolation and characterization of a large panel of monoclonal neutralizing antibodies SERO, as well as preliminary clinical results from several COVID-19 vaccine candidates. In this review, we summarize the recent progress and discuss the implications of these findings in vaccine development.

    Clinical Mortality Review in a Large COVID-19 Cohort

    Authors: Mark P Jarrett; Susanne F Schultz; Julie S Lyall; Jason J Wang; Lori Stier; Marcella De Geronimo; Karen L Nelson

    doi:10.1101/2020.08.05.20168146 Date: 2020-08-06 Source: medRxiv

    Background: Northwell Health (Northwell), an integrated health system in New York, treated more than 15000 inpatients with coronavirus disease MESHD (COVID-19) at the US epicenter of the severe acute respiratory syndrome MESHD coronavirus 2 (SARS-CoV-2) pandemic. We describe the demographic characteristics of COVID-19 mortalities, observation of frequent rapid response teams (RRT)/ cardiac arrest HP (CA) calls for non-intensive care unit (ICU) patients, and factors that contributed to RRT/CA calls. Methods: A team of registered nurses reviewed medical records of inpatients who tested positive for SARS-CoV-2 via polymerase chain reaction (PCR) before or on admission and died between March 13 (first Northwell inpatient expiration) and April 30, 2020 at 15 Northwell hospitals. Findings for these patients were abstracted into a database and statistically analyzed. Findings: Of 2634 COVID-19 mortalities, 56.1% had oxygen saturation levels greater than or equal to 90% on presentation and required no respiratory support. At least one RRT/CA was called on 42.2% of patients at a non-ICU level of care. Before the RRT/CA call, the most recent oxygen saturation levels for 76.6% of non-ICU patients were at least 90%. At the time RRT/CA was called, 43.1% had an oxygen saturation less than 80%. Interpretation: This study represents one of the largest cohorts of reviewed mortalities that also captures data in non-structured fields. Approximately 50% of deaths MESHD occurred at a non-ICU level of care, despite admission to the appropriate care setting with normal staffing. The data imply a sudden, unexpected deterioration in respiratory status requiring RRT/CA in a large number of non-ICU patients. Patients admitted to a non-ICU level of care suffer rapid clinical deterioration MESHD, often with a sudden decrease in oxygen saturation. These patients could benefit from additional monitoring (eg, continuous central oxygenation saturation), although this approach warrants further study.

    Signatures and mechanisms of efficacious therapeutic ribonucleotides against SARS-CoV-2 revealed by analysis of its replicase using magnetic tweezers

    Authors: Mona Seifert; Subhas C. Bera; Pauline van Nies; Robert N. Kirchdoerfer; Ashleigh Shannon; Thi-Tuyet-Nhung Le; Tyler L. Grove; Flavia S. Papini; Jamie J. Arnold; Steven C. Almo; Bruno Canard; Martin Depken; Craig E. Cameron; David Dulin

    doi:10.1101/2020.08.06.240325 Date: 2020-08-06 Source: bioRxiv

    Coronavirus Disease MESHD 2019 (COVID-19) results from an infection MESHD infection by the severe HP by the severe acute respiratory syndrome MESHD coronavirus 2 (SARS-CoV-2), the third coronavirus outbreak to plague MESHD humanity this century. Currently, the most efficacious therapeutic against SARS-CoV-2 infection MESHD is the Remdesivir (RDV), an adenine-like ribonucleotide analogue that is very efficiently incorporated by the SARS-CoV-2 replicase. Understanding why RDV is so well incorporated will facilitate development of even more effective therapeutics. Here, we have applied a high-throughput, single-molecule, magnetic-tweezers platform to study thousands of cycles of nucleotide addition by the SARS-CoV-2 replicase in the absence and presence of RDV, a Favipiravir-related analog (T-1106), and the endogenously produced ddhCTP. Our data are consistent with two parallel catalytic pathways of the replicase: a high-fidelity catalytic (HFC) state and a low-fidelity catalytic (LFC) state, the latter allowing the slow incorporation of both cognate and non-cognate nucleotides. ddhCTP accesses HFC, T-1106 accesses LFC as a non-cognate nucleotide, while RDV efficiently accesses both LFC pathway. In contrast to previous reports, we provide unequivocal evidence against RDV functioning as a chain terminator. We show that RDV incorporation transiently stalls the replicase, only appearing as termination events when traditional, gel-based assays are used. The efficiency of ddhCTP utilization by the SARS-CoV-2 replicase suggests suppression of its synthesis during infection MESHD, inspiring new therapeutic strategies. Use of this experimental paradigm will be essential to the development of therapeutic nucleotide analogs targeting polymerases.

    Camostat mesylate inhibits SARS-CoV-2 activation by TMPRSS2-related proteases and its metabolite GBPA exerts antiviral activity

    Authors: Markus Hoffmann; Heike Hofmann-Winkler; Joan C. Smith; Nadine Krueger; Lambert K. Sorensen; Ole S. Sogaard; Jorgen Bo Hasselstrom; Michael Winkler; Tim Hempel; Lluis Raich; Simon Olsson; Takashi Yamazoe; Katsura Yamatsuta; Hirotaka Mizuno; Stephan Ludwig; Frank Noe; Jason M. Sheltzer; Mads Kjolby; Stefan Poehlmann

    doi:10.1101/2020.08.05.237651 Date: 2020-08-05 Source: bioRxiv

    Antiviral therapy is urgently needed to combat the coronavirus disease MESHD 2019 (COVID-19) pandemic, which is caused by severe acute respiratory syndrome MESHD coronavirus 2 (SARS-CoV-2). The protease inhibitor camostat mesylate inhibits SARS-CoV-2 infection MESHD of lung cells by blocking the virus-activating host cell protease TMPRSS2. Camostat mesylate has been approved for treatment of pancreatitis MESHD pancreatitis HP in Japan and is currently being repurposed for COVID-19 treatment. However, potential mechanisms of viral resistance as well as camostat mesylate metabolization and antiviral activity of metabolites are unclear. Here, we show that SARS-CoV-2 can employ TMPRSS2-related host cell proteases for activation and that several of them are expressed in viral target cells. However, entry mediated by these proteases was blocked by camostat mesylate. The camostat metabolite GBPA inhibited the activity of recombinant TMPRSS2 with reduced efficiency as compared to camostat mesylate and was rapidly generated in the presence of serum SERO. Importantly, the infection MESHD experiments in which camostat mesylate was identified as a SARS-CoV-2 inhibitor involved preincubation of target cells with camostat mesylate in the presence of serum SERO for 2 h and thus allowed conversion of camostat mesylate into GBPA. Indeed, when the antiviral activities of GBPA and camostat mesylate were compared in this setting, no major differences were identified. Our results indicate that use of TMPRSS2-related proteases for entry into target cells will not render SARS-CoV-2 camostat mesylate resistant. Moreover, the present and previous findings suggest that the peak concentrations of GBPA established after the clinically approved camostat mesylate dose (600 mg/day) will result in antiviral activity.

    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

    Risk of hospitalisation with coronavirus disease MESHD 2019 in healthcare workers and their households:a nationwide linkage cohort study

    Authors: Anoop SV Shah; Rachael Wood; Ciara Gribben; David Caldwell; Jennifer Bishop; Amanda Weir; Sharon Kennedy; Martin Reid; Alison Smith-Palmer; David Goldberg; Jim McMenamin; Colin Fischbacher; Chris Robertson; Sharon Hutchinson; Paul M McKeigue; Helen M Colhoun; David McAllister

    doi:10.1101/2020.08.03.20164897 Date: 2020-08-04 Source: medRxiv

    Objective: Many healthcare staff work in high-risk settings for contracting and transmitting Severe Acute Respiratory Syndrome MESHD Coronavirus 2. Their risk of hospitalisation for coronavirus disease MESHD 2019 (COVID-19), and that of their households, is poorly understood. Design and settings and participants: During the peak period for COVID-19 infection MESHD in Scotland (1st March 2020 to 6th June 2020) we conducted a national record linkage study to compare the risk of COVID-19 hospitalisation among healthcare workers ( age TRANS: 18-65 years), their households and other members of the general population. Main outcome: Hospitalisation with COVID-19 Results: The cohort comprised 158,445 healthcare workers, the majority being patient facing (90,733 / 158,445; 57.3%), and 229,905 household members. Of all COVID-19 hospitalisations in the working age TRANS population (18-65-year-old), 17.2% (360 / 2,097) were in healthcare workers or their households. Adjusting for age TRANS, sex, ethnicity, socio-economic deprivation and comorbidity, the risk of COVID-19 hospitalisation in non-patient facing healthcare workers and their households was similar to the risk in the general population (hazards ratio [HR] 0.81; 95%CI 0.52-1.26 and 0.86; 95%CI 0.49-1.51 respectively). In models adjusting for the same covariates however, patient facing healthcare workers, compared to non-patient facing healthcare workers, were at higher risk (HR 3.30; 95%CI 2.13-5.13); so too were household members of patient facing healthcare workers (HR 1.79; 95%CI 1.10-2.91). On sub-dividing patient-facing healthcare workers into those who worked in front-door, intensive care and non-intensive care aerosol generating settings and other, those in front door roles were at higher risk (HR 2.09; 95%CI 1.49-2.94). For most patient facing healthcare workers and their households, the estimated absolute risk of COVID-19 hospitalisation was less than 0.5% but was 1% and above in older men with comorbidity. Conclusions: Healthcare workers and their households contribute a sixth of hospitalised COVID-19 cases. Whilst the absolute risk of hospitalisation was low overall, patient facing healthcare workers and their households had 3- and 2-fold increased risks of COVID-19 hospitalisation.

    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.

    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.

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MeSH Disease
Human Phenotype

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